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June 2011 Volume 97 Supplement I
97
Volume 97 Supplement I Pages A1–A104
heart
HEART
British Cardiovascular Society
Annual Conference
13–15 June 2011
Manchester Central
June 2011
heart.bmj.com www.bcs.com
Young Research Workers’ Prize
A
ENDOTHELIAL CELL NITRIC OXIDE BIOAVAILABILITY AND
INSULIN SENSITIVITY ARE REGULATED BY IGF-1 AND
INSULIN RECEPTOR LEVELS
doi:10.1136/heartjnl-2011-300110.1
A Abbas, H Viswambharan, H Imrie, A Rajwani, M Kahn, M Gage, R Cubbon, J Surr,
S Wheatcroft, M Kearney. Leeds Institute of Genetics Health and Therapeutics, Leeds, UK
Background In a similar manner to insulin, the growth promoting
hormone Insulin-like Growth Factor-1 (IGF-1), may be an important
regulator of endothelial nitric oxide (NO) bioavailability. We have
previously reported evidence of increased basal NO production in
the vasculature in two murine models of reduced IGF-1 receptor
(global hemizygous knockout (IGFRKO) and endothelial cell specific
IGF-1R knockout (ECIGFRKO)). Augmentation of this increase in
NO is relative to progressive decrease in IGF-1R number (WT vs
ECIGFRKO hemizygotes pВј0.01, WT vs ECIGFRKO homozygotes
pВј0.001). Furthermore, by decreasing IGF-1R numbers in the
insulin resistant hemizygous insulin receptor knockout (IRKO)
model (IRKO 3 IGFRKO) we have shown insulin sensitivity in the
vasculature can be restored. In this study, we have investigated
further these receptor interactions with the generation of a mouse
overexpressing the human IGF-1R specifically in the endothelium
under control of the Tie-2 promoter-enhancer (hIGFREO), and by
targeted knockdown of the IGF-1R in human umbilical vein endothelial cells (HUVECs).
Methods Metabolic function was assessed in mice by tolerance tests
using whole-blood micro-sampling after insulin or glucose intraperitoneal injection. Cardiovascular function was assessed by
thoracic aortic vasomotion ex vivo in the organbath. Complimentary
in vitro studies were conducted by siRNA mediated downregulation
of the IGF-1 receptor in HUVECs with and wihout insulin stimulation. Nitric oxide synthase activity was measured using an assay
measuring conversion of [14C]-L-arginine to [14 C]-L-citrulline.
Results Glucose and insulin tolerance testing showed no difference
between hIGFREO mice and wild-type (WT) littermates. Murine
thoracic aorta from hIGFREO mice were hypercontractile to
phenylepherine (PE) compared to WT (Emax hIGFREOВј
0.9160.045 g; WTВј0.6260.045 g, pВј0.0036) with decreased
response
to
LNMMA
(Emax
hIGFREOВј47.7069.87 g;
WTВј106.1630.10 g, pВј0.048). These data indicate reduced endothelial NO bioavailability in hIGFREO mice compared to WT.
HUVECs transfected with IGF1R-siRNA showed increased basal
and insulin mediated eNOS phosphorylation in the presence of
insulin (Ins: 16464.9% vs siRNA+Ins: 19260.7%, p<0.05). eNOS
activity (L-arginine, L-citrulline assay) was enhanced upon trans-
Abstract A Figure 2
Abstract A Figure 3
Abstract A Figure 4
Abstract A Figure 1
Heart June 2011 Vol 97 Suppl 1
fection with IGF1R-siRNA (Scrambled siRNA: 95.7613.7% vs
IGF1R-siRNA: 188.7648.3%, p<0.05).
Implications These data demonstrate that increasing numbers of
IGF-1R specifically in murine endothelium leads to reduced NO
bioavailability. Complementary siRNA studies confirm results of
previous murine studies that reducing IGF-1R numbers enhance NO
bioavailability. Therefore this raises the intriguing possibility that
manipulation of IGF-1R numbers may represent a novel therapeutic
A1
Young Research Workers’ Prize
intervention (PCI) were prospectively enrolled and underwent full
3-vessel VH-IVUS pre-PCI. Troponin-I (cTnI), IL-6, IL-18, hsCRP,
neopterin, MCP-1 and sICAM-1 were measured pre-PCI and 24-h
post-PCI. LTL was determined by qPCR. The combined primary
endpoint (MACE) included unplanned revascularisation, myocardial
infarction (MI) and death, with a secondary endpoint of post-PCI
MI (MI 4a).
Results 18 MACE occurred in 16 patients (median follow-up: 625
(463e990) days). 30 372 mm of VH-IVUS were analysed and 1106
plaques classified (Abstract B Figure 1) locally and via a core-lab.
After multivariable regression:
Abstract A Figure 5
1. Total number of non-calcified VH-IVUS-identified thin
capped п¬Ѓbroatheromata (VHTCFA) was the only factor
independently associated with MACE (HRВј3.16, (95%
CIВј1.16 to 8.64), pВј0.025).
2. Total VHTCFA number (ORВј1.26 (1.03 to 1.53) pВј0.021)
and total stent length (ORВј1.04 (1.01 to 1.08), pВј0.01) were
the only factors independently associated with MI 4a.
3. A novel 3-vessel vulnerability index (necrotic core: п¬Ѓbrous
tissue ratio) and side branch loss were independently associated
with stenting-related cTnI rise (standardised beta coefficient
(sb)Вј0.29, pВј0.004 and sbВј0.23, pВј0.019 respectively).
4. Necrotic core area at the minimum luminal area frame was
the only factor independently associated with ACS presentation (ORВј1.59, pВј0.030).
5. Stented vessel VHTCFA number (ORВј1.75 (1.22 to 2.51),
pВј0.002) was independently associated with the lower LTL
tertile (DNA-based cardiovascular risk predictor).
6. Stenting-related IL-6 rise was the only biomarker independently associated with MACE (HRВј1.03 (1.01e1.05),
pВј0.007).
Abstract A Figure 6
strategy by which to modify vascular NO bioavailability and
endothelial cell insulin sensitivity.
B
Conclusion We present the п¬Ѓrst report of an association between
VHTCFA and MACE. This provides novel evidence that VHTCFA
definitions are important in their own right (rather than as
analogues of histological TFCA definitions). We also present the first
report of associations between VHTCFA and MI 4a as well as a
novel vulnerability index that is association with stenting-related
troponin rise. Finally, we report a novel association between
VHTCFA and DNA-based cardiovascular risk prediction (LTL).
VH-IVUS FINDINGS PREDICT MAJOR ADVERSE
CARDIOVASCULAR EVENTS. THE VIVA STUDY (VIRTUAL
HISTOLOGY INTRAVASCULAR ULTRASOUND IN
VULNERABLE ATHEROSCLEROSIS)
doi:10.1136/heartjnl-2011-300110.2
1
P A Calvert, 1D R Obaid, 2N E J West, 2L M Shapiro, 2D McNab, 2C G Densem,
P M Schofield, 2D Braganza, 2S C Clarke, 2M O’Sullivan, 3K K Ray, 1M R Bennett.
1
University of Cambridge, Cambridge, UK; 2Papworth Hospital NHS Foundation Trust,
Cambridge, UK; 3St George’s University of London, London, UK
2
Background Identification of high-risk atherosclerotic plaques offers
opportunities for risk stratification and targeted intensive treatment
of patients with coronary artery disease. Virtual Histology intravascular ultrasound (VH-IVUS) has been validated in human atherectomy and post-mortem studies and can classify plaques into
presumed high- and low-risk groups. However, VH-IVUS-defined
plaques have not been shown to be associated with major adverse
cardiovascular events (MACE), or biomarkers that confer increased
cardiovascular risk, such as serum cytokines or shortened leukocyte
telomere length (LTL).
Methods 170 patients with stable angina or troponin-positive acute
coronary syndrome (ACS), referred for percutaneous coronary
A2
Abstract B Figure 1
Heart June 2011 Vol 97 Suppl 1
Young Research Workers’ Prize
C
INSULIN RESISTANCE IMPAIRS ANGIOGENIC PROGENITOR
CELL FUNCTION AND DELAYS ENDOTHELIAL REPAIR
FOLLOWING VASCULAR INJURY
doi:10.1136/heartjnl-2011-300110.3
M B Kahn, N Yuldasheva, R Cubbon, J Surr, S Rashid, H Viswambharan, H Imrie,
A Abbas, A Rajwani, M Gage, M T Kearney, S Wheatcroft. Leeds University, Leeds, UK
Introduction Insulin-resistance, the primary metabolic abnormality
underpinning type-2-diabetes mellitus (T2DM) and obesity, is an
important risk factor for the development of atherosclerotic cardiovascular disease. Circulating-angiogenic-progenitor-cells (APCs)
participate in endothelial-repair following arterial injury. Type-2
diabetes is associated with fewer circulating APCs, APC dysfunction
and impaired endothelial-repair. We set out to determine whether
insulin-resistance per se adversely affects APCs and endothelialregeneration.
Research Design and Methods We quantified APCs and assessed
APC-mobilisation and function in mice hemizygous for knockout of
the insulin receptor (IRKO) and wild-type (WT) littermate controls.
Endothelial-regeneration following femoral artery wire-injury was
also quantified at time intervals after denudation and following APC
transfusion.
Results The metabolic phenotype of IRKO mice was consistent
with compensated insulin resistance, with hyperinsulinaemia after a
glucose challenge but a normal blood glucose response to a glucose
tolerance test. IRKO mice had fewer circulating Sca-1+/Flk-1+
APCs than WT mice at baseline. Culture of mononuclear-cells
demonstrated that IRKO mice had fewer APCs in peripheral-blood,
but not in bone-marrow or spleen, suggestive of a mobilisation
defect. Defective VEGF-stimulated APC mobilisation was confirmed
in IRKO mice, consistent with reduced eNOS expression in bone
marrow and impaired vascular eNOS activity. Paracrine-angiogenicactivity of APCs from IRKO mice was impaired compared to those
from WT animals. Endothelial-regeneration of the femoral artery
following denuding wire-injury was delayed in IRKO mice
compared to WT (re-endothelialised area 35.864.8% vs 66.665.2%
at day 5 following injury and 35.664.8% vs 59.866.6% at day 7;
P<0.05) (Abstract C Figure 1A). Transfusion of mononuclear-cells
from WT mice normalised the impaired endothelial-regeneration in
IRKO mice (5764% vs 2565%; p<0.002). Transfusion of c-kit+
bone-marrow cells from WT mice also restored endothelial-regeneration in IRKO mice (6262% vs 2565%; p<0.002). However,
transfusion of c-kit+ cells from IRKO mice was less effective at
improving endothelial-repair (6262% vs 4564%; p<0.02) (Abstract
C Figure 1B).
Conclusions Insulin-resistance impairs APC function and delays
endothelial-regeneration following arterial injury. These п¬Ѓndings
support the hypothesis that insulin-resistance per se is sufficient to
jeopardise endogenous vascular repair. Defective endothelial-repair
Abstract C Figure 1 (A) Time-dependent endothelial regeneration
following vascular injury (n=5 mice per group; *denotes p<0.05). (B) Effects
on endothelial regeneration 5 days after wire-injury of transfusion of spleenderived MNCs or BM-derived c-kit (CD117)+ve cells from WT or IRKO mice
(n=4 mice per group).
Heart June 2011 Vol 97 Suppl 1
may be normalised by transfusion of APCs from insulin-sensitive
animals but not from insulin-resistant animals. These data may
have important implications for the development of therapeutic
strategies for insulin-resistance associated cardiovascular disease.
D
UPTAKE OF ULTRASMALL SUPERPARAMAGNETIC
PARTICLES OF IRON OXIDE PREDICTS GROWTH IN
ABDOMINAL AORTIC ANEURYSMS: A PILOT STUDY
doi:10.1136/heartjnl-2011-300110.4
J M J Richards, S I Semple, T J Mac Gillivray, C Gray, J P Langrish, M Williams,
M Dweck, W Wallace, G McKillop, R T A Chalmers, O J Garden, D E Newby. University
of Edinburgh, Edinburgh, UK
Background Prediction of abdominal aortic aneurysm (AAA)
expansion and rupture is challenging and currently relies on serial
measurements of maximum aneurysm diameter. Using ultrasmall
superparamagnetic particles of iron oxide (USPIO) and MRI, we
aimed to assess whether areas of cellular inflammation correlated
with the rate of abdominal aortic aneurysm expansion.
Methods and Results An image acquisition and data analysis algorithm for the detection of focal USPIO accumulation in tissues was
developed. Patients (nВј29; 27 male; aged 7065 years) with asymptomatic AAA (4.0e6.6 cm) were recruited from an outpatient
surveillance programme and underwent 3T MRI before and 24e36 h
after administration of USPIO. The change in T2* value on T2*weighted imaging was used to detect accumulation of USPIO within
the abdominal aortic aneurysm. Histology of aortic wall tissue samples
confirmed co-localisation and uptake of USPIO in areas with macrophage infiltration. Patients were classified into one of three groups on
the basis of imaging п¬Ѓndings (Abstract D Figure 1). Group 1: periluminal USPIO uptake only. Group 2: USPIO uptake throughout the
thrombus. Group 3: USPIO uptake in the aortic wall. Patients in group
3 with distinct mural uptake of USPIO had a threefold higher growth
rate (nВј13; 0.66 cm/yr; pВј0.020) than those with no (Group 1; nВј7;
0.22 cm/yr) or non-specific USPIO uptake (Group 2; n¼9; 0.24 cm/yr)
despite having similar aneurysm diameters (5.460.6, 5.160.5 and
5.060.5 cm respectively; p>0.05) and patient characteristics
(p>0.05). In one patient with an inflammatory aneurysm, USPIO
uptake and inflammation extended beyond the aortic wall into
surrounding tissues.
Conclusion USPIO uptake in the aortic wall detects cellular inflammation in patients with AAA and appears to predict more rapidly
progressive AAA expansion. This technique therefore holds major
promise as a new method of risk-stratifying patients with AAA that
extends beyond the simple anatomical measure of aneurysm diameter.
Abstract D Figure 1
A3
Young Research Workers’ Prize
(Abstract E Figure 2B) and potentially causative sequence variants
in these 3 candidate genes have been identified. We have translated
these п¬Ѓndings to humans using data from a genome-wide association study population.
Conclusions We have identified a new genomic locus for HR, which
does not contain genes in pathways already known to determine
HR. We prioritised three candidate genes at the locus, which may be
targets for therapeutic modulation of HR in patients with heart
disease.
Abstract D Figure 2
E
INTEGRATIVE GENOMICS APPROACHES IDENTIFY NEW
GENES CONTROLLING HEART RATE
doi:10.1136/heartjnl-2011-300110.5
1,2
J S Ware, 3H Dobrzynski, 4M Pravanec, 1P J Muckett, 1S Wilkinson,
Y Jamshidi, 1T J Aitma, 6N S Peters, 1,2S A Cook. 1MRC Clinical Sciences Centre,
Imperial College London, London, UK; 2National Heart & Lung Institute, Imperial
College London, London, UK; 3School of Medicine, University of Manchester,
Manchester, UK; 4Institute of Physiology, Czech Academy of Science, Prague, UK;
5
Division of Clinical Developmental Sciences, St. George’s University of
London, London, UK; 6National Heart & Lung Institute, Imperial College London,
London, UK
5
Introduction Heart rate (HR) is a fundamental measure of cardiac
function, and is of prognostic and therapeutic significance. We
applied genetic and genomic approaches to identify new loci and
genes controlling HR in a rat model that has previously been used to
п¬Ѓnd human cardiovascular disease genes.
Methods Telemetric aortic pressure transducers were implanted into
226 animals from 33 rat strains: the Brown Norway, the Spontaneously Hypertensive Rat, and 31 strains from a recombinant inbred
panel derived from these parental strains and HR was measured over
several weeks. Statistical analyses were carried out using the R
package, and quantitative trait loci (QTL) identified by linkage
mapping using QTL Reaper. Potential covariates of HR were
analysed in SPSS. The sinus node (SN) and right atria (RA) of 20 rats
were microdissected (Abstract E Figure 1). Gene expression data
were generated with the Affymetrix Rat Gene 1.0 ST microarray
and analysed using Bioconductor. Differentially expressed genes
were identified using SAM & Limma. Genes in the QTL that were
expressed in the SN were resequenced to identify potential causative
sequence variants.
Results Narrow sense heritability of HR in this population was
51%, suggesting a large genetic contribution to HR. Linkage
mapping identified a region on rat chromosome 13 controlling HR,
with peak LOD score 6.7 (Abstract E Figure 2A). This QTL has not
previously been identified in human, rat or mouse. Mean nocturnal
HR in strains carrying the SHR allele was 388, compared with 357
in BN-like strains; an allelic effect of 31bpm (8.7%, p<0.00005)
that is equivalent to 5e9 bpm in humans, corresponding to a
decreased risk of cardiovascular death of 10%e29%. Two independent approaches (linear regression modelling & correlation
analysis) confirmed that this effect was independent of potential
physiological covariates, suggesting that the effect may be intrinsic
to the heart, rather than due to neurohumeral influences.We have
generated the first genomewide transcript expression profile of the
SN. Three genes at the new HR locus were enriched in the SN
A4
Abstract E Figure 1 Small (1 mm2) pieces of tissue were isolated from
the rat SN and distant trabeculated RA and RNA extracted for gene
expression profiling.
Abstract E Figure 2 (A) Interval mapping revealed a linkage peak on
chr13. Linkage was strongest for nocturnal HR, with a LOD score of 6.7
(p>0.00005). The horizontal line approximates to genomewide
significance. (B) A volcano plot showing 3 genes significantly enriched in
SN compared with RA.
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
difference in outcome was noted by route of admission for either inhospital or 1-year events.
Abstracts
1
ROUTE OF ADMISSION IN STEMI: DO PATIENTS WHO
PRESENT DIRECTLY TO A PCI-CAPABLE HOSPITAL DIFFER
FROM INTER-HOSPITAL TRANSFERS?
Abstract 1 Table 2
doi:10.1136/heartjnl-2011-300198.1
D Austin, Z Adam, J Shome, M Awan, A G C Sutton, J A Hall, R A Wright, D F Muir,
N M Swanson, J Carter, MA de Belder. James Cook University Hospital, Middlesbrough, UK
Background Rapid delivery of reperfusion therapy with PPCI is the
gold standard treatment in STEMI. Systems have been developed,
such as direct admission to a PCI-capable hospital, to minimise the
time from diagnosis to PPCI. Despite this, a significant minority of
patients are initially admitted to non-PCI capable hospitals. The aim
of this study was to determine whether patients differed in their
characteristics, time to PPCI, and outcome by route of admission.
Methods The study was performed in a single tertiary centre in
North England. Data are collected routinely on all patients undergoing PPCI and include demographic, clinical and procedural variables. In-hospital MACCE (death, re-infarction or CVA) and mortality
are collected providing relevant outcome measures. Baseline clinical
variables by route of admission were compared and unadjusted inhospital MACCE rates determined. One-year mortality by route of
admission was calculated using the K-M product limit estimate. Inhospital and 1-year outcomes were analysed after adjustment for
factors known to be predictors of early mortality following STEMI
(models 1 and 3). To determine the relative importance of delays in
treatment, call-to-balloon time was added (models 2 and 4). Logistic
regression was used for the adjusted in-hospital outcomes, and Coxproportional regression for adjusted 1-year mortality.
Results 2268 patients were included in the analysis. 510 patients
(22.5%) were treated with PPCI following transfer from a non-PCI
capable centre. Analysis of baseline variables (Abstract 1 table 1)
showed the transfer group were more likely to have an LAD
occlusion treated, and previous MI. Despite shorter DTB times, the
transfer group had a greater median CTB time (52 minutes longer)
compared with direct admissions. Other baseline variables were
statistically no different between groups. There were 110 in-hospital
MACCE events, and 168 deaths within 1-year follow-up. The transfer
group had significantly higher unadjusted in-hospital MACCE rates
(2.4% absolute, 58% relative increase (Abstract 1 table 2)). At 1 year,
the transfer group had significantly higher unadjusted mortality
(2.7% absolute, 48% relative increase (Abstract 1 table 2)). After
adjustment for relevant co-variates (models 1 and 3) route of
admission remained a significant predictor of in-hospital and 1-year
mortality. With the addition of call-to-balloon time, no significant
Abstract 1 Table 1
Direct
Transfer
64.3 (12.7)
1252 (71.2)
63.9 (12.4)
367 (72.0)
177 (10.1)
225 (12.6)
55 (10.8)
89 (17.3)
LMS
LAD
24 (1.4)
630 (36.1)
13 (2.5)
218 (42.9)
LCx
RCA
249 (14.3)
812 (46.6)
83 (16.3)
188 (37.0)
28 (1.7)
28 (1.7)
5 (1.1)
35 (6.9)
Age (years6SD)
Male
Diabetes
Previous MI
Treated vessel
Graft
Cardiogenic shock
p
0.17
0.74
0.68
0.001
0.001
0.61
Smoking (ex/current)
Call-to-balloon time
1331 (75.7)
102 (82e135)
377 (73.9)
154 (107e235)
0.42
<0.001
Door-to-balloon time
44 (29e76)
34 (24e50)
<0.001
Heart June 2011 Vol 97 Suppl 1
In-hospital MACCE
Direct
Transfer
4.3%
6.7%
OR (В±95% CI)
p
1.58 (1.04 to 2.39)
0.03
Adjusted in-hospital
MACCE (model 1)
1.64 (1.00 to 2.28)
0.05
Adjusted in-hospital
MACCE (model 2)
1.34 (0.79 to 2.29)
0.27
1-year mortality
Adjusted 1-year
mortality (model 3)
Adjusted 1-year
mortality (model 4)
Direct
Transfer
HR (В±95% CI)
p
7%
9.7%
1.48 (1.06 to 2.07)
1.41 (0.99 to 2.01)
0.02
0.05
1.29 (0.87 to 1.89)
0.20
Conclusion In this study, patients who presented directly had
superior in-hospital and 1-year outcomes compared with those who
required transfer from other hospitals. Adjustment for longer call-toballoon times attenuated the п¬Ѓnding of poorer outcomes in these
patients, suggesting that delays in treatment are critical. Systems of
care should be designed to avoid admission of STEMI patients to
non-PCI hospitals, and facilitate more rapid transfer of patients
where this has not been possible.
2
A “DIRECT” TRANSFER PROTOCOL FOR PATIENTS WITH
NON ST-ELEVATION MYOCARDIAL INFARCTION REDUCES
TIME TO CORONARY ANGIOGRAPHY
doi:10.1136/heartjnl-2011-300198.2
S M Gallagher, M J Lovell, D Jones, E Ferguson, S Antoniou, S Mohiddin, M Westwood,
A Mathur, R A Archbold, C Knight, A K Jain. London Chest Hospital, Barts and the
London NHS Trust, London, UK
Introduction Patients with non-ST elevation myocardial infarctions
(NSTEMI) are at high risk of further cardiac events. National
guidelines recommend “early” coronary angiography within 96 h of
presentation. Most patients with NSTEMI present to their district
general hospital (DGH), and await transfer to the regional cardiac
centre for angiography. This care model has inherent time delays,
and delivery of early angiography is problematic.
Methods A novel clinical care pathway for the management of
NSTEMI, known locally as the Heart Attack Centre-Extension or
HAC-X, has been investigated. This pathway identifies patients with
NSTEMI by clinical assessment and rapid point-of-care troponin
testing while in the emergency department (ED). Patients meeting
criteria for urgent transfer receive evidence based medical therapy for
NSTEMI (see Abstract 2 table 1) in the ED, and are transferred to the
tertiary centre within 1 h without referral. All unstable patients are
taken straight to the cardiac catheterisation laboratory. For stable
patients, coronary angiography is undertaken on the same day, or if
patients arrive after 17:00 on the next available routine list. The study
group consists of 775 patients divided into two groups; 464 patients
treated before the instigation of the HAC-X pathway (Pre-HACX),
and 311 patients treated via the novel pathway (Post-HACX). We
have undertaken a prospective observational study of post-HAC-X
patients, assessing need for angiography and or revascularisation
along with discharge diagnosis. We have also compared the waiting
time for angiography of pre-HAC-X and post-HAC-X groups.
Results 250/311 (80.4%) of HACX patients underwent angiography.
Following angiography, 144/250 (57.6%) were treated with coronary
revascularisation (108 (75%) PCI and 36 (25%) CABG). 106/250
A5
BCS Abstracts 2011
Abstract 2 Table 1
Inclusion criteria
Inclusion and exclusion criteria for HACX
Symptoms suggestive of myocardial ischaemia
With ECG changes including: ST depression; T wave
inversion in V1-4; Dynamic T wave changes
OR positive troponin I assay
Exclusion criteria
Unexplained anaemia (Hb<10)
Hypoxia
Acute renal failure
Loss of consciousness
wait for transfer to tertiary centre was 4.1 (64.7) days. Median length
of stay for HACX patients was 3 days. HAC-X has reduced wait for
coronary angiography by 3.4 days per patient.
Conclusions This novel care pathway allows delivery of early
angiography to NSTEMI patients in accordance with national
guidance. Importantly, the pathway allows accurate diagnosis of
NSTEMI, and inappropriate transfers are infrequent. Its introduction has resulted in a significant reduction in time to angiography for NSTEMI patients, and significant reductions in total
hospital bed occupancy for patients with NSTEMI.
Recent trauma
Overt sepsis
3
Immediate medical therapy includes Aspirin 300 mg
SURVIVAL FOLLOWING ACUTE MYOCARDIAL INFARCTION
IN PATIENTS OF SOUTH ASIAN AND WHITE EUROPEAN
ETHNICITY IN THE UK
Clopidogrel 600 mg
Fondaparinux 2.5 mg
Eptifibatide bolus (180 mg/kg) as long as no
bleeding contraindications
(42.4%) of patients were treated with medical therapy alone. NSTEACS (encompassing NSTEMI and unstable angina) was the discharge
diagnosis for 75.4% of HACX patients. 10% of patients had another
cause for chest pain symptoms (including pericarditis and, myocarditis); 14.6% had a non-cardiac diagnosis. Mean time from presentation
to angiography was pre-HAC-X 7349 mins (66836) and post HAC-X
754 mins (6458) (p<0.0001) (see Abstract п¬Ѓgure 1). Pre-HAC-X mean
Abstract 2 Figure 1
angiography.
A6
Time from ED presentation to coronary
doi:10.1136/heartjnl-2011-300198.3
1
2
2
2
N N Gholap, R L Mehta, K Khunti, M J Davies, 2I B Squire. 1University Hospitals of
Leicester, Leicester, UK; 2University of Leicester, Leicester, UK
Introduction Some UK studies have suggested higher case-fatality
rates following acute myocardial infarction (AMI) in British South
Asian (SA), compared to white European (WE) people, driven by
higher prevalence of diabetes in the SA ethnic group. However other
studies have suggested similar or even better adjusted overall post-AMI
survival for these ethnic groups. In patients with AMI, both prior
diagnosis of diabetes as well as acutely elevated blood glucose regardless
of diabetes status are associated with adverse outcomes. The aim of
this study was to compare survival rates following AMI in SA and
WE patients drawn from a contemporary, multi-ethnic UK population.
Methods: We conducted a retrospective cohort study of total 4111
(SA 18%) consecutive patients with AMI admitted between October
2002 and September 2008. Baseline differences between the ethnic
subgroups were examined using independent two-sample t tests for
continuous and c2 tests for categorical variables. Cox regression
models were constructed to identify determinants of 30-days and 1year mortality, entering ethnicity, random admission blood glucose
and antecedent diabetes individually and together along with other
relevant variables.
Results: SA patients were younger (62 vs 67 years, p<0.005) and less
likely to have smoked (16% vs 40%, p<0.005) but more likely to
have hypertension (55% vs 49%, pВј0.004) or diabetes (40% vs 16%,
p<0.005) at presentation compared to WE patients. All cause 30-day
and 1-year mortality proportions were 10.0 % and 15.2% in SA
compared to respectively 9.9 % and 16.7 % in WE patients. For SA
ethnicity, the univariate HR of 30-day mortality was 1.01 (95% CI
0.79 to 1.30) compared to WE ethnicity. On multivariate analysis
(excluding antecedent diabetes and admission blood glucose) this
association of SA ethnicity and mortality became significant (HR
1.56, CI 1.10 to 2.23) and remained so when antecedent diabetes
was added to the analysis (HR 1.48, CI 1.03 to 2.13). However when
admission blood glucose was added to the model, association of
ethnicity with mortality became non-significant (HR 1.31, CI 0.86
to 1.99). Conversely each unit (mmol/l) increase in admission blood
glucose was associated with 7% increase in mortality (HR 1.07, CI
1.04 to 1.10) in this model, after adjusting for all the covariates.
Furthermore exclusion of ethnicity and antecedent diabetes from
the model did not alter the predictive value of admission blood
glucose (HR 1.08, CI 1.05 to 1.10). Similar associations were
observed for 1-year mortality.
Conclusions Despite higher prevalence of diabetes in SA patients,
their mortality post AMI was similar to WE patients. Furthermore,
admission hyperglycaemia more so than antecedent diabetes was an
important predictor of increased mortality post AMI. To improve
survival, active management of admission hyperglycaemia should be
considered in patients admitted with AMI, regardless of their
diabetes status or ethnicity.
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
4
A RATIONAL APPROACH TO RAISED TROPONINS ON A
HYPERACUTE STROKE UNIT: COPING WITH THE IMPACT ON
CARDIOLOGY SERVICES
Cardiovascular Science, Edinburgh University, Edinburgh, UK; 2Edinburgh Heart Centre,
Royal Infirmary of Edinburgh, Edinburgh, UK; 3Epidemiology and Statistics Core, Wellcome Trust Clinical Research Facility, Edinburgh, UK; 4Department of Clinical Biochemistry, Royal Infirmary of Edinburgh, Edinburgh, UK
doi:10.1136/heartjnl-2011-300198.4
S S Nijjer, G Banerjee, J Barker, S Banerjee, S Connolly, K F Fox. Imperial College
Healthcare NHS Trust, London, UK
Introduction Troponin is frequently measured on admission to
hyperacute stroke units (HASUs). Modest elevations in stroke are
common but whether patient management changes in response to
the blood test is unclear. Raised troponin without chest pain or
dynamic ECG changes create diagnostic dilemmas. Management
strategies were assessed with the introduction of the Imperial HASU
covering North West London.
Methods Consecutive HASU admissions over 6 months were
assessed for measurement of troponin, the result, and the cardiac
investigations performed. Clinical parameters guided investigations
lead by two Consultant Cardiologists (KF, SC) rather than strict
research protocol.
Results 412 patients were admitted: 245 patients had a total of 435
troponin-I levels measured, without chest pain or dynamic
ischaemic ECG changes. 70 (29%) patients had positive levels
(>0.032 ng/l): 53 (22%) were “low” (0.032e0.3 ng/l), 17 (7%) were
“high” (>0.3 ng/l). 237 had diagnoses readily available: 170 had
stroke (ischaemic or haemorrhagic), 67 had non-stroke (eg, seizure).
Troponin was more likely to be raised if stroke, OR 4.3 (2.0e9.7,
p¼0.0001). Five patients with “high” troponins had non-invasive
stress testing (1 perfusion scan and 4 stress echos): all were negative.
All positive troponins had echocardiography and cardiology review
with no change in management in 91% of cases. 6 patients had
invasive coronary angiography: 3 “high” and 3 “low” troponin. Only
2 patients (3% of those with positive troponin) required percutaneous coronary intervention (PCI); both had troponin >0.3 and
multiple cardiac risk factors. Patients with troponin <0.3 did not
require PCIeall three had normal coronary arteries.
Conclusions Every positive troponin necessitated a review and
additional tests, increasing demand on cardiology services without
increase in resources. However only 2 patients required PCI with
the majority medically managed. We propose a pragmatic pathway
for when troponin is performed as a routine test. Raised troponins
>0.3 ng/l should be assessed for chest pain and ECG changes
suggesting true myocardial infarction. Without these, non-invasive
assessment and optimal medical therapy is sufficient in the
majority. Minor troponin rise (0.032e0.3 ng/l) represents myocytolysis: cerebral insular damage causes sympathoadrenal activation
and patchy myocyte damage. Without chest pain or ECG changes,
optimal medical management without further investigation is
appropriate. Since this does not represent true acute coronary
syndrome, an early invasive strategy confers no additional benefit
over medical therapy. In contrast, aspirin and statins benefit
both stroke and any coronary disease present. The п¬Ѓnancial and
medical implications of performing non-indicated tests in a routine
manner when the result will be disregarded is significant. Therefore, we caution against routine measurement of troponin in
stroke.
5
IMPLEMENTATION OF A SENSITIVE TROPONIN I ASSAY
REDUCES DEATH AND RECURRENT MYOCARDIAL
INFARCTION IN PATIENTS WITH SUSPECTED ACUTE
CORONARY SYNDROME
doi:10.1136/heartjnl-2011-300198.5
1
1
1
K K Lee, N L Mills, A M D Churchhouse, A Anand, 1D Gamble, 1A Shah, 1E Paterson,
M MacLeod, 3C Graham, 4S Walker, 1M A Denvir, 1K A A Fox, 1D E Newby. 1Centre for
2
Heart June 2011 Vol 97 Suppl 1
1
Introduction Although troponin assays have become increasingly
more sensitive, it is unclear whether further reductions in the
threshold of detection for plasma troponin concentrations impact
on clinical outcomes in patients with suspected acute coronary
syndrome. The aim of this study was to determine whether
lowering the diagnostic threshold for myocardial infarction with a
sensitive troponin assay will improve clinical outcomes.
Methods Consecutive patients admitted with suspected acute
coronary syndrome before (nВј1038; validation phase) and after
(nВј1054; implementation phase) lowering the threshold of detection for myocardial necrosis from 0.20 to 0.05 ng/ml with a sensitive
troponin I assay were stratified into three groups: <0.05, 0.05e0.19
and $0.20 ng/ml. During the validation phase, only concentrations
above the original diagnostic threshold of $0.20 ng/ml were
reported to clinicians. Event-free survival (reinfarction and death) at
1 year were compared in patients grouped by plasma troponin
concentrations.
Results Plasma troponin concentrations were <0.05 ng/ml in 1340
(64%), 0.05e0.19 ng/ml in 170 (8%) and $0.20 ng/ml in 582 (28%)
patients. During the validation phase, 39% of patients with
undisclosed plasma troponin concentrations of 0.05e0.19 ng/ml
were dead or had recurrent myocardial infarction at 1 year,
compared to 7% and 24% of those with troponin concentrations
<0.05 ng/ml (p<0.001) or $0.20 ng/ml (pВј0.007) respectively.
During the implementation phase, lowering the diagnostic
threshold to 0.05 ng/ml reduced 1-year death and recurrent
myocardial infarction from 39% to 21% in patients with troponin
concentrations of 0.05e0.19 ng/ml (OR 0.42, 95%CI 0.24 to 0.84,
pВј0.013), whereas clinical outcomes were unchanged in patients
with troponin concentrations <0.05 ng/ml or $0.20 ng/ml
(Abstract 5 п¬Ѓgure 1).
Abstract 5 Figure 1
Conclusions In patients with suspected acute coronary syndrome,
implementation of a sensitive troponin assay increases the diagnosis
of myocardial infarction by a third, and identifies those at high-risk
of reinfarction and death. Lowering the diagnostic threshold of
plasma troponin is associated with major reductions in morbidity
and mortality.
A7
BCS Abstracts 2011
6
doi:10.1136/heartjnl-2011-300198.6
1
7
CARDIAC MORBIDITY AND MORTALITY CAN BE
ACCURATELY PREDICTED IN PATIENTS PRESENTING WITH
ACS USING MULTIPLE BIOMARKERS MEASURED ON AN
ADMISSION BLOOD SAMPLE
1
1
2
2
1
I R Pearson, K Viswanathan, N Kilcullen, A S Hall, C P Gale, U M Sivananthan,
J H Barth, 2C Morrell. 1Leeds Teaching Hospitals, Leeds, UK; 2University of Leeds,
Leeds, UK
1
Background Rapid assessment of patients with suspected acute
coronary syndrome (ACS) allows the right patients to receive the
right treatment at the right time. Discrimination of risk permits
clinical triage into pathways of immediate inpatient or deferred
outpatient care. It is known that a significant proportion of the
ACS patients sent home following an “MI screen”, based on a
negative 12-h troponin level, are misdiagnosed as having noncardiac chest pain when in fact they are at high risk of cardiac
events. It has been shown that the novel biomarker H-FABP can
detect myocardial ischaemia even in the absence of myocyte
necrosis. We hypothesise that a multi biomarker blood test incorporating troponin I, CK-MB and H-FABP, taken on admission,
can accurately discriminate those patients with a non-cardiac
cause of chest pain who are at low risk of cardiac morbidity or
mortality.
Methods We studied 519 patients with suspected ACS admitted to
a single UK Teaching Hospital. A risk scoring model was
constructed based on tertile values for Randox Cardiac-Array
measurement of troponin I, H-FABP and CK-MB. These were
measured on a blood sample taken at the time of hospital admission. The lowest two lower tertiles were each given a score of 1 and
the top tertile a score of 3. The scores were then combined by
summation resulting in an overall score of between 3 and 9.
Outcome measures up to 12 months were: (i) death from all causes;
(ii) repeat acute coronary syndrome (ACS) (iii); readmission for
heart failure; (iv) readmission for cerebrovascular event (CVA); (v)
coronary revascularisation.
Results The distribution of Cardio-Array scores was: 3 (nВј164;
31.6%); 5 (nВј134; 25.8%); 7 (nВј110; 21.2%); 9 (nВј111; 21.4%). The
cumulative incidence of events according to the Cardiac-Array score
is shown in Abstract 6 table 1.
IN ACUTE CORONARY SYNDROMES, HEART-TYPE FATTY
ACID BINDING PROTEIN IS A MORE ACCURATE PREDICTOR
OF LONG TERM PROGNOSIS THAN TROPONIN
doi:10.1136/heartjnl-2011-300198.7
1
2
2
1
I R Pearson, A S Hall, C P Gale, U M Sivananthan, 1K Viswanathan, 1N Kilcullen,
C Morrell, 1J H Barth. 1Leeds Teaching Hospitals, Leeds, UK; 2University of Leeds,
Leeds, UK
2
Introduction We have previously shown that heart-type fatty acid
binding protein (H-FABP) has a role in predicting all-cause
mortality after acute coronary syndromes (ACS) and after multivariable analysis, provides additional information to that gained
from the GRACE clinical risk factor score, troponin and highly
sensitive CRP. H-FABP is released into the circulation during
myocardial ischaemia and after myocardial necrosis, in contrast to
troponin which is released after myocardial necrosis only. We
have also shown that there is a group of ACS patients who are at
high risk of cardiac events and death despite normal troponin
levels on admission. This group may benefit from an early invasive
strategy.
Hypothesis Plasma H-FABP level, taken between 12 and 24 h after
admission, can identify troponin negative ACS patients who are at a
high long term risk of death.
Methods Six-year mortality data is now available for patients
enrolled in the FAB 1 study, for which 1-year mortality data was
published in 2007. In this study, 1448 unselected patients admitted
to hospital with ACS had serum H-FABP level measured in addition
to usual care. Mortality was tracked by the UK Office of National
Statistics.
Results At 6 years overall all-cause mortality, available for 1421
patients (98.1%), was 43.5%. If troponin ГЂve/H-FABP ГЂve
mortality was 20.9%; troponin ГЂve/H-FABP +ve 56.4%; troponin
+ve/H-FABP ГЂve 20.2%; troponin +ve/H-FABP +ve 49.1%.
Mortality rate was independent of troponin status but strongly
related to H-FABP status.
Conclusion The current system of stratification of ACS patients for
early invasive management if troponin positive will miss a cohort of
patients who are at high risk of death despite being troponin
negative, and who may benefit from invasive investigation.
Conversely, it is likely that some ACS patients undergo angiography
based on a false positive troponin level. The addition of H-FABP
measurement to the management of ACS could avoid this.
Abstract 6 Table 1 The cumulative incidence of events according to
the Cardiac-Array Score
Score
Death
or ACS
or HF
or CVA
or Revasc
3
5
0.61%
3.21%
3.07%
5.77%
3.11%
5.81%
3.11%
5.81%
4.28%
6.41%
7
9
11.11%
12.98%
17.78%
16.23%
19.05%
18.37%
20.93%
18.92%
24.44%
22.08%
Ratio (9/3)
p Value
21.28
<0.0001
5.29
<0.0001
5.91
<0.0001
6.08
<0.0001
5.16
<0.0001
Conclusion Patients presenting with possible ACS who have a
Cardiac-Array biomarker score of 3 or 5, as measured on their
admission blood sample, have a very low rate of cardiovascular
events. This tool could be used to safely triage patients towards
early discharge and outpatient care, based upon available resources.
A score of 7 or 9 would merit admission to hospital, and consideration of early cardiac catheterisation.
A8
Abstract 7 Figure 1
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
8
DOES THE ADDITION OF A RADIAL ARTERY GRAFT
IMPROVE SURVIVAL AFTER HIGHER RISK CORONARY
SURGERY? A PROPENSITY-SCORE ANALYSIS
doi:10.1136/heartjnl-2011-300198.8
1
2
2
1
C H Yap, P A Hayward, W Y Shi, D T Dinh, 1C M Reid, 3,4G C Shardey,
J A Smith. 1Department of Epidemiology and Preventative Medicine, Monash
University, Melbourne, UK; 2Department of Cardiac Surgery, Austin Hospital, University
of Melbourne, Melbourne, UK; 3Department of Cardiothoracic Surgery and Surgery,
Monash Medical Centre, Monash University, Melbourne, UK; 4Department of Surgery,
Monash Medical Centre, Monash University, Melbourne, UK
3,4
Introduction The use of the radial artery as a second arterial graft
during coronary surgery has become popular due to high patency,
encouraging clinical outcomes and low harvest site complication
rates. However it is not clear whether higher risk patients derive
such benefits. We sought to assess this by examining outcomes in
higher risk subgroups.
Methods A multicentre database was analysed. From 2001 to 2009,
11 388 patients underwent isolated multivessel coronary surgery. We
identified a higher risk subgroup (n¼3149) according to emergent
status, coronary instability, low ejection fraction, aortic counterpulsation or anticoagulant status. Among these, 2231 (71%) received
at least 1 radial artery graft in addition to a left internal thoracic
artery (LITA). The remaining 918 (29%) received LITA and veins
only. Propensity-score matching and adjustment was performed to
correct for group differences.
Results Patients who did not receive a radial artery were more likely to
be older (mean age, radial: 66610 years vs vein: 71610, p<0.0001)
female (22% vs 27%, pВј0.002), have poor left ventricular function
(16% vs 23%, p<0.0001), left main stenosis (35% vs 41%, pВј0.002) or
be of emergent status (11% vs 24%, p<0.0001). These patients experienced higher unadjusted 30-day mortality (2.2% vs 7.1%, p<0.0001)
and poorer 7-year survival (p<0.0001). Furthermore, 548 patients in
the radial group were propensity-score matched to 548 receiving LITA
and veins. At 30 days, there were comparable rates of mortality (radial:
2% vs vein: 3%, pВј0.19), stroke (1% vs 1%, pВј0.51), myocardial
infarction (1% vs 1%, pВј0.77), major adverse cardiac or cerebrovascular events (MACCE) (2% vs 4%, pВј0.12), return to theatre
(5% vs 7%, pВј0.19), hospital readmissions (12% vs 12%, p>0.99) and
combined any mortality/morbidity (30% vs 32%, pВј0.33). At 7 years,
survival between radial and vein groups was similar (7962.5% vs
8062.5%, pВј0.74). Propensity-adjusted multivariable regression did
not show radial artery to be protective from 30-day mortality (pВј0.14,
OR 0.67, 0.40 to 1.13), 30-day MACCE (pВј0.23, OR 0.76, 0.48 to 1.20),
or mid-term mortality (pВј0.79, HR 0.97, 0.78 to 1.20).
Conclusions This multicentre analysis suggests that patients with
the greatest coronary instability, urgency of surgery, or impairment
of ventricular function are not disadvantaged in the early and midterm by use of a single arterial graft. Limitations include the inability
to correct for unquantifiable variables retrospectively. Despite this,
surgeons may utilise clinical judgement to select radial or venous
conduits to supplement the LITA according to other patient factors
or technical preference without prejudicing outcome.
elevation myocardial infarction (STEMI), resulting in shorter
hospital stays. Discharge at 72 h in selected patients has been
suggested. We investigated the feasibility and safety of very early
discharge (<48 h) coupled with regular outpatient support for lowrisk patients following PPCI.
Methods 2317 patients underwent PPCI for STEMI between
October 2003 and May 2010 at a regional Heart Attack Centre
(HAC). Demographic and procedural data were documented at the
time of intervention. Patients with TIMI 3 flow, ST segment resolution, good or moderate left ventricular function, and no
dysrhythmia were stratified to 48 h discharge. Remaining patients
were discharged according to physician preference. All patients were
reviewed at 1, 8 and 52 weeks with a multidisciplinary team
including rehabilitation, heart failure, and psychology. The primary
endpoint was major adverse cardiac events (MACE) included death,
myocardial infarction (MI), stroke and target vessel revascularisation (TVR). All-cause mortality data were provided by the Office of
National Statistics via the BCIS CCAD national audit. Outcomes
were compared between those discharged at #48 h, 72 h, and >72 h,
out to 5 years of follow-up.
Results 1079 patients (46.5%) were stratified to 48-h discharge,
14% discharged at 72 h and the remainder discharged at a median of
6 days (4.3e10), including those with complications. Patients
discharged at #48 h were significantly younger and had a lower
incidence of multi-vessel disease than those discharged at 72 h
(Abstract 9 table 1). Remaining baseline characteristics were similar.
MACE at 3 years was similar between 48-h discharge patients
and 72- h discharge (9.1% vs 8.7%, pВј0.7). This persisted out to
5 years (9.6% vs 9%, pВј0.55). As expected patients with length
of stays >72 h had significantly worse outcomes (Abstract 9
п¬Ѓgure 1).
Abstract 9 Table 1
48 h (n[1079)
72 h (n[323)
p Value
Age
Previous MI
60.7
130 (12.0%)
64.0
35 (10.8%)
0.0002
0.5569
Previous CABG
Previous PCI
21 (1.9%)
102 (9.4%)
7 (2.2%)
29 (9.0%)
0.8019
0.8007
DM
HTN
156 (14.4%)
455 (42.1%)
52 (16.1%)
148 (45.8%)
0.4632
0.2854
Hchol
3 vessel disease
403 (37.3%)
448 (46.4%)
124 (38.4%)
156 (54.9%)
0.7858
0.0112
O Guttmann, D A Jones, K S Rathod, M Akhtar, A Ludman, A K Jain, C Knight,
A Mathur, S Mohiddin, A Wragg, E J Smith. Barts and the London NHS trust, London,
UK
Abstract 9 Figure 1
MACE after primary PCI.
Introduction Reperfusion therapy with primary PCI (PPCI) has
reduced rates of recurrent ischaemia and arrhythmia following ST
Conclusion Early discharge at 48 h is feasible and appears to be safe
for patients undergoing contemporary Primary PCI.
9
EARLY HOSPITAL DISCHARGE AT 48 H FOLLOWING
PRIMARY PCI FOR MYOCARDIAL INFARCTION IS BOTH
SAFE AND FEASIBLE
doi:10.1136/heartjnl-2011-300198.9
Heart June 2011 Vol 97 Suppl 1
A9
BCS Abstracts 2011
10
doi:10.1136/heartjnl-2011-300198.10
1
2
2
2
2
1
N V Joshi, B R Bawamia, S Jamieson, A Zaman, R Edwards. Centre for
Cardiovascular Science, The University of Edinburgh, Edinburgh, UK; 2The Cardiothoracic Centre, Freeman Hospital, Newcastle Upon Tyne, UK
Background The Freeman Hospital (FRH) performs over 900 pPCI a
year. Patients with suspected Acute Myocardial Infarction (AMI) are
referred either by paramedics or networked hospitals for consideration of pPCI via a Telmed system, which is triaged by experienced
CCU nurses. The pPCI Pathway can be activated in patients with
LBBB suspected of having an AMI. However, there remains
considerable variation in the clinical utility of new or presumed new
LBBB as a ST-elevation myocardial infarction (STEMI)-equivalent
ECG diagnostic criterion. The major discriminators the triage staff
use in this population are ECG п¬Ѓndings and symptoms suggestive of
AMI. Our aim was to evaluate outcomes in patients with LBBB
accepted to FRH or referred to local hospitals for assessment.
Methods Consecutive patients referred to FRH with LBBB and
suspected AMI from 1st August 2009 to 30th November 2009 were
analysed by recording: 1) Peak Troponin Level 2) Angiographic
п¬Ѓndings 3) Revascularisation rates.
Results 1069 patients were referred for consideration of pPCI. 177
(16.6%) of patients had new or presumed new LBBB. 33 (18.6%)
patients were accepted by FRH and 144 patients (81.4%) were
declined and referred to their local hospitals for assessment. Abstract
10 Table 1 Troponin levels in patients with LBBB referred for
consideration of pPCI. 26.5% of patients with LBBB referred for
consideration of pPCI had moderately to highly raised troponin. Of
the 33 patients admitted to FRH, 13 underwent inpatient angiography and 9 patients had significant coronary disease (coronary
stenosis 70%e100% in at least one coronary artery). Of those, 5 had
PCI and 1 required urgent CABG. Only one patient had a 100%
coronary occlusion believed to be an acute occlusion. 4 patients had
unobstructed coronaries and were managed medically. Of the 132
patients declined for pPCI only 2 (1.5%) were referred back to FRH
for PCI. Neither of these patients was found to have a 100% acute
occlusion of a coronary artery.
Abstract 10 Table 1
FRH Assessed
FRH Declined
Number of patients
Number analysed
33
33
144
132 (Biochemistry
data not found for
12 patients)
Troponin levels
Trop I<0.04 or Trop T<0.01 (Normal)
19 (57.6%)
84 (63.6%)
Trop I 0.04e0.1 or Trop T 0.01e0.1 (Mildly raised)
Trop I or Trop T 0.1e1.0 (Moderately raised)
2 (6.1%)
1 (3.0%)
25 (18.9%)
17 (12.9%)
Trop I or Trop T>1.0 (High)
11 (33.3%)
6 (4.5%)
Conclusion Revascularisation was performed in only 6/33 (18.2%)
accepted for assessment and only 2/132 (1.5%) were referred back to
the centre for PCI. The sensitivity of the triage process in detecting
patients with LBBB requiring urgent revascularisation is 75% and
the specificity is 83%. The sensitivity of detecting patients with an
acutely occluded artery diagnosed at angiography is 100% with a
specificity of 81%. In a high volume Heart Attack Centre a nurse led
triage is effective at discriminating patients with LBBB requiring
immediate coronary intervention.
A10
11
EVALUATING A NURSE LED TRIAGE PROCESS IN TREATING
PATIENTS WITH LEFT BUNDLE BRANCH BLOCK (LBBB)
REFERRED FOR PRIMARY PERCUTANEOUS CORONARY
INTERVENTION (PPCI)
COPEPTIN IMPROVES EARLY RISK STRATIFICATION BY
GRACE SCORE IN NON ST-ELEVATION MYOCARDIAL
INFARCTION; NT-PROBNP DOES NOT
doi:10.1136/heartjnl-2011-300198.11
1
1
1
2
O S Dhillon, H K Narayan, P A Quinn, J Struck, 1I B Squire, 1J E Davies, 1L L Ng.
University of Leicester, Leicester, UK; 2Brahms, Hennigsdorf, UK
1
Background Risk stratification is vital to the optimal management of
patients with non ST-elevation myocardial infarction (NSTEMI)
however, current tools are not fully discriminatory. Copeptin, the
stable 39 amino acid C-terminal portion of pro-vasopressin, is a
recognised prognostic marker in ST elevation myocardial infarction
(STEMI) that is also useful to exclude MI as levels rise early after onset.
Copeptin has not been evaluated in a NSTEMI population to date.
Aims We hypothesised that copeptin is an independent predictor of
mortality following NSTEMI and, in accordance with AHA criteria
for the evaluation of novel biomarkers, assess whether copeptin adds
prognostic information to GRACE risk score (GRACE-RS). We use
NT-proBNP for comparison.
Methods and Results In this prospective observational study plasma
copeptin and NT-proBNP was measured in 754 NSTEMI patients (519
men, median age 70613 years) within 36 h of symptoms. The
primary endpoint of all-cause mortality at 6 months was reached by
56 (7.4%) patients. Median copeptin levels were 7.9 range 0.3 to
523.0 pmol/l and were significantly higher in those that reached the
primary endpoint than the event free survivors; median (IQR), 32.0
(12.0e88.7) vs 7.2 (4.0e16.7) respectively p<0.001. Both copeptin and
NT-proBNP were predictive of the primary endpoint on univariate
Cox regression analysis (HR 5.98 p<0.0005 and HR 6.07 p<0.0005
respectively). On adjustment for baseline clinical and biochemical
variables copeptin remained predictive (HR 3.03 pВј0.009) but NTproBNP did not (pВј0.70). Kaplan-Meier analysis revealed that supramedian levels of copeptin were associated with increased mortality
(log rank 28.4 p<0.001). ROC curve c-statistics for GRACE-RS of
0.799 increased to 0.835 when combined with copeptin (0.785), when
combined with NT-proBNP (0.730) increased to 0.802. Re-classification analysis shows that copeptin improves accuracy of risk
stratification when combined with the GRACE-RS as determined by
net reclassification improvement (NRI 13.3% p¼0.008) whereas, NTproBNP does not (NRI À4.9% p¼0.21). The relative utilities for
logistic regression models using GRACE-RS alone, GRACE-RS +
copeptin and GRACE-RS + NTproBNP as covariates are shown in
Abstract 11 п¬Ѓgure 1. The relevant region was the region to the right of
the sample risk for 6 months mortality, 0.074. The relative utility for
GRACE-RS + copeptin was consistently more than the relative utility
for GRACE-RS + NTproBNP across a range of risks; for example at a
risk threshold of 15% the additional utility of adding copeptin to the
GRACE-RS was 0.097 compared to 0.009 for NTproBNP.
Abstract 11 Figure 1
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
Conclusions High plasma copeptin levels indicate a worse outcome
in NSTEMI patients. We have demonstrated that copeptin fulfils
AHA criteria by improving risk stratification over established
markers GRACE score and NT-proBNP. Copeptin is also useful for
rapid rule-out of MI and the current п¬Ѓndings further support clinical
uptake.
13
NEUTROPHIL ACTIVATION AT THE CULPRIT LESION IN
ACUTE ST-SEGMENT ELEVATION MYOCARDIAL
INFARCTION WITH MULTIPLE COMPLEX CORONARY
PLAQUES
doi:10.1136/heartjnl-2011-300198.13
1
C J Marshall, 1J L Mckenzie, 2T Moccata, 3M Nallaratnam, 3J Blake, 3C Frampton,
M Richards, 2A J Kettle, 3D R Mcclean. 1Sunderland Royal Hospital, Sunderland, UK;
2
Free Radical Research Group, University of Otago, Christchurch, New Zealand;
3
Department of Cardiology, Christchurch Hospital, Christchurch, New Zealand
3
12
THE RELATIONSHIP BETWEEN PSYCHOLOGICAL FACTORS
AND IMPAIRED HEALTH-RELATED QUALITY OF LIFE POST
ST-ELEVATION MYOCARDIAL INFARCTION
doi:10.1136/heartjnl-2011-300198.12
1
1
2
1
1
L McGowan, H Iles-Smith, C Dickens, M Campbell, 1C Rogers, 2F Fath-Ordoubadi.
University of Manchester, Manchester, UKI; 2CMFT, Manchester, UK
Introduction Evidence suggests that psychological factors, such as
depression and anxiety, are independent risk factors for increased
morbidity and mortality post ST-elevation myocardial infarction
(STEMI). Since improved treatments have increased survival rates
post STEMI the emphasis has turned to more patient related
outcome measures such as health-related quality of life (HRQoL).
The aim of the study was to assess the contribution of anxiety
and depression to HRQoL in post STEMI patients, after
controlling for possible confounding factors, including type of
treatment.
Methods We conducted a prospective cohort study of 385 postSTEMI patients who had undergone either lysis (183) or PPCI (202).
The mean age was 60.0 years (SD 11.8) and 78% were male.
Patients were assessed on a range of demographic, clinical and
psychosocial variables, including measures of cardiac risk,
cardiac severity and comorbidity (Charlson Comorbidity Indexd
CCI). Psychosocial assessment included anxiety and depression
(Hospital Anxiety and Depression Scale), illness perceptions (brief
IPQ), and health-related quality of life (SF-36). The main outcome
was the SF-36 Physical Component Score (PCS) at 6 months postSTEMI.
Results Baseline results revealed a small number significant differences between groups on a range of clinical variables, including
higher GRACE scores for PPCI group (pВј0.007) but no differences in
LV function. Lysis patients had more comorbid illness as measured
by the CCI (pВј0.037). Regarding psychological variables the total
HADS score was significantly higher in the PPCI vs lysis group at
baseline (means 13.2 (SD 7.9) and 11.4 (SD 8.9), pВј0.035), while
anxiety and depression almost reached significance, with raised
anxiety and depression scores in the PPCI group. In order to identify
variables at baseline that may contribute to SF-36 PCS at 6 months,
we conducted a hierarchical multiple regression with four blocks of
independent variablesddemographic, comorbidity-related, clinical
and psychological. Factors which contributed to the п¬Ѓnal model
were cholesterol levels (pВј0.031) and depression (p<0.001). Treatment group did not play a role (pВј0.199). The addition of anxiety
and depression contributed significantly to the reporting of lower
physical health-related quality of life (PCS) at 6 months (Г„R2Вј0.12,
p<0.001).
Conclusion The п¬Ѓndings have shown that raised levels of depression and anxiety predicted impairment in health-related quality of
life at 6 months post-STEMI, regardless of mode of treatment. The
results indicate that the assessment of psychological factors is
important in both groups. Despite PPCI having improved clinical
outcomes, there will always be a group of patients receiving
lysis. As such it is important to assess anxiety and depression in
post STEMI patients, and to include these potentially modifiable
factors in the design of suitable interventions for this patient
group.
Heart June 2011 Vol 97 Suppl 1
Introduction The activation of neutrophils at the culprit coronary
lesion following acute plaque disruption has not been reported. We
hypothesised that neutrophil activation occurs in ST elevation
myocardial infarction (STEMI) prior to percutaneous intervention
(PCI), and that differences in activation may be detectable locally at
the culprit lesion, particularly in patients with multiple complex
coronary plaques.
Methods Forty STEMI patients having primary PCI were compared
to 10 controls with chronic stable angina (CSA) undergoing elective PCI. The clinical, demographic and angiographic characteristics
of patients and controls are shown in Abstract 13 table 1. The
culprit lesion was sampled after passage of a guide wire across the
lesion and use of a low profile sampling catheter (Multifunctional
probing catheter, Boston Scientific Corporation, Natick, Massachusetts, USA) at the site of occlusion, prior to further mechanical
intervention. Neutrophil activation was measured by flow
cytometry using neutrophil intracellular myeloperoxidase content
(MPO Index) and the expression of the b2- integrin CD11b, a
leukocyte adhesion and activation marker at the culprit coronary
lesion (CA), the aorta at the coronary ostium (Ao), the coronary
sinus (CS), and femoral artery (FA) prior to primary PCI. A lower
MPO content indicates the depletion of intracellular MPO and cell
activation.
Abstract 13 Table 1
Variable
STEMI
(n[40)
Elective PCI
(n[10)
Age (years) mean6SD
62612
6869.1
0.9
Male (%)
Culprit coronary artery lesion treated (%)
28 (70)
7 (70)
1
Left anterior descending
Diagonal
17 (42)
2 (5)
5 (50)
1 (10)
0.73
0.5
Circumflex
Right coronary
1 (3)
20 (50)
2 (20)
2 (20)
0.1
0.15
Time to presentation (mins) mean6SD
Baseline TIMI flow 0e1
2226155
28 (70)
NA
0
p Value
<0.001
Results A marked decrease in MPO content occurred at the CA, Ao
and FA in STEMI compared to elective controls (p<0.01). Furthermore, MPO content was lower at the CA (ГЂ23.1, (ГЂ25.6 to ГЂ17.1),
nВј37) compared to Ao (ГЂ22.0, (ГЂ24.7 to ГЂ16.2), nВј37), CS (ГЂ20.6,
(ГЂ24.8 to ГЂ16.9), nВј30) and FA (ГЂ20.4, (ГЂ24.4 to ГЂ13.1), nВј40), all
p<0.001 (Abstract 13 п¬Ѓgure 1). Neutrophil MPO content was
correlated with CD11b expression only at the culprit CA in STEMI
(rВјГЂ0.4, pВј0.03, nВј31) (Abstract 13 п¬Ѓgure 2). Neutrophil MPO
content at the CA in patients with multiple complex plaques was
similar to those with a single culprit however only in those with
multiple complex plaques was a correlation between MPO content
and CD11b (rВјГЂ0.7, pВј0.02) shown. Conclusion: In acute STEMI,
neutrophils are activated systemically, regionally and locally at the
culprit coronary lesion. In patients with multiple complex plaques,
there may be an extended local role for the activated neutrophil
following acute plaque destabilisation.
A11
BCS Abstracts 2011
Abstract 14 Figure 1
MI, relating these to global and segmental myocardial function at
6 months.
Methods and Results CMR scans were performed on 30 patients
with ST elevation MI (STEMI) treated by primary PCI at each of 4
time points: 12e48 h (TP1); 5e7 days (TP2); 14e17 days (TP3); and
6 months (TP4). All patients showed oedema at TP1. The mean
volume of oedema (% LV) was 37616 at TP1 and 39617 at TP2
Abstract 13 Figure 1
Abstract 13 Figure 2
14
DYNAMIC CHANGES OF OEDEMA AND LATE GADOLINIUM
ENHANCEMENT AFTER ACUTE MYOCARDIAL INFARCTION
AND THEIR RELATIONSHIP TO FUNCTIONAL RECOVERY
AND SALVAGE INDEX
doi:10.1136/heartjnl-2011-300198.14
1
1
1
1
E Dall’Armellina, N Karia, A Lindsay, T D Karamitsos, 1V Ferreira, 1M D Robson,
P Kellman, 1J M Francis, 3C Forfar, 3B Prendergast, 3A P Banning, 1K Channon,
3
R J Kharbanda, 1S Neubauer, 1R P Choudhury. 1NIHR Biomedical Research Centre,
Department of Cardiovascular Medicine, University of Oxford, Oxford, UK; 2NIH,
Bethesda, USA; 3NIHR Biomedical Research Centre, Department of Cardiology, John
Radcliffe Hospital, Oxford, UK
2
Introduction Changes in myocardial tissue in acute ischaemia are
dynamic and complex and the characteristics of myocardial tissue
on cardiovascular magnetic resonance (CMR) in the acute setting
are not fully defined. We investigated changes in oedema and late
gadolinium enhancement (LGE) with serial imaging early after acute
A12
Abstract 14 Figure 2
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
with a reduction to 24613 (p<0.01) by TP 3. Myocardial segments
with oedema also had increased signal on LGE at TP1 (kВј0.77;
p<0.001). At TP1, the proportion of segments with wall motion
impairment increased in relation to the extent of both myocardial
oedema (p<0.01) and LGE (p<0.01). The volume of LGE decreased
significantly between TP1 and TP4 (27615% vs 22612%; p¼0.002).
Of segments showing LGE at 48 h, 50% showed resolution by
6 months. In segments with such a reduction in LGE, 65% also
showed improved wall motion (p<0.0001). The area of LGE measured at 6 months correlated more strongly with 48-h troponin
(R2Вј0.84; p<0.01) than at TP1 (R2Вј0.5). The difference in LGE
between TP1 and TP4 had profound effects on the calculation of
salvage index (26621% at TP1 vs 42623% at TP4; p<0.02).
Conclusions (1) Myocardial oedema was unchanged over the п¬Ѓrst
week but decreased by 15 days; (2) a large majority of segments that
were positive for oedema also showed LGE, assessed at 12e48 h; (3)
In 46% of patients, LGE present on early scans had diminished in
size by 6 months, (4) resolution of LGE was associated with
improvement in function; (5) the reduction in LGE at the later time
had a profound effect on the calculation of salvage index, which
varied by up to w60%, depending on the time point used. (6) From a
clinical perspective, the use of acute LGE may severely underestimate salvaged myocardium and should not be used to predict
recovery of myocardial function.
15
INVESTIGATION OF IL-1 INHIBITION IN PATIENTS
PRESENTING WITH NON-ST ELEVATION MYOCARDIAL
INFARCTION ACUTE CORONARY SYNDROMES (THE MRC
ILA HEART STUDY)
doi:10.1136/heartjnl-2011-300198.15
1
A C Morton, 2C Foley, 1A Rothman, 1J Gunn, 3J P Greenwood, 3A Hall, 4K Fox,
B Lees, 2M Flather, 1D Crossman. 1NIHR Cardiovascular Biomedical Research Unit,
Sheffield, UK; 2CTEU, Royal Brompton and Harefields NHS Trust, London, UK;
3
Academic Unit of Cardiovascular Medicine, Leeds, UK; 4Royal Infirmary of Edinburgh,
Edinburgh, UK
2
Background Inflammatory mechanisms are involved in both coronary atherogenesis and its presentation as acute coronary syndromes
(ACS). To date, drugs used at the time of ACS, or for primary and
secondary prevention have not primarily targeted inflammatory
mechanisms. Studies with aspirin and statin drugs indicate that
anti-inflammatory properties of these compounds may contribute to
their beneficial effects. Pre-clinical studies from our group have
indicated that the pro-inflammatory cytokine IL-1 drives a
number of vascular events relevant to coronary artery disease and
ACS. IL-1 can be inhibited by IL-1 receptor antagonist (IL-1ra,
Anakinra, Amgen) which is licensed for the treatment of rheumatoid
arthritis.
Aims To investigate the effects of interleukin-1 receptor antagonist
(IL-1ra) on inflammatory biomarkers in patients with ACS <48 h
from symptom onset, and to evaluate the safety and tolerability of
treatment.
Design and methods The UK MRC ILA-HEART study is an investigator-initiated, non-industry sponsored, phase 2, multi-centre,
placebo-controlled trial, comparing the IL-1ra (100 mg) with
matching placebo given as a single, daily subcutaneous injection
over 2 weeks. The primary outcome of the study was area under the
curve (AUC) of high sensitivity CRP (hs-CRP) over the п¬Ѓrst 7 days
of treatment, and the main secondary outcomes are AUC of
troponin and safety and compliance of trial treatment. Patients were
encouraged to self-administer trial treatment, and underwent daily
assessment of hs-CRP, troponin, von Willebrand factor and other
biomarkers up to 7 days, and again at 2 weeks and 30 days. Patients
were followed up to 12 months for safety (Abstract 15 table 1).
Heart June 2011 Vol 97 Suppl 1
Abstract 15 Table 1
secondary outcomes
Log transformed values for the primary and
Variable
Active
n
Active
mean (SD)
Placebo
n
Placebo
mean (SD)
hsCRP AUC (days 1e7)
hsCRP at day 7
82
78
3.51 (1.42)
1.03 (1.46)
78
78
3.55 (1.46)
1.09 (1.91)
0.86
0.83
hsCRP at day 14
hsCRP at day 30
77
76
1.14 (1.54)
1.13 (0.32)
76
76
0.89 (1.56)
0.92 (1.15)
0.32
0.30
Troponin AUC (days 1e7)
82
1.35 (1.88)
78
1.50 (1.96)
0.61
Troponin at day 14
Troponin at day 30
77
76
ГЂ3.73 (2.31)
ГЂ4.83 (2.44)
76
76
ГЂ4.14 (2.35)
ГЂ4.74 (2.51)
0.27
0.82
p
vWF AUC (days 1e3)
89
1.33 (0.35)
84
1.31 (0.35)
0.66
vWF at day 14
vWF at day 30
77
78
0.36 (0.35)
0.37 (0.34)
84
75
0.28 (0.41)
0.29 (0.43)
0.23
0.19
IL-6 AUC (days 1e3)
86
2.62 (1.13)
83
2.56 (1.02)
0.74
IL-6 at day 14
IL-6 at day 30
77
73
1.32 (1.35)
1.22 (0.92)
77
75
0.92 (0.75)
1.08 (0.77)
0.028
0.31
Results Five UK centres randomised 182 patients with non-ST
elevation (NSTEMI) ACS to IL-1ra or placebo. Enrolment completed
in March 2010. Mean age was 61 years, 32% female, 28% prior MI,
15% diabetes, 90% were receiving a statin at the time of randomisation and 64% had early PCI or CABG. Compliance was good with
85% of patients receiving daily injections during the п¬Ѓrst 7 days, and
70% of patients were able to self-administer the injections. Injection
site reactions reported as adverse events occurred in 14% of patients.
There was no significant difference in area under the curve for
hsCRP between active and placebo groups. The MACE and serious
adverse event rates are shown in Abstract 15 table 2.
Abstract 15 Table 2
MACE and other SAE
Event
Active (n (95% CI))
Placebo (n (95% CI))
p
MACE at 30 days
MACE at 3 months
6 (0.19 to 1.79)
10 (0.32 to 1.84)
10 (1)
13 (1)
0.35
0.54
MACE at 1 year
20 (0.59 to 2.22)
18 (1)
0.69
MI (%)
Stroke (%)
3.26
1.09
7.78
0
0.18
1.00
Death (%)
CV hospitalisation (%)
4.35
19.86
4.44
25
1.00
0.31
Revascularisation (%)
Injection site reactions
(%)
Other SAE (%)
69.56
15.22
60
15.56
0.8
0.95
47.83
44.44
0.65
Discussion NSTEMI ACS treated with all the current evidencedbased therapies still has significant recurrent events. MRC ILAHEART is the first study to evaluate the effects of the anti-inflammatory IL-1ra in ACS. The data indicates that despite encouraging
pre-clinical evidence, the inflammatory driver for NSTEMI-ACS is
not IL-1 mediated.
16
ACUTE STENT THROMBOSIS RESULTING IN ST ELEVATION
MYOCARDIAL INFARCTION (STEMI) IS ASSOCIATED WITH
WORSE CLINICAL OUTCOMES THAN STEMI DUE TO NATIVE
CORONARY THROMBOSIS
doi:10.1136/heartjnl-2011-300198.16
E C Sammut, A Graham, D A Jones, K Rathod, S May, A Jain, S Mohiddin, C Knight,
A Mathur, A Wragg. The London Chest Hospital, London, UK
Background Stent thrombosis (ST) is a recognised cause of ST
Elevation Myocardial infarction (STEMI) in patients with previous
A13
BCS Abstracts 2011
percutaneous coronary interventions (PCI). The incidence is
increasing and to date outcomes are not well characterised, though
there is a suggestion that there is a worse clinical outcome.
We therefore sought to compare STEMI caused by ST vs de novo
coronary thrombosis to evaluate procedural risk and clinical outcome.
Methods Clinical information was analysed from a prospective
database on 2421 patients who underwent Primary PCI following
STEMI between October 2003 and May 2010 at a London centre.
Information was entered at the time of procedure, diagnosis of stent
thrombosis made at the time by primary operator and outcome
assessed by all-cause mortality information provided by the Office
of National Statistics via the BCIS CCAD national audit.
Results Stent thrombosis (ST) accounted for 7.4% (180/2421) of all
STEMIs with a frequency that has increased over time (5.4% in 2005
to 9.8% 2009). ST occurred early (0e30 days) in 36% (65/180), late
(30 dayse1 year) in 22% (40/180) and very late (>1 year) in 42% (75/
180) of pts. Drug-eluting stents (DES) accounted for 48% of SToverall
and 70% over the past 3 years. Proposed mechanisms included
premature discontinuation of anti-platelets (11%), under-deployment
of previous stent insertion (22%) and underlying prothrombotic
conditions (eg, SLE) (6%). Pts with ST compared to native artery
occlusion had higher rates of previous MI (53.9% vs 11%, p<0.0001)
and incidence of multi-vessel disease (59.8% vs 51.7%, pВј0.04
There was no difference in age, diabetes or cardiogenic shock. See
Abstract 16 table 1. Infarct size based on peak enzyme markers was
similar (2.5 vs 2.2, pВј0.45). In patients with ST, angiographic success
(postprocedural Thrombolysis In Myocardial Infarction grade III
flow) was worse than in patients with de novo STEMI (87.2% vs
93.7%, pВј0.02). Pts with STEMI due to ST had higher in-hospital
MACE (11% vs 3%, pВј0.0001), MACE at 30 days (19% vs 6%,
p<0.0001), this persisted up to 3 years (41% vs 12%, p<0.0001). See
Abstract 16 п¬Ѓgure 1. MACE was driven by higher rates of MI (7% vs
2%, p<0.0001), TVR (14% vs 3%, p<0.0001) and death (18% vs 6%,
pВј0.0001). After adjusting for comorbidities, stent thrombosis was an
independent predictor of long-term adverse outcome (ORВј2.1, 95%
CIВј1.3 to 2.8, p<0.001).
Abstract 16 Table 1
AST (n[180)
No AST (n[2241)
Significance
(p value)
Age
63.9618
62.964
0.406
Multi-vessel disease
Previous MI
101 (59.76%)
96 (53.93%)
1011 (51.74%)
246 (10.96%)
0.045
<0.0001
9 (5.06%)
46 (25.84%)
60 (2.67%)
407 (18.14%)
0.020
0.061
Hypertension
Hypercholesterolaemia
101 (56.74%)
108 (60.67%)
975 (43.45%)
768 (34.30%)
0.002
<0.0001
Cardiogenic shock
108 (60.67%)
768 (34.30%)
<0.0001
Previous CABG
Diabetes mellitus
Abstract 16 Figure 1
A14
Conclusion Primary PCI for treatment of ST is less effective, and
these patients are at increased risk for in-hospital and long-term
mortality compared with patients undergoing primary PCI due to de
novo STEMI.
17
SUDDEN CARDIAC DEATH AND ACUTE MYOCARDIAL
INFARCTION: HOW HAS THE PICTURE CHANGED?
doi:10.1136/heartjnl-2011-300198.17
1
G Mole, 2D Watson, 3C Davidson. 1Brighton & Sussex Medical School, Brighton, UK;
Deprtment of Informatics, University of Sussex, Brighton, UK; 3Brighton & Sussex
University Hospital, Brighton, UK
2
Introduction Coronary heart disease (CHD) is a major burden
worldwide, particularly in economically developed countries such as
the UK. Between 1980 and 2000, deaths from CHD fell by over 50%,
and have continued to fall. The cost of CHD manifests itself in
mortality, disability and economic impact: this should be looked at
in the context of a disease that is preventable.
Methods Data from death certificates and studies with strict clinicopathological criteria on mortality from CHD were accessed. These
were analysed in terms of hospital admissions, revascularisation
rates and index of multiple deprivation (IMD). Trends in mortality
overall and for different age groups were analysed over time to
determine how the picture has changed and predict what may
happen going into the future. The mortality rates from the catchment area of the Royal Sussex County Hospital and York Hospital
were analysed to assess reliability of official figures against strict
clinico-pathological inclusion criteria. A range of statistical tests
including, linear regression, ANOVA and JoinPoint regression were
employed.
Results Between 1993 and 2008 deaths from CHD have fallen by
over 50%. The decline has been greater in older age groups particularly the 65e74 age group (the oldest age group analysed).
Comparison with data from studies with strict clinico-pathological
criteria showed this to be the age group in which official statistics
were least accurate. Regression analysis demonstrated that a higher
IMD is associated with increased mortality from CHD (r2Вј0.69,
p<0.001). Increased admission rates was not significantly associated
with decreased mortality from CHD (r2Вј0.004, pВј0.239). Increased
revascularisation was significantly associated with decreased
mortality from CHD (r2Вј0.99, p<0.001). JoinPoint regression
analysis shows a constant rate of decline in mortality from 1993 to
2001 which then decreases faster between 2001 and 2006 before
Abstract 17 Figure 1
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
slowing dramatically from 2006 to 2008. JoinPoint regression analysis of different age groups demonstrates that the slower rate of
decline from 2006 may be due to stubbornly high numbers of deaths
in the 35e44 age group. Lastly the National п¬Ѓgures on mortality
from CHD are shown to be misleading as many people are still
dying from CHD just when they have crossed the 75-year old
exclusion criteria; as a result a delay in mortality is presented as
prevention of mortality from CHD.
Discussion There is a danger that previous successes are being offset
by high rates in the younger cohorts, and that the overall trend may
be eventually be reversed. There is still work to be done in reducing
risk factors and also applying treatments that have had a proven
positive impact (such as revascularisation) more effectively. Statistically significant changes in declining CHD mortality rates.
Future work This 10 000 word report formed the basis of a funding
application to the British Heart Foundation for a follow-up to the
United Kingdom Heart Attack Study.
п¬Ѓgure 1. After adjusting for comorbidities, anaemia remained an
independent predictor of long-term adverse outcome (ORВј2.4, 95%
CIВј1.1 to 3.7, p<0.001). Patients with baseline anaemia who
received a blood transfusion were significantly more likely to suffer
an adverse outcome than those that did not receive a transfusion
(21% vs 6%, p<0.0001).
Abstract 18 Figure 1
All cause mortality after PCI for STEMI.
Conclusion Patients presenting with anaemia undergoing primary
PCI appear at significantly higher risk of an adverse outcome. This
risk increases further in population receiving RBC transfusions
during index hospitalisation.
19
TREATMENT OF MULTIVESSEL CORONARY ARTERY
DISEASE IN PRIMARY PCI FOR ST ELEVATION MYOCARDIAL
INFARCTION: CULPRIT ONLY REVASCULARISATION IS
ASSOCIATED WITH HIGHER MACE RATES
doi:10.1136/heartjnl-2011-300198.19
Abstract 17 Figure 2
K S Rathod, L A McGill, E Sammut, V S Rathod, D A Jones, R Weerackody, A Jain,
C Knight, A Mathur, A Wragg. London Chest Hospital NHS Trust, London, UK
18
PATIENTS PRESENTING WITH ANAEMIA UNDERGOING
PRIMARY PCI APPEAR AT SIGNIFICANTLY HIGHER RISK OF
AN ADVERSE OUTCOME
doi:10.1136/heartjnl-2011-300198.18
K R Rathod, D A Jones, B Rathod, A Graham, E Sammut, S Gallagher, J Behar,
A K Jain, C Knight, A Mathur, A Wragg, R Amersey. Barts and the London NHS trust,
London, UK
Background Previous studies have demonstrated a relationship
between pre-existing anaemia and inpatient mortality after percutaneous coronary intervention (PCI). There is limited data looking
at the impact of baseline Haemoglobin and long term outcome after
primary PCI.
Methods Clinical information was analysed from a prospective
database on 2357 STEMI patients who underwent Primary PCI
between January 2004 and May 2010 at a London centre. Information was entered at the time of procedure and outcome assessed
by all-cause mortality information provided by the Office of
National Statistics via the BCIS/CCAD national audit. Anaemia
was defined according to WHO definition of Hb greater than or
equal to 12 g/dl for females and 13 g/dl for males.
Results 471 (20%) patients were anaemic at presentation. The
anaemic cohort, were older (72.2 vs 62.4, p<0.0001), had higher
incidence of diabetes (27% vs 15%, p<0.0001), hypertension (42 vs
35%, pВј0.01), hypercholesterolaemia (40 vs 30%, pВј0.007),
previous PCI (13 vs 7%, pВј0.01), and previous MI (23% vs 12%,
p<0.0001). There were similar incidences of three-vessel disease and
cardiogenic shock. Over a 3-year follow-up period there was significantly higher all cause mortality in the anaemic group compared to
the normal Hb group (20.4% vs 13.5%, p<0.0001). See Abstract 18
Heart June 2011 Vol 97 Suppl 1
Background Multi-vessel disease occurs in 40%e65% of patients
undergoing Primary PCI for STEMI and is associated with adverse
prognosis. Contemporary guidelines recommend treating the infarct
related artery alone (culprit) during the urgent procedure. There is
limited data comparing outcomes of complete with infarct-related
artery (IRA)-only revascularisation in primary PCI for STEMI with
few studies including the option of later date elective procedures for
the other lesions (staged revascularisation). We therefore sought to
clarify the outcome of patients with multi-vessel disease undergoing
primary PCI dependent on management strategy.
Methods Clinical information was analysed from a prospective data
base on 2131 STEMI patients who underwent Primary PCI between
January 2004 and May 2010 at a London centre. Patients with
previous CABG were excluded. Information was entered at the time
of procedure and outcome assessed by all-cause mortality information provided by the Office of National Statistics via the BCIS/
CCAD national audit. Patients were split into three different
treatment groups: culprit vessel angioplasty-only (COR group);
staged revascularisation (SR group) and simultaneous treatment of
non-IRA (CR group). The primary end point used was major adverse
cardiac events (MACE), defined as death, myocardial infarction
(MI), stroke and target vessel revascularisation (TVR).
Results There were 963 (45%) consecutive patients with STEMI and
multivessel CAD undergoing primary angioplasty. There were
similar baseline characteristics between the 3 groups, aside from
cardiogenic shock, which was significantly higher in the complete
revascularisation group. See Abstract 19 table 1. At 30-days of
follow-up, 23/263 (9%) patients in the CR group experienced at
least one major adverse cardiac event (MACE), 1 (1%) in the SR
group and 35 (5%) in the COR group, pВј0.01. This trend continued
A15
BCS Abstracts 2011
up to 1-year of follow-up with the lowest rates of events in the SR
group. However after 3 years MACE rates are significantly increased
in the COR group (24%) but were similar in the CR (18%) and SR
(17%) groups. See Abstract п¬Ѓgure 1. MACE rates were driven mainly
by death in the CR with high rates of TVR in the COR and SR
groups. See Abstract п¬Ѓgure 2.
20
WHAT HAPPENS TO PLATELET FUNCTION AND VASCULAR
INFLAMMATION WHEN CLOPIDOGREL IS WITHDRAWN?
INSIGHTS USING SHORT THROMBELASTOGRAPHY
doi:10.1136/heartjnl-2011-300198.20
1
2
3
2
3
N Sambu, H Dent, T Warner, N Englyst, P Leadbeater, 1A Hobson, 1A Calver,
S Corbett, 1H Gray, 1I Simpson, 1N Curzen. 1Southampton University Hospitals NHS
Trust, Southampton, UK; 2University of Southampton, School of Medicine, Southampton, UK; 3The William Harvey Research Institute, Barts and the London School of
Medicine and Dentistry, London, UK
1
Abstract 19 Table 1
COR N[638
SR N[100
CR N[263
Age
64.77
61.46
64.32
Significance
0.144
Gender (female)
Ethnicity (Caucasian)
156 (23.7%)
441 (67.0%)
13 (13.0%)
79 (79.0%)
74 (27.9%)
185 (69.8%)
0.0114
0.0511
Previous MI
Previous CABG
109 (16.6%)
15 (2.3%)
11 (11.0%)
2 (2.0%)
36 (13.6%)
3 (1.1%)
0.2414
0.5231
Previous PCI
Diabetes Mellitus
83 (12.6%)
129 (19.6%)
5 (5.0%)
16 (16.0%)
23 (8.7%)
55 (20.8%)
0.031
0.5932
Hypertension
Hypercholestrolaemia
312 (48.1%)
269 (41.5%)
40 (40.0%)
37 (37.0%)
91 (41.2%)
92 (41.6%)
0.1205
0.7751
GPIIb/IIIa Inhibitor
Cardiogenic Shock
572 (87.7%)
29 (4.7%)
93 (93.0%)
2 (2.0%)
231 (89.5%)
31 (12.26%)
0.1724
p<0.0001
Introduction A clustering of adverse events, in particular stent
thrombosis (ST) has been observed following clopidogrel cessation
1-year after drug-eluting stenting (DES), the aetiology of which is
poorly understood. We investigated the effect of withdrawing
clopidogrel in DES patients using a simple, rapid, reproducible nearpatient platelet function test known as short Thrombelastography
(s-TEG) that has been developed and validated by this group.
Methods 33 patients on aspirin and due to stop clopidogrel at 1 year
following DES were investigated. Venesection was performed at (i)
4 weeks and 24 h pre clopidogrel cessation (ii) 24 h, 48 h, 1, 2 and
4 weeks post clopidogrel cessation. At all time-points, platelet
reactivity was determined using s-TEG and thromboxane (TX) B2,
IL-6, CD40 ligand and high sensitivity CRP were measured.
Results Clopidogrel cessation produced (i) a predictable increase in
ADP-induced platelet aggregation, and (ii) an unexpected and
significant rise in AA-induced platelet aggregation. TXB2 was
consistently suppressed confirming inhibition of COX by aspirin.
Abstract 20 Figure 1
Abstract 19 Figure 1
disease.
Comparison of MACE between multivessel
Conclusion We have described for the п¬Ѓrst time an aspirin-independent increase in AA-induced clotting following clopidogrel
withdrawal in DES patients. As well as potentially helping to
explain the observed clustering of ST events early after clopidogrel
withdrawal, these п¬Ѓndings raise the question as to whether AAinduced clotting is an appropriate test of aspirin sensitivity. Our
results also confirm s-TEG as a plausible candidate for near-patient
platelet function testing in this п¬Ѓeld.
21
INFLUENCE OF FRACTIONAL FLOW RESERVE
MEASUREMENT ON TREATMENT-DECISIONS IN PATIENTS
WITH RECENT ACUTE NON-ST ELEVATION MYOCARDIAL
INFARCTION
doi:10.1136/heartjnl-2011-300198.21
1
D Carrick, 1M Behan, 1F Foo, 1J Christie, 2J Norrie, 1K Oldroyd, 1C Berry. 1Department
of Cardiology, Golden Jubilee National Hospital, Glasgow, UK; 2Robertson Centre for
Biostatistics, University of Glasgow, Glasgow, UK
Abstract 19 Figure 2
Breakdown of MACE at 5 years.
Conclusions Culprit vessel-only angioplasty was associated with the
highest rate of long-term MACE compared with multivessel treatment. Patients scheduled for staged revascularisation experienced a
similar rate of MACE to patients undergoing complete simultaneous
treatment of non-IRA.
A16
Introduction Non-ST elevation acute myocardial infarction
(NSTEMI) is the most common form of acute coronary syndrome
and has a relatively poor prognosis. Visual interpretation of the
coronary angiogram is the standard approach to guide treatment
decisions in patients with recent acute NSTEMI. The aim of our
study was to determine whether measurement of coronary pressure
derived fractional flow reserve (FFR), compared to coronary
angiography alone, might influence treatment decisions.
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
Setting The cardiac catheterisation laboratory in a regional heart
centre in the UK.
Definitions The clinical indication for FFR measurement was the
presence of an intermediate coronary stenosis (50%e75% of the
reference vessel diameter) which resulted in diagnostic and treatment uncertainty. FFR measurement was used to provide functional
information on lesion severity and an FFR <0.80 was taken to
represent a flow-limiting stenosis.
Methods The study involved three accredited interventional cardiologists and a study coordinator. The cardiologists separately
reviewed the coronary angiograms and together with the clinical
history, made a decision for medical therapy, PCI, CABG/MDT, or
deferred management. The FFR results were then disclosed and the
initial management decision was reviewed in light of the FFR result
and changed as appropriate.
Results Of 1621 acute NSTEMI patients (January 2009eMarch 2010)
in our hospital, 100 (6.2%) had FFR recorded. The treatment decisions
for each cardiologist were: medical therapy 7%, 10%, 1%; PCI 64%,
70%, 60%; CABG/MDT 13%, 12%, 15%; deferred management 16%,
8%, 24%). The proportion of patients allocated to each treatment
group differed between the 2nd and 3rd Cardiologist (pВј0.02).
Following FFR disclosure, each cardiologist changed his/her treatment
decision in 58%, 50% and 62% of patients (p<0.05). Of the new
decisions made following FFR disclosure, the proportion of patients
allocated to medical therapy increased by 26%, 19% and 29%, whereas
the proportion of patients allocated to deferred management or multivessel PCI decreased by 16%, 8%, 24% and by 5%, 7% and 5%,
respectively (all p<0.05). The number of patients in whom the treatment decisions made by each cardiologist independently conformed
(and so represented a consensus in at least 2 of the 3 decisions)
increased from 74% to 92% as a result of FFR disclosure (p<0.001).
Conclusion In our hospital about 1 in 20 NSTEMI had a coronary
pressure wire study because of diagnostic uncertainty based on
coronary angiography alone. In NSTEMI patients selected for FFR
measurement, the FFR resulted in a change in management in at
least half of the patients. FFR use increased the proportion of
patients in whom treatment decisions conformed suggesting FFR
use may also help to reduce the variation in treatment decisions
using angiography alone. These results support further studies of
the clinical utility and prognostic implications of FFR measurement
in patients with NSTEMI.
22
COMPARISON OF 4-H HEART FATTY ACID BINDING
PROTEIN WITH 12-H TROPONIN I TO ASSESS 6-MONTH
RISK FOLLOWING PERCUTANEOUS CORONARY
INTERVENTION IN ACUTE CORONARY SYNDROMES
doi:10.1136/heartjnl-2011-300198.22
1
1
1
I R Pearson, U M Sivananthan, J H Barth, C P Gale, 1A S Hall. 1Leeds Teaching
Hospitals, Leeds, UK; 2Division of Biostatistics, University of Leeds, Leeds, UK
Abstract 22 Figure 1
23
SERUM NGAL IDENTIFIES CONTRAST NEPHROPATHY
EARLY IN PATIENTS WITH DIABETES MELLITUS AND
CHRONIC KIDNEY DISEASE UNDERGOING CORONARY
ANGIOGRAPHY AND ANGIOPLASTY
doi:10.1136/heartjnl-2011-300198.23
1
2
3
4
A C Qureshi, R Rampat, S M Harwood, M Roughton, 2M M Yaqoob, 1A Kapur.
The London Chest Hospital, Barts and The London NHS Trust, London, UK; 2The Royal
London Hospital, Barts and The London NHS Trust, London, UK; 3The William Harvey
Research Institute, London, UK; 4The Royal College of Physicians, London, UK
1
2
Background It is known that PCI can cause myocardial injury leading
to the release of cardiac biomarkers into the circulation (procedural
MI). This occurs in approximately one third of procedures and has
been shown to impact negatively on prognosis. Monitoring for
procedural MI, although not yet standard practice, is increasingly
undertaken as a measure of quality control, and may be a factor when
deciding time of discharge from hospital following the procedure. The
use of TnI to screen for procedural MI requires a wait of 12-h post
procedure before the blood sample may be taken, and an impact on
length of hospital stay is inevitable. Heart-type Fatty Acid Binding
Protein (H-FABP) is a small protein released rapidly and in large
quantities from the myocardium into the circulation, both during
ischaemia and following necrosis. It allows detection of myocardial
injury associated with PCI earlier than with TnI.
Hypothesis H-FABP at 4 h provides equivalent prognostic information to TnI at 12 h following PCI-induced myocardial injury.
Heart June 2011 Vol 97 Suppl 1
Methods We studied 94 patients with ACS admitted to a single UK
Teaching Hospital for PCI. We used the Randox Cardiac-Array to
measure H-FABP at 4 hrs after PCI and troponin I at 12 h after PCI.
Comparison of specificity and sensitivity of each biomarker for
adverse cardiac events was made. Endpoint assessment consisted of
one of the following three events (i) PC-induced MI (ii) readmission
with MI by 6 months (iii) death by 6 months.
Results The area under the receiver operator curve was 0.73 for
H-FABP measured at 4 h as compared to 0.72 for TnI measured as 12 h.
Conclusion Early assessment of PCI-induced myocardial injury using
the Randox Cardiac-Array to measure H-FABP is as sensitive and
specific for adverse prognosis as is TnI measurement taken at 12 h
post PCI. This approach should help to expedite early, safe hospital
discharge following PCI.
Background The incidence of contrast nephropathy (CIN) following
coronary angiography or percutaneous coronary intervention (PCI)
in patients with diabetes mellitus (DM) may be up to 30% and is
associated with increased long term morbidity and mortality.
Methods We recruited 208 consecutive patients undergoing elective or
urgent coronary angiography or PCI with known DM and chronic
kidney disease (CKD) (defined as eGFR <60 ml/min). CIN was defined
as a post procedure rise in creatinine at day 3 of >25% from baseline or
an absolute rise of 44.5 mmol/l. Severity of coronary disease was
assessed using the SYNTAX Score and risk of CIN using the Mehran
risk score. We evaluated serum and urine neutrophil gelatinase-associated lipocalin (NGAL) and albuminuria for additional information
about CIN risk. N-acetylcysteine and intravenous hydration were given
to all patients with eGFR <50 ml in accordance with local guidelines.
Results Baseline characteristics are summarised in table 1. 116
patients underwent coronary angiography and 92 underwent PCI. 39
patients (18.8%) developed CIN. Contrast dose was similar in the CIN
and non-CIN group (pВј0.249). The Mehran risk score was strongly
A17
BCS Abstracts 2011
predictive of CIN development (p<0.001). The SYNTAX score did not
differ between those who did or did not develop CIN (pВј0.188). A
significant rise in serum NGAL was seen as early as 2 h post procedure
in the CIN arm (pВј0.03) and this persisted at 4 h (pВј0.007) and
12e24 h (p¼0.0015). Urine NGAL levels did not change significantly
during the п¬Ѓrst 24 h. Neither albumin:creatinine ratio (pВј0.149) or
protein:creatinine ratio (pВј0.635) predicted development of CIN.
Abstract 23 Table 1
No CIN outcome
(n[169)
CIN outcome
(n[39)
Age, (mean, SD)
70.8 (8.5)
71.5 (9.5)
Hypertension (%)
Hyperlipidaemia (%)
155 (91.7)
165 (97.6)
33 (86.8)
37 (97.4)
0.35
0.92
Previous MI (%)
Ex or current smoker (%)
66 (39.1)
96 (55.9)
15 (39.5)
19 (50.0)
0.96
0.75
Heart failure (%)
Valvular heart disease (%)
32 (19.1)
28 (16.6)
7 (18.4)
7 (18.4)
0.93
0.78
84 (49.7)
28.6 (5.4)
20 (52.6)
29.2 (6.1)
0.74
0.54
Family history IHD (%)
BMI, (mean, SD)
p Value
0.64
follow-up to date, 10 patients (59%) had a reduction in MR to #
grade 2+ and 8 patients (47%) had $2 grade reduction in MR
(p¼0.001). The reduction in MR grade remained significant for the 8
patients with echo data at 6-month follow-up (pВј0.038). One
patient had persistent grade 3+ MR at 1-month follow-up due to late
partial detachment of one of the 2 clips deployed. NYHA class
reduced significantly following intervention. Prior to Mitraclip, 63%
of patients were in NYHA class III/IV. At 1-month follow-up postMitraclip only one patient (4%) was in NYHA class III (pВј0.042) and
15 patients (83%) had at least 1 grade reduction in NYHA class. There
was no significant change in left ventricular size following intervention, although there was a trend towards reduced left ventricular
volumes at 1-month follow-up (end diastolic volume 175 vs 160 ml,
pВј0.102; end systolic volume 92 vs 79 ml, pВј0.076).
Conclusion In selected patients Mitraclip edge-to-edge repair
successfully reduces the severity of mitral regurgitation and
improves symptoms. Further studies are needed to examine whether
these results are durable and associated with improved outcome.
Conclusions The current gold standard for measuring CIN is a rise in
serum creatinine but this is of limited value as it does not increase
until 48e72 h post renal injury. Neither the SYNTAX score, nor
urinary albuminuria or proteinuria are predictive of CIN development. A rise in serum NGAL levels within the п¬Ѓrst 12 h following
coronary angiography or PCI appears to be a very promising marker
in the early diagnosis of CIN.
24
PERCUTANEOUS MITRAL VALVE REPAIR WITH THE
MITRACLIP DEVICE: A TERTIARY CARDIAC UK EXPERIENCE
doi:10.1136/heartjnl-2011-300198.24
J Dungu, C S R Baker, M F Bellamy. Hammersmith Hospital, Imperial College London,
London, UK
Introduction Percutaneous mitral valve repair using the transcatheter
Mitraclip device is a novel therapy for patients with severe mitral
regurgitation (MR) who are too high risk for conventional surgery.
We report the largest UK series to date.
Methods Patients were screened with transthoracic (TTE) and
transoesophageal echocardiography (TOE). Mitral regurgitation was
graded by British Society of Echocardiography criteria. Twenty-four
patients with $ grade 3+ symptomatic MR underwent percutaneous mitral valve repair under general anaesthesia between
February 2009 and October 2010. The Mitraclip device was deployed
under 2- and 3-Dimensional TOE and fluoroscopic guidance. All
patients were discussed with the manufacturing company (Evalve)
and in a multidisciplinary meeting including >2 cardiologists and 2
cardiothoracic surgeons with a special interest in mitral valve
surgery prior to being accepted.
Results Mitraclip therapy was attempted in 24 patients aged
71611 years with an average Euroscore of 16%. The indication for
intervention was functional MR in 10 patients (42%), ischaemic MR
in 7 patients (29%) and degenerative MR in 7 patients (29%). Twenty
patients had successful deployment of the Mitraclip device (83%).
Fifteen patients (75%) had 2 clips deployed. There were no vascular
complications or strokes. We were unable to grasp the mitral valve
leaflets in 2 patients due to an excessive coaptation gap. There was 1
procedural death due to leaflet tear in a patient with end-stage
ischaemic cardiomyopathy and a grossly dilated left ventricle. All
patients (100%) treated with the Mitraclip had severe MR (grade 3
+/4+) prior to intervention. Mitral regurgitation was graded by
colour Doppler alone following intervention as standard quantitative
analyses are not validated in the presence of a Mitraclip. At 1-month
A18
Abstract Figure 1
Change in MR grade post-Mitraclip.
Abstract Figure 2
Change in NYHA class post-Mitraclip.
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
25
26
TAVI OPERATOR RADIATION DOSE COMPARED TO PCI AND
ICD OPERATORS: DO WE NEED ADDITIONAL RADIATION
PROTECTION FOR TRANS-CATHETER STRUCTURAL HEART
INTERVENTIONS
THE EFFECTS OF PRE-EXISTING SIGNIFICANT CORONARY
ARTERY DISEASE UPON OUTCOME AFTER TRANSCATHETER
AORTIC VALVE IMPLANTATION USING THE EDWARDS
BIOPROSTHESIS
doi:10.1136/heartjnl-2011-300198.25
M Drury-Smith, A Maher, C Douglas-Hill, R Singh, M Bhabra, J Cotton, S Khogali.
Heart and Lung Centre, New Cross Hospital, Wolverhampton, UK
Introduction Trans-catheter cardiac aortic valve implantation
(TAVI), implantable cardiac defibrillators (ICD), and percutaneous
coronary intervention (PCI), are common procedures associated
with radiation exposure to the operator and the patient. Radiation
dose exposure is cumulative and if above the recommended annual
levels may have significant consequences for the operator. The
radiation dose TAVI operators are exposed to is not widely known,
but it is an important consideration in view of the increasing
volume of procedures and the potential risks of over-exposure. Our
aim was to monitor and compare, radiation exposure time, dose, and
individual operator dose, in TAVI, PCI and ICD.
Method Ten TAVIs were performed, 6 via the trans-femoral route and 4
via the subclavian approach. Radiation protection was employed in all
cases using standard lead skirts and screens. During each procedure the
radiation dose exposure was monitored for each operator using ThermoLuscent Dosemeters (TLD) on the left п¬Ѓnger (LF), right п¬Ѓnger (RF)
and forehead. The six TAVI procedures performed via the transfemoral
approach used only two operators, while the subclavian approach
involved three operators. The third operator was a surgeon who was
nearest to the x-ray images. Radiation exposure doses were also
collected from ICD and PCI operators during the same period, using the
same type of TLDs on LF and RF. Operator specific radiation doses were
obtained from a central RRPPS Approved Dosimetry Service. PCI was
considered a standard trans-catheter procedure. TAVI and ICD operator doses were compared to the mean standardised PCI operator dose.
Results The mean exposure times and doses for the different types
of trans-catheter procedures performed are detailed in the tables
below. Despite the use of standard radiation protection measures,
the mean dose to operators undertaking TAVI was 6 times higher
than the trans-femoral PCI operator (pВј0.008). The mean radiation
exposure time of TAVI was seven times more than PCI. Although
subclavian TAVI and ICD procedures were expected to be comparable with respect to operator dose, subclavian TAVI operators have
an unexpectedly higher dose (pВј0.03).
Conclusions Overall TAVI operators are exposed to significantly
higher radiation doses compared to PCI and ICD operators. Additional radiation protection for TAVI operators is strongly advocated.
We are currently evaluating the impact of using a RADPAD as
additional protection during TAVI procedures.
Abstract 25 Table 1
Variable
Mean exposure Time (mins)
Mean exposure Dose
(Gy/cmq) 6 SD
TAVI
27.0*
196.256150.96y
ICD
PCI
p Value
3.26
3.825
<0.001*
11.0369.01
33.09611.5
0.008y
*Significantly increased radiation exposure time in TAVI procedures compared to ICD and PCI.
ySignificantly increased radiation exposure dose in TAVI procedures compared to ICD and PCI.
Abstract 25 Table 2
doi:10.1136/heartjnl-2011-300198.26
1
M Z Khawaja, 2H Haran, 1I Nadra, 1K Wilson, 1L Clack, 1K Macgillivray, 1J Hancock,
C Young, 1V Bapat, 1M Thomas, 1S Redwood. 1Guy’s & St. Thomas’ Hospitals NHS
Foundation Trust, London, UK; 2King’s College School Of Medicine & Dentristry, London, UK
1
Introduction Patients undergoing surgical aortic valve replacement
(sAVR) routinely undergo simultaneous coronary artery bypass
grafting (CABG) for significant coronary artery disease (CAD) due to
adverse prognostic impact. While manufacturers advise percutaneous intervention (PCI) of significant CAD prior to transcatheter
aortic valve implantation (TAVI) there is considerable variation
among operators.
Methods We performed a retrospective analysis of 168 patients who
underwent TAVI using the Edwards bioprosthesis from March 2008 to
October 2010 at St. Thomas Hospital, London. They were divided into
two groups according to the results of the pre-TAVI coronary angiogram: (Group 1) patients with $1 coronary stenosis of $70% severity
and those without (Group 2). The end-point was all-cause mortality.
Results In total, 70 patients (41.7%) had significant CAD prior to
TAVI, with 10 (6.0%) undergoing PCI prior to their procedure. There
were no significant differences in either the baseline characteristics
or access approach between the two groups (Abstract 26 tables 1
and 2). At a mean follow-up of 3356277 days (mean6SD), the
overall mortality was 22.6%; Group 1 mortality was 30% and in
group 2 was 17.3% (pВј0.124) (see Abstract 26 п¬Ѓgure 1) There was
no difference seen in the length of stay in the intensive care unit
(2.766.2 vs 4.1614.9 days, pВј0.462) nor in the number of days to
discharge (12.6610.1 vs 12.8613, pВј0.928). Among those patients
who underwent PCI in Group 1, 8 had single vessel intervention and
2 had PCI to 2 vessels. The target vessels were left main stem (LMS)
(nВј2), proximal left anterior descending artery (LAD) (nВј5),
circumflex (n¼1), right coronary artery (RCA) (n¼2), saphenous
vein graft (SVG) to LAD (n¼1) and SVG to circumflex (n¼1).
Mortality in this sub-group was not significantly different from the
CAD patients who did not receive PCI (50% vs 26.7%, pВј0.272).
Abstract 26 Table 1
Group 1 Significant
CAD (n[70)
Group 2 No significant
CAD (n[98)
p Value
Age (years6SD)
83.767.5
81.768.5
0.112
Diabetes Mellitus
Cerebrovascular disease
16 (22.9)
11 (15.7%)
27 (27.6%)
17 (17.3%)
0.492
0.780
Peripheral vascular disease
Glomerular filtration rate
15 (21.4%)
48.4627.9
12 (12.2%)
46.8623.1
0.110
0.685
Logistic Euroscore (%6SD)
LV ejection fraction (%6SD)
23.5612.9
48.8611.3
21.5616.2
47.9612.4
0.399
0.658
Aortic valve area (cm26SD)
Previous CABG
0.6360.20
18 (25.7%)
0.6760.22
27 (27.6%)
0.219
0.791
Previous PCI
16 (22.9%)
12 (12.2%)
0.070
Abstract 26 Table 2
Group 1 Significant
CAD (n[70)
Mean radiation dose
(Gy/cmq) per operator
В±SD
p value
Trans-femoral TAVI
1.67
1.23
0.03
Subclavian TAVI
ICD
2.53
1.95
3.09
0.14
0.03
0.03
PCI
0.18
Group 2 No significant
CAD (n[98)
p value
0.778
Transfemoral
44 (44.9%)
29 (41.4%)
Transapical
Transaortic
47 (48.0%)
7 (7.1%)
37 (52.9%)
4 (5.7%)
0.36
Conclusion The presence of significant CAD had no significant
impact upon the all-cause mortality of patients after TAVI in our
Heart June 2011 Vol 97 Suppl 1
A19
BCS Abstracts 2011
Results As expected CwP was higher in patients with NSTEMI
(46.5 (SD) 18.8) compared with the stable angina patients (Mean
(SD) 21.1 (9.3) pВј0.01). IMR was also higher in patients with
NSTEMI (Mean (SD) 27.6 (12.6)) compared with patients with
stable angina (Mean (SD) 20.7 (5.4) p¼0.2). Total PMAs were nonsignificantly higher in patients with NSTEMI (Mean (SD) 14
(4.8)) compared with stable angina (Mean (SD) 10.9 (4.3) pВј0.07).
CD62+ PMAs were significantly higher in patients with NSTEMI
(Mean (SD) 26.9 (12.2)) compared with stable angina (Mean (SD)
13.7 (5.1) pВј0.02) Abstract 27 п¬Ѓgure 1. CwP correlated positively
with total PMA (pВј0.01) in NSTEMI but not in stable angina
patients. However, IMR correlated positively with total PMAs in both
stable angina (pВј0.02) and NSTEMI (pВј0.08) Abstract 27 п¬Ѓgure 2.
Abstract 26 Figure 1
study. As yet, the impact of PCI to significant CAD upon outcome
after TAVI is not known and will be assessed in a prospective,
randomised controlled trial currently underway.
27
PLATELET MONOCYTE AGGREGATES ARE DETERMINANTS
OF MICROVASCULAR DYSFUNCTION DURING
PERCUTANEOUS CORONARY INTERVENTION FOR STABLE
ANGINA AND NON-ST SEGMENT ELEVATION MYOCARDIAL
INFARCTION
Abstract 27 Figure 1
doi:10.1136/heartjnl-2011-300198.27
1
1
2
1
C A Mavroudis, B Majumder, M Lowdell, R D Rakhit. 1Cardiology Department, Royal
Free Hospital, London, UK; 2Haematology Department, Royal Free Hospital, London, UK
Background Microvascular dysfunction is associated with adverse
outcome in patients with acute coronary syndrome (ACS). During
ACS platelet and monocyte derived chemokines, in conjunction
with adhesion molecule expression, promote the inflammatory
process. Activated platelets express p-selectin which binds to the pselectin glycoprotein ligand on the monocyte forming platelet
monocyte aggregates (PMA). PMA expression is a sensitive marker
of platelet activation and inflammation. Although platelet monocyte interaction is a normal physiological process, in the presence of
platelet activation, activated (CD62+ PMA) may be directly
involved in the pathophysiology of intracoronary inflammation and
microvascular dysfunction in ACS.
Aim To investigate the relationship between microvascular
dysfunction and PMA expression in patients with stable angina and
non-ST elevation myocardial infarction (NSTEMI).
Methods Six patients with stable angina undergoing elective PCI and
six patients with NSTEMI undergoing non-elective PCI were recruited.
Microvascular dysfunction was assessed by measuring the coronary
wedge pressure (CwP) and the index of Microvascular resistance (IMR)
using a single pressure-temperature sensor-tipped coronary wire from
the simultaneous measurement of distal coronary pressure and thermodilution derived mean transit time (Tmn) of a bolus of saline
injected at room temperature into the coronary artery during
maximum hyperaemia. Blood samples were taken from the coronary
artery (distal to the culprit lesion), aorta and the right atrium for PMA
estimation. PMAs were assessed using fluorescent monoclonal antibodies and flow cytometry. Total PMAs were calculated and expressed
as a percentage of the total monocyte count. Activated CD62+ PMAs
were expressed as a percentage of total PMAs.
A20
Abstract 27 Figure 2
Conclusions PMAs are elevated in stable coronary disease and ACS
with elevated activated CD62+ PMA a hallmark of ACS. PMAs
correlate with measured microvascular dysfunction during PCI in
stable angina and NSTEMI. This study supports the hypothesis that
PMA formation may be important determinants of platelet activation,
inflammation and microvascular dysfunction in coronary disease.
28
LOW FRAME RATE SCREENING DURING PERCUTANEOUS
CORONARY ANGIOPLASTY SIGNIFICANTLY REDUCES
RADIATION EXPOSURE, GIVES GOOD IMAGE QUALITY
WITHOUT AFFECTING PATIENT OUTCOME
doi:10.1136/heartjnl-2011-300198.28
1
1
2
1
S J Wilson, P Venables, O Gosling, V Suresh. 1South West Cardiothoracic Centre,
Plymouth, UK; 2Royal Devon and Exeter Hospital, Exeter, UK
Introduction Minimisation of radiation exposure during cardiac
procedures is required by statute (IRMER 2000). During coronary
angioplasty 47% of radiation dose is related to screening at standard
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
Abstract 28 Table 1
Screening
DAP (mGycm2)
Total DAP
(mGycm2)
Fluoro time
(seconds)
Number of
acquisitions
Standard (15 fps)
Low (7.5 fps)
28564.5
19248.5
60746.9
50953.4
770
800
26.7
26.8
Mean DAP reduction
Significance
ГЂ33%
p<0.01
ГЂ16%
n/s
e
n/s
e
n/s
frame rate (15 frames per second). Digital fluoroscopic technology
has improved imaging making the use of lower frame rates
feasible. This study assessed whether low frame rate screening (7.5
frames per second) reduced radiation without affecting patient
outcomes.
Method We prospectively collected data from consecutive coronary
angioplasty procedures performed at reduced screening frame rate
(7.5 frames per second). We included elective, urgent and emergency
procedures. Audit data from procedures performed at standard frame
rate with the same inclusion criteria were used as a control group.
Phillips Allura flat plate XPER FD10 catheterisation equipment was
used. The frame rate could be increased at the operator’s request,
and any safety concerns were reported immediately.
Data collection
Patient data:
times and number of acquisition runs were similar in each group.
In every case image quality was acceptable, with no requirement
for increased screening frame rate. No safety concerns were
reported. 30-day incidence of major adverse cardiovascular events
(MACE) was similar in both groups. In the screening group there
was 1 MACE event at 30 days (2%), with 2 MACE events (2%) in
the control group. Screening and Total DAPs (mean mGycm2) were
33% and 16% lower respectively in the low frame rate group.
Statistical comparison was made with the Man-Whitney
U-test. This showed a significant reduction in the Screening DAP
(p#0.01) with low frame rate screening. See Abstract 28 table 1
and graph.
Conclusions Low frame rate screening is a practical way of reducing
radiation exposure in line with the ALARA “As Low As Reasonably
Acheivable” principle. Having shown that low frame rate screening
for coronary angiography gives good imaging quality and is safe, we
now demonstrate that low frame rate screening coronary angioplasty is also safe. Radiation exposure from screening is significantly
reduced by 33% and total exposure is reduced by 16%. Low frame
rate screening should be standard practice where modern facilities
allow. We suggest that centres currently using 15 frames per second
screening should undertake a similar assessment in order to minimise radiation.
< Age
< Weight (Kg)
< Height (cm)
29
Radiation data:
<
<
<
<
Screening DAP (mGycm2)
Total DAP (mGycm2)
Total Fluoroscopy time (mm:ss)
Number of acquisition runs
Operator outcome:
< Need to increase screening frame rate
Patient outcome:
< 30 day incidence of major adverse cardiovascular event
(MACE): death, non-fatal myocardial infarction or need for
urgent revascularisation.
Results 55 consecutive studies were examined at low-frame rate
and compared with the audit control group (nВј105). Mean age
was 67 in the low screening rate group and 65 in the control group.
Weight was similar in both groups (83 kg vs 82 kg). The screening
Abstract 28 Figure 1
Heart June 2011 Vol 97 Suppl 1
BIVALIRUDIN IN PATIENTS UNDERGOING PRIMARY
PERCUTANEOUS CORONARY INTERVENTION FOR ACUTE
ST-ELEVATION MYOCARDIAL INFARCTION: OUTCOMES IN
A LARGE REAL-WORLD UK POPULATION
doi:10.1136/heartjnl-2011-300198.29
1
C Eftychiou, 1R J Shelton, 1A Liu, 1K Somers, 1P Tooze, 2L Makri, 1D Barmby,
J M McLenachan, 1J M Blaxill, 1S B Wheatcroft, 1J P Greenwood, 1D J Blackman.
1
Leeds General Infirmary, Leeds, UK; 2Statistical service of Cyprus, Nicosia, Cyprus
1
Background The HORIZONS-AMI trial demonstrated a significantly lower early and late mortality in patients undergoing primary
PCI (PPCI) treated with bivalirudin compared to a Glycoprotein IIb/
IIIa inhibitor (GPI) + heparin. However, concerns remain regarding
the increased incidence of acute stent thrombosis (ST) with
bivalirudin, the apparently worse outcomes in the absence of
additional pre-procedural heparin, and the translation of trial
results into a real-world population. We evaluated the outcomes of
patients undergoing PPCI with bivalirudin in a large all-comers UK
setting.
Methods All patients who underwent PPCI in Leeds General Infirmary from 1 January 2009 to 31 December 2009 were prospectively
entered into a dedicated registry. Demographic, procedural, and 30day outcome data were obtained by abstraction from the ONS
mortality database and BCIS PCI database, review of hospital notes,
and telephone follow-up. Bivalirudin was administered as a bolus,
high-dose intra-procedural infusion, and low-dose infusion for 4 h
post-PCI. Additional heparin was not routinely given, but was
favoured by some operators. Bail-out GPI was administered
according to physician judgement. Primary endpoints were death,
MACE (death, re-infarction, stroke, unplanned target vessel revascularisation (TVR)), and stent thrombosis (ST) (ARC definition
definite/probable) at 30-days follow-up.
Results 968 patients (age 63.5613 years, 71.9% male, 13.2%
diabetics) underwent PPCI. Bivalirudin was given in 882 patients
(91.1%), and GPI + heparin in 85 (8.8%). Of bivalirudin-treated
patients 100 (11.3%) also received heparin (29 pre-PCI and 80
during) while bail-out GPI was used in 91 (10.3%). Thirty-day
outcomes are shown in Abstract 29 table 1. All-cause mortality was
5.2% in the bivalirudin treated patients. Acute SToccurred in 1.0%, a
median of 2 h post-PCI, and within 6 h in 90%. Mortality in
A21
BCS Abstracts 2011
patients who suffered acute ST was 20%, compared to 80%
following subacute ST. There was no difference in outcomes
between bivalirudin treated patients who also received heparin
compared to those who didn9 t (death 7.0% vs 5.0%, p value: 0.80;
MACE 14.0% vs 10.8%, p value: 0.32; acute ST 0% vs 1.2%, p: 0.61).
Abstract 29 Table 1
Outcomes at 30 days
All patients Bivalirudin
GPI + heparin p value
No. of patients
Death
968
52 (5.4%)
882
46 (5.2%)
85
6 (7.1%)
0.450
Cardiac death
Re-infarction
45 (4.7%)
16 (1.7%)
39 (4.4%)
14 (1.6%)
6 (7.1%)
2 (2.4%)
0.277
0.645
Unplanned TVR
Stroke
12 (1.2%)
56 (5.8%)
10 (1.1%)
54 (6.1%)
2 (2.4%)
2 (2.4%)
0.286
0.222
Abstract 30 Table 1
Death, re-infarction, stroke or TVR 110 (11.4%) 100 (11.3%) 10 (11.8%)
Acute stent thrombosis
10 (1.0%)
9 (1.0%)
1 (1.2%)
0.906
0.604
Subacute stent thrombosis
0.386
15 (1.6%)
13 (1.5%)
2 (2.4%)
pВј1.0 respectively). Even though the bleeding risk was higher in the
abciximab group when compared with bivalirudin, this was not
significant (5.8% vs 3.1%, p¼0.27). There was also no difference in
the outcomes between the bivalirudin and “UFH only” groups for
mortality, stent thromboses (acute and 30-day) and major bleeding.
The abciximab group had significantly higher major bleeding rates
than the “UFH only” group (5.8% vs 2.4%, p¼0.04); all other
outcomes were similar.
Conclusion Routine use of bivalirudin in a large UK all-comers
primary PCI population was associated with excellent 30-day
outcomes, including all-cause and cardiac mortality. Acute stent
thrombosis was infrequent, despite the absence of routine additional
heparin.
Abciximab +
UFH (n[346)
Bivalirudin +
UFH (n[162)
UFH only
(n[253)
Age in yrs (range)
64614.1
(25e99)
65613.0
(31e94)
67613.2
(30e96)
Male (%)
Diabetes (%)
77.7
12.4
72.2
6.2
66.8
11.5
Pre-procedure cardiogenic shock (%)
Drug eluting stent (at least one) (%)
7.8
56.1
6.2
56.8
4.7
53.8
No of stents
Single vessel PCI (%)
1.460.9
91.3
1.460.8
87
1.460.9
89.3
Three vessel PCI (%)
Radial procedure (%)
1.4
28
1.9
26.5
2
31.2
Abstract 30 Table 2
30
COMPARISON OF BIVALIRUDIN VS ABCIXIMAB VS
“UNFRACTIONATED HEPARIN ONLY” FOR PRIMARY
PERCUTANEOUS CORONARY INTERVENTION IN A HIGHVOLUME CENTRE
doi:10.1136/heartjnl-2011-300198.30
R Showkathali, J Davies, N Malik, W Taggu, J Sayer, R Aggarwal, P Kelly. The Essex
Cardiothoracic Centre, Basildon, UK
Introduction Primary percutaneous coronary intervention (PPCI) has
been established as a standard therapy for ST elevation myocardial
infarction (STEMI). In addition to thrombectomy and unfractionated heparin (UFH), thrombus burden in STEMI may require use
of more potent antithrombotic agents. Bivalirudin is shown to be
superior to abciximab in reducing the net adverse clinical events and
major bleeding in STEMI in the HORIZONS-AMI trial (Stone et al
NEJM, 2008). We aimed to carry out a “real world” comparison of
different anti-thrombotic regimes in patients undergoing PPCI in
our unit.
Methods Our PPCI service started in September 2009 and we
included all patients undergoing PPCI between September 2009 and
September 2010. Prospectively entered data were obtained from our
dedicated cardiac service database system (Philips CVIS). Mortality
data were obtained from the summary care record (SCR) database.
We used Fisher9 s exact test to compare clinical outcomes between
the groups.
Results Of the 998 patients admitted with suspected STEMI to our
unit during the study period, 776 (77.8%) underwent PPCI. After
excluding patients who had both bivalirudin and abciximab during
their procedure (nВј15), we divided the others (nВј761) into 3 groups
according to the anti-thrombotic regime used (Grp 1- Abciximab
+UFH, Grp 2- Bivairudin+UFH and Grp 3- “UFH only”). Patient
demographics and procedural information are given in Abstract 30
table 1. Continuous data are presented as mean6 SD. Clinical
outcomes are shown in Abstract 30 table 2. In-hospital and 30-day
mortality did not differ between patients who had bivalirudin vs
abciximab (5.6% vs 3.8%, pВј0.35 and 6.8% vs 5.2% pВј0.53
respectively). Both acute and 30 day stent thrombosis rates were
also similar in the two groups (0.6% vs none, pВј0.3, 0.6% vs 0.9%,
A22
Abciximab +
UFH (n[346)
Bivalirudin +
UFH (n[162)
UFH only
(n[253)
In-hospital Mortality (including
cardiogenic shock)
30 day Mortality (including cardiogenic
shock)
30 day Mortality (excluding cardiogenic
shock)
Stent Thrombosis (within 30 days)
3.8
5.6
5.1
5.2
6.8
7.1
3.5
4.9
5.5
0.9
0.6
1.2
Acute stent Thrombosis (24 h) #
Major bleed requiring blood transfusion
(non CABG related)
0
5.8
0.6
3.1
0.4
2.4
Access related bleed requiring
transfusion (includes IABP related)
3.8
1.9
1.2
%
Conclusion These “real-world” data do not show any significant
difference in the clinical outcome for patients who had bivalirudin
or abciximab. There was no advantage seen with the more expensive
agent (abciximab) in keeping with previous trial data. Therefore
bivalirudin should be considered as a non-inferior alternative to
abciximab. This would have considerable economic benefits in the
present situation. The “UFH only” group had similar outcomes to
both bivalirudin and abciximab, which suggests that this may be a
viable alternative in its own right. However, our study is clearly
limited by not being randomised and those patients treated with
UFH alone may have been a lower risk group.
31
ASSESSMENT OF LEFT VENTRICULAR FUNCTION WITH
CARDIAC MRI AFTER PERCUTANEOUS CORONARY
INTERVENTION FOR CHRONIC TOTAL OCCLUSION
doi:10.1136/heartjnl-2011-300198.31
1
G A Paul, 2K Connelly, 1A J Dick, 1B H Strauss, 3G A Wright. 1Sunnybrook Health
Sciences Centre, Toronto, Ontorio, Canada; 2St Michaels Hospital, Toronto, Ontorio,
Canada; 3University of Toronto, Toronto, Ontorio, Canada
Objective To assess the role of CMR in the treatment of true chronic
total occlusions (CTO) with percutaneous coronary intervention
(PCI) and drug eluting stent implantation.
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
Introduction Successful PCI for CTO may confer an improved
prognosis and a reduction in major adverse cardiac events (MACE).
However most trials have included occlusions of short duration (less
than 4 weeks). In this study we assessed the impact of PCI on LV
function in patients with true CTOs (TIMI flow grade 0 and greater
than 12 weeks duration) using serial CMR imaging as well as the
predictive value of late gadolinium enhancement when performed
prior to revascularisation.
Methods Thirty patients referred for PCI to a single vessel CTO
underwent CMR examination prior to and 6 months after PCI.
Technical success was defined as recanalisation of the occluded
vessel and DES implantation with a п¬Ѓnal residual diameter stenosis
<30%. LV function and infarct size were assessed using a 1.5T GE
MRI system. Segmental wall thickening (SWT) was measured
within the perfusion territory of the CTO using the 16-segment
model and segments were dysfunctional if the SWT was #45%. The
transmural extent of infarction (TEI) was calculated by dividing the
hyperenhanced area by the total area3100; a score of #25% were
considered viable.
Results Technical success was achieved in 19 of the 30 patients
(63%). CTO duration was greater in patients with failed revascularisation but other baseline demographics were well matched
between groups (Abstract 31 table 1). PCI-CTO success resulted in a
significant increase in LVEF when compared to both baseline (50 6
13 vs 54 6 11; p<0.01) and with PCI-CTO failure (11.8 6 19.8 vs
-2.3 6 5.1, p<0.01, Abstract 31 п¬Ѓgure 1). In dysfunctional but viable
segments only PCI success conferred a significant improvement in
SWT compared to baseline (26 6 6 vs 40 6 10; p<0.001, Abstract 31
п¬Ѓgure 2). There were no episodes of MACE in either group at
21 months follow-up.
Abstract 31 Table 1
Abstract 31 Figure 2
Conclusion PCI-CTO success of true CTOs can improve global LV
function. The TEI, assessed with CMR, can be used to help predict
improvements in regional wall function. PCI-CTO failure was not
associated with increased MACE at medium-term follow-up.
32
DOES COMPLETE REVASCULARISATION CONFERS A LONG
TERM SURVIVAL BENEFIT IN PATIENTS WITH
CHRONICALLY OCCLUDED CORONARY VESSELS?
doi:10.1136/heartjnl-2011-300198.32
Total (n[30)
CTO-PCI Success
(n[19)
Age/ years
62.2610.2
62.469.8
61.8611.4
0.89
Male, n (%)
CCS Anginal Class
25 (83)
2.1360.68
14 (74)
2.2160.63
11 (100)
2.060.77
0.13
0.42
LVEF/ %
CTO duration, months
53.0611.6
36.9670.8
50.3612.6
12.6626.4
57.668.1
78.86101.1
0.09
0.01
Vessel, n (%)
RCA
16 (53)
9 (47)
7 (64)
0.35
11 (37)
3 (10)
7 (37)
3 (16)
4 (36)
0
Prior MI, n (%)
Diabetes Mellitus, n (%)
17 (59)
7 (23)
11 (58)
5 (26)
6 (56)
2 (18)
0.61
0.61
Hypertension
23 (77)
14 (74)
9 (82)
0.61
LAD
LCx
Abstract 31 Figure 1
Heart June 2011 Vol 97 Suppl 1
CTO-PCI Failure
(n[11)
p value
N H Shah, M F Khan, T Ungvari, P H Loh, L Buchanan, A Hoye, R M Oliver, S Thackray,
J L Caplin, M F Alamgir. Castle Hill Hospital, Kingston upon Hull, UK
Introduction Chronic total occlusion (CTO) of coronary vessels is a
relatively common п¬Ѓnding on diagnostic angiography. There has
been increasing interest in this clinically important area with
development of technologies resulting in improved recanalisation
rates. However, long term survival data in this cohort is lacking. In
this study we looked at survival of patients in whom complete,
successful revascularisation was achieved.
Methods We identified consecutive patients, found to have CTO of
at least one vessel of more than 1-month duration, on angiography
performed between January 1999 and August 2000 in a single
tertiary centre. We used a dedicated database to record data on
variables and used central National Health Service database to
obtain survival data. Results were analysed using SPSS statistics
version 17.
Results We included 331 patients in the analysis. Mean age was 56.8
619.8 years, 76.1% were male and 21.8% (nВј71) were diabetic.
Mean duration of CTO was 29.5625.9 months and was only reliably estimated in 82.5% of cases. Median follow-up duration was
10.0963.3 years. Complete revascularisation was successfully
achieved in 53.5% (nВј177) patients, while 46.5% (nВј154) were
either treated medically from the outset or had failed or incomplete
revascularisation. Both groups were age matched. Overall 10-year
survival was 66.5%; those with complete revascularisation had
significantly improved survival over those with incomplete revascularisation or medical therapy (75.1% vs 56.5%, p<0.001).
Conclusion Complete revascularisation confers a significant long term
survival in patients with CTO and underscores the importance of
improved recanalisation rates when performing angioplasty in this
patient group. Overall survival was relatively poor and emphasises the
importance of optimal medical therapy in this cohort.
A23
BCS Abstracts 2011
dysfunction. Over a follow-up period of 2.661.1 years there were 42
deaths. All-cause mortality was inversely related to baseline BCIS-1
JS (HR 2.20 (1.34 to 3.62), pВј0.002) and to post-PCI BCIS-1 JS (HR
3.98 (2.33 to 6.78), pВј0.0001). Increasing degrees of revascularisation
were associated with improved survival (Abstract 33 п¬Ѓgure 1); a
revascularisation index of $ 0.67 was associated with a survival
advantage compared to a RI #0.66 (HR 0.39 (0.24 to 0.54), pВј0.0001)
(Abstract 33 table 2). A multiple regression model, incorporating age,
acuity of presentation, LV function and renal failure, demonstrated
that RIВј0.67e1 continued to be an independent predictor of survival
(HR 0.51 95% CI 0.35 to 0.81, pВј0.004) (Abstract 33 п¬Ѓgure 1).
Abstract 32 Figure 1
33
COMPLETENESS OF REVASCULARISATION PREDICTS
MORTALITY FOLLOWING PERCUTANEOUS CORONARY
INTERVENTION: UTILITY OF THE BCIS-1 JEOPARDY SCORE
doi:10.1136/heartjnl-2011-300198.33
K De Silva, G Morton, P Sicard, E Chong, A Indermeuhle, B Clapp, M Thomas,
S Redwood, D Perera. St. Thomas’ Hospital, King’s College London, London, UK
Introduction Many coronary-scoring systems are complicated to use
on a day-to-day basis, have varying degrees of reproducibility and
exclude important subsets of patients such as those with previous
coronary artery bypass grafts (CABG) or left main stem (LMS)
disease (Abstract 33 table 1). The recently described BCIS-1
Myocardial Jeopardy score (BCIS-1 JS), a modification of the Duke
Jeopardy score to include LMS and CABG, is simple to use and
overcomes many of these limitations. We assessed the prognostic
relevance of the BCIS-1 JS in patients undergoing percutaneous
coronary intervention (PCI).
Abstract 33 Figure 1
tion Index (RI).
Abstract 33 Table 2
Univariate analysis
HR (95% CI)
p value
Multivariate
analysis HR (95% CI)
p value
Revascularisation
Index (0.67e1)
BCIS-1 JS pre PCI
0.36 (0.24 to 0.54)
0.0001
0.51 (0.33 to 0.81)
0.004
Variables
Abstract 33 Table 1
Cumulative survival according to Revascularisa-
Left Main
Stem Disease
classified
Patients
with CABG
classified
1.26 (1.14 to 1.39)
0.0001
1.14 (0.65 to 2.02)
0.65
Ease
of use
Relevance to
contemporary PCI
Prognostic
validation
BCIS-1 JS post PCI
LV impairment
1.35 (1.23 to 1.48)
3.76 (2.53 to 5.58)
0.0001
0.0001
1.78 (0.93 to 3.39)
1.97 (1.21 to 3.20)
0.08
0.007
Duke Jeopardy
Score (Original)
Syntax Score
x
x
O
x
O
Age
Renal dysfunction
1.04 (1.01 to 1.08)
5.82 (2.77 to 12.24)
0.01
0.0001
1.04 (1.00 to 1.08)
3.74 (1.60 to 7.37)
0.05
0.002
O
x
x
O
O
0.008
1.30 (0.63 to 2.66)
0.47
O
O
O
O
x
Acute coronary
syndrome
2.31 (1.24 to 4.30)
BCIS-1 JS
Cardiogenic shock
Previous CABG
14.56 (6.45 to 32.88)
3.35 (1.80 to 6.25)
0.0001
0.0001
2.83 (0.69 to 11.54)
1.83 (0.88 to 3.82)
0.15
0.10
Methods Consecutive patients undergoing PCI between 2005 and
2009 a single cardiac centre were screened. Patients were eligible if
they had undergone assessment of left ventricular function before
PCI and the sample was enriched for coronary artery bypass graft
(CABG) cases by using the following weightingd1 CABG: 3 nonCABG. Clinicians (who were blinded to clinical or outcome data)
scored diagnostic and procedural coronary angiograms. The BCISd1
JS was recorded before and after PCI (range: 0 to 12) and a Revascularisation Index (RI) calculated as RIВј(JSPREdJSPOST)/JSPRE.
RIВј1.0 indicates full revascularisation and 0 indicates no revascularisation. The primary end-point was all-cause mortality. Mortality
data was captured by tracking the database of the UK Office of
National statistics. Predictors of outcome were assessed by
univariate and multivariate analyses.
Results 660 patients were included (6869 years). 44% presented as
acute coronary syndromes with 41% having left ventricular
A24
Conclusion The BCIS-1 Jeopardy Score predicts mortality following
PCI. Furthermore, it can be used to assess the degree of revascularisation, with more complete revascularisation (RI$0.67) conferring
a survival advantage in the medium term.
34
COMPARISON OF PCI VS CABG IN INSULIN TREATED AND
NON-INSULIN TREATED DIABETIC PATIENTS IN THE
CARDIA TRIAL
doi:10.1136/heartjnl-2011-300198.34
1
2
3
4
A Baumbach, S Kesavan, K Beatt, E Cruddas, 4M Flather, 2G Angelini, 5R Hall,
A Kapur. 1Bristol Heart Institute, Bristol, UK; 2Bristol Heart Institute, Bristol, UK;
6
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
3
Mayday University Hospital, London, UK; 4Royal Brompton, London, UK; 5Imperial
College, London, UK; 6London Chest Hospital, London, UK
Aims The CARDia trial randomised diabetic patients to coronary
artery bypass grafting (CABG) or percutaneous coronary intervention
(PCI) and concluded that PCI is a potentially safe and feasible alternative to CABG in selected patients with diabetes mellitus (DM) and
multivessel coronary artery disease. The impact of insulin treatment
on clinical outcomes after revascularisation is unclear. The present
study is a sub group analysis of the CARDia trial comparing the
cardiovascular outcomes at 12 months following revascularisation
between the insulin treated (IT) and non-insulin treated (NIT) group.
Methods 508 patients with an established diagnosis of DM and de
novo coronary artery disease were identified and randomised to
CABG or PCI. Of those, 316 patients were treated with oral antidiabetic medication and the rest were treated with additional
subcutaneous insulin injections. Demographics, clinical presentation,
history, haemodynamic parameters, anti diabetic therapy, concomitant medications, duration of DM and HBA1C were documented.
Death, stroke and myocardial infarction were classified as the primary
outcome events. The secondary outcome events included death, MI,
Stroke, repeat revascularisation and TIMI major bleed. The clinical
results of patients in the IT and NIT groups were compared.
Results There were 192 patients in the IT group (37.8%). Asian
patients constituted one п¬Ѓfth of the total population with a slightly
higher representation (24.5% vs 21.6%) in the NIT. The clinical
severity of dyspnoea, heart rate, systolic and diastolic BP, body mass
index, risk factors for coronary artery disease appeared similar in the IT
and NIT groups, but more patients in the IT group had a prior MI
(30.7% vs 19.6%, pВј0.004) and duration of diabetes was longer in the
IT group (14 vs 6 yrs, p<0.001). For the comparison of CABG vs PCI for
the primary outcome events the HR and 95% CI in the IT and NIT
groups respectively were 1.66 (0.76 to 3.76) and 1.01 (0.51 to 2.01). For
death, MI, stroke, repeat revascularisation they were 2.47 (1.18 to 5.20)
in the ITand 1.41 (0.71 to 2.57) in the NIT group. The results suggest
that IT patients may have a worse outcome with PCI compared to
CABG, whereas no difference was found for NIT patients.
Conclusion Our data suggest that insulin treatment is a marker for
higher risk for PCI when compared with CABG. Treatment with
insulin rather than diabetic status alone should be considered when
choosing the mode of revascularisation.
35
to 4 years (mean 2.961.6) and stratified according to successful or
unsuccessful CTO recanalisation.
Abstract 35 Table 1
Successful
(n[572)
Unsuccessful
(n[264)
p value
Age
Male
62.460.47
433 (75.7%)
63.760.69
209 (79.2%)
0.1
0.3
Diabetes
Hypertension
151 (26.9%)
320 (63.8%)
74 (28.6%)
160 (66.6%)
0.6
0.5
Hypercholesterolaemia
Previous MI
281 (56.0%)
174 (31.7%)
147 (61.2%)
94 (36.4%)
0.2
0.2
Radial access
Femoral access
123 (21.5%)
416 (72.7%)
47 (17.8%)
193 (73.1%)
0.3
0.6
Dual site access (bilateral femoral
or radial + femoral)
23 (4.0%)
18 (6.8%)
0.5
Results 572 (68.4%) CTO procedures were successful. Coronary
stents were implanted in 96.9% (mean 2.360.1 stents per patient,
70% drug eluting). Prior revascularisation was more frequent among
patients with unsuccessful CTO-PCI than successful; prior CABG
16.5% unsuccessful vs 7.4% successful, (p<0.0001), PCI 36.0% vs
21.2%, (p<0.0001). Baseline characteristics were otherwise similar
(Abstract 35 table 1). Intra-procedural complications (coronary
dissection, perforation, access site (dissection, haematoma) were
more frequent in unsuccessful cases (19% (52) vs 4.1% (20)
(p<0.0001) but did not have an impact on in-hospital MACE (2% vs
1.8%, pВј0.6). All cause mortality was 8% (21) in the unsuccessful
group and 3% (17) in the successful group out to 4 years, (Abstract
35 п¬Ѓgure 1). Mortality following successful CTO-PCI was similar to
that of the non-CTO elective PCI group (5.1%, pВјNS).
SUCCESSFUL RECANALISATION OF CHRONIC TOTAL
OCCLUSIONS IS ASSOCIATED WITH INCREASED LONG
TERM SURVIVAL
doi:10.1136/heartjnl-2011-300198.35
1
J M Behar, 1D A Jones, 1R Weerackody, 1K Rathod, 1C J Knight, 1A K Kapur, 1A Jain,
A Wragg, 2C A Thompson, 1A Mathur, 1E J Smith. 1The London Chest Hospital, Barts
and the London NHS Trust, London, UK; 2Department of Cardiology, Yale University,
New Haven, Connecticut, USA
1
Introduction Chronic total occlusion (CTO) remains a challenging
lesion subset. Despite advances in equipment and expertise, many
CTO patients may not be offered PCI as physicians perceive
procedural success may be lower, and the anatomy is stable. The aim
of this study was to investigate the impact of procedural success on
mortality following CTO-PCI in a large cohort of patients in the
drug eluting stent era.
Methods 6122 consecutive patients underwent elective PCI at a
single centre (October 2003eMay 2010), 836 (13.7%) for CTO.
Demographic and procedural data were collected at the time of
intervention (Abstract 35 table 1). In-hospital MACE (myocardial
infarction, urgent revascularisation, stroke or death) was documented at discharge. All cause mortality data was obtained from the
Office of National Statistics via the BCIS/CCAD national audit out
Heart June 2011 Vol 97 Suppl 1
Abstract 35 Figure 1
All cause mortality after PCI for elective patients.
Conclusion A successful angiographic outcome following CTO-PCI is
associated with a survival advantage out to 4 years following intervention. These data suggest that the adoption of new techniques and
technologies to improve procedural success may improve prognosis.
36
IN-STENT RESTENOSIS PRESENTS AS AN ACUTE
CORONARY SYNDROME (ACS) IN 40% OF CASES: NOT
SIMPLY A BENIGN CLINICAL ENTITY
doi:10.1136/heartjnl-2011-300198.36
H Abu-Own, E Sammut, K Rathod, L A McGill, D A Jones, A Jain, C Knight, A Mathur,
A Wragg. Barts and the London NHS Trust, London, UK
Background In-stent restenosis (ISR) following stent implantation
may occur in 20% to 40% of the cases according to patient and lesion
complexity. Although in the past ISR used to be seen as a “benign”
A25
BCS Abstracts 2011
event, more recent studies suggested that a reasonable amount of
patients with ISR many develop ACS as the п¬Ѓrst manifestation of this
adverse event. The aim of this study was to determine the different
clinical presentations of ISR in a large cohort of consecutive, nonselected patients and compare with native coronary disease.
Methods 14 445 consecutive patients underwent PCI at a single centre
(October 2003eMay 2010), we identified 922 (6.4%) cases presenting
with restenosis after previous PCI. All patients with restenosis
presented with new or recurrent symptoms. Demographic and procedural data were collected at the time of intervention (Abstract 36
table 1). In-hospital MACE (myocardial infarction, urgent revascularisation, stroke or death) was documented at discharge. All cause
mortality data was obtained from the Office of National Statistics via
the BCIS/CCAD national audit out to 3.2 years (mean 3.161.8 years).
Abstract 36 Table 1
Total
Restenosis
n[922
Native disease
n[13 523
Sig
e
Age
Ethnicity (cau)
63.09
683 (74.2%)
63.76
9160 (97.8%)
0.0868
p<0.0001
Previous MI
Previous CABG
411 (44.6%)
120 (13.0%)
2160 (23.1%)
648 (6.9%)
p<0.0001
p<0.0001
DM
HTN
299 (32.5%)
545 (59.1%)
1986 (21.2%)
4170 (44.5%)
p<0.0001
p<0.0001
Hchol
Card Shock
544 (59.0%)
6 (0.7%)
3540 (37.8%)
100 (1.1%)
p<0.0001
0.2339
Results Restenosis presented in 60.4% as stable angina, 30.6% as
unstable angina/Non-ST elevation MI and 9% with ST-elevation
Myocardial Infarction. Cardiogenic shock was reported in 6 patients
(0.65%). Women had a higher incidence of unstable angina/nonSTEMI compared with men (32.6% vs 29.1%) but a lower incidence of
STEMI (5% vs 10.4%). Baseline characteristics are listed in Abstract 36
table 1. Mortality rate was 0.98% at 30 days, 3.9% at 1 year and 8.7%
at 5 years in patients with restenosis. Comparing the restenotic group
with those undergoing PCI for de novo coronary artery disease, there
were similar ages and incidence of cardiogenic shock but the restenotic
group had higher rates of baseline risk factors (diabetes, hypertension,
hyerpcholesterolaemia) and higher rates of previous CABG and MI.
There was also a higher proportion of South Asians in the restenotic
group. See Abstract 36 table 1. Comparing outcome measures, there
were similar rates of inhospital MACE in the 2 groups and over a 5year follow-up period, there was no difference in all cause mortality.
There was no difference in outcome of patients with restenosis vs de
novo coronary artery disease regardless of presentation (angina, UA/
NSTEMI/STEMI). See Abstract 36 п¬Ѓgures 1 and 2.
Abstract 36 Figure 1 Comparison of mortality between restenosis and
no restenosis in STABLE.
A26
Abstract 36 Figure 2 Comparison of mortality between restenosis and
no restenosis in ACS.
Conclusions Clinical in-stent restenosis can frequently present as MI
and such patients are more likely to have an aggressive angiographic
pattern of restenosis. Drug-eluting stents with improved designs or
drug elution systems that further decrease the incidence of ISR are
needed.
37
DECREASE IN MACE RATES ASSOCIATED WITH DRUG
ELUTING STENT USE IN PATIENTS WITH DIABETES
UNDERGOING PCI IN LARGE DIAMETER CORONARY
ARTERIES
doi:10.1136/heartjnl-2011-300198.37
1
A Dixit, 2S Nair, 2P Williams, 2A Wiper, 2B Clarke, 2C Deaton, 2M El-Omar, 2D Fraser,
R Khattar, 2V Mahadevan, 2L Neyses, 2F Ordoubadi, 2M Mamas. 1University Hospital
Manchester MHC, Manchester, UK; 2Manchester Royal Infirmary, Manchester, UK
2
Introduction Both large multi centre trials and registry studies have
demonstrated that PCI with drug eluting stents (DES) is associated
with reduced MACE and restenosis rates compared to bare metal
stents (BMS) in native coronary vessels, although this benefit is less
evident in those patients with a larger coronary vessel diameter and
MACE rates may actually paradoxically increase in this cohort as
observed in the BASKET trial. In diabetic patients, a similar or even
greater absolute reduction in MACE rates / restenosis risk is seen
associated with DES use, although it is unclear as to whether any
benefit persists in those with larger diameter native coronary vessels.
Previous data derived from diabetic patients in large diameter native
coronary vessels has come from registry studies in which numbers
were either small (<200 patients) or were from highly selected
patient sub groups excluding high-risk individuals (SCAAR registry).
Methods We therefore retrospectively studied 1165 consecutive
diabetic patients with target vessel diameter $3 mm admitted to
our centre for PCI from 2003 to 2009, the largest series of its kind to
date. Primary endpoint was defined as total mortality and secondary
endpoint was major adverse cardiac event (MACE) defined as
composite endpoint of Death, Stroke, MI, Stent Thrombosis and
Target Lesion / Vessel Re-Vascularisation.
Results Of the 1165 patients studied, 170 had BMS and 995 had
DES. Mean follow-up period was 43.3621.8 months (median
41.8 months). 73.5% were male in the BMS cohort vs 73.1% in the
DES cohort (p>0.05). Mean age was 62.8611.2 in BMS and 62.36
10.4 years old in DES (pВј0.55). Other demographic parameters were
similar in both groups. There were a total of 23/170 deaths in BMS
cohort (13.5%) and 91/995 in DES cohort (9.1%), (HR 1.38; 95% CI
0.83 to 2.27, pВј0.21). A total of 42/170 (24.7%) and 163/995 (16.3%)
MACE events were observed in the BMS and DES cohort respectively (HR 1.49; 1.02 to 2.19, pВј0.04). Multivariate analysis
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
illustrated that use of BMS was independently associated with
increased risk of MACE (HR 1.54; 95% CI 1.05 to 2.25, pВј0.03),
driven through an increase in revascularisation.
Conclusion In conclusion, in one of the largest analyses of its kind,
use of DES in patients with diabetes in a real world setting undergoing PCI in large diameter coronary vessels ($3 mm) is safe and is
independently associated with a reduction in MACE events. This is
in contrast to that of non-diabetic patients where the benefits of
DES in large diameter coronary vessels are less evident.
38
FALSE ACTIVATION FOR PRIMARY PERCUTANEOUS
CORONARY INTERVENTION IS NOT A BENIGN
PHENOMENON
doi:10.1136/heartjnl-2011-300198.38
U Chaudhry, C Mavroudis, R D Rakhit. Cardiology Department, Royal Free Hospital,
London, UK
Introduction Primary percutaneous coronary angioplasty (PPCI) is
the preferred reperfusion strategy following an acute ST elevation
myocardial infarction (STEMI). Since 2005 24/7 primary PCI has
been the п¬Ѓrst line treatment for an acute STEMI in our centre. 93%
of patients are direct access admissions by London Ambulance but a
significant proportion (up to 20%) do not fulfil the diagnostic
criteria for STEMI and are termed “false activations”. Data on the
outcome of this cohort of patients is limited.
Aim To review the clinical outcome of patients presenting to our
heart attack centre with false activation PPCI.
Method From January 2008 until October 2010, we identified 209
false PPCI activations defined as patients with incomplete diagnostic criteria for acute STEMI: absence of chest pain and/or typical
ECG features (ST elevation or new LBBB). Data was collected via a
“false activation” database together with retrospective review of case
records.
Results Complete data was available in 165 cases. 71% were male
and 29% were female (mean age 67). The mean length of stay was
4 days (range 1e33). 71% presented with chest pains and 29% had
no chest pains, but presented with breathlessness, palpitations or
syncope. The ECG abnormality was non-specific ST-T changes in
22%, LBBB in 19%, left ventricular hypertrophy in 15%, п¬Ѓxed ST
elevation or Q waves in 14%, early repolarisation changes in 10%,
RBBB in 8% and other ECG abnormalities in 12%. The п¬Ѓnal diagnosis was non-ST elevation acute coronary syndrome (NSTEACS) in
19%, sepsis in 19% and congestive heart failure (CHF) in 15%. Stable
angina was observed in 8% and syncope in 7%. Musculoskeletal or
non-cardiac chest pains were noted in 8% and 7% of the patients
respectively. 2% of the patients had pulmonary embolism and in 5%,
a gastric cause for presentation was diagnosed. 14% had other
cardiac problems, including arrhythmia, dilated cardiomyopathy,
hypertension, pericarditis, pericardial effusion and late presentation
STEMI. 15% had other diagnoses. The mean follow-up period was
18.7 months, during which 21.5% of false PPCI activation admissions died (nВј45). 25% (nВј11) died during the index admission and
33% (nВј15) died within 30 days of admission. The overall 30-day
mortality for false activations was 7.2%, which is higher than the
overall PPCI mortality of 6.0% (including cardiogenic shock)
(pВј0.008) and 3.3% (excluding shock) (p<0.0001) in our centre. 49%
of deaths were cardiac (NSTEACS and CHF), 29% sepsis and 22%
other causes. The mean age for this cohort was 83.
Conclusion Patients presenting with false PPCI activation have a
high observed mortality. This is probably due to significant associated comorbidities, including occult cardiac disease. Thus, false
PPCI activation is not a benign phenomenon and masks underlying
significant disease. Robust pathways are required to minimise delay
in further investigations and a need for risk stratification for a
significant proportion who present with NSTEACS.
Heart June 2011 Vol 97 Suppl 1
39
A RANDOMISED CONTROLLED TRIAL COMPARING
CONVENTIONAL CORONARY ARTERY BYPASS GRAFT
SURGERY WITH A COMPOSITE ARTERIAL GRAFT
TECHNIQUE
doi:10.1136/heartjnl-2011-300198.39
1
A Alahmar, 2R A Perry, 2R H Stables. 1Leicester University Hospital Glenfield,
Leicester, UK; 2Liverpool Heart and Chest Hospital, Liverpool, UK
Background Composite (Y/T) coronary artery bypass graft surgery
(CABG) confers full arterial revascularisation, and “hands off ” aorta
compared to conventional bypass graft surgery. However, the
composite surgical configuration could lead to preferential blood flow
down one arm than the other (left internal mammary artery LIMA or
radial artery RA) with its potential impact on graft patency.
Aim To investigate the impact of bypass graft configuration on
short-term grafts patency and cardiac related quality of life.
Methods and Results This is a single centre randomised, controlled trial
Between March 2006 and July 2007, 322 patients undergoing isolated
bypass graft surgery at our institution were screened and 89 (27%) met
the inclusion criteria and were randomised. Patients were allocated to
conventional (conv nВј46) or composite (comp nВј43). The two
primary end points were graft patency defined as (Thrombolysis In
Myocardial Infarction) TIMI III flow in distal anastomosis at angiography 12e24 months after surgery, and cardiac-related health status
assesses by Seattle angina questionnaire (SAQ). Baseline characteristics
were similar between the two groups apart from diabetes where there
were more diabetic patients in the composite arm than the conventional one (15(35%) vs 5(11%) p<0.01 respectively). Trial was stopped
prematurely following 18 months interim analysis which showed
significant graft failure in the composite arm (40%). Final Analysis was
performed on intention to treat basis. Sixty-п¬Ѓve (73%) had follow-up
angiography (34 conv, 31 comp), with total of 116 graft in conventional
arm and 100 grafts in composite arm. All patients in both groups had
LIMA graft to left anterior descending artery (LAD). Graft patency rate
was significantly higher in the conventional compared to composite
arm (95(82%) vs 59(59%) p<0.001 respectively). Three main domains
of the SAQs there was significant improvement between before and
6 months after surgery in both groups. There were no significant
differences between the two groups in the percentage of improvement
in these four domains (Physical limitation, Angina stability, Angina
frequency, Quality of life).
Conclusions In our randomised trial, composite bypass graft surgery
was associated with higher graft failure rate at 12e24 months after
surgery compared to conventional type. This difference may be due
to the composite conduit configuration. Further blood flow characteristics study in this configuration can help understand such an
important п¬Ѓnding and its implication on our clinical practice.
Despite the difference in graft patency there were no differences in
physical limitation, angina stability, angina frequency, or quality of
life between the two groups.
40
PATIENT VS PHYSICIAN REPORTED ANGINA BEFORE AND
AFTER REVASCULARISATION OF CORONARY ARTERY
DISEASE: EVIDENCE FROM A LARGE RANDOMISED
CONTROLLED TRIAL (THE SOS TRIAL)
doi:10.1136/heartjnl-2011-300198.40
C Appleby, I Kemp, R H Stables. Liverpool Heart and Chest Hospital, Liverpool, UK
Introduction The success of revascularisation therapies for coronary
artery disease (CAD) must be measured by both an improvement in
hard clinical endpointsdmortality, repeat revascularisation procedures and myocardial infarction, the traditional focus of clinical
trialsdand, critically for patients, the relief of angina symptoms.
Interest in patient reported outcomes (PROMs) has increased,
although their use in cardiovascular trials is far from universal. In
A27
BCS Abstracts 2011
particular the differences between physician and patient reported
outcomes has not been analysed. High quality data from the Stent
or Surgery (SOS) trial allows such an analysis.
Methods The SoS trial was a large RCT (nВј988) comparing stentassisted percutaneous coronary intervention (PCI) with coronary
artery bypass grafting (CABG) in patients with multivessel CAD.
Participation in the SoS trial included an appraisal of angina symptoms
by both patient and physician according to the Canadian Cardiovascular Society (CCS) Classification System prior to, and subsequently
at 6 and 12 months following coronary intervention. In this study
patient and doctor reported outcomes were compared systematically.
Results Paired CCS scores at baseline, 6 months and 12 months were
available for 919, 886 and 888 cases respectively. At baseline the overall
level of agreement was good with >75% paired data sets demonstrating
a difference of #61 CCS class. Patterns of discordance change however
between baseline and follow-up time points. Abstract 40 п¬Ѓgure 1 shows
the paired scores at baseline, charting the patient score and, for each
CCS grade, the observed differenceddoctor (D) minus patient (P).
Doctors are reluctant to record scores of 0 or 4, preferring CCS grades 2
and 3. Thus there is little overall difference in mean CCS score (P 2.2 vs
D 2.5, p<0.001). Yet at follow-up, doctors record freedom from angina
(CCSВј0) in a more substantial proportion of the population, considerably more so than patients self-report (p<0.0001) (Abstract 40 п¬Ѓgure
2). The published results of the SOS trial used doctor gradings to report
freedom from angina at 1 year in 79% of CABG patients vs 66% of PCI
patients (p<0.0001). If patient gradings are used instead these п¬Ѓgures
are reduced to 57% in CABG and 44 % in PCI (p<0.0001), rendering
both treatment strategies significantly less effective at relieving angina
from a patients perspective (p<0.0001), Abstract 40 table 1.
Abstract 40 Table 1
PCI (%)
CABG (%)
p
Doctor scoring CCS class 0
66
79
<0.0001
Patient scoring CCS class 0
44
57
<0.0001
Conclusions This is the п¬Ѓrst randomised study to compare the
improvement in angina status reported by patients and clinicians
following revascularisation therapy for coronary artery disease. The
observed trend for doctors to insist that all patients must have some
symptoms at baseline, and more importantly, to suggest that a
greater proportion of patients have been rendered symptom free at
follow-up (than is suggested by self-reported estimates) has important implications and may call into question our current understanding of the impact of revascularisation.
41
REDUCED ARTERIAL WAVE REFLECTION AND ENHANCED
LV RELAXATION CONTRIBUTE TO WARM-UP ANGINA
doi:10.1136/heartjnl-2011-300198.41
1
T P E Lockie, 2A Guilcher, 3C Rolandi, 1D Perera, 1K De Silva, 1R Williams, 3M Siebes,
P Chowienczyk, 1S Redwood, 1M Marber. 1Rayne Institute, St Thomas Hospital, KCL,
2
Abstract 40 Figure 1 Difference between doctor and patient
classification of Angina before revascularisation.
Abstract 40 Figure 2 Difference between doctor and patient
classification of Angina at 12 m Fup.
A28
Abstract 41 Figure 1 (A) shows aortic pressure traces taken at peak
exertion with a reduction in pressure augmentation during Ex2; (B)
shows WIA with an increase in the backward expansion, or “sucking”
wave originating from the microvasculature.
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
London, UK; 2Clinical Pharmacology, St Thomas Hospital, KCL, London, UK; 3Department of Bio-Engineering, University of Amsterdam, AMC, Amsterdam, The Netherlands
Background The mechanisms of the clinically observed phenomenon of reduced angina on second exertion, or warm-up angina, are
poorly understood. This study compared changes in central
haemodynamics, peripheral wave reflection and patterns of coronary blood flow during serial exercise that may contribute.
Methods and Results 16 patients (15 male, 6164.3 yrs) with a positive
exercise stress test and exertional angina completed the protocol.
During cardiac catheterisation via radial access they performed 2
consecutive exertions (Ex1, Ex2) using a supine cycle ergometer.
Throughout exertions, distal coronary pressure (Pd) and flow velocity
(V) were recorded in the culprit vessel using a dual sensor coronary
guide wire while aortic pressure was recorded using a second wire.
Time to 1 mm ST depression was longer in Ex2 (pВј0.003) and rate
pressure product (RPP) was higher (p¼0.025) confirming warm-up. A
33% decline in aortic wave reflection (p<0.0001) in Ex2 (see Abstract
41 п¬Ѓgure 1A) coincided with a reduction in both tension time index
and diastolic time index (p<0.0001). However, the latter was offset by
reduced microvascular resistance (Pd/V), pВј0.0002, and enhanced left
ventricular relaxation during Ex2 as suggested by a larger backwardtravelling suction wave (pВј0.01) on wave intensity analysis (WIA) of
the intra-coronary signals. See Abstract 41 п¬Ѓgure 1B. The energy of the
forward compression wave and overall coronary blood flow, as
measured by the velocity time integral, did not change.
Conclusions In patients with warm-up angina, exercise induces
changes in the aortic pressure waveform, microvascular function
and LV relaxation. These combine to reduce afterload without
compromising myocardial diastolic blood flow thereby likely
enabling improved performance on second exercise.
42
RETROSPECTIVE CALCULATION OF SYNTAX SCORE IN 200
PATIENTS UNDERGOING ELECTIVE CORONARY ARTERY
BYPASS GRAFTING (CABG) AND PERCUTANEOUS
CORONARY INTERVENTION (PCI); ARE WE FOLLOWING
BEST PRACTICE?
doi:10.1136/heartjnl-2011-300198.42
L J Mullen, R Edwards, R Taylor, B Nyawo. Freeman Hospital, Newcastle upon Tyne
Introduction Cardiologists are generally the gatekeepers of coronary
artery disease and have been much criticised for not discussing all
patients being considered for revascularisation therapy at an MDT
(multi-disciplinary team) meeting or not referring patients with traditional “surgical disease” for CABG. At the Freeman Hospital (FRH), a
large cardiothoracic unit in the North of England, patients are typically
referred for PCI or CABG by cardiologists working within the Newcastle
upon Tyne Trust or from district general hospitals within the network.
Patients are not routinely discussed at MDT but can be brought to the
weekly meeting at the discretion of the referrer. The recently reported
SYNTAX study allows objective quantification of the degree of coronary disease and facilitates an evidence based decision between CABG
and PCI. This gives us the opportunity to examine whether elective
revascularisation is being performed appropriately at our institution.
Methods We performed a retrospective analysis at the Freeman
Hospital. 200 patients who had elective revascularisation between
April 2009 and April 2010 were selected. This included 100 cases of
CABG and 100 of PCI. Half of each were referrals from other hospitals.
Patients’ SYNTAX scores were calculated using pre-procedure angiograms. MDT meeting records and patients’ notes were reviewed.
Results The average SYNTAX score for patients undergoing elective
PCI was 15, compared to 29 for those undergoing CABG. 84% of
patients undergoing elective PCI had SYNTAX scores less than 22.
35% of all patients referred for elective CABG had scores greater
than 33. The average SYNTAX score for CABG referrals from
outside the trust was lower (25) than from within the trust (31).
Heart June 2011 Vol 97 Suppl 1
Discussion The majority of patients undergoing PCI at the FRH have
SYNTAX scores in the lowest tertile. There is no difference in the
SYNTAX scores in patients having PCI from referral bases within the
centre or from outside. In total almost one quarter of all patients
undergoing CABG have a SYNTAX score in the lowest tertile. And this
rises to almost one third in those patients referred from district general
hospitals. Only a small number of these patients have an additional
clear indication for CABG over PCI. Furthermore we found that a
significant proportion of these do not go through MDT planning. These
results may indicate that cardiologists are more likely to bring patients
to MDT meetings than surgeons and, according to SYNTAX scoring,
more patients are inappropriately having CABG than are inappropriately having PCI. Based on this data in our institution discussing all
patients at an MDTand the use of SYNTAX scoring at point of referral
would be more likely to increase PCI revascularisation rates.
Abstract 42 Table 1
% Patients with
SYNTAX score
% Patients with
in middle third
SYNTAX score in
(23e32)
higher third (>33)
% Patients with
Average SYNTAX score
SYNTAX in lower third
score
(0e22)
All Referrals for PCI 14.9
84
11
5
Referrals for PCI
from within trust
Referrals for PCI
from outside trust
15.0
84
12
4
14.8
84
10
6
Abstract 42 Table 2
% Patients with
Average SYNTAX score
SYNTAX in lower third
score
(0e22)
% Patients with
SYNTAX score % Patients with
in middle third SYNTAX score in
(23e32)
higher third (>33)
All Referrals for CABG 28.8
24
40
35
Referrals for CABG
from within trust
Referrals for CABG
from outside trust
31.0
19
34
47
25.0
32
50
18
43
PROGNOSIS AFTER PRIMARY PERCUTANEOUS CORONARY
INTERVENTION FOR STEMI: CAN THE SYNTAX SCORE HELP?
doi:10.1136/heartjnl-2011-300198.43
A J Brown, L M McCormick, N E J West. Papworth Hospital, Cambridge, UK
Background Factors affecting prognosis after primary percutaneous
coronary intervention (PPCI) for ST-elevation myocardial infarction
(STEMI) include age at presentation, the presence of diabetes mellitus,
left ventricular function and/or cardiogenic shock. Although the
debate continues over a strategy of complete revascularisation
(immediate or staged) vs culprit-only, little is known about the impact
of the extent of coronary disease at presentation on prognosis after
PPCI. The SYNTAX score, designed to stratify outcomes in multivessel
PCI and CABG, has been validated in unselected populations undergoing elective PCI; to date, no studies have assessed its utility in PPCI.
Methods Consecutive patients attending a single UK tertiary centre
for PPCI between September 2008 and June 2010 (nВј695) were
included. SYNTAX scoring was performed by a single trained
operator blinded to patient details and outcome. Scoring was validated by analysis of 3 separate cohorts by 2 other experienced
operators. Patients were split into 3 subgroups as in the SYNTAX
trial (score #22 (low, L), 22.5e32 (intermediate, IM) and $32.5
(high, H)), and patient data and outcome measures obtained by
interrogation of local and national databases.
Results 671 of 695 patients were included in the analysis with 24
being excluded owing to inability to score (previous CABG, images
A29
BCS Abstracts 2011
unavailable). The ability to allocate a SYNTAX tertile was reproducible between observers (rВј0.94). Median scores in the 3 groups were:
L 14, IM 26, H 36 (Abstract 43 п¬Ѓgure 1A). Although there was no
correlation between SYNTAX score and patient sex or diabetic status,
there was a linear relationship with patient age (r2Вј0.03; p<0.0001).
1-year absolute survival (Abstract 43 п¬Ѓgure 1B) followed SYNTAX
score groups: L 94.7%, IM 88.7%, H 82.1% (pВј0.0002). Similar results
were obtained for freedom from death or unplanned revascularisation
(p<0.0001) and death or any revascularisation (p<0.0001).
maximum clinically tolerated doses. We examined whether medical
therapy is being applied appropriately in patients referred for PPCI.
Methods Consecutive patients with STEMI referred for PPCI to a
large tertiary centre between 1st March and 1st August 2009 were
included (nВј167). The case records of all patients were reviewed.
Myocardial infarction was diagnosed according to standard criteria.
Medications and doses on admission, discharge and follow-up were
recorded. Contraindications and limits to dose escalation were noted
(symptoms, systolic blood pressure <90 mm Hg, heart rate
<50 bpm, serum creatinine and potassium).
Results Mean age was 62.0611.9 years, 72% were male. On discharge,
100% of patients were prescribed clopidogrel, 95.8% aspirin, 98.8%
statin, 88.6% b-blockers, and 91.0% ACEI/ARB. However, the inpatient dose of b-blocker or ACEI/ARB was maximum or clinically
limited in only 13% and 15% of patients respectively (Abstract 44
п¬Ѓgure 1). Outpatient follow-up at a mean of 5.0 months was equally
concerning. The majority of patients (83%) were neither receiving
maximum tolerated doses of b-blocker or ACEI/ARB, nor received
instructions to escalate the dose (Abstract 44 п¬Ѓgure 2).
Abstract 44 Figure 1
Inpatient titration of b-blocker and ACEI/ARB.
Abstract 43 Figure 1
Abstract 44 Figure 2
Outpatient titration of b-blocker and ACEI/ARB.
Conclusions The SYNTAX score, when applied to an unselected
population of patients undergoing PPCI for STEMI, provides
important prognostic information regarding 1-year survival from
death and revascularisation. These п¬Ѓndings may provide supporting
evidence towards routine complete revascularisation of obstructive
coronary artery disease after PPCI.
Conclusion The national service framework and target driven
initiatives such as advancing quality promote “tick box” medicine.
Quantitative prescribing of secondary prevention is excellent.
Qualitative follow-up and titration is not. Whether suboptimal
doses convey the mortality benefits observed in landmark clinical
trials is unknown. Frameworks to deliver titration of medical
therapy must be explored. Options include nurse or pharmacy led
services and expansion of cardiac rehabilitation. Reorientation is
needed to focus on both quantity and quality.
44
PRIMARY PERCUTANEOUS INTERVENTION: HAVE WE
TAKEN OUR EYE OFF THE MEDICINE BALL?
doi:10.1136/heartjnl-2011-300198.44
1
2
2
2
2
2
1
J D Jones, E Damm, M Nijjar, S Pettit, N M Hawkins, R Perry. University
Hospital Aintree NHS Foundation Trust, Liverpool, UK; 2Liverpool Heart and Chest
Hospital, Liverpool, UK
Introduction Primary percutaneous intervention (PPCI) improves
survival in patients with ST elevation myocardial infarction
(STEMI). Significant resources have been directed to achieving timely
reperfusion throughout the UK. However, intensive medical therapy
is of equal importance, with landmark clinical trials demonstrating
unequivocal morbidity and mortality benefits from b-blockers,
angiotensin-converting enzyme inhibitors (ACEI), and angiotensin II
receptor blockers (ARB). All trials employed rigorous titration to
A30
45
SHOULD PRIMARY PERCUTANEOUS CORONARY
INTERVENTION BE THE ROUTINE REPERFUSION STRATEGY
IN OCTOGENARIANS AND NON-AGENARIANS PRESENTING
WITH ST ELEVATION MYOCARDIAL INFARCTION?
doi:10.1136/heartjnl-2011-300198.45
R Showkathali, E Boston-Griffiths, J Davies, G Clesham, J Sayer, P Kelly, R Aggarwal.
The Essex Cardiothoracic Centre, Basildon, UK
Introduction Primary percutaneous coronary intervention (PPCI) has
been established as standard therapy for ST elevation myocardial
infarction (STEMI). Very few trials have looked at the outcome of
PPCI in elderly patients. Even in trials which claimed to have looked
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
at PPCI in elderly patients such as SENIOR PAMI (Grines, 2005) and
TRIANA (Bueno, 2009) the minimum age for inclusion was 70 yrs
and 75 yrs respectively. With an ageing population in the western
world, about 20% of patients admitted for suspected STEMI are
$80 yrs. We evaluated the outcome of PPCI in patients $80 yrs
who were admitted to our unit with STEMI.
Methods Our PPCI service was started in September 2009 and we
analysed all the patients who were $80 yrs presenting to the PPCI
service between September 2009 and September 2010 (13 months).
Prospectively entered data were obtained from our dedicated cardiac
service database system (Philips CVIS). Mortality data were
obtained from the summary care record (SCR) database. Follow-up
data were obtained from patients’ respective district general hospitals and general practitioners medical records.
Results Of the 998 patients who were admitted to our unit for
primary PCI for suspected STEMI during the study period, 183
(18.3%) were $80 yrs of age. After excluding 51 patients (27.9%)
who did not undergo PPCI, we included 132 (70.1%) patients for
analysis. Of those who were included in the study (nВј132, 63
female), the mean age was 8563.95 yrs (range 80e99 yrs, median
85 yrs). There were 20 diabetics (15.2%) and 39 (29.5%) had
previous myocardial infarction. Ten patients (7.6%) were in cardiogenic shock on arrival of which 9 (90%) had an Intra aortic balloon
pump (IABP). The infarct related vessel was the right coronary in
42.4% and left anterior descending in 37.1%. Drug eluting stents
were used in 40.2% of patients. In-hospital and 30-day mortality
was 14.4% and 19.7% respectively. There was a significant difference
in the mortality between patients age <80 yrs and those $80 yrs
(Abstract 45 п¬Ѓgure 1). In patients $80 yrs, mortality and bleeding
risk increased markedly with advancing age (Abstract 45 table 1).
46
PROGNOSTIC VALUE OF BASELINE RENAL FUNCTION ON
LONG TERM OUTCOME IN PATIENTS UNDERGOING
PRIMARY PERCUTANEOUS CORONARY INTERVENTION FOR
ST-ELEVATION MYOCARDIAL INFARCTION
doi:10.1136/heartjnl-2011-300198.46
O P Guttmann, K Rathod, B Rathod, E Wicks, S Gallagher, D A Jones, A Jain, C Knight,
A Mathur, A Kapur, A Wragg. Barts and the London NHS Trust, The London Chest
Hospital, London, UK
Background Renal impairment is associated with increased cardiovascular mortality following acute coronary syndromes (ACS),
however there is limited data assessing this relationship in the
context of primary PCI and whether it exists with other major
adverse cardiovascular events.
Methods Clinical information was analysed from a prospective data
base on 2310 STEMI patients who underwent primary PCI between
January 2004 and May 2010 at a London centre. Information was
entered at the time of procedure and outcome assessed by all-cause
mortality information provided by the Office of National Statistics
via the BCIS/CCAD national audit. Estimated glomerular п¬Ѓltration
rate (eGFR) was calculated using the modified diet in renal disease
equation and patients were divided into groups based on eGFR (<40,
40e50, 50e60, >60 ml/min/1.73 m2). 3-year composite of MACE
(death, reinfarction, stroke and target vessel revascularisation) were
compared between groups.
Results The average eGFR in all patients was 73.40623.37 (95% CI
72.25 to 74.56) ml/min/1.73 m2. The prevalence of coexisting risk
factors (hypertension, diabetes mellitus, hypercholesterolaemia),
previous MI, previous CABG and cardiogenic shock were higher among
patients with reduced eGFR. There was a progressive increase in MACE
with declining eGFR (ORВј4.84, 95% CI 2.94 to 7.96, for comparison
between the highest and lowest eGFR groups). See Abstract 46 п¬Ѓgure 1.
After adjustment for baseline characteristics including age, diabetes and
cardiogenic shock renal function based on the GFR at admission
remained a strong independent predictor of outcome.
Abstract 45 Figure 1
Abstract 45 Table 1
%
Inhospital mortality
30-day mortality
30-day MI
30-day CVA
Major bleeding requiring blood transfusion
80e84 yrs
(N[62)
85e89 yrs
(N[51)
‡90 yrs
(N[19)
9.7
15.7
26.3
14.5
3.2
23.5
2.0
26.3
0
1.6
1.6
0
3.9
0
10.5
Conclusion This study clearly demonstrates a significant mortality
difference between patients aged <80 yrs and those $80 yrs treated
with PPCI. Our 30-day mortality outcome in patients $80 yrs
(19.7%) was similar to the subgroup analysis of the PPCI arm in
similar SENIOR-PAMI patients (19%). In the same analysis, the
thrombolytic group had a lower (16%) mortality. Further studies are
required to determine whether PPCI should be routinely used in very
elderly patients presenting with STEMI.
Heart June 2011 Vol 97 Suppl 1
Abstract 46 Figure 1
All MACE after PCI for STEMI.
Conclusion Baseline renal dysfunction in patients undergoing
primary PCI is associated with an increased risk for combined death,
re-infarction and recurrent angina. This risk increases linearly with
declining eGFR.
47
CARDIOVASCULAR EVALUATION OF ENGLISH PREMIERSHIP
RUGBY PLAYERS
doi:10.1136/heartjnl-2011-300198.47
1
S Ghani, 1H Raju, 1A Zaidi, 1N Sheikh, 1S Gati, 2J Somauroo, 3S Kemp, 1S Sharma.
St Georges University London, London, UK; 2Countess of Chester Hospital; 3Rugby
Football Union (RFU)
1
Introduction Recent experience of pre-participation cardiovascular
evaluation (PPCE) in Italian athletes demonstrates a significant
A31
BCS Abstracts 2011
reduction in mortality from cardiomyopathies and cardiac conduction disorders. Although PPCE is endorsed by large medical and
sporting organisations, including the European Society of Sports
Cardiology, the International Olympic Committee and FIFA, the
state health system in the UK (and many other Western countries)
does not support cardiovascular evaluation of athletes. Certain elite
sporting organisations in the UK mandate PPCE in all athletes prior
to competition. In 2010 the English Premier Rugby league introduced formal PPCE in all competing players.
Methods Athletes participating in the English Premiership Rugby
underwent PPCE with a structured clinical questionnaire and 12lead ECG. Trans-thoracic echocardiogram (TTE) and additional
investigations were performed where indicated.
Results A total of 606 players were assessed (mean age 22.9 years;
range 15e37). Of these, 45 (7.4%) required TTE (35 (5.7%) due to
ECG abnormalities; 5 (0.08%) due to family history of sudden death;
5 (0.08%) due to symptoms). ECG abnormalities warranting TTE
included right axis deviation (nВј4), left axis deviation (nВј17), right
bundle branch block (nВј3), right ventricular hypertrophy (nВј1),
abnormal T wave inversion (nВј5) and prolonged QT (nВј1). Six of
the 45 subjects demonstrated mild changes on TTE (markedly
dilated LV cavity (nВј3), mitral regurgitation (nВј1), pulmonary
stenosis (nВј1), dilated aortic root (nВј1)), requiring serial surveillance. Five demonstrated abnormalities on TTE and/or ECG that
warranted referral for further evaluation including exercise stress
test (nВј5), 24-h ECG (nВј5) and cardiac MRI (nВј3). The reasons for
these tests included possible arrhythmogenic right ventricular
cardiomyopathy (nВј3), suspicion of hypertrophic cardiomyopathy
(nВј1) and QT prolongation on ECG (nВј1). None of the players
exhibited a cardiac disorder that warranted disqualification from
sport. Overall 7.4% of athletes required further investigation
following initial ECG, and 1.8% required further tests following
TTE. False positive rate was 5.6%.
Conclusion Cardiovascular evaluation of British rugby players with a
structured questionnaire and ECG resulted in clearance of 92.6%
following initial tests, and 5.6% were reassured after TTE. Only 1%
players required surveillance echocardiograms and 0.8% were
referred for further diagnostic evaluation. False positive rate was
5.6%. The results indicate that PPCE carried out in an expert setting
results in a relatively small number of athletes requiring further
tests, and a low false positive rate.
48
enhanced by ischaemia; whether they are present in humans is
unknown. We examined whether the erythropoietin analogue
darbepoetin improves flow mediated dilatation (FMD), a measure of
endothelium-derived NO, and whether this is influenced by
preceding ischaemia-reperfusion.
Methods 36 patients (50e75 years) with stable coronary artery
disease were randomised to receive a single dose of darbepoetin 300 mg
or saline placebo. Immunoreactive erythropoietin was measured by
an enzyme linked immunospecific assay. FMD was measured at the
brachial artery using high resolution ultrasound. CD34+/VEGFR2
+/133+ circulating EPC were enumerated by flow cytometry.
Measurements were made immediately before darbepoetin/placebo
and at 24 h, 72 h and 7 days. At 24 h FMD was repeated after 20 min
ischaemia-reperfusion of the upper limb. A further group of 11
patients were studied according to the same protocol, all receiving
darbepoetin, with omission of forearm ischaemia-reperfusion at 24 h.
Results Immunoreactive erythropoietin peaked at 24 h in the
darbepoetin group (median value of 724 U/l (IQR 576e733 U/l),
compared to 12 U/l (IQR 9e21 U/l) in the placebo group) and
remained elevated at approximately 500 fold baseline at 72 h. FMD
did not differ significantly between groups at 24 h (before ischaemiareperfusion). At 72 h, (48 h after ischaemia-reperfusion) FMD
increased from baseline in the darbepoetin group but not in the
placebo group so that FMD (and change in FMD from baseline) was
significantly greater in the darbepoetin group (change from baseline
1.760.3% and ГЂ0.660.4% in darbepoetin and placebo groups
respectively, p<0.001).The increase in FMD at 72 h after darbepoetin and ischaemia-reperfusion at 24 h was significantly greater
than that without preceding ischaemia-reperfusion (p<0.01). A
w20% increase in CD133+/VEGFR2+ cells after darbepoetin was
temporally dissociated with the increase in FMD.
Conclusions Preceding ischaemia-reperfusion is required for darbepoetin to enhance endothelial function, possibly by increasing
expression of the erythropoietin receptor and by a mechanism likely
to involve Akt/NO rather than circulating EPC.
DARBEPOETIN ENHANCES ENDOTHELIAL-DEPENDENT
VASOMOTOR FUNCTION IN PATIENTS WITH STABLE
CORONARY ARTERY DISEASE ONLY AFTER PRECEDING
ISCHAEMIA-REPERFUSION
doi:10.1136/heartjnl-2011-300198.48
1,2
L M Tilling, 1,2J Hunt, 1,2A Donald, 1,2B Clapp, 1,2P Chowienczyk. 1British Heart Foundation
Centre, King’s College London, St Thomas’, London, UK; 2Department of Clinical
Pharmacology, Cardiovascular Division, King’s College London, St Thomas’, London, UK
Background Vasoprotective effects of erythropoietin in animal
models are mediated by endothelium-derived nitric oxide (NO) and/
or mobilisation of endothelial progenitor cells (EPC) and may be
Abstract 48 Table 1
Endothelial function
Abstract 48 Figure 1 Change from baseline in FMD at 72 h, 48 h after
ischaemia-reperfusion (+IR), after placebo and darbepoetin (study 1) and
after darbepoetin without preceding ischaemia-reperfusion (ГЂIR, study 2).
Endothelial function and EPC
Placebo
Baseline
Placebo
24 h
Placebo
72 h
Placebo
7d
Darbepoetin
Baseline
Darbepoetin
24 h
Darbepoetin
72 h
4.460.97
5.260.9***
Darbepoetin
7d
FMD%
3.560.80
3.460.73
2.960.63
3.460.75
3.560.92
Progenitor cells
CD133+/VEGFR2+
110617.6
117619
101619
123621
146613
180613*
180611*
182616*
4.160.6
17.362.9
3.960.5
17.061.9
3.160.6
17.763.6
4.760.8
20.463.2
8.763.07
23.662.4
11.163.9
29.364*
7.161.4
31.664.6*
13.364.5
29.964.8*
CD34+/VEGFR2+
CD133+/CD34+
3.760.61
Values are means6SE.
* p<0.05, ***p<0.001
A32
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
49
ETHNIC VARIATION IN QT INTERVAL AMONG HIGHLY
TRAINED ATHLETES
doi:10.1136/heartjnl-2011-300198.49
1
H Raju, 1M Papadakis, 2V Panoulas, 2J Rawlins, 2S Basavarajaiah, 1N Chandra,
E R Behr, 1S Sharma. 1St George’s University of London, London, UK; 2University
Hospital Lewisham, London, UK
1
Background Studies in Caucasian (white) athletes indicate that a
significant proportion exhibit an isolated prolonged corrected QT
interval (QTc), raising concerns for potentially false diagnoses and
disqualification from competitive sport. The prevalence of prolonged
QTc interval in athletes of African/Afro-Caribbean (black) descent is
unknown. However, this ethnic group generally exhibits a high
proportion of ECG repolarisation changes and increased left
ventricular wall thickness, that may impact on QTc.
Aim We aimed to assess the impact of ethnicity on QTc in young
elite athletes.
Methods We assessed 3035 elite athletes, aged 14e35 years, who
were participating at national and international level in a variety of
sporting disciplines. Athletes were evaluated with ECG and 2D
echocardiography. Athletes diagnosed with structural heart disease
or hypertension were excluded from analysis.
Results Demographic and cardiological results are summarised in
Abstract 49 table 1. Black male athletes exhibited shorter QTc than
white male athletes, but QTc was similar among black and white
female athletes. Bivariate analysis revealed that none of T wave
inversions, ST segment elevation, or left ventricular wall thickness
were associated with QTc. No ethnic difference was observed in
prevalence of QT prolongation, as defined by ESC Sports Consensus
criteria (male >440 ms; female >460 ms).
Abstract 49 Table 1
Characteristics of athletes evaluated
Black Male White Male Black Female White Female
(n[901)
(n[1652)
(n[122)
(n[360)
Mean Age, years
Mean Heart Rate, bpm
Aim We determined the diagnostic yield of exercise tolerance testing
(ETT) in investigation of inherited cardiac conditions following
familial premature SCD.
Methods Between 2006 and 2010, we evaluated 308 blood relatives
of 148 SCD victims, who completed at least 3 min of the Bruce
protocol. ETTs were analysed for: QT prolongation; Brugada type 1
pattern; ST depression: blood pressure (BP) response; multiple
ventricular ectopics or arrhythmia. Individual pathological phenotypes were determined by a combination of 12-lead ECG, echocardiogram, 24-h holter monitor, with additional MRI, CT coronary
angiography and genetic mutation analysis, as appropriate.
Results Thirty (9.8%) patients had an abnormality during ETT,
details of which are summarised in Abstract 50 п¬Ѓgure 1. All ETTs
with abnormal QT prolongation and dynamic Brugada pattern were
associated with diagnoses of long QT syndrome and Brugada
syndrome respectively. An example of dynamic Brugada phenotype
is given in Abstract 50 п¬Ѓgure 2. Ventricular ectopy was seen in 15
patients, of whom 5 demonstrated phenotypic cardiomyopathy or
channelopathy on further investigations. No patients with significant ST depression had evidence of coronary abnormalities on
imaging. No hypotensive BP response was seen, but exertional
hypertension was associated with systemic hypertension.
2265
61612
Mean QRS duration, ms
88614
Mean LV wall thickness, mm 10.661.6
1764
56610
2165
63610
1864
5969
96610
9.4*61.2
84610
9.261.2
8869
7.9*62.9
ST segment elevation, n (%)
T wave inversions, n (%)
570 (63.3%) 406 (24.6%) 20 (16.3%)
204 (22.6%) 66* (4.0%) 18 (14.6%)
64 (17.8%)
15* (4.2%)
Mean QTc (Bazett’s), ms
QTc >440 ms, n (%)
393626
20 (2.2%)
404*620
49 (3.0%)
407625
13 (10.6%)
412627
39 (10.9%)
QTc >460 ms, n (%)
4 (0.4%)
7 (0.4%)
1 (0.8%)
5 (1.4%)
Abstract 50 Figure 1
familial evaluation.
ETT abnormalities and associated diagnoses at
Means presented as mean 6 SD.
*p<0.001 white vs black athletes.
Conclusion Despite demonstrating a higher prevalence of repolarisation changes and morphological left ventricular hypertrophy,
black athletes do not exhibit a longer QTc than white counterparts.
Based on ESC Sports Consensus criteria, prevalence of a long QTc in
black and white athletes is similar, obviating the need for ethnicity
specific criteria for defining a long QTc.
50
DIAGNOSTIC ROLE OF EXERCISE TOLERANCE TESTING IN
FAMILIAL PREMATURE SUDDEN CARDIAC DEATH
doi:10.1136/heartjnl-2011-300198.50
H Raju, M Papadakis, R Bastiaenen, A Zaidi, N Chandra, M Muggenthaler, N Spath,
S Sharma, E R Behr. St George’s University of London, London, UK
Abstract 50 Figure 2 Exercise tolerance test demonstrating dynamic
Brugada ECG pattern. Stage 1 of Bruce protocol exercise (left) and postexercise recovery (right).
Background Investigation of blood relatives for evidence of an
inherited cardiac condition is advocated following an unexplained
sudden cardiac death (SCD).
Conclusion The ETT is a useful diagnostic adjunct when evaluating
relatives of victims of premature SCD. Reliable diagnostic indicators
include inappropriate QT prolongation and dynamic Brugada
Heart June 2011 Vol 97 Suppl 1
A33
BCS Abstracts 2011
pattern. Ventricular ectopy is non-specific, but is associated with
both cardiomyopathic and channelopathic processes in a significant
minority. ST segment depression, however, is unhelpful and should
be viewed in the context of the patient’s cardiovascular risk profile.
51
of DPSV/DHR were different in the saline/ischaemia group compared
to the three other groups (ie, saline/ischaemia Вј3.760.6 cm/s/s,
NO2-/ischaemia Вј8.261.0 cm/s/s, saline/control Вј10.561.1 cm/s/s,
NO2-/control Вј8.460.7 cm/s/s; p<0.01, repeated-measures ANOVA
with Bonferroni post-test). No difference was present between the
three other groups.
LOW-DOSE SODIUM NITRITE RELIEVES MYOCARDIAL
ISCHAEMIA IN PATIENTS WITH CORONARY ARTERY
DISEASE: A TARGETED NO-DONOR EFFECT
doi:10.1136/heartjnl-2011-300198.51
1
1
T E Ingram, 2R A Bleasdale, 2C Templeton, 2C Williams, 1A Margulescu, 1A G Fraser,
P E James. 1Cardiff University, Cardiff, UK; 2Royal Glamorgan Hospital, Llantrisant, UK
Introduction Sodium nitrite (NaNO2) became a popular means of
treating angina in the 19th century, as its stable chemical structure
allowed for cheap preparation and easy storage. However, the effects
were slow and unpredictable and so it fell out of favour as more
potent and faster-acting agents became available, (eg, organic
nitrates). Recent in vitro evidence shows that nitrite (NO2-) exhibits
an enhanced vasodilator effect in hypoxia; an environmental
modification which encourages its reduction to nitric oxide (NO).
Therefore NaNO2 could potentially be an anti-ischaemic agent at
much lower doses than those used historically, and be without the
adverse side effects associated with organic nitrates (eg, systemic
hypotension and tachyphylaxis).
Method A double-blind, placebo-controlled, cross-over study was
performed in 10 subjects with proven myocardial ischaemia documented by exercise tolerance testing and coronary angiography. Two
dobutamine stress echocardiography (DSE) studies were performed
on each subject: one with 0.9% saline and one with NaNO2,
1.5 mmol/min for 20 min. This dose of NaNO2 has previously been
shown to be inert in normoxia but to vasodilate hypoxic tissue.
Myocardial ischaemia was identified by the peak systolic velocity
(PSV) response during DSE in a six basal-wall segment model of the
left ventricle. Using placebo study data-set, walls were classified into
tertiles: the lowest tertile of responders of PSV to an increase in
heart rate (DHR) labelled ischaemia (nВј18) and the upper tertile
control (nВј18). Data was divided into four groups according to the
study-infusion received and the myocardial-wall examined: saline/
ischaemia, NO2-/ischaemia, saline/control and NO2-/control.
Results Data from each stage of each DSE was plotted on a scatter
plot graph with change in (DHR) on the x-axis and corresponding
change in PSV (DPSV) on the y-axis (increase in both values
compared to baseline), see Abstract 51 п¬Ѓgures 1 and 2. Linear
regression analysis of the saline/ischaemia group was lower than the
NO2-/ischaemia group, with no overlap in their 95% CI, see Abstract
51 п¬Ѓgure 1. In addition, the linear regression gradient of the NO2-/
ischaemia group was similar to the saline/control and the NO2-/control
gradient, see Abstract 51 п¬Ѓgure 2. The peak-dose dobutamine values
Abstract 51 Figure 1
A34
Abstract 51 Figure 2
Conclusions Low-dose NaNO2 delivers a therapeutic effect to
ischaemic myocardial tissue in the absence of a vasodilator effect on
normoxic tissue. This is the п¬Ѓrst study in patients to demonstrate a
targeted vasodilator effect of NO2- to tissues in need only.
52
BRAIN NATRIURETIC PEPTIDE PREDICTS ALL CAUSE
MORTALITY IN PATIENTS WITH TYPE 2 DIABETES AND
NORMAL EJECTION FRACTIONS
doi:10.1136/heartjnl-2011-300198.52
1
1
2
1
B R Szwejkowski, D H J Elder, A Dawson, A D Struthers. 1University of Dundee,
Dundee, UK; 2Department of Cardiology, NHS Tayside, Dundee, UK
Introduction The use of brain naturetic peptide (BNP) to predict
outcome in patients with normal ejection fractions (EF) and type 2
diabetes (T2DM) is understudied. Only three previous studies have
specifically addressed the question as to whether BNP adds prognostic
information in T2DM. There appears to be a link between survival
and BNP in T2DM, however these studies included small numbers of
patients and did not fully exclude left ventricular systolic dysfunction
(LVSD). We therefore studied the 5-year survival in a cohort of 500
T2DM patients prospectively phenotyped with echocardiography.
Methods 500 patients with T2DM where studied with echocardiography between April 2002 and October 2003. Patients were recruited
from the diabetes clinics at Ninewells Hospital, Dundee. Transthoracic
echocardiography was performed by one trained operator and left
ventricular (LV) assessment was performed using modified biplane
Simpson’s method over three cycles. We excluded individuals with EF of
<55%. Follow-up data was linked via the Health Informatics Centre
(HIC), to mortality data, laboratory test data, hospitalisation, and
prescribing via the community health index (CHI) number. Cox
proportional hazards model was used to examine the effects of BNP
(bedside stick measurement) measure on all-cause mortality using age,
sex, smoking status, hypertension, IHD, duration of diabetes, and diabetic
drug prescription as co-variants. Outcome was all cause mortality.
Results In total we followed 316 patients over 8 years. 56 patients
died over this time. After adjusting for confounding factors we
have shown that for every 10-unit increase in BNP there is a 6%
increased risk of death. HR 1.06 (95% CI 1.02 to 1.10) (pВј<0.01).
Conclusions In patients with normal EF, BNP is an independent
predictor of death in a cohort of T2DM patients. Although more
research is needed, BNP may become an important tool in risk
stratifying T2DM patients in the future.
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
53
B-TYPE NATRIURETIC PEPTIDE PERFORMS BETTER THAN
CURRENT CARDIOVASCULAR RISK SCORES IN IDENTIFYING
SILENT “PANCARDIAC” TARGET ORGAN DAMAGE IN
ALREADY TREATED PRIMARY PREVENTION PATIENTS
doi:10.1136/heartjnl-2011-300198.53
1
1
A Nadir, 1S Rekhraj, 2J Davidson, 1T M MacDonald, 1C C Lang, 1A D Struthers.
University of Dundee, Dundee, UK; 2Ninewells Hospital, Dundee
Background Primary prevention needs to be improved because up to
70% of cardiovascular (CV) events occur outwith those classified as high
risk by CV risk scores currently used in clinical practice (eg,
Framingham). One possible way to improve primary prevention of CV
disease is to identify those patients who may already harbour silent
pancardiac target organ damage in the form of left ventricular hypertrophy (LVH), systolic dysfunction (LVSD), diastolic dysfunction
(LVDD), left atrial enlargement (LAE) or silent myocardial ischaemia.
This could be achieved by reapplying traditional CV risk scores to
primary prevention patients after they have been treated or by screening
with a simple biomarker like B-type natriuretic peptide (BNP).
Methods We prospectively recruited 300 asymptomatic individuals
without known cardiovascular disease already on primary prevention
therapy. Patients with valvular heart disease, atrial п¬Ѓbrillation and
renal impairment were excluded. We measured BNP and calculated 10year global CV risk scores (based on Framingham, QRISK and
ASSIGN) in each participant. Transthoracic echocardiography was
used to assess LV mass, LV systolic and diastolic function, and left
atrial volume while the presence of inducible ischaemia was assessed
by dobutamine stress echocardiography or dipyridamole myocardial
perfusion imaging. Patients were divided into low, intermediate and
high risk groups based on 10-year global CV risk. The prevalence of
various cardiac TOD in each group was compared and ROC curves
were constructed for BNP and for 10-year global CV risk scores to
assess their ability to detect presence of silent cardiac TOD.
Results One hundred and two (34%) patients (Mean age
6466.0 years, 58% males) had evidence of silent cardiac TOD
(29.7% LVH, 18% LAE, 17.3% LVDD, 7.3% LVSD and 6.3%
Ischaemia). The prevalence of cardiac TOD ranged from 19 to 28%
in the low risk, 26%e33% in the intermediate risk and 36%e41% in
the high risk groups based on three commonly used CV risk equations. BNP levels were significantly higher (median (IQR); 21.6
(13.6e40.0) vs 11.4 (6.3e20.0) pg/ml, p<0.0001) in those with
cardiac TOD compared to those without. The AUC for BNP to
identify any form of cardiac TOD was 0.77 (p<0.0001) overall and
0.83 (p<0.0001) in males. However, discrimination power of CV risk
scores was poor with area under curve of only 0.58 (pВј0.02) for
QRISK, 0.62 (pВј0.001) for Framingham and 0.62 (pВј0.001) for
ASSIGN to detect presence of any form of TOD.
Conclusion Silent cardiac TOD is highly prevalent (34%) in already
treated primary prevention population but current CV risk estimation alone performs poorly in the detection of these silent cardiac
abnormalities. However, a raised BNP is able to identify existing
silent cardiac TOD of various subtypes particularly in males. Using
BNP to identify silent cardiac TOD could, in the future, become a
new way to improve the primary prevention of CV events.
54
CAN MICROALBUMINURIA IDENTIFY SILENT
“PANCARDIAC” TARGET ORGAN DAMAGE IN A
NON-DIABETIC PRIMARY PREVENTION POPULATION?
doi:10.1136/heartjnl-2011-300198.54
1
1
A Nadir, 1S Rekhraj, 2J Davidson, 1T M MacDonald, 1C C Lang, 1A D Struthers.
University of Dundee, Dundee, UK; 2Ninewells Hospital, Dundee, UK
Background Microalbuminuria is associated with increased cardiovascular mortality and is a marker of generalised vascular dysfuncHeart June 2011 Vol 97 Suppl 1
tion. We sought to investigate whether micoalbuminuria identified
the presence of silent “pancardiac” target organ damage (TOD) ie, left
ventricular hypertrophy (LVH), systolic dysfunction (LVSD), diastolic
dysfunction (LVDD), left atrial enlargement (LAE) or silent myocardial ischaemia in a non-diabetic primary prevention population.
Methods Two hundred and sixty-three asymptomatic individuals
without diabetes or previous cardiovascular disease on primary
preventive therapy were prospectively recruited. Each participant
underwent a comprehensive echocardiographic examination for the
assessment of LV mass, LV systolic and diastolic function, and left
atrial volume while the presence of inducible ischaemia was assessed
by dobutamine stress echocardiography or dipyridamole myocardial
perfusion imaging. A spot urine sample was analysed for microalbuminuria and urinary creatinine by a trained laboratory technician blinded to clinical or echocardiographic data. Microalbuminuria
was defined as urinary albumin to creatinine ratio of $2.5 mg/mmol
in males and $3.5 mg/mmol in females.
Results Out of 263 participants (Mean age 6466.3 years, 57%
males) 89 (33.8%) had evidence of silent cardiac TOD (29.7% LVH,
16.7% LAE, 17.1% LVDD, 6.8% LVSD and 6.1% Ischaemia). The
prevalence of cardiac TOD was significantly higher (53% vs 29%,
pВј0.002) among those with microalbuminuria than those without.
In multivariate analysis adjusted for age, gender, hypertension and
dyslipidemia, presence of microalbuminuria was an independent
predictor of cardiac TOD with an adjusted HR of 2.54 (95% CI, 1.2
to 4.4, pВј0.005). The utility of UACR in discriminating between
those with or without cardiac TOD was assessed by receiver operating characteristic analysis but the area under curve was only
0.6160.04, pВј0.003.
Conclusion Microalbuminuria is an independent predictor of silent
“pancardiac” target organ damage in a non-diabetic primary prevention population. Presence of microalbuminuria may help to identify
those primary prevention patients who are at a particularly higher risk.
55
GENE-GENE INTERACTIONS IN CORONARY ARTERY
DISEASE
doi:10.1136/heartjnl-2011-300198.55
1
2
3
4
M D Musameh, W Y S Wang, A J Balmforth, S G Ball, 5A S Hall, 1M Tomaszewski,
N J Samani. 1Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital; Leicester BRU, Leicester, UK; 2School of Medical Sciences and Institute
for Biomedical Research, University of Sydney, Sydney, Australia; 3Division of Cardiovascular and Diabetes Research, University of Leeds, Leeds, UK; 4LIGHT Research
Institute, Faculty of Medicine and Health, University of Leeds, Leeds, UK; 5Division of
Cardiovascular and Neuronal Remodelling, University of Leeds, Leeds, UK
1
Background Only a small fraction of the heritability of coronary
artery disease (CAD) has been explained by common variants
identified by genome-wide association studies. Among the stones to
be turned in the hunt for the missing heritability of CAD are genegene interactions. We investigated whether interactions between
common alleles in genes and pathways of known importance to
cardiovascular regulation may contribute to the heritability of CAD.
Methods 2101 CAD cases and 2426 controls of Caucasian origin
recruited into Wellcome Trust Case Control Consortium were
genotyped using 50 K IBC gene-centric array containing 45 707 single
nucleotide polymorphisms (SNPs) of the highest biological relevance
to cardiovascular system. After applying appropriate quality control
п¬Ѓlters, 11 332 common (minor allele frequency >10%), independent
(r2 linkage disequilibrium coefficient of #0.5) were included in
pair-wise SNP-SNP interaction analysis using two complementary
statistical approaches: logistic regression (PLINK and INTERSNP
software packages) and Bayesian model (BEAM software).
Results None of the analysed SNP-SNP interactions was statistically significant after correction for multiple testing (p¼7.8310-10).
The most significant interaction identified in this analysis was
A35
BCS Abstracts 2011
between rs727139 (KCNH8) on chromosome 3 and rs11167496
(PDGFRB) on chromosome 5 (pВј2.45310ГЂ8). Analysis of subsets
of SNPs pre-selected based on their nominal association with CAD
(p<0.05) or molecular functionality (non-synonymous SNPs) did
not contribute more significant findings than investigation of
random set of SNPs.
Conclusion Our analysis suggests that common SNP-SNP interactions are unlikely to account for a large proportion of the missing
heritability of CAD.
56
CLINICAL AND FINANCIAL REPERCUSSIONS OF THE
MARCH 2010 NATIONAL INSTITUTE FOR HEALTH AND
CLINICAL EXCELLENCE (NICE) GUIDELINE “CHEST PAIN OF
RECENT ONSET” ON THE RAPID ACCESS CHEST PAIN
CLINIC (RACPC)
Abstract 56 Figure 1
doi:10.1136/heartjnl-2011-300198.56
T Rogers, S Claridge, K Al Fakih. University Hospital Lewisham, London, UK
Background The RACPC is a well-established “one-stop” service,
with goal to identify patients with stable chest pain due to coronary
artery disease (CAD) and quickly reassure those with non-cardiac
pain. In March 2010, NICE published a new guideline, which
advocates assessing likelihood of CAD based on age, gender, history
and risk factors (RF). If estimated likelihood is >60%, invasive
coronary angiography (ICA) is recommended as the п¬Ѓrst-line diagnostic investigation. If estimated likelihood is 30%e60%, functional
imaging is recommended. If estimated likelihood is <30%, CT
calcium scoring CT coronary angiography (CTCA) is recommended.
Significantly, the guideline discourages the use of ETT to diagnose or
exclude stable angina in patients without known CAD.
Methods 167 consecutive patients referred to RACPC between
October 2009 and March 2010 were retrospectively assessed for
likelihood of CAD according to the new NICE guideline. Choice of
investigations and eventual outcome (confirmed CAD vs no
evidence of CAD) were compared between subgroups defined by
estimated likelihood of CAD. An economic analysis of cost of
investigation per patient was undertaken using current Payment by
Results national tariffs.
Results Our patient population had a high prevalence of RF with
38.1% having a total of three or more RF. Consequently 23.2% of
patients had an estimated likelihood of CAD of <30%. 27.4% had an
estimated likelihood of 30%e60%. 49.4% had an estimated likelihood of >60%. 7.2% of patients were lost to follow-up. 14.4% of
patients were ultimately confirmed to have CAD on ICA, which
correlated with pre-test estimated likelihood. 6% of patients with
likelihood <30%, 8.7% of those with likelihood 30%e60% and
23.2% of those with likelihood >60% were confirmed to have CAD.
Average cost of investigation per patient was ВЈ528. A negative ETT
resulted in average cost per patient of ВЈ347. An inconclusive ETT
resulted in higher cost (ВЈ728) as did inability to exercise (ВЈ435) due
to the need for further investigations. A positive ETT resulted in
average cost of ВЈ1174 due to the high cost of ICA. Were the NICE
guideline strictly applied to our patient population, average cost per
patient would have been substantially higher at ВЈ838 (ВЈ362 per
patient if likelihood <30%, ВЈ566 if likelihood 30%e60% and ВЈ1218 if
likelihood >60%). Overall this corresponds to a 60% increase in cost.
Conclusion The 2010 NICE guideline appears to significantly overestimate the true risk in our patient population. Were the guideline
strictly applied, almost half of our patients would proceed to ICA as
a п¬Ѓrst-line investigation, but many of them would be found to have
unobstructed coronary arteries. As ICA is an expensive investigation, this would inevitably result in a significant increase in
average cost per patient. Relatively few patients would be eligible
for CTCA, which is an excellent non-invasive “rule-out” test for
CAD and relatively inexpensive compared with other investigations.
A36
Abstract 56 Table 1
All
Men
Numbers (%)
167
86 (51.5)
Women
51 (48.5)
Age (mean 6 SD)
Diabetes (%)
56.0612.6
29 (17.4)
55.2613.3
15 (17.4)
57.0611.8
14 (17.3)
Hypertension (%)
Hypercholesterolaemia (%)
72 (43.1)
100 (59.9)
40 (46.5)
53 (61.6)
32 (39.5)
47 (58.0)
Family history (%)
Smoking (%)
58 (34.7)
87 (52.1)
28 (32.6)
54 (62.8)
30 (37.0)
33 (40.7)
Systolic BP (mean 6 SD) /
Diastolic BP (mean 6 SD)
134621 /
79611
131618 /
80611
137623 /
78610
Fasting glucose (mean 6 SD)
Total cholesterol (mean 6 SD)
5.261.0
5.1761.04
5.761.0
5.0661.06
5.361.1
5.2961.01
LDL (mean 6 SD) / HDL
(mean 6 SD)
3.1960.90 /
1.3060.43
3.1460.90 /
1.2360.46
3.3360.86 /
1.3860.38
BMI (mean 6 SD)
30.166.0
29.464.9
30.966.9
Abstract 56 Table 2
Average cost per
patient prior to NICE
guideline implementation
Average cost per
patient were NICE
guideline strictly
implemented
Predicted likelihood <30%
Predicted likelihood 30%e60%
ВЈ324
ВЈ467
ВЈ362
ВЈ566
Predicted likelihood >60%
OVERALL AVERAGE COST PER
PATIENT
ВЈ661
ВЈ528
ВЈ1218
ВЈ838
57
THE IMPACT OF PREOPERATIVE RENAL DYSFUNCTION AND
THERAPY TYPE IN PATIENTS WITH TYPE 2 DIABETES
UNDERGOING CORONARY ARTERY BYPASS SURGERY
doi:10.1136/heartjnl-2011-300198.57
A Menon, J Hodson, D Pagano, J Mascaro, I C Wilson, S J Rooney, T R Graham,
R S Bonser. University Hospital Birmingham, Birmingham, UK
Introduction There is limited data addressing the impact of preoperative renal dysfunction in type 2 diabetics (T2DM) undergoing firsttime coronary artery bypass surgery (CABG); specifically exploring
the influence of diabetic management (oral hypoglycaemic (OH) and
insulin therapy (IN)). We assessed the impact of preoperative renal
status and diabetic management on the post operative renal status,
morbidity, 30-day and long-term survival in T2DM-CABG.
Methods We reviewed prospectively accrued data from 1/1/1999 to
31/12/2009. Pre and 4 to 5-day postoperative creatinine clearance
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
(CrCl) was calculated using Cockcroft-Gault formula. Patients were
subgrouped into 5 grades based on preoperative CrCl; Group I
CrCl$90 ml/min; II 60e89; III 30e59; IV 15e29; V <15 or
haemodialysis. Late KaplaneMeier survival data (compared by log
rank method), censored at 1/10/2009 were obtained from the UK
CCAD. Surgical morbidity outcomes included re-exploration for
bleeding, stroke (type 1 deficit) and low cardiac output state (LCOS)
requiring inotropes 6 intra-aortic balloon counterpulsation were
compared using Fisher’s Exact tests.
Results 1215 patients (921 males) with a mean age of 64 years
(31e89 years) underwent CABG; 742 on OH and 472 on IN. Preoperative renal status in the groups were Group I -209(17%), II-584
(48%), III-387(32%), IV-26(2%) and V (8(1%). Similar percentages in
each group had $1 grade deterioration of renal function postoperatively 19%, 18%, 16% and 23% (grades IeIV respectively;
pВј0.470). When examined as a continuous variable, higher preoperative CrCl correlated with a better postoperative improvement in
CrCl (rВј0.073, pВј0.012 Spearman Rank). Overall 30-day mortality
was 3.33% (CI 2.32 to 4.34%) and was not different by group I-3.37%
(CI 0.92 to 5.82), II-2.09% (CI 0.92 to 3.26%), III 4.92% (CI 2.76 to
7.08%), IV 8% (CI 0 to 18.6%) and Stage V 0% (CI 0 to 0.4%; pВј0.101)
or by therapy type; (pВј0.411). IN patients had similar preoperative
renal function (median CrCl 66.8 vs 68.6; pВј0.828) but a higher rate
of postoperative renal deterioration (53.3 vs 46.7%, p<0.001). Stroke
(pВј1.000), bleeding (pВј0.755) and LCOS (pВј0.335) incidence were
not different between therapy type. Overall mean survival was
9 years (CI 8.7 to 9.2 years) and was not different by renal function
grade (pВј0.612). However, IN patients had shorter mean survival 8.7
(8.3 to 9.0) vs OH 9.1(8.8 to 9.4) years; pВј0.03.
Conclusions In T2DM-CABG, 36% of patients have CrCl <60 ml/min.
Higher CrCl protects against postoperative renal deterioration. Renal
dysfunction does not appear to affect hospital outcome or survival.
However, preoperative IN requirement increases the risk of renal
dysfunction and is associated with worse longer-term survival.
58
TEMPORAL EVALUATION OF REFERRAL FOR AND LONGTERM SURVIVAL FROM CARDIAC REHABILITATION FOR
ACUTE MYOCARDIAL INFARCTION
doi:10.1136/heartjnl-2011-300198.58
1
EMMACE risk score, revascularisation, reperfusion, ACE-inhibitor, ablocker, statins, anti-platelet agent, admitting cardiologist) was used
to compare the temporal long-term survival estimates (all cause
mortality) by CR referral.
Results 4341 had AMI. CR referral was 44% in 1995 and 59 % in 2003
(p<0.001). CR referral was associated with reduced mortality in 2003
(RRR, 95%CI: 0.54; 0.50 to 0.60), but was not in 1995 (1.02; 0.96 to
1.09). Unadjusted survival for patients not referral for CR in 1995 was
similar to that for patients referred for CR in 1995; (Abstract 58
п¬Ѓgure.1). For those referred for CR, the mean mini-GRACE score for
CR referrals was lower in 2003 than 1995; 0.53 and 0.72, p<0.001.
After adjustment using the min-GRACE score (Model 1), the impact
(HR, 95% CI) of CR referral was 0.63, 0.55 to 0.73 in 2003 and 1.07,
0.92 to 1.3 in 1995. After adjustment using Model 2, the impact
(HR, 95% CI) of CR referral was 0.57, 0.48 to 0.66 in 2003 and 1.31,
1.04 to 1.60 in 1995.
Conclusion Between 1995 and 2003, referral for CR increased and
became a significantly important factor contributing to reduced
mortality rates post-AMI. This is despite the differences in patient
and treatment factors between the 2 studies periods. Even so, rate of
referral for CR remain sub-optimal.
1
2
1
3
Abstract 58 Figure 1
KaplaneMeier survival estimates.
4
C L Lewinter, M B Bland, P D Doherty, B L Lewin, A S H Hall, C P G Gale.
University of York, York, UK; 2York St John University, York, UK; 3Yorkshire Heart
Centre, Leeds, UK; 4University of Leeds, Leeds, UK
1
Background Cardiac rehabilitation (CR) is a cost-effective, evidencebased approach to managing heart disease. Rates of uptake have and
continue to vary despite recommendations from the NSF for CHD
and NICE. The Evaluation of the Management and Methods of
Acute Coronary Events (EMMACE) 1 and 2 studies are 2 large
prospective multi-centre registries of care of acute coronary
syndromes (ACS) in Yorkshire undertaken in 1995 and 2003 in
respectively. We studied the temporal changes in referral for and
long-term survival from CR in patients who were admitted to
hospital with an acute myocardial infarction (AMI).
Methods Baseline characteristics were described as numbers (%) or as
means with IQRs. For Continuous variables, the Kruskal Wallis test
was used for comparisons. Discrete variables were assessed by the c2
test. Unadjusted relative risk ratios (RRR) were calculated to assess
mortality after referral for CR. KaplaneMeier (KM) curves compared
unadjusted survival stratified by CR referral and EMMACE study. Log
rank tests compared the survival estimates. Sex, age, STEMI, heart
failure, diabetes, COPD and mini-GRACE score, revascularisation,
reperfusion, ACE-inhibitors, a-blockers, statins, anti-platelet agents
and admitting cardiologist were regressed (backward logistic, p<0.10
and goodness of п¬Ѓt with a group of 10) on CR referral and represented
as 95% CI OR. A Cox proportional model (Model 1: mini-GRACE
score, Model 2: sex, age, STEMI, heart failure, diabetes, COPD,
Heart June 2011 Vol 97 Suppl 1
59
SHORT TERM ELEVATION OF CHOLESTEROL LEVEL IN
NEONATAL LIFE AND LONG TERM CHANGES IN AORTIC
STIFFNESS: INSIGHTS FROM USE OF INTRAVENOUS LIPIDS
doi:10.1136/heartjnl-2011-300198.59
1
A J Lewandowski, 1M Lazdam, 1E Davis, 1R Poole, 1J Diesch, 1J Francis,
S Neubauer, 2A Lucas, 2A Singhal, 1B Kelly, 1P Leeson. 1Cardiovascular Medicine,
University of Oxford, Oxford, UK; 2Institute of Child Health, University College London,
London, UK
1
Introduction Offspring born to hypercholesterolaemic mothers have
increased fatty streak formation in the fetal aorta, which persists into
adolescence. To understand whether exposure to elevated cholesterol
in early life, independent of a maternal history of hypercholesterolaemia, also has a long-term impact on the cardiovascular
system we studied the vascular phenotype of adults in whom cholesterol levels were artificially elevated for a short period postnatally.
Methods We prospectively followed-up 102 subjects born premature
now aged 23 to 28 years. Individuals exposed to maternal hypercholesterolaemia were excluded. 18 received intravenous (IV) lipids
during the п¬Ѓrst nine weeks of life and were matched 2:1 for pregnancy and early life complications, age, sex, birthweight and gestational age with controls that did not receive IV lipids. Aortic pulse
wave velocity (aPWV), regional aortic distensibility, left ventricular
mass and ejection fraction were determined by cardiovascular
A37
BCS Abstracts 2011
magnetic resonance. Detailed lifestyle information and anthropometric measurements were collected during childhood and
adolescence. Metabolic parameters were measured multiple times
per week for the п¬Ѓrst 9 weeks of life and again at follow-up visits.
Results Individuals that received IV lipids achieved significantly
higher maximum cholesterol levels during the п¬Ѓrst 9 weeks of life
than those that did not (mean6SDВј4.3861.65 vs 3.1260.78 mmol/
l, pВј0.006). Dose given and number of days on IV lipids also associated with maximum cholesterol level during this period (rВј0.557,
p<0.001 and rВј0.567, p<0.001, respectively). There was a graded
relation between the maximum elevation in circulating cholesterol
postnatally and aortic stiffness (aPWV) in young adulthood
(rВј0.596, p<0.001). The greatest increase in stiffness was seen in
the abdominal aorta, where distensibility was significantly reduced
in the group that received IV lipids (mean6SDВј9.7464.27 vs
12.9164.11/mm Hg3103, pВј0.012). There were no differences
between the groups in other vascular or left ventricular measures. In
a stepwise regression model, maximum cholesterol level achieved
in the п¬Ѓrst few weeks of life was an independent predictor of aPWV
in young adulthood (bВј0.596, p<0.001) and accounted for 30.9% of
the variance in hierarchical multiple regression (bВј0.584, p<0.001).
Conclusions Brief artificial elevation of cholesterol level in immediate
postnatal life is associated with long term changes in aortic function
independent of later cholesterol levels. The association is graded
depending on the degree of elevation of circulating cholesterol. High
cholesterol exposure during sensitive periods of early postnatal life
may have long term impacts on the cardiovascular system.
elite level, since extrapolation of ECG and echocardiographic criteria,
solely derived from Caucasian cohorts, would result in 25.6% of BA
requiring further investigations for cardiac pathology.
Abstract 60 Figure 1 Bar chart depicting the distribution of left
ventricular wall thickness in black and white adolescent athletes.
61
FIVE-MIN HEART RATE VARIABILITY CAN PREDICT
OBSTRUCTIVE ANGIOGRAPHIC CORONARY DISEASE
doi:10.1136/heartjnl-2011-300198.61
60
ETHNIC DIFFERENCES IN REPOLARISATION PATTERNS AND
LEFT VENTRICULAR REMODELLING IN HIGHLY TRAINED
MALE ADOLESCENT (14e18 YEARS) ATHLETES
doi:10.1136/heartjnl-2011-300198.60
1
N Sheikh, 1M Papadakis, 2F Carre, 2G Kervio, 1J Rawlins, 3V Panoulas, 1N Chandra,
H Raju, 1R Bastiaenen, 1E Behr, 1S Sharma. 1St. George’s University of London,
London, UK; 2French Institute of Health and Medical Research, University of Rennes,
Rennes, France; 3University Hospital Lewisham, London, UK
1
Purpose Studies in adult, black athletes (BA) demonstrate a high
prevalence of ECG repolarisation changes and echocardiographic left
ventricular hypertrophy (LVH) that may overlap with hypertrophic
cardiomyopathy (HCM). The prevalence of ECG repolarisation
changes and echocardiographic LVH in adolescent BA, the group most
vulnerable to exercise-related sudden death from HCM, is unknown.
Methods This study evaluated 219 male adolescent BA (14e18 years,
inclusive) with 12-lead ECG and 2-D echocardiography. Results were
compared with 1440 male adolescent WA. Athletes with T wave
inversions and morphological LVH were invited for further investigation with exercise stress test, 24 h Holter and CMR.
Results ST segment elevation was common in both groups but more
frequent in BA (63.5% vs 14.9%, p<0.001), while ST segment
depression was exceedingly rare. Both T wave inversions (21.5% vs
2.9%, p<0.001) and deep T wave inversions (11% vs 0.3%, p<0.001)
were commoner in BA. Black athletes demonstrated greater left
ventricular wall thickness (10.461.6 vs 9.461.2 mm, p<0.001)
compared to WA. Twenty-three (10.5%) BA exhibited a left
ventricular wall thickness >12 mm vs only 6 (0.4%) WA (p<0.001).
None of the athletes exhibited the broader phenotype of HCM on
further investigation. In multivariable analysis black ethnicity was
the strongest independent predictor for the presence of T wave
inversions (OR 3.56, 95% CI 1.56 to 8.13, pВј0.003) and LVH (OR
3.17, 95% CI 1.77 to 5.71, p<0.001).
Conclusions As with adult athletes, Twave inversions and LVH were
more prevalent in adolescent BA compared to WA. These п¬Ѓndings
have important implications in the pre-participation screening era,
particularly in countries with a high proportion of BA competing at
A38
1
D Kotecha, 2G New, 1M Flather, 3D Eccleston, 3H Krum. 1Royal Brompton Hospital,
London, UK; 2Box Hill Hospital, Melbourne, UK; 3Monash University, Melbourne, UK
Background Obstructive coronary artery disease (CAD) is evident in
only half of patients referred for diagnostic coronary angiography.
Five-minute heart rate variability (HRV) is a marker for autonomic
control of the vasculature, which we hypothesised could be used to
risk-stratify cardiac patients (the Alternative Risk Markers in
Coronary Artery Disease (ARM-CAD) study.
Methods Resting HRV prior to elective coronary angiography was
analysed in 470 participants with predominantly normal cardiac
rhythm, regardless of comorbidity. The presence of obstructive CAD
($50% stenosis) was regressed in a multivariate model including risk
factors, ECG variables and medications.
Results Mean age was 65 years (SD 11), 67% were male, 21% had
diabetes, mean blood pressure was 144/79 mm Hg (SD 21/10) and
16% had impaired left-ventricular function. Patients with obstructive CAD had significantly reduced HRV, particularly in the low
frequency (LF) range (median 180 vs 267 ms2 without CAD;
p<0.001). There was a linear trend according to the severity of
CAD; the median LF power (IQR) in patients with normal coronaries was 275 (612), with minor coronary irregularities 255 (400),
Abstract 61 Figure 1
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
single-vessel CAD 212 (396) and more severe disease 170 (327) ms2;
p-value for trendВј0.003. There was a similar reduction in LF power
regardless of the anatomical location of coronary stenoses (see
Abstract 61 п¬Ѓgure 1). Comparing patients with LF<250 and
$250 ms2, the OR for obstructive CAD was 2.42, 95% CI 1.33 to
4.38 (pВј0.004) after adjusting for risk factors, medications and heart
rate. No interactions were noted in sub-group analysis of age,
gender, diabetes, prior cardiovascular disease or high-sensitivity CRP.
In addition, HRV added to risk prediction irrespective of baseline
Framingham risk (p<0.0001).
Conclusion Low HRV is strongly predictive of angiographic coronary
disease regardless of other comorbidities and is clinically useful as a
risk predictor in patients with sinus rhythm.
Abstract 62 Figure 1
62
Comparison CHADS2 & CHA2DS2-VASc scores.
WILL THE NEW EUROPEAN AF GUIDELINES LEAD TO MORE
PATIENTS RECEIVING ORAL ANTICOAGULATION THERAPY?
doi:10.1136/heartjnl-2011-300198.62
T Kaier, R Williams, S Khan. West Middlesex University Hospital, London, UK
Atrial п¬Ѓbrillation (AF) confers a 5-fold risk of stroke and the risk of
death from AF-related stroke is doubled; it is the most common
sustained cardiac arrhythmia, occurring in 1%e2% of the general
population. Meta-analysis of anti-platelet therapy demonstrate a
non-significant 19% reduction in the incidence of stroke, proving
oral anticoagulation (OAC; such as warfarin) to be far superior
(64% relative risk reduction) in stroke prevention. Recent guidelines
have been published by the European Society of Cardiology (ESC)
which focus on the most effective antithrombotic therapy in AF
and propose a new risk scoring system, the CHA2DS2-VASc score.
In our institution the prescription and documentation of antithrombotic therapy in AF has been the focus of a previous audit that
demonstrated poor compliance with the guidelines and documentation of decision making. The focus of this audit was twofold:
п¬Ѓrst to determine whether compliance with the guidelines and
documentation had improved and second determine the effect of
the new risk scoring system on prescription of OAC. A random
10% of cases of patients discharged with a coding diagnosis of AF
were selected (125 cases). They were risk assessed using the NICE
2006 stroke risk stratification, CHADS2 and CHA2DS2-VASc score.
In all cases the agent used for thromboprophylaxis was reviewed as
to whether NICE recommendations had been met. The scoring
systems were compared to identify patients in whom the ESC
guidelines would change treatment―ie, OAC instead of Aspirin or
as п¬Ѓrst line antithrombotic therapy. Of the 125 selected case notes
114 arrived in time for analysis; out of these 8 were excluded due to
erroneous coding as AF. 106 patients were risk stratified, of whom
68.22% (73) were high risk, 28.04% (30) moderate and 2.80% (3)
low risk according to NICE guidelines. 74.77% (80) scored 2 or
more points on the CHADS2 risk assessment―this number
increased to 93.46% (100) if CHA2DS2-VASc was applied, for
whom OAC would be the recommended antithrombotic therapy
(see Abstract 62 п¬Ѓgure 1). Only 57.50% or 61 patients were on the
appropriate choice of thromboprophylaxis if the NICE guideline
was used as risk assessment. 73.77% (45) of patients had no formal
documentation why NICE guideline had not been followed; this
mostly comprised patients who were on Aspirin but, correctly risk
assessed, were candidates for OAC. We extrapolate our п¬Ѓndings to
suggest that in an average sized DGH, 200 patients more per year
would be considered high thromboembolic risk and hence
appropriate for OAC. This audit shows that the rate of appropriate
anti-coagulation among patients with AF is still low and could
be improved further. The new ESC guidelines add to this
challenge as significantly more patients will be considered for
OAC therapy.
Heart June 2011 Vol 97 Suppl 1
63
IMPLICATIONS OF A LIKELIHOOD BASED APPROACH TO
DIAGNOSTIC TESTING IN CORONARY ARTERY DISEASE:
IMPACT OF THE NEW NICE GUIDELINES
doi:10.1136/heartjnl-2011-300198.63
I U Haq, J S Skinner, P C Adams. Royal Victoria Infirmary, Newcastle upon Tyne, UK
Background The NICE clinical guideline for chest pain of recent
onset (NCG 95) published in March 2010 recommends diagnosing
angina based on clinical assessment and likelihood of coronary
artery disease (CAD). If the estimated likelihood of CAD is 61%e
90%, coronary angiography should be offered. If 30%e60%, functional imaging should be offered, and if 10%e29%, CT calcium
scoring should be offered. We determined the number and types of
different investigations to diagnose coronary artery disease in
patients referred with suspected cardiac pain before the publication
of NCG 95 and compared this with the predicted investigations
after the application of the guidelines.
Methods Data was collected prospectively in a bespoke database
for patients referred to the Rapid Access Chest Pain Clinic,
Newcastle upon Tyne, UK. Patients with chest pain of suspected
cardiac origin were referred from primary care between February
2002 and March 2010. Patients with previous MI, PCI or CABG
were excluded. The analysis comprised 5598 men and women with
no past history of coronary disease. Likelihood of CAD was
calculated by the Pryor equation using the variables age, sex, type
of chest pain (typical or atypical), ECG Q waves, smoking,
hyperlipidaemia, diabetes and ST/T changes on ECG. The main
outcome measures were actual and predicted future frequency of
exercise tests, CT coronary angiograms, functional imaging tests
and invasive coronary angiograms by pretest likelihood of coronary
artery disease.
Results The proportion of the study population before and after the
guidelines undergoing exercise testing was 50.1% vs 0.0%; for
calcium score/CT coronary angiography 0.0% vs 14.7%; for functional imaging 25.6% vs 13.4%; and for invasive coronary angiography 15.3% vs 25.8%. The proportion not requiring further testing
was unchanged (30.0% vs 31.0%).
Conclusions Application of NICE CG95 will change the investigation of patients with chest pain substantially. A significant
reallocation of resources will be required. Exercise testing will be
replaced by anatomic or functional imaging. CT coronary angiography will play an important role and replace functional imaging in
some patients. Invasive angiography will take on a more important
role in the diagnosis of coronary artery disease. It will, however,
empower us to reassure almost a third of referrals that they do not
have angina on clinical assessment alone.
A39
BCS Abstracts 2011
64
DIAGNOSTIC ACCURACY OF EXERCISE STRESS TESTING IN
INDIVIDUALS WITHOUT KNOWN CORONARY ARTERY
DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS
doi:10.1136/heartjnl-2011-300198.64
1
2
2
2
A Banerjee, D Newman, A Van den Bruel, C Heneghan. 1West Midlands Deanery,
Birmingham, UK; 2Department of Primary Care, University of Oxford, Oxford, UK
Background Exercise stress testing offers a non-invasive, less
expensive way of risk stratification prior to coronary angiography,
and a negative stress test may actually avoid angiography.
However, previous meta-analyses have not included all exercise
test modalities, or patients without known coronary artery
disease.
Objectives To systematically review the literature to determine the
diagnostic accuracy of exercise stress testing for coronary artery
disease on angiography.
Search methods MEDLINE (January 1966eNovember 2009) and
EMBASE (1980e2009) databases were searched for articles on
diagnostic accuracy of exercise stress testing.
Selection criteria We included prospective studies comparing exercise stress testing with a reference standard of coronary angiography
in patients without known coronary artery disease. Results From
6055 records, we included 34 studies with 3352 participants.
Overall, we found published studies regarding п¬Ѓve different exercise
testing modalities: treadmill ECG, treadmill echo, bicycle ECG,
bicycle echo and myocardial perfusion imaging. The prevalence of
CAD ranged from 12% to 83%. Positive and negative likelihood
ratios of stress testing increased in low prevalence settings. Treadmill echo testing (LR+ Вј7.94) performed better than treadmill ECG
testing (LR+ 3.57) for ruling in CAD and ruling out CAD (echo LRГЂ
Вј0.19 vs ECG LRГЂ Вј0.38). Bicycle echo testing (LR+ Вј11.34)
performed better than treadmill echo testing (LR+ Вј7.94), which
outperformed both treadmill ECG and bicycle ECG. A positive
exercise test is more helpful in younger patients (LR+ Вј4.74) than
in older patients (LR+ Вј2.8).
Conclusions The diagnostic accuracy of exercise testing varies,
depending upon the age, sex and clinical characteristics of the
patient, prevalence of CAD, and modality of test used. Exercise
testing, whether by echocardiography or ECG, is more useful
at excluding CAD than confirming it. Clinicians have concentrated on individualising the treatment of CAD, but there is great
scope for individualising the diagnosis of CAD using exercise
testing.
Abstract 64 Figure 1
A40
Abstract 64 Figure 2
Probability of coronary artery disease.
Abstract 64 Figure 3
65
OUTCOMES AFTER CARDIAC SURGERY: ARE WOMEN OF
SOUTH ASIAN ORIGIN AT INCREASED RISK?
doi:10.1136/heartjnl-2011-300198.65
1
1
2
1
D A George, D Morrice, A M Nevill, M Bhabra. 1New Cross Hospital,
Wolverhampton, UK; 2University of Wolverhampton, Wolverhampton, UK
Objectives The population served by our centre has a relatively high
proportion of people originating from the Indian subcontinent
(“South Asians”) compared to the national average (14.3% vs 4.6%).
We observed that the mortality rate in South Asian women undergoing cardiac surgery in our unit appeared to be relatively high. We
investigated this observation further to determine whether ethnic
origin was an independent risk factor for postoperative death in
females.
Methods Data for all patients undergoing cardiac surgery were
collected prospectively in a registry. Retrospective analysis was
carried using SPSS on data for 4901 patients operated on in the 6year period April 2004 to March 2010. Categorical data associated
with mortality were analysed using c2 tests. Risk factors for inhospital mortality were subjected to univariate analysis, and those
found to be significant were tested for independence using multivariate logistic regression.
Results During the study period, 1160 female patients underwent
surgery with a mortality rate of 4.7%. Mortality in 113 South Asians
was 8.9% vs 4.3% in non-Asians (pВј0.03). Of 20 risk factors tested
with univariate analysis, 16 were significantly associated with
mortality. Logistic regression showed the following to be independent predictors of postoperative mortality: urgency of operation
(OR 32.0; p<0.001), older age (OR 24.2; p<0.001), preoperative
renal dysfunction (OR 15.8; p<0.001), diabetes (OR 7.8; pВј0.005),
South Asian ethnicity (OR 7.3; pВј0.007), extra-cardiac arteriopathy
(OR 4.8; pВј0.028), and an operation other than isolated CABG (OR
5.8; pВј0.016).
Conclusions In our population, South Asian ethnicity appears to be
an independent risk factor for mortality in females undergoing
cardiac surgery. Studies in larger populations are warranted.
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
66
ETHNIC DIFFERENCES IN CAROTID INTIMAL MEDIAL
THICKNESS AND CAROTID-FEMORAL PULSE WAVE
VELOCITY ARE PRESENT IN UK CHILDREN
doi:10.1136/heartjnl-2011-300198.66
1
1
2
2
P H Whincup, C M Nightingale, A Rapala, D Joysurry, 2M Prescott, 2A E Donald,
E Ellins, 1A Donin, 2S Masi, 1C G Owen, 1A R Rudnicka, 1D G Cook, 2J E Deanfield.
1
Division of Population Health Sciences, St George’s, University of London, London, UK;
2
Vascular Physiology Unit, Institute of Child Health, UCL, London, UK
2
Introduction There are marked ethnic differences in cardiovascular
disease risks in UK adults; South Asians have high risks of coronary
heart disease and stroke while black African-Caribbeans have high
risks of stroke and slightly low risks of coronary heart disease when
compared with white Europeans. Ethnic differences in cardiovascular risk factors are apparent in childhood, but little is known abut
ethnic differences in vascular structure and function during childhood. We set out to measure two vascular markers of cardiovascular
risk, common carotid intimal-medial thickness (cIMT) and carotidfemoral pulse wave velocity (PWV) in UK children from different
ethnic groups.
Methods We conducted a school-based study examining the cardiovascular risk profiles of 9e10 year-old UK children, including
similar numbers of South Asian, black African-Caribbean and white
European participants. Following a baseline cardiovascular risk
survey with measurements of body build, blood pressure, fasting
blood lipids, insulin and HbA1c, 1400 children were invited to have
measurements of cIMT (bilateral measurements were made with a
Zonare ultrasound scanner). A subgroup of these children (nВј900)
was also invited for PWV measurements, made with a Vicorder
device. All analyses were adjusted for age, gender and allowed for
clustering at school level.
Results In all, 939 children (67% response) had measurements of
cIMT and 631 children (70% response) had measurements of PWV.
Mean cIMT was 0.475 mm (SD 0.035 mm); mean PWV was 5.2 m/s
(SD 0.7 m/s). Compared with white European children, black
African-Caribbeans had higher cIMT (mean difference 0.014 mm,
95%CI 0.008 to 0.021 mm) and PWV (% difference 3.3, 95%CI 0.4 to
6.2); South Asian children had similar cIMT to white Europeans but
slightly higher PWV (% difference 2.7, 95%CI ГЂ0.1 to 5.5%). cIMT
was positively associated with systolic and diastolic blood pressure
but not with other cardiovascular risk markers. In contrast, PWV
was positively associated with adiposity, diastolic blood pressure
and insulin resistance. Black African-Caribbean children had lower
LDL-cholesterol levels and higher insulin and HbA1c levels than
white Europeans; South Asian children had higher insulin, HbA1c
and triglyceride levels. However, adjustment for these risk factors
had little effect on the ethnic differences in cIMT and PWV observed.
Conclusions Ethnic differences in cIMT and PWV, markers of longterm cardiovascular risk, are apparent in childhood. These differences
are not fully explained by the ethnic differences in established cardiovascular risk markers observed. The results suggest that there may be
important opportunities for prevention of cardiovascular disease
before adult life, particularly in high-risk ethnic minority groups.
reported at around 30% in many pivotal heart failure studies. DM is
an independent predictor of mortality in patients with HF, however
molecular mechanisms that contribute to HF development in the
diabetic population are poorly understood. Using a novel human
relevant mouse model of DM (GENA348), identified through the
MRC mouse mutagenesis programme with a point mutation in the
pancreatic glucokinase (GLK) gene we investigate the molecular
mechanisms that contribute to the HF phenotype in DM. GLK is
the glucose sensor which regulates insulin secretion and GLK
activity is reduced by 90% by the GENA348 point mutation
resulting in severe hyperglycaemia. Similar mutations underlie
Maturity Onset Diabetes of the Young Type 2 (MODY 2) in
humans. Mean random blood glucose was found to be increased in
the GENA348 mutant (HO) mice compared to wild type (WT)
littermates (WT 6.960.3 mmol/l vs HO 20.660.8 mmol/l,
p<0.001). Serial echocardiography was performed, at 3, 6 and
12 months. No significant changes in echocardiographic parameters
were observed at 3 months, although by 6 months development of
significant cardiac hypertrophy in HO mice was observed. At
12 months of age left ventricular dilatation was evident, characterised by an 8% increase in diastolic diameter (WT 4.0860.10 vs
HO 4.4160.12, p<0.05). Systolic function was preserved although
significant diastolic dysfunction was evident at 6 and 12 months
with a 31% reduction in the E:A ratio. Histological staining illustrated significant cellular hypertrophy with real time PCR data
demonstrating a relative 150% increase in the hypertrophic marker
BNP. Hypertrophic pathways were examined through western blot
analysis revealing an age dependant increase in Akt phosphorylation
(3 months- no increase, 6 months-140%, 12 months-460%). Serum
levels of advanced glycation end products (AGE) were also elevated
by 86% (WT 2163.5 ng/ml vs HO 3968.3 ng/ml, p<0.05) as was
the protein expression level of the receptor for AGEs (RAGE). In
vitro cellular experiments also revealed AGEs directly activate Akt
through phosphorylation and increase levels of the receptor RAGE.
AGE induced phosphorylation of Akt is inhibited in the presence of
wortmannin, suggesting a PI3K dependent signalling mechanism.
This was further confirmed in vivo where a bolus injection of
wortmannin in 6-month old mutant mice returned Akt phosphorylation levels to those seen in WT mice. In conclusion, using the п¬Ѓrst
human relevant mouse model of diabetes, GENA348 we demonstrate the development of a progressive cardiac phenotype including
cardiac hypertrophy, LV dilatation and diastolic dysfunction similar
to the clinical manifestations of diabetic cardiomyopathy. We
propose that the RAGE/PI3K/Akt pathway contributes to the
molecular mechanisms associated with the cardiac phenotype.
68
RARE ALLELES IN GENETIC PREDISPOSITION TO CORONARY
ARTERY DISEASE: INSIGHTS FROM THE NOVEL ANALYSIS
OF GENE-CENTRIC ARRAY
doi:10.1136/heartjnl-2011-300198.68
1
P Christofidou, 1R Debiec, 1C P Nelson, 1P S Braund, 1L D S Bloomer, 2S G Ball,
A J Balmforth, 2A S Hall, 1M Tomaszewski, 1N J Samani. 1University of Leicester,
Leicester, UK; 2University of Leeds, Leeds, UK
2
67
SPONTANEOUS CARDIAC HYPERTROPHY AND ADVERSE LV
REMODELLING IN A NOVEL HUMAN RELEVANT MOUSE
MODEL OF DIABETES; A MECHANISTIC INSIGHT
doi:10.1136/heartjnl-2011-300198.67
1
S M Gibbons, 1Z Hegab, 1M Zi, 1S Prehar, 1T M A Mohammed, 2R D Cox,
E J Cartwright, 1L Neyses, 1M A Mamas. 1University of Manchester, Manchester, UK;
2
MRC mammalian genetics unit, oxford, UK
1
Heart failure (HF) is one of the commonest cardiovascular complications of Diabetes Mellitus (DM) with the prevalence of DM
Heart June 2011 Vol 97 Suppl 1
Background Genome-wide association studies have been successful
in identifying association between several common variants and
coronary artery disease (CAD). However, collectively these variants
explain only a small proportion of CAD heritability. It is becoming
increasingly clear that the remainder of the “missing CAD heritability” could be explained by low frequency/rare alleles. Because of
the small number of observations for any given rare allele, the power
to detect its association with a phenotype is a major limiting factor
in genetic analysis. In this study we have undertaken a novel statistical approach that combines information from all low frequency
A41
BCS Abstracts 2011
(MAF<5%) SNPs at one locus in gene-centric analysis of CAD. We
hypothesised that patients with CAD will show over-representation
of rare alleles compared to controls.
Methods To examine associations between rare alleles and CAD, we
have used data from 2119 CAD cases and 2440 healthy controls
recruited to the Welcome Trust Case-Control Consortium
(WTCCC) Study. DNA from each subject was genotyped for
approximately 45 000 SNPs in more than 2000 genes/loci using 50K
IBC array (version 1). Association analysis was based on the
CCRaVAT (Case-Control Rare Variant Analysis Tool) algorithm that
maximises statistical power by combining all rare alleles within
defined regions into a single “super locus”. Differences in the
proportion of cases and controls carrying rare “super loci” were
tested by Pearson’s or Fisher’s exact test. Empirical p values were
generated by permuting case-control status a predefined number of
times and repeating the analysis for each replicate.
Results 5 candidate regions (MMP23B, VEGFA, DVL1, RIPK1,
LPAL2) showed an over-accumulation of rare alleles in patients with
CAD when compared to controls (FDR<50%). The number of
analysed rare alleles at each of these loci ranged from 4 to 42. The
most significant over-representation of rare variants were identified
at MMP23B (matrix metallopeptidase 23B gene; pВј1.3/104), a gene
previously unsuspected to play a major role in CAD and VEGFA
(vascular endothelial growth factor A; pВј2.6310ГЂ4). Only one of
the identified genes (LPAL2; p¼1.7310À3) lies within the locus that
was previously shown to harbour rare variants associated with
susceptibility to CAD.
Conclusions Rare alleles are associated with predisposition to CAD
and this gene-centric analysis combining information from lowfrequency variants of the same locus has a potential to uncover, at
least a proportion of, the “missing heritability” of CAD.
69
GENOME WIDE METHYLATION ANALYSIS IN CORONARY
ARTERY DISEASE
doi:10.1136/heartjnl-2011-300198.69
K J Dick, C P Nelson, P S Braund, A H Goodall, N J Samani. University of Leicester,
Leicester, UK
Background Using genome-wide association studies several genes
have been identified that affect the risk of CAD. However, these
genes only explain part of the heritability. There is increasing
evidence of the role of epigenetic regulation in complex diseases that
may explain part of the missing heritability. DNA methylation is an
important epigenetic change that regulates gene expression. Any
role of methylation in CAD is poorly understood. Therefore we
undertook an exploratory genome-wide screen to identify genes
differentially methylated in CAD cases and controls.
Methods We characterised DNA methylation in 24 CAD patients
with a documented history of MI and 24 matched controls from the
Cardiogenics case-control cohort. All subjects were male, ranging in
age from 40 to 57 years. For each subject, genomic DNA, isolated
from whole blood, was bisulphite converted and run on Illumina
HumanMethylation27 bead chips. The HumanMethylation27 chips
interrogate 27 578 CpG sites spanning 14 495 genes with an average
of 2 CpG sites per gene.
Results Global DNA methylation level was significantly higher in
cases compared to controls (p¼9.0310À4). Furthermore, 686 individual CpG sites, spanning 633 genes showed statistically significant
differences in methylation levels between cases and controls.
Significant signals after Bonferroni correction for multiple comparisons included GNAS (p¼7.94310À5), which is involved in receptormediated signal transduction, PCMT1 (p¼7.94310À5), ACD
(pВј3.48310ГЂ4 part of the telosome/shelterin complex), ATXN2 and
APOA1 (pВј5.6310ГЂ3 and pВј0.01). To explore the potential funcA42
tional importance of differences in methylation level in cases and
controls for individual genes, we examined the relationship of
methylation level to transcript level in monocytes and macrophages
on a gene by gene basis and identified several genes including GNAS
and PCMT1 that showed significant correlations between gene
expression and methylation. Pathway enrichment analysis of the
differentially methylated genes using the DAVID bioinformatics
resource identified a number of pathways that showed significant
enrichment
including
the
calcium
signalling
pathway
(pВј3.85310ГЂ7).
Conclusions This pilot study has shown several significant differences in gene methylation patterns between CAD cases and
controls. We also found a correlation between methylation level and
gene expression for a number of these genes. Genes differentially
methylated in CAD are significantly enriched for a number of
pathways including the calcium signalling pathway. While these
п¬Ѓndings require further validation they suggest that epigenetic
changes may play an important role in the pathogenesis of CAD.
70
GENE EXPRESSION AT THE 9p21 LOCUS AND CAD RISK
doi:10.1136/heartjnl-2011-300198.70
1
2
1
1
C P Nelson, P Lundmark, V Codd, A H Goodall, 2A C SyvaВЁnen, 1N J Samani.
Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital,
Leicester, UK; 2Department of Medical Sciences, Molecular Medicine, Science for Life
Laboratory, Uppsala University, Uppsala, Sweden
1
Background Human chromosome 9p21 harbours a locus that affects
risk of coronary artery disease (CAD) through an unknown mechanism. The variants at the locus most strongly associated with CAD
lie in non-coding regions suggesting that the affect on CAD risk may
be mediated through regulation of gene expression. We investigated
the association of single nucleotide polymorphisms (SNPs) across
the locus with expression of genes in the locus and compared this
with association of the same SNPs with CAD risk.
Methods We quantified transcript levels for CDKN2A, CDKN2B,
ARF and MTAP in circulating monocytes from 422 healthy blood
donors and 386 CAD cases and obtained genotypes for SNPs in the
9p21 region in the same subjects using genome-wide platforms. We
also quantified allelic expression (AE) for these genes and for ANRIL
in 186 of the healthy blood donors. We compared expression
quantitative trait loci (eQTL) associations for the genes with association п¬Ѓndings for the same SNPs for CAD in the Wellcome Trust
Case Control Consortium study.
Results In the global gene expression analysis, we found strong cis
eQTLs for both CDKN2B (pВј1.3310ГЂ38) and MTAP
(pВј6.6310ГЂ23), explaining 17.0% and 8.0% of the expression of
these genes. AE analysis confirmed these findings (CDKN2B,
p¼6.0310À64; MTAP, p¼1.4310À38) and also showed a significant
cis-eQTL effect on ANRIL expression (pВј3.5310ГЂ28). Interestingly,
the SNPs associated with CDKN2B and ANRIL expression were the
same. However, the SNPs showing e-QTL effects were distinct from
SNPs that showed an association with CAD risk (pВј2.2310ГЂ12).
Even in the region with a physical overlap of variants affecting
expression of CDKN2B/ANRIL and CAD risk, the effects of the
respective variants were independent of each other. Expression of
CDKN2A and ARF was low but did not show any obvious
eQTL effect, or differences according to genotype at CAD-associated
SNPs.
Conclusions Our п¬Ѓndings in monocytes do not support the
hypothesis that the chromosome 9p21 locus mediates CAD risk by
affecting expression of the genes at the locus. The mechanism by
which the chromosome 9p21 locus affects CAD risk requires further
elucidation.
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
71
A GENOME-WIDE ASSOCIATION STUDY IN INDIAN ASIANS
IDENTIFIES FOUR SUSCEPTIBILITY LOCI FOR TYPE-2
DIABETES
doi:10.1136/heartjnl-2011-300198.71
1,2
3
4
5
J Sehmi, D Salaheen, Y Yeo, W Zhang, 1,2D Das, 6M I McCarthy, 4E S Tai,
J Danesh, 1,2J Kooner, 2,7J Chambers. 1National Heart and Lung Institute, Imperial
College, London, UK; 2Ealing Hospital NHS Trust, London, UK; 3Department of Public
Health and Primary care, Cambridge University, Cambridge, UK; 4Department of
Medicine, National University of Singapore, Singapore; 5Department of Epidemiology
and biostatistics, Imperial College London, London, UK; 6Wellcome Trust for human
Genetics, Oxford University, Oxford, UK; 7Department of Epidemiology and biostatistics,
Imperial College London, London, UK
3
Background Type-2 diabetes (T2D) is a major risk factor for cardiovascular disease, and a leading causing of mortality worldwide.
T2D is 2e4 fold more common among Indian Asians than Europeans, and contributes to higher cardiovascular disease mortality in
Asians. Little is known of the genetic basis of T2D in Indian Asians.
Methods We carried out a genome-wide association (GWA) study of
T2D in 5561 Indian Asian cases and 14 458 controls from LOLIPOP,
PROMIS and SINDI cohorts. Whole genome scans were performed
using the Illumina 317 k or 610 k arrays. Further testing of suggestive SNPs was carried out in independent cohorts of Indian Asian
(12 K T2D cases and 25 K controls) and European ancestry
(DIAGRAM+, 8 K T2D cases and 39 K controls).
Results There were two novel loci associated with T2D at p<10ГЂ6,
and an additional 57 loci associated with T2D at p<10ГЂ4 in the
GWA study. We used results from DIAGRAM+ to prioritise 19 loci
for further testing in Indian Asians. In combined analysis of results
from GWA and further testing, four loci now reached genome-wide
significance (p<5310À8) among Indian Asians. Coding variant and
eQTL studies at these loci identify genes closely involved in insulin
secretion and signalling.
Conclusion We identify four novel genetic loci associated with T2D
in Indian Asians. Our observations provide new insights into the
biological mechanisms underlying T2D, a major risk factor for
cardiovascular disease.
72
sodium nitroprusside (NO donor) (100mM) from 24-h post fertilisation (hpf) until imaging at 4dpf.
Results Imaging of the developing trunk vasculature revealed that
vhl mutant embryos display excessive and aberrant angiogenesis
from 3dpf (Abstract 72 п¬Ѓgure 1A, B). Cardiac troponin T2 knockdown prevented any cardiac contraction, but embryos develop
normally due to passive oxygen diffusion. Loss of blood flow did not
alter normal intersegmental vessel patterning in either controls
(Abstract 72 п¬Ѓgure 1C) or vhl mutants (Abstract 72 п¬Ѓgure 1D).
However, loss of blood flow completely prevented excessive angiogenesis in vhl mutants (Abstract 72 figures 1D and 2), implying that
both blood flow and hypoxic signalling are required for “pathological” angiogenesis but not developmental angiogenesis (vasculogenesis). NO synthase inhibition with L-NAME had no effect,
suggesting that the contribution of flow to excessive angiogenesis in
response to upregulated hypoxic signalling is NO independent.
Abstract 72 Figure 1
ANGIOGENESIS IN RESPONSE TO UPREGULATED HYPOXIC
SIGNALLING IS DEPENDENT ON HAEMODYNAMIC FLOW
doi:10.1136/heartjnl-2011-300198.72
1
1
1
2
O J Watson, F J van Eeden, C Gray, T J A Chico. 1MRC Centre for Developmental
Biology and Genetics, University of Sheffield, Sheffield, UK; 2NIHR Cardiovascular
Biomedical Research Unit, Sheffield Teaching Hospitals NHS Foundation Trust,
Sheffield, UK
Introduction Hypoxia drives angiogenesis in a range of pathologies.
Mutations in von hippel lindau protein (vhl) lead to excessive
angiogenesis via upregulation of hypoxic signalling, due to impaired
HIF-1a degradation. Physical forces exerted by blood flow have been
shown to contribute to vascular remodelling. We therefore used vhl
mutant zebrafish to observe the interplay between hypoxic signalling, haemodynamic flow and vascular development. Since NO has
been shown to be both pro-angiogenic and released in response to
haemodynamic force, we assessed whether NO contributed to
angiogenesis in this model.
Methods Vhl mutant zebrafish were crossed with a fli1; GFP
transgenic that expresses Green Fluorescent Protein (GFP) in the
endothelium. Embryonic vascular development was observed in
mutants and wild type siblings by confocal microscopy. To determine the role of blood flow in the angiogenic response, cardiac
troponin t2 was knocked down by morpholino antisense injection.
To assess the contribution of nitric oxide, embryos were treated
with either L-NAME (nitric oxide synthase inhibitor) (1mM) or
Heart June 2011 Vol 97 Suppl 1
Abstract 72 Figure 2
length.
Effect of troponin T knockdown on total vessel
Conclusion Angiogenesis in response to hypoxic signalling is critically dependent upon haemodynamic force, compared with developmental vasculogenesis that can proceed in the absence of any
blood flow. This indicates a different mechanism of development for
hypoxia driven angiogenesis and vasculogenesis which may have
important therapeutic implications.
73
HERITABILITY OF CORONARY FLOW RESERVE
doi:10.1136/heartjnl-2011-300198.73
R Ahmed, P Muckett, S Cook. Clinical Sciences Centre, Imperial College, London, UK
Introduction Coronary flow reserve (CRF) is the ratio of peak coronary flow during maximal coronary artery dilatation to basal
A43
BCS Abstracts 2011
coronary flow and is an important predictor of coronary microvascular function. A variety of environmental stimuli have been
shown to affect CFR but little is known about the genetic
component of CFR. To characterise the genetics of CFR we initially
measured in vivo blood pressure (BP) and ex vivo cardiac phenotypes including CFR in two inbred rat strains, Brown Norway
(BN) and Spontaneously Hypertensive Rat (SHR) which is a
genetic model for hypertension and microvascular dysfunction. We
then studied BP and coronary flow (CF) phenotypes in F1 and F2
crosses derived from BN and SHR to estimate the heritability of
CFR and its relationship with BP.
Methods Animals were anaesthetized using a mixture of Oxygen and
Isoflurane. BP was measured invasively by cannulation of carotid
artery. Following BP measurement hearts were excised and rapidly
transferred to the ex vivo perfusion apparatus where retrograde
perfusion was established using the Langendorff technique. Hearts
were perfused with Carbogen buffered Kreb9 s solution and paced
constantly at 360 bpm. A fluid filled balloon was placed in the left
ventricular (LV) cavity to measure the pressure indices. CF, LV
developed pressure, myocardial contractility (LV dP/dtmax) and
myocardial relaxation (LV dP/dtmin) were recorded at baseline, during
peak hyperaemia, regional ischaemia (induced by ligation of the
proximal left anterior descending artery) and reperfusion.
Results 1) CFR differs significantly between the two inbred parental
rat strains. (BNВј2.1 6 0.32, SHRВј1.5 6 0.18, pВј2.6310ГЂ7, nВј16
each). 2) Heritability of CFR: Broad sense heritability (the proportion of total phenotypic variance attributable to total genetic
variance) for CFR is 62% indicating a large and previously unrecognised genetic component of CFR. 3) Relationship between CFR
and BP: We did not find statistically significant correlation between
CFR and BP in the F2 intercross (rВј0.11, pВј0.11, nВј176). 4) Relationship between CF and myocardial relaxation (LV dP/dtmin): LV
dP/dtmin correlated strongly with CF during all stages of the
experiment (baseline CF, rВјГЂ0.36, p<0.0001, reperfusion CF,
rВјГЂ0.40, p<0.0001).
Conclusions Our results demonstrate that CFR has a significant
genetic component and is largely independent of BP effects.
Furthermore we demonstrate a very significant relationship between
CF and LV dP/dtmin indicating a link between LV diastolic
dysfunction and impaired CF. Using 768 SNP genotyping assay for
linkage mapping and gene expression analysis with Affymetrix rat
gene chip, we will determine the quantitative trait loci and transcripts associated with CFR to improve our understanding of the
genomic architecture of CFR.
Abstract 73 Figure 1
A44
Coronary flow reserve.
Abstract 73 Figure 2
74
Correlation between BP and CFR.
MECHANISTIC STUDY FOR THE ROLE OF ADVANCED
GLYCATION END PRODUCTS IN THE DEVELOPMENT OF
DIABETIC HEART FAILURE
doi:10.1136/heartjnl-2011-300198.74
Z Hegab, T M A Mohammed, L Neyses, M Mamas. Manchester University,
Manchester, UK
Advanced glycation end products (AGEs) are thought to play a
crucial role in the development of diabetic complications including
heart failure, a leading cause of morbidity and mortality in diabetic
patients. However, the molecular mechanisms that underlie the
pathophysiological contribution of AGEs to heart failure development are not yet fully understood. We therefore investigated the
effects and mechanisms of action of AGEs on isolated neonatal rat
cardiomyocytes (NRCM). Standard molecular techniques were
applied. Western blot showed that RAGE receptor is expressed in
NRCM and adult mouse cardiomyocytes. Incubation of NRCM for
24 h with AGEs showed a dose dependant reduction of calcium
transient amplitude with a maximum of 52% at 1 g/l (p<0.01)
accompanied with 32% reduction in SR calcium content with no
significant changes in the protein expression of calcium handling
proteins. We demonstrated a 24% increase (p<0.01) in the production of reactive oxygen species ROS in AGE treated cardiomyocytes
mediated through increased NADPH oxidase activity (p<0.05).
Subsequent translocation of NF-KB, a transcriptional factor from
the cytoplasm to the nucleus together with increased NF-KB
activity resulted in a 56% increase in iNOS gene protein expression
(p<0.01), a downstream target of NF-KB. The latter was associated
with 10% increase in NO production (p<0.05) with subsequent
nitrosylation of the Ryanodine receptor shown through immunofluoresence. Changes in calcium transient were completely inhibited
when we incubated the cardiomyocytes with inhibitors of NADPH
oxidase, NOS or NF-KB prior to their incubation with AGEs. In
conclusion, AGEs directly decline cardiomyocytes function through
binding to their RAGE receptor leading to calcium handling
impairment through increased ROS production inducing activation
and translocation of NF-KB to the nucleus. The latter increased
transcription of iNOS with increased NO production. Coexistence
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
of ROS and NO favours the production of peroxynitrite that is
capable of nitrosylation of key cellular proteins such as the
Ryanodine receptor that has a crucial role in cardiac excitationcontraction coupling. This study provides novel insights into the
mechanisms of cardiac damage in diabetes that occur independent of
vascular disease through AGEs.
75
OPTIMISATION OF MEDICAL THERAPY AFTER CARDIAC
RESYNCHRONISATION: A NURSING OPPORTUNITY NOT TO
BE MISSED
doi:10.1136/heartjnl-2011-300198.75
1
S J Russell, 2J Bell, 3L Edmunds, 4J Davies, 3H Rose, 3Z R Yousef. 1Wales Heart
Research Institute, Cardiff, UK; 2Cardiff University, Cardiff, UK; 3University Hospital of
Wales, Cardiff, UK; 4University Hospital Llandough, Cardiff, UK
Introduction Cardiac resynchronisation therapy (CRT) is indicated in
patients with left ventricular dysfunction (EF#35%), electromechanical dyssynchrony, and limiting heart failure (HF) symptoms
despite optimal medical therapy. In many cases target doses of HF
medications prior to CRT are not achieved due to bradycardia and/or
limiting hypotension. CRT however provides bradycardia backup
and improved haemodynamics, thus providing an opportunity to
further optimise HF medical therapies known to confer substantial
morbidity and mortality benefits. We conducted the present study
to evaluate the potential to further optimise medical treatments in
patients receiving CRT within the framework of nurse-led pre and
post CRT clinics.
Methods Our unit operates an integrated CRT service with preassessment, implantation, and follow-up components. Pre-assessment and follow-up incorporate dedicated HF nurse clinics to
support protocol-driven optimisation of medical therapies. We
therefore conducted a retrospective analysis of our CRT database
over a 9-month period to quantify the frequency of use, and dose of
HF medications (bblockers; bB, angiotensin converting enzyme
inhibitors: ACE-I or angiotensin receptor blockers: ARB, aldosterone
antagonists, digoxin, and loop diuretics) before and 6 months after
CRT. Total daily dose equivalences within each class of medication
(bisoprolol for bB, lisinopril for ACE-I/ARB, spironolactone for
aldosterone antagonists, and frusemide for loop diuretics) and
titration protocols were based on National Institute of Clinical
Excellence guidelines for HF (guideline 5).
Results Between October 2009 and Jun 2010, 74 patients (age:
67611 yrs, 86% male) underwent implantation of a CRT device. All
Abstract 75 Table 1 Heart Failure nurse supervised use of medications
before and 6 months After CRT
Pre-CRT
Post-CRT
p Value
78%
88%
<0.01
b-Blocker: exemplar bisoprolol
Frequency of use
Daily dose equivalent
5.363.1 mg/day
ACE-I/ARB: exemplar lisinopril
Frequency of use
Daily dose equivalent
93%
11.864.5 mg/day
Aldosterone Antagonist: exemplar spironolactone
Frequency of use
32%
Daily dose equivalent
16.666.2 mg/day
Cardiac Glycoside: exemplar digoxin
Frequency of use
43%
Daily dose equivalent
83.8611.4 mg/day
Loop Diuretic: exemplar frusemide
Frequency of use
Daily dose equivalent
100%
63.065.8 mg/day
Heart June 2011 Vol 97 Suppl 1
6.963.2 mg/day
93%
12.463.8 mg/day
0.02
28%
0.32
15.567.3 mg/day
48%
<0.01
96.1613.6 mg/day
100%
48.168.4 mg/day
<0.01
patients attended the pre and post CRT nurse clinic to optimise
medical therapies and provide adjunctive HF support. Abstract 75
table 1 describes the frequency of use and daily dose equivalent of
each class of medication used in the patients prior to and 6 months
after device implantation. The frequency of bB and digoxin use
increased by 10% and 5% respectively. In addition, the dose of bB,
ACE-I/ARB, and digoxin significantly increased, while the dose of
loop diuretics significantly reduced in the 6 months after CRT
implantation.
Conclusions The beneficial haemodynamic and pacing profiles
provided by CRT offer important opportunities to further optimise
heart failure medications after device implantation. In a dedicated
nurse-led CRT follow-up clinic, we successfully initiated b blockers
and digoxin in previously naive patients, and significantly uptitrated
the doses of b blockers, ACE-I/ARB, and digoxin, while
significantly reducing loop diuretic use in the 6 months after device
implantation.
76
EXPANDING THE ROLE OF CARDIAC CARE UNIT NURSES TO
REDUCE TIME TO TREATMENT FOR PATIENTS REQUIRING
PRIMARY ANGIOPLASTY
doi:10.1136/heartjnl-2011-300198.76
S Young, G Pretsell, A Gibbins, G Dixon, A de Belder. Royal Sussex County Hospital,
Brighton, UK
Introduction In Brighton, UK, 24-h Primary Angioplasty has been
used for the treatment of ST segment elevation myocardial infarction (STEMI) since October 2008, with local patients being
admitted via the Accident and Emergency (A&E) department. With
the publication of the National Infarct Angioplasty project report
(DH 2008) it was evident that direct admission into the cardiac
catheter lab from the ambulance could further reduce time to
treatment. Call to Balloon time (CTBT) <150 mins is a nationally
recognised indicator measuring the time the patient п¬Ѓrst calls for
professional help (usually the ambulance) to the opening of the
coronary artery on the catheter lab Abstract 76 table 1.
Abstract 76 Table 1
% CTBT ВЈ150 mins
Median CTBT
Financial Year 2009e2010
59/78 76%*
125 mins
Quarter 1 (AprileJune 2010)
Quarter 2 (JulyeSeptember 2010)
32/36 89%
44/45 98%*
111 mins
99 mins
*pВј0.0013.
Methods The on-call cardiology team are non-resident out of hours.
It was therefore agreed the point of contact and immediate decision
making would lie with the Cardiac Care Unit (CCU) nurses. A
pathway was developed following consultation with the multidisciplinary team at an educational and mapping day, and risks were
addressed. It was agreed that the ambulance crew would telephone
the CCU nurse who would review the clinical history and the
telemetry ECG. They would then make the decision to activate the
catheter lab team. Patient Group Directions for the administration
of GTN, diamorphine, metoclopramide and clopidogrel were developed so that immediate treatment could be delivered by the CCU
nurse without medical prescription before the cardiac catheter lab
team arrived, if required. The nurses were trained in their use and
assessed as competent. Nurses were already competent in ECG
interpretation, defibrillation, cannulation and venepuncture.
Nursing documentation was developed to prioritise the patient9 s
emergency care. CTBT were monitored.
A45
BCS Abstracts 2011
Results Following the implementation of the direct entry pathway
in May 2010 the CTBT for all patients admitted direct to our
hospital have reduced. This is statistically significant when looking
at Quarter 2 results from baseline. Patient safety has not been
compromised. Patients who were admitted directly have been asked
about their experience and if anything could be done differently
from their perspective. They have said:
<
<
<
<
The process is quick which is good from their perspective
They are fully informed
The ambulance crews deal with them competently
The lab staff are waiting for their arrival.
Conclusions The CCU nurses have embraced this development and
expansion of their nursing practice, allowing major changes to be
made to the Primary Angioplasty pathway within the existing
infrastructure, despite the challenges of working within the
complex nature of traditional geographical referral patterns. Along
with the work of all members of the multi disciplinary team this has
significantly reduced times to treatment for patients.
77
Abstract 77 Table 1 Screening outcomes of 221 at risk subjects
identified from 64 index cases of hypertrophic cardiomyopathy
Number of Patients
New screening initiated (local heart muscle clinic)
52
New screening initiated (local paediatric clinic)
New screening initiated (out of area service)
19
6
Pre-existing screening in place
Personal preference (declined screening)
63
28
Awaiting response from subject (literature delivered)
Complex family relationships (unable to deliver literature)
19
14
Geographical/Logistical constraints
Subject deceased (non-hypertrophic cardiomyopathy)
10
3
Subject deceased (hypertrophic cardiomyopathy)
7
Conclusions Proactive screening for HCM can be effectively facilitated by cardio-genetic nurse services. Each new index case generates
3e4 at risk relatives who require long-term surveillance. Of 71
asymptomatic at risk subjects screened in our unit, we diagnosed 15
new cases of HCM, and 3 patients at high risk of sudden cardiac
death who subsequently received primary prevention defibrillator
implantation.
SCREENING FIRST DEGREE RELATIVES FOR HYPERTROPHIC
CARDIOMYOPATHY: 12-MONTH EXPERIENCE OF A CARDIOGENETICS NURSE SERVICE
doi:10.1136/heartjnl-2011-300198.77
1
2
2
1
1
1
S Finch, S Russell, D Kumar, Z R Yousef. University Hospital of Wales, Cardiff, UK;
Wales Heart Research Institute, Cardiff, UK
Introduction Hypertrophic cardiomyopathy (HCM) is an autosomally transmitted cardiomyopathy with an estimated gene prevalence of 1:500, and an important cause of sudden cardiac death.
Screening to identify at risk п¬Ѓrst degree relatives is therefore
recommended. The British Heart Foundation (BHF) recently funded
nine Nationwide cardio-genetic nurses to support local initiatives.
Our application for a nurse was successful and we present our
12-month experience of HCM screening.
Methods We mapped the course of patients with suspected HCM
referred to our tertiary heart muscle clinic which serves a population
of 1.4million. Following phenotype confirmation, a family tree and
contact details from the index case were recorded by the cardiogenetic nurse. The index case was given literature to pass onto at
risk relatives. The information pack included an open invitation
(referral via primary care) to attend for screening. For relatives
residing outside our catchment area screening was arranged via links
with the BHF cardio-genetic network and other health care
providers. Relatives domiciled outside UK were given our details
with offers to support screening. Throughout, strict adherence to
patient confidentiality was maintained.
Results Over 12 months, 64 index HCM cases presented to our
heart muscle clinic. Pedigree analysis identified 221 first degree
relatives at risk of carrying the HCM gene; mean index-to-at RR:
1-to-3.4 (range 0e14 subjects). Of the 221 at risk subjects, 71
(19 through paediatrics) have undergone screening through
clinical assessment at our unit with plans for long-term 2e5 yearly
follow-up in view of variable gene penetrance. Of the 71 screened
subjects, 15 were newly diagnosed with HCM. Newly diagnosed
HCM patients underwent further risk stratification for sudden
cardiac death; where we identified 3 patients at high risk ($2
conventional high sudden death risk factors). After appropriate
counselling, these 3 patients have received primary prevention
defibrillators. Despite our approach, 52 subjects remain unscreened
(Abstract 77 table 1), either due to complex family relationships
(nВј14), personal preference (nВј28) and/or geographical/logistical
reasons (nВј10).
A46
Abstract 77 Figure 1
78
FIRST YEAR EXPERIENCE OF A DEDICATED “RADIAL
LOUNGE” FOR PATIENTS UNDERGOING ELECTIVE
PERCUTANEOUS CORONARY PROCEDURES
doi:10.1136/heartjnl-2011-300198.78
S Brewster, R Weerackody, K Khimdas, A Little, N Cleary, A Penswick, M Rothman,
A Archbold. London Chest Hospital, London, UK
Introduction The potential to achieve safe early mobilisation and
same day discharge on a consistent basis after radial artery access
has provided us with the opportunity to make a step change in the
way we deliver elective care to patients undergoing percutaneous
coronary procedures. We designed a dedicated “radial lounge” to
accommodate patients before and after their procedure with the aim
of minimising the feeling of “hospitalisation” that accompanies
most encounters with health services. The lounge is a day case unit
that has no beds, only chairs, and televisions but no cardiac monitors. Patients remain in their clothes throughout their hospital visit.
Here we report our п¬Ѓrst year9 s experience of this facility. Methods:
The study population comprised all patients who attended the
radial lounge between July 2009eJune 2010 for coronary angiography or percutaneous coronary intervention (PCI). Patients were
suitable for the radial lounge if they were elective cases who had a
satisfactory radial pulse and no pre-procedure contraindication to
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
same day discharge. Patients were excluded if they had any of the
following: an unsuitable radial pulse, planned femoral access, prior
coronary artery bypass surgery, or the requirement for an overnight
hospital stay for planned complex/high risk PCI, renal impairment,
or social reasons. The п¬Ѓnal decision regarding route of arterial access
was left to the operator.
Results In the one year study period, 1548 patients were managed in
the radial lounge. 1109 patients underwent coronary angiography,
114 (10.2%) of whom also had a pressure wire or intravascular
ultrasound, and 439 underwent PCI. This represented approximately 88% of our unit9 s elective angiograms and 60% of our
elective PCIs. Among the patients who underwent angiography, 938
(84.5%) were performed radially and 1076 (97.0%) were discharged
from the radial lounge on the same day as their procedure. Among
the PCI patients, 359 (81.8%) were performed radially and 372
(84.7%) were discharged the same day. The PCI group included 326
(74.3%) patients who had a single vessel treated, 105 (23.9%) who
had two vessels or a bifurcation with a significant side branch
treated, and 8 (1.8%) patients who had three vessels treated. There
were no deaths or arrhythmias in the radial lounge. Requirement for
overnight admission was significantly more common after femoral
access compared with radial access for both angiography (4.1% vs
2.8%; p<0.05) and PCI (21.3% vs 14.2%; p<0.01).
Conclusions A dedicated radial lounge free of cardiac monitors is a
safe environment in which to manage most patients before and after
elective coronary angiography and PCI. The lack of monitoring
necessitates patient selection but this does not prevent the lounge
being suitable for the majority of elective patients. Femoral access is
associated with a significantly greater requirement for overnight
admission.
79
REMAINING CLOTHED FOR RADIAL DIAGNOSTIC
CORONARY ANGIOGRAPHY: AN IMPROVEMENT IN THE
PATIENT JOURNEY
doi:10.1136/heartjnl-2011-300198.79
S Eve, M Sinha, T A Wells. Salisbury District Hospital, Salisbury, UK
Background Patients undergoing invasive diagnostic coronary
angiography (DCA) for the п¬Ѓrst time often display high levels of
anxiety at the time of their procedure as they are unfamiliar with
the cardiac catheter laboratory set up. It is therefore part of the
cardiac catheter laboratory staff9 s role to reduce patient fears and
hence improve their journey through the cardiac catheter laboratory.
Several Cardiac centres have recently introduced radial lounges
whereby patients feel less “hospitalised” by not needing to undress
for their procedure.
Methods Following infection control approval, between mid-August
2010 and the end of October 2010, patients undergoing radial DCA
at Salisbury District Hospital were offered the option of remaining
clothed for their procedure. Each patient was given an information
leaflet included in which was explained possible downsides to being
dressed including if CPR were needed then clothes would be cut,
failure of radial access and the subsequent need for femoral access,
and the possibility of soiling the clothes with either blood or iodine.
The only caveat stated was that female patients were not allowed to
wear an underwire bra. Following their DCA, patients were then
asked to п¬Ѓll in an anonymous questionnaire in which they were
asked about their experience and whether not having to undress
made them feel more relaxed.
Results 57 consecutive patients underwent (DCA) during this time
period (100% uptake) with an average age of 68.1 6 9.6 years. 71%
were male and 21% (12/57) had undergone a DCA previously. Of
Heart June 2011 Vol 97 Suppl 1
these 12 patients 92% (11/12) stated that not having to undress was
a good idea while an identical number felt much more relaxed than
their previous DCA experience. Of the 45 patients that had not had
a previous DCA, 96% (43/45) stated that not having to undress was
a good idea while 96% (43/45) felt that this had made them feel very
relaxed during their pathway. The other two patients felt that it
made no difference. No patients required cross-over to femoral
access and there were no blood or iodine stains on any clothes.
Having patients remain dressed did not reduce fluoroscopic image
quality and there were no issues with infection.
Conclusion Offering patients the option of having their radial DCA
done without undressing is safe and helps to improve the patient
journey through the cardiac catheter laboratory by making them
feel more relaxed and less hospitalised. This is now standard at our
Institution.
80
PPCI: IS THERE A ROLE FOR THE ACS ANP?
doi:10.1136/heartjnl-2011-300198.80
V Oriolo, J Tagney. Bristol Heart Institute University Hospital Bristol NHS FT, Bristol, UK
Introduction Primary Percutaneous Coronary Intervention (PPCI) is
now considered the treatment of choice for patients experiencing ST
Elevation Myocardial Infarction (STEMI) (European Society of
Cardiology/European Association for Cardio-Thoracic Surgery
2010). One of the many benefits claimed is reduced length of stay
due to decreased morbidity (Zahn et al 2000, Kalla et al 2006). To
assess performance of one English PPCI 24/7 provider organisation
against the national average length of stay (LOS) for patients post
PPCI, a retrospective baseline audit was conducted. This demonstrated an average LOS of 4.4 days which is above the National
Infarct Angioplasty Project 2008 average LOS of 3 days. A 48 h nurse
led discharge (NLD) protocol was therefore developed and introduced by the acute coronary syndromes advanced nurse practitioner
to streamline the patient journey. This instructed the nurse and/or
physician to ensure appropriate investigation and documentation
was carried out in a timely manner to avoid unnecessary delays in
patient discharge.
Method Suitability criteria for the 48-h NLD protocol were established, which included: absence of acute complications (eg,:
bleeding, haemodynamic instability, ongoing chest pain, ejection
fraction <40%, respiratory compromise); appropriate support at
discharge. Following the baseline audit, data were electronically
collected prospectively for 5 months, measuring date of admission
to date of discharge to the usual place of residence. After 5 months
the audit was repeated to assess the average length of stay for
patients presenting with STEMI.
Result Between 1st April 2010 and 31st August 2010, a total of 274
patients were admitted with STEMI. Of these, 122 (45%) met the
NLD criteria and were discharged by the ACS ANP. The remaining
152 (55%) were discharged by the medical physicians. It was noted
that introduction of the protocol also facilitated a structured
approach to discharge for the medical team. The average LOS for all
PPCI patients (nВј274) decreased from 4.4 days to 3 days (30%). For
patients that were seen and discharged solely by the advanced nurse
practitioner (nВј122), the average LOS decreased from 4.4 days to
2.0 days (55%).
Conclusions/Implications In the current п¬Ѓnancial climate, a decrease
in LOS can have a significant impact on any organisational resources
thus increasing efficiency saving and patient throughput. This
demonstrates part of the added value the advanced nurse practitioner brings to patient care and to tertiary centres that provide a
24/7 PPCI service.
A47
BCS Abstracts 2011
Results As previously described apical rotation was reduced at rest
and on exercise Basal rotation was comparable at rest but significantly reduced on exercise in patients. The SD for four different
systolic peak motions (basal and apical rotation, longitudinal and
radial displacement) was comparable at rest but on exercise controls
showed a significantly reduced SD compared to patients showing a
greater ability to synchronise motions. Furthermore a ratio of
untwist during IVRT and longitudinal extension (Ratio Untwist
/Extension in IVRT) showed a significant deeper slope on exercise
for patients indicating a loss of synchrony in diastole, too. All results
are presented in Abstract 81 table 1.
PPCI NURSE LED DISCHARGE PROTOCOL
PPCI -REPERFUSION
TIME 0
CCU
12HRS
PATIENT STABLE*
(SYSTOLIC BP> 100 mmHg - NO NEW ECG CHANGES - PAIN FREE - SaO2>93%)
REG/SENIOR NURSE TO
BOOK ECHO & TRANSFER
TO WARD (IF APPLICABLE)
24 HRS
PATIENT STABLE * (AS ABOVE)
Abstract 81 Table 1
DEMONITOR +
ECHOCARDIOGRAM+
REHAB REFERRAL
EF≤ 39%
DR R/V
SCREEN FOR
ICD
36 HRS
PATIENT STABLE* (AS ABOVE)
EF≥ 40% & KILLIP I
ECHO PERFORMED?
Y
N
ARRANGE
ASAP
TTA’S, D/C LETTER,
MINAP, REHAB TO SEE
48 HRS
PATIENT STABLE* (AS ABOVE)
BLOODS, ECG, COPY OF
PROCEDURE,
VENFLON OUT, MINAP
TO BE SEEN BY
ACS NURSE/DR
HOME
Patients
Rest
Controls
Rest
Patients
p value Exercise
Apical Rotation (8)
9.964.4
13.464.0 <0.001 12.564.7 16.663.9 <0.001
Basal Rotation (8)
Twist (8)
ГЂ8.363.3 ГЂ8.063.4 0.676
18.065.7 21.064.9 0.01
SD Systolic Motions (ms) 48.6632.9 43.1625.3 0.38
Ratio Untwist/Extension 25.3651.4 7.1610.7 0.059
in IVRT (8/mm)
Controls
Exercise
p value
ГЂ7.763.2 ГЂ9.763.0 0.011
19.565.9 25.966.0 <0.001
40.1627.1 25.9615.5
9.6614.7 3.363.8
0.01
0.034
Conclusion Patients with HFNEF show a deterioration of basal
rotation and a systolic and diastolic three plane dyssynchrony
particularly on exercise. This might further contribute to the deterioration of early diastolic suction and therefore decrease stroke
volume on exercise. This might be a major contribution to their
symptoms.
IF PATIENT UNSTABLE AT ANY STAGE PLEASE D/W DR/ACS NURSE
82
Abstract 80 Figure 1
81
PPCI nurse LED discharge protocol.
DYSSYNCHRONOUS THREE PLANE MOTION AND IMPAIRED
LEFT VENTRICULAR TWIST IN PATIENTS WITH HEART
FAILURE AND NORMAL EJECTION FRACTION
doi:10.1136/heartjnl-2011-300198.81
1
2
3
3
Y T Tan, F W G Wenzelburger, F Leyva, J E Sanderson. 1Department of Cardiovascular Medicine, Birmingham, UK; 2Institute for Science and Technology in Medicine,
Keele University, Stoke on Trent, Keele, UK; 3Department of Cardiovascular Medicine,
University of Birmingham, Birmingham, UK
Background The pathophysiology of heart failure with normal
ejection fraction (HFNEF) is complex and not fully understood.
Recent publications showed a loss of apical rotation and longitudinal function particularly on exercise in these patients. Whether
a deterioration of basal rotation and a dyssynchrony of different
three plane motions on exercise might contribute to symptoms in
these patients is not known.
Method 72 Patients (age 7367 years, 48 female) with breathlessness
on exertion and normal EF (6067%) underwent cardiopulmonary
exercise test to rule out alternative clinical reasons (VO2max
18.464.9 ml/min/kg). Data were compared to 38 age-matched
control subjects (age 7167 years, 29 female, EF 6367%) with a
normal exercise tolerance (VO2max 28.665.1 ml/min/kg). All
underwent full Doppler 2D-echocardiography at rest and on supine
exercise. Echo images were analysed off-line. Apical and basal rotation, longitudinal and radial displacement were measured by speckle
tracking. Speckle tracking pictures and colour TDI curves were
loaded into custom made software. The software interpolated all
curves and calculated twist as the difference of rotation at apex and
at base. The software offered timing information to calculate SD
and time delays for different motions.
A48
MANAGEMENT OF ADVANCED HEART FAILURE IN THE UK:
TRENDS IN HEART TRANSPLANTATION AND MECHANICAL
CIRCULATORY SUPPORT
doi:10.1136/heartjnl-2011-300198.82
1
A Emin, 2C A Rogers, 3H L Thomas, 4S Tsui, 5S Schueler, 5G MacGowan, 6A Simon,
R S Bonser, 4J Parameshwar, 8N R Banner. 1Clinical Effectiveness Unit, The Royal
College of Surgeons of England, London, UK; 2Clinical Trials and Evaluation Unit,
University of Bristol, Bristol, UK; 3NHS Blood and Transplant, Bristol, UK; 4Cardiopulmonary Transplantation, Papworth Hospital NHS Foundation Trust, Cambridge, UK;
5
Cardiopulmonary Transplantation, Freeman Hospital, Newcastle, UK; 6Heart and Lung
Transplantation, Royal Brompton and Harefield NHS Trust, Middlesex, UK; 7Cardiopulmonary Transplantation, Queen Elizabeth Hospital, University of Birmingham,
Birmingham, UK; 8Royal Brompton and Harefield NHS Trust - on behalf of the UK VAD
Forum and UKCTA Steering Group, Middlesex, UK
7
Introduction Patients with advanced heart failure due to systolic
ventricular dysfunction require “pump replacement” therapy.
Previously, heart transplantation (HTx) met this need but waiting
times have increased due to shortage of donor hearts. Consequently,
more patients require a ventricular assist device (VAD) as a bridge to
transplant (BTT). We report UK activity, trends and outcome for
HTx and BTT VAD.
Methods Data were acquired from a comprehensive national database using 3 eras for analysis: E1: 5/2002e12/2004, E2: 1/2005e12/
2007 & E3: 1/2008e6/2010. Paediatric and multi-organ transplants
were excluded from the transplant cohort. Patients who received
prior short-term support (bridge to bridge) were excluded from the
VAD group.
Results 1278 patients were listed for HTx over the 3 eras: E1 155 per
year, E2 165 per year, E3 148 per year. The number of adult HTx fell
from 132 per year in E1 to 94 per year in E3. The median waiting
time for non-urgent HTx increased from 87 days in E1 (95%CI 55 to
119) to 321 days in E3 (95%CI 203 to 439) (p<0.001). 239 patients
needed left VAD support as BTT; 75 (31%) also received a right VAD.
Activity rose from 26 per year in E1 to 41 per year in E3. Device
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
choice has changed in favour of rotary pumps; 19%, 69% and 96%
for E1, E2 and E3 respectively. Median duration of VAD support
increased from 84 days (IQR 20e209) in E1 to 280 days (IQR
86e661) in E3 (p<0.01). Overall survival to 1 year after VAD
implant rose from 52.9% (95%CI 40 to 64) in E1 to 65.6% (95%CI 54
to 75) in E3 (pВј0.10). Of the 239 patients implanted, 83 (35%) have
undergone HTx, 52 (22%) are alive on VAD support & 84 (35%) died
on support. Twenty were explanted following myocardial recovery;
18 of these remain alive & 2 died. Survival after HTx for patients
with or without a pre-HTx VAD was 81.4% (95%CI 71 to 88) &
90.3% (95%CI 88 to 92) respectively at 30-days (p<0.01) and 80.0%
(95%CI 63 to 82) & 84.3% (95%CI 82 to 87) respectively at 1-year
(p<0.01). 1-year survival conditional on 30-day survival was similar
with & without a pre-HTx VAD (93% vs 91%, pВј0.48).
Conclusion Heart transplant activity has declined and waiting times
have become prolonged leading to an increased need for bridging to
transplantation. There has been a shift from volume displacement
VADs to rotary blood pumps and the duration of support has
increased. Post VAD survival has improved. While bridging appears to
increase mortality early after HTx, longer term survival is unaffected.
83
CLINICAL AND HAEMODYNAMIC STATUS BEYOND
3 MONTHS OF MECHANICAL SUPPORT WITH THE
HEARTWARE VENTRICULAR ASSIST DEVICE
doi:10.1136/heartjnl-2011-300198.83
B Gordon, A McDiarmid, N Robinson, N Wrightson, G Parry, S Schueler, G MacGowan.
Freeman hospital, Newcastle upon Tyne, UK
Introduction Limited data exist on the longer term clinical and
haemodynamic impact of the HeartWare left ventricular assist
device (HVADГ’) when used as a bridge to heart transplantation.
Patients who had a device longer than 3 months were reviewed.
Methods 26 patients had a HVAD implanted from 07/2009 to 07/
2010 (mean age 46.8 years, 18 male, 5174 total days of support).
Baseline and follow-up NYHA functional class, peak VO2 (bicycle
exercise), right heart haemodynamics, biochemistry and mortality
outcome were compared using paired t test. Results: 22/26 (85%)
patients survived beyond 3 months. 4 patients died before (mean
survival 40 days, 2 stroke and 2 multi-organ failure) and 2 died after
(mean survival 173 days, 1 stroke, 1 right heart failure) discharge
from hospital. 2 patients were transplanted (at 3 and 241 days after
implant) and 1 had recovery of LV function. Follow-up data is
available for 14/20 survivors (mean 197 days from implant).
Significant results are shown in the Abstract 83 table 1. There was
no significant change in peak VO2 (9.961.8 to 12.963.8, p¼0.08),
haemoglobin (12.761.7 to 12.161.2, pВј0.3) or creatinine (122641
to 105638, pВј0.19).
84
TREATMENT OF REFRACTORY RIGHT HEART FAILURE AFTER
IMPLANTATION OF A LEFT VENTRICULAR ASSIST DEVICE.
IS THE LEVITRONIX CENTRIMAG RIGHT HEART SUPPORT A
SOLUTION?
doi:10.1136/heartjnl-2011-300198.84
B Zych, A F Popov, A Barsan, M Hedger, R Hards, N R Banner, A R Simon. Royal
Brompton&Harefield NHS Foundation Trust, Harefield Hospital, Harefield, UK
Introduction Right heart failure after left Ventricular Assist Device
(LVAD) implantation is a severe complication, in extreme cases
necessitating additional mechanical assist. We present our institutional experience with the Levitronix CentriMag used for right
ventricular support commencing LVAD implantation with refractory right ventricular failure.
Material and Methods Between March 2001 and November 2010 109
patients underwent implantation of long term, total implantable,
continuous flow LVADs: 60 HeartMate II, 25 Jarvik 2000 and 24
HeartWare. All patients requiring right ventricular support were
included (nВј24), for which the Levitronix CentriMag continuous
flow, paracorporeal device was used. The analysis included patient
demographics as well as overall duration of support and outcome
parameters, including survival at 30, 90 days and 1 year.
Results 24 pts. underwent implantation, age 37.9613.7 years,
gender: M/F-15/9, underlying disease: dilated cardiomyopathy 22
(92%), peripartum cardiomyopathy 1(4%), viral myocarditis 1(4%).
Median duration of support: 28 days (5e146). 3(12.5%) pts. underwent heart transplantation (HTx) on RV support, 14(58.5%)
underwent RVAD explantation. Of these, 3 underwent successful
HTx, 4 recovered LV function and underwent successful LVAD
explantation, 3 remain on continuing LVAD support, 4 patients died
after RVAD explantation (post explantation day 1, months 3 and 4
and at 2 years), 7(29%) patients died during RV support. Median
ITU/hospital stay: 19.5 days (6e145)/78.5 days (10e219). 30-day/
90-day/1-year survival: 79%/71%/60%. 15(62.5%) patients were
discharged from hospital after treatment. Median survival after
procedure: 473.5 days (10e1917).
Conclusion Levitronix CentriMag right ventricular support is an
excellent option for post LVAD implantation treatment of refractory
RV failure. It allows either bridging to transplantation or RV function improvement and provides an acceptable rate of survival.
85
PREDICTION OF RESPONSE TO BIVENTRICULAR PACING
FROM DYSSYNCHRONY INDICES: THE ABSOLUTE LIMIT ON
PREDICTABILITY, AND ITS CLINICAL IMPLICATIONS
doi:10.1136/heartjnl-2011-300198.85
1
S S Nijjer, 2P Pabari, 3B Stegemann, 4V Palmieri, 5N Freemantle, 2A Hughes, 2D P Francis.
Imperial College Healthcare NHS Trust, London, UK; 2Imperial College London, London,
UK; 3Medtronic Bakken Research Center, Maastricht, The Netherlands; 4Ospedale dei
Pellegrini, Naples, Italy; 5University of Birmingham, Birmingham, UK
1
Abstract 83 Table 1
Parameter
Baseline
Follow-up
p Value
NYHA functional class
3.660.4
2.160.6
<0.001
Mean PA pressure (mm Hg)
Mean PW pressure (mm Hg)
3869
2565
2168
1065
<0.001
<0.001
Transpulmonary gradient (mm Hg)
Right atrial pressure (mm Hg)
1265
1166
963
564
0.02
0.006
PA oxygen saturation (%)
Cardiac Output (l/min)
5168
2.960.8
6667
4.360.9
Sodium (mmol/l)
13464
13963
0.003
<0.001
0.002
Conclusions The HVADÒ results in significant improvement in
functional class, right heart haemodynamics, cardiac output and
sodium levels beyond 3 months of therapy. Ongoing randomised
clinical trials will establish the long-term outcome of this device.
Heart June 2011 Vol 97 Suppl 1
Background It may be incorrect to believe that, with a good echocardiographic marker of mechanical dyssynchrony, response to
biventricular pacing (BVP) should be predictable with a high r2
value. Variability between repeat echocardiographic measurements,
and between successive dyssynchrony measurements, may reduce
r2. Both will mandatorily limit the achievable r2; we determine this
“contraction factor”.
Method and Results We compared correlation coefficients of dyssynchrony indices with response markers, in externally monitored
randomised controlled trials (EMRCTs) and highly skilled single
centre studies (HSSCSs). DLVEF in CRT recipients comprises true
CRT effect plus unpredictable spontaneous variability present in
control patients (Abstract 85 п¬Ѓgure 1, upper panel). The resultant
depression in r2 is calculated. HSSCSs overstate r2 between
A49
BCS Abstracts 2011
dyssynchrony and remodelling response in contrast to EMRCTs
(p<0.0000000001), whether response is LVEF (0.40 vs 0.01), ESV (0.26
vs 0.01); EDV (0.53 v 0.01). An “averaged” reported r2 between
differing dyssynchrony markers to commonly used echocardiographic
response markers is shown in Abstract 85 п¬Ѓgure 1, lower panel.
Abstract 85 Figure 1
EMRCT data shows maximal r2 between dyssynchrony and
DLVEF is 0.57 (DESV, 0.54; DEDV, 0.50). Dyssynchrony indices’ own
2
variability further contracts observable r values (by x0.68). The
overall ceiling to r2 is between dyssynchrony and DLVEF is 0.39
(DESV, 0.37; DEDV, 0.34). All EMRCT r2 values obey these statistical
limits; 29% of HSSCSs results do not.
Conclusions HSSCSs suggest dyssynchrony markers strongly predict
response to BVP but EMRCTs cannot confirm this. Natural variability forces observed correlation coefficients between dyssynchrony
and response to be low. EMRCTs, being less susceptible to publication
bias, reflect this reliably. Frequent citation (without verification in
independent cohorts) of the most exuberant values, from HSSCSs
creates mathematically unviable, unrealistic, expectations. Simply
searching for progressively more extreme correlations is therefore
misguided. Rationally, we should concentrate on improving testretest reproducibility of markers of dyssynchrony and of response.
86
HOW OFTEN IS IMPORTANT ADJUSTMENT OF PACING
INTERVALS REQUIRED FOR OPTIMAL RESPONSE
FOLLOWING CRT?
doi:10.1136/heartjnl-2011-300198.86
1
1
1
1
2
V Nayar, F Z Khan, A Rawling, L Ayers, M S Virdee, 2D Begley, 1D P Dutka,
P J Pugh. 1Addenbrooke’s Hospital, Cambridge, UK; 2Papworth Hospital, Cambridge,
UK
1
Introduction A significant minority of patients do not experience
clinical benefit following cardiac resynchronisation therapy (CRT).
Haemodynamically-guided adjustment of the intervals between
chambers paced (“optimisation” of atrio-ventricular (AV) and leftA50
right ventricular (VV) delays) may be undertaken to improve the
chance of response to CRT. However, data to support this approach
as standard management are lacking and many institutions
programme CRT devices to deliver “out-of-the-box” intervals, only
undertaking optimisation when clinical response is lacking. We
sought to determine how often the “out-of-the-box” settings are
optimal or acceptable and how often CRT optimisation results in
significant alteration of the pre-programmed pacing intervals.
Methods Data were collected from 180 consecutive patients who
underwent CRT followed by optimisation within 24 h. Optimisation was performed with serial adjustment of AV and VV
intervals. Haemodynamic assessment was undertaken using either
echocardiography or Non-Invasive Cardiac Output Measurement.
The optimal pacing intervals were considered to be those which
resulted in greatest acute augmentation of cardiac output and the
device was programmed accordingly. The п¬Ѓnal settings were
compared with the pre-programmed settings for that device and the
difference (AV or VV Adjustment) derived, taking into account the
preset paced or sensed AV delay. An AV or VV Adjustment of more
than 40 ms was considered to be clinically significant. Data are
presented as mean (SD).
Results Optimal AV delay ranged from 60 to 200 ms (mean 124 ms
(30)), VV delay ranged from 0 to 100 ms (mean 23 ms (19)). With
the pre-set pacing parameters, cardiac output was acutely
augmented by 13.1 (34)%. Optimised CRT produced further
improvement of cardiac output, to 24.9 (32)% augmentation. “Outof-the-box” settings were found to be optimal in 11 (6.1%), or
requiring only minor alteration in 120 (66.7%). A clinically significant alteration in AV delay was made in 40 (22.2%), in VV delay in
12 (6.7%) or in either parameter in 49 (27.2%).
Conclusions Significant adjustment of AV or VV delay is required in
over a quarter of patients receiving CRT. Optimisation of pacing
intervals provides augmentation of cardiac output over and above
the “out-of-the-box” settings. The findings suggest that optimisation
is an important component of resynchronisation therapy.
Abstract 86 Table 1
optimisation of CRT
0
Adjustment of pacing intervals following
1e20 mS 21e40 mS 41e60 mS 61e80 mS 81e100 mS
AV Adjustment 29 (16.1) 89 (49.4)
VV Adjustment 50 (27.6) 65 (35.9)
22 (12.2)
53 (29.3)
32 (17.8)
11 (6.1)
7 (3.9)
0
1 (0.6)
1 (0.6)
Data as N (%).
87
OPTIMISATION OF VV DELAY OF CRT IS MORE
REPRODUCIBLE USING PEAK VELOCITIES THAN USING
VELOCITY TIME INTEGRAL, AS WELL AS BEING QUICKER
doi:10.1136/heartjnl-2011-300198.87
P A Pabari, A Kyriacou, M Moraldo, C Manisty, A D Hughes, J Mayet, D P Francis.
Imperial College London, London, UK
Background It is not obvious which is a better echocardiographic
marker for optimisation of AV or VV delay: stroke distance (VTI) or
peak velocity. The biggest problem is genuine physiological variability between beats. Because optimisation of VV delay requires
detection of persistent changes in cardiac function (“signal”), which
may be small in relation to beat-to-beat variability (“noise”), we
should choose measurements with the best signal-to-noise ratio and
reproducibility. The standard echocardiographic method of choice
for VV delay optimisation is to maximise left ventricular outflow
tract velocity time integral (LVOT VTI). An alternative is peak
velocity instead of VTI as the parameter to be measured. But surely
VTI, which is encompassing and cumulating more data, is more
immune to disruption by spontaneous variability between beats,
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
and therefore simply using peak velocity might give a less reliable
optimum? Surely the time saved by using peak would have a price
to pay in poorer reproducibility of the optimum? In this study, we
evaluate whether peak velocity is a suitable alternative to VTI,
having regard to both time consumed and reproducibility. We also
examine whether averaging multiple replicate measurements
improves optimisation.
Methods & Results VV optimisation was performed on 40 subjects
with biventricular pacemakers using LVOT velocity (VTI or peak) as
the echocardiographic marker being maximised. Importantly, 6
successive replicate optimisations were performed per patient at a
single session. Scatter of apparent VV optimum between repeat
optimisations was threefold smaller for peak than VTI (p<0.03), with
a single measurement for each. Peak velocity had a higher intraclass
correlation coefficient (ICC) than VTI (0.66 vs 0.53, p¼0.003). Scatter
between replicate optimisations is reduced if, instead of single
measurements, we use pairs, or triplicates (ANOVA p<0.0001). This
benefit occurs with both peak and VTI (p<0.001 among each). Time
taken for acquisition and analysis of a single optimisation (6 settings)
was 17.5 s for peak and 57.5 s for VTI (p<0.0001).
Conclusions Doppler optimisation of VV delay using peak velocity
rather than VTI is (as expected) quicker but (surprisingly) more
accurate. Making replicate measurements further improves reproducibility. Perhaps guidelines should favour peak over VTI and
mandate multi-replicate averaging? These data suggest a rare
opportunity to reduce labour while increasing reliability of optimisation. Indeed, triplicate peak velocity assessment takes the same
amount of time as a single VTI, and identifies the VV optimum 3
times more confidently. While VTI measurement remains essential
for assessing stroke volume and cardiac output, for optimisation
purposes it comparison of peak velocity between different settings is
both faster and more reliable.
ments of left ventricular (LV) pulse pressure (systolic minus diastolic),
aortic flow velocity and myocardial oxygen consumption (MVO2) at
four settings: 3 AV delays during biventricular (BiV) pacing (reference
BiV-AV120 ms; BiV-AV40 ms; individualised haemodynamic BiVAVoptimum), and at intrinsic ventricular conduction (LBBB). Atrial
pacing at 100 bpm ensured a п¬Ѓxed heart rate.
Results LV pulse pressure rose from LBBB to BiV-AV120 ms by
1062% (p<0.001) and 261% more (p<0.05) at the haemodynamic
BiV-AVoptimum. At BiV-AV40 ms, pressure was 1062% worse than
BiV-AV120 ms (p<0.001), no different to LBBB (DВј0.860.4%,
p¼ns). Invasive aortic flow velocity, measured at a fixed position
throughout each individual’s study (ie, cardiac output index), rose
by 962% (p<0.01) from LBBB to BiV-AV120 ms, rising a further
361% (p<0.01) at BiV-AVoptimum. At BiV-AV40 ms, aortic flow
was, no different to LBBB (pВјNS). MVO2 increased from LBBB to
BiV-AV120 ms by 964% (pВј0.035) and to BiV-AVoptimum by
1263% (pВј0.002). MVO2 at At BiV-AV40 ms and LBBB was not
significantly different (D463%, p¼ns), The 4 pacing states lay on
a straight line: for Dpressure against Dflow, r¼0.99 (p<0.01),
Abstract 88 figure 1. Dexternal work (Dpressure 3Dflow) correlated
with D MVO2, r¼0.99 (p<0.01), with slope 1.6160.17, significantly
greater than 1.00 (p<0.05), Abstract 88 п¬Ѓgure 2.
Abstract 88 Figure 1 The correlation of LV pulse pressure and aortic
flow velocity during acute biventricular pacing, (at three AV delays) and
during LBBB, at a fixed heart rate.
Abstract 87 Figure 1
88
EVALUATION OF THE IMPACT OF AV DELAY VARIATION ON
THE ACUTE MECHANOENERGETIC EFFICIENCY OF CARDIAC
RESYNCHRONISATION THERAPY AND ASSESSMENT OF
PERFORMANCE OF NON-INVASIVE VS INVASIVE
HAEMODYNAMIC OPTIMISATION
doi:10.1136/heartjnl-2011-300198.88
A Kyriacou, P Pabari, K Willson, R Baruah, S Sayan, D W Davies, J Mayet, N S Peters,
P Kanagaratnam, Z Whinnett, D P Francis. International Centre for Circulatory Health,
London, UK
Background The impact of varying AV delay on the acute mechanoenergetic efficiency of cardiac resynchronisation therapy (CRT) is not
known; nor is known if non-invasive haemodynamic optimisation by
blood pressure agrees with invasive haemodynamic measures during
optimisation. We studied these invasively, in contemporary patients.
Methods Eleven patients with heart failure (EF 2968%) and left
bundle branch block (LBBB, QRS 154626 ms) underwent measureHeart June 2011 Vol 97 Suppl 1
Abstract 88 Figure 2 The correlation of cardiac work and myocardial
oxygen consumption during acute biventricular pacing, (at three AV
delays) and during LBBB, at a fixed heart rate.
A51
BCS Abstracts 2011
The correlations of optimal AV delays by non-invasive (Finometer) systolic blood pressure (SBP) vs invasive measures were as
follows; aortic SBP, r2¼0.96, p<0.01; aortic flow velocity, r2¼0.81,
p<0.01; LV dP/dtmax, r2Вј0.68, p<0.01.
Conclusions During acute biventricular pacing, at a п¬Ѓxed heart rate,
changing the AV delay affects the cardiac mechanoenergetics. When
an AV delay improves external cardiac work, compared to LBBB or a
physiologically too short AV delay (eg, AV 40 ms), it also increases
the myocardial oxygen consumption. However, only 1% more
energy is consumed per 1.6% more external work (pressure3flow)
done; as a result cardiac efficiency improves. Haemodynamic optimisation of AV delay can be achieved with high precision using non
invasive beat-to-beat pressure measurements. This should enable
routine haemodynamic optimisation (easily automated) of CRT
devices in clinical practice.
89
Abstract 89 Figure 1
ELECTROMECHANICAL INTERACTION IN PATIENTS
UNDERGOING CARDIAC RESYNCHRONISATION THERAPY:
COMPARISON OF INTRACARDIAC ACTIVATION MAPS AND
EARLY SEPTAL CONTRACTION IN LEFT BUNDLE BRANCH
BLOCK
doi:10.1136/heartjnl-2011-300198.89
1
S G Duckett, 2O Camara, 1M Ginks, 3J Bostock, 1P Chinchapatnam, 1M Sermesant,
A Pashaei, 3J S Gill, 3G Carr-White, 2A F Frangi, 1R S Razavi, 2B H Bijnens,
3
C A Rinaldi. 1Kings College London, London, UK; 2UPF, Barcelona, Spain; 3Guy’s and
St Thomas’ Hospital, London, UK
2
Abstract 89 Figure 2
Introduction Early inward motion and thickening/thinning of the
ventricular septum associated with left bundle branch block (LBBB)
is known as the septal flash (SF). Correction of SF corresponds with
CRT response. We hypothesise that electromechanical interactions
induced by SF are associated with functional changes in conductivity and a “U-shaped” activation pattern. Characterising the
spatio-temporal relationship between electrical and mechanical
events may explain why patients with a SF respond to CRT.
Methods 13 patients (63610 years, 10 men) with severe heart
failure (EF 22.865.8%) undergoing CRT underwent echocardiography and non-contact mapping (NCM) pre-implant. Presence and
extent of a SF was defined visually and with M-mode and fused
with NCM bull9 s eye plots of endocardial activation patterns. LV
dP/dtmax was measured during different pacing modes.
Results Five patients had a large SF, four small SF and four no SF.
Patients with large SF had areas of conduction block in noninfarcted regions whereas those with small or no SF did not
(Abstract 89 п¬Ѓgure 1). Patients with large SF had greater acute
response to left ventricular (LV) and biventricular (BIV) pacing vs
those with small/no SF (% increase dP/dt 28614% vs 11619% for
LV pacing and 42628% vs 22621% for BIV pacing). The lines of
conduction block disappeared after LV and BIV pacing, while
remaining present with RV pacing (Abstract 89 п¬Ѓgure 2). Abstract
89 п¬Ѓgure 1 Patient with a large SF. Unipolar isochronal map with
NCM electrograms showing fragmented signals (development of
split potentials) indicating a reduction of conduction and inability
to cross throughout the inferior region. The NCM mapping electrograms show the criteria used by Auricchio et al to define block,
with the emergence of R-wave, smallest and earliest at the superior
part of the block (where area of block begins) with largest negative
peak. Bold white arrows on the electrogram indicate how the electrical activation spreads superiorly in a U-shape pattern leading to
the development of split potentials. Abstract 89 п¬Ѓgure 2 Activation
maps of patient with a large SF. Row A, baseline with area of block
and late anterior breakthrough. Row B, RV pacing showing the area
of anterior block remains. Row C, BIV pacing. Functional conduction block has disappeared.
A52
Conclusion A strong interaction exists between electrical activation
and mechanical deformation of the septum. Correction of both
mechanical synchrony and the functional conduction block by CRT
may explain the large positive response in patients with a SF.
90
INVASIVE ACUTE HAEMODYNAMIC RESPONSE TO GUIDE
LV LEAD IMPLANTATION PREDICTS CHRONIC
REMODELLING IN PATIENTS UNDERGOING CARDIAC
RESYNCHRONISATION THERAPY
doi:10.1136/heartjnl-2011-300198.90
1
S G Duckett, 1M Ginks, 1A Shetty, 2J Bostock, 2J S Gill, 2S G Hamid, 2S Kapetanakis,
E Cunliffe, 1R S Razavi, 2G Carr-White, 2C A Rinaldi. 1Kings College London, London,
UK; 2Guy’s and St Thomas’ Hospital, London, UK
2
Introduction Cardiac resynchronisation therapy (CRT) reduces
mortality and morbidity in heart failure patients, however up to 30%
of patients do not derive symptomatic benefit. Higher proportions do
not remodel. Multi-centre trials have shown echocardiographic
techniques are poor at improving response rates. We hypothesised
that the degree of acute haemodynamic response (AHR) at implant
can predict which patients remodel. We evaluated the relationship
between AHR and reverse remodelling (RR) in CRT. Methods 33
patients undergoing CRT (21 dilated & 12 ischaemic cardiomyopathy) were studied. Left ventricular (LV) volumes were assessed pre
and post CRT. AHR (LV-dP/dtmax) was assessed at implant using a
pressure wire in the LV cavity. The LV lead was placed in potential
target veins and the largest percentage rise in LV-dP/dtmax from
baseline (AAI or RV pacing with atrial п¬Ѓbrillation) to DDDLV was
used to determine optimal LV lead position. RR was defined as
reduction in LV end systolic volume (ESV) $15% at 6 months.
Results LV-dP/dtmax increased significantly from baseline
(8016194 mm Hg/s to 9246203 mm Hg/s (p<0.001)) with
DDDLV pacing for the optimal LV lead position. There was a
significant difference in the percentage rise in LV-dP/dtmax between
the best and worst LV lead position (Abstract 90 п¬Ѓgure 1). LVESV
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
decreased from 186668 ml to 157668 ml (p<0.001). 18 (56%)
patients exhibited RR. There was a significant relationship between
percentage rise in LV-dP/dtmax and RR for DDDLV pacing
(p<0.001) (Abstract 90 п¬Ѓgure 2). A similar relationship for AHR and
RR in DCM and ICM (pВј0.01 & pВј0.006) was seen.
Abstract 90 Figure 1
CRT has not been investigated. Cardiovascular magnetic resonance
(CMR) is an important tool in the assessment of HF and is
considered the gold-standard in estimating RV function. We used
this technique to assess the impact of RV dysfunction on clinical
outcomes following CRT implantation.
Methods We evaluated 48 consecutive patients attending a heart
failure pacing clinic who had a CMR study within 6 months prior to
CRT implantation. Clinical, biochemical, ECG and imaging data
were collected. Biventricular function and myocardial scar were
assessed by CMR including gadolinium enhancement. The primary
end-point was a composite of all cause mortality (ACM) or
unplanned cardiovascular hospitalisation.
Results The mean age was 64.5612.7 years. HF was ischaemic in
42% of patients, and 85% were in NYHA class III/IV at the time of
implantation. Atrial fibrillation/flutter was found in 27% of
patients. The mean LVEF estimated by CMR was 2768%, while the
median RVEF was 52% (IQR 35%e63%). The mean tricuspid
annular plane systolic excursion (TAPSE) was 14.066.0 mm, and
the mean pulmonary artery pressure (on echocardiography) was 37
610 mm Hg. Ten patients (21%) met the primary end-point over a
mean follow-up of 28.6 months. On time-to-event analysis, only
atrial п¬Ѓbrillation (HR 4.8, pВј0.02) and RV dysfunction, ie, reduced
RVEF (HR 0.96 per 1% EF, pВј0.01) or TAPSE (HR 0.80 per mm,
p<0.01) were independent predictors of the primary end-point.
Atrial п¬Ѓbrillation and low RVEF were the only independent predictors of mortality (pВј0.03 and 0.04, respectively).
Conclusions RV dysfunction is an independent predictor of adverse
clinical outcomes following CRT. The assessment of RV function
may be considered in patient selection for CRT implantation.
92
IDENTIFYING PATIENTS WITH CHRONIC HEART FAILURE: A
COMPARISON OF THE GOLD STANDARDS FRAMEWORK
WITH A CLINICAL PROGNOSTIC MODEL
doi:10.1136/heartjnl-2011-300198.92
1
K K Haga, 2S A Murray, 3J Reid, 3A Ness, 3M O’Donnell, 4D Yellowlees, 5M A Denvir.
University of Edinburgh, School of Medicine and Veterinary Medicine, Edinburgh, UK;
2
Primary Palliative Care Research Group, University of Edinburgh, Edinburgh, UK;
3
Heart Failure Nursing Service, NHS Lothian, Edinburgh, UK; 4University of Edinburgh,
Edinburgh, UK; 5Department of Cardiology, University of Edinburgh, School of Medicine
and Veterinary Medicine, Edinburgh, UK
1
Abstract 90 Figure 2
Conclusions Acute haemodynamic response to LV pacing is useful
for predicting which patients are likely to remodel in response to
CRT both for DCM and ICM. There is much variation in the rise in
LV-dP/dtmax depending on LV lead position. Using acute haemodynamic response measured with a pressure wire during CRT
implant has the potential to guide LV lead positioning and improve
response rates in the future.
91
RIGHT VENTRICULAR DYSFUNCTION IDENTIFIES CLINICAL
OUTCOMES FOLLOWING CARDIAC RESYNCHRONISATION
THERAPY
doi:10.1136/heartjnl-2011-300198.91
1
K Guha, 2F Alpendurada, 2S Prasad, 2T McDonagh, 1M R Cowie, 2R Sharma. 1Royal
Brompton Hospital, Imperial College, London, UK; 2Royal Brompton Hospital, London,
UK
Background Cardiac resynchronisation therapy (CRT) is an established treatment for patients with advanced heart failure (HF).
However, a proportion of patients do not derive benefit post
implantation of CRT. Despite an established predictive role in HF,
the significance of RV dysfunction in gauging clinical benefit from
Heart June 2011 Vol 97 Suppl 1
Introduction Heart failure has a worse survival rate than many
common cancers, yet few patients receive any palliative care input
during the course of their illness. One of the main difficulties in
providing palliative care for heart failure patients is the uncertainty
around the course of the disease and the patient9 s life expectancy.
The aim of this study was to compare the “Gold Standards
Framework” (GSF) criteria, which were developed to determine the
need for palliative care in non-cancer patients, with the “Seattle
Heart Failure (SHF) Model”, which provides a method of calculating
a patient9 s predicted mean life expectancy using physiological variables.
Methods Chronic heart failure patients, in NYHA class III or IV,
who were being managed in the specialist, heart failure nursing
service, were identified from a clinical heart failure database. GSF
criteria were assessed by interviewing the specialist nurse responsible for each patient9 s care. Clinical data required for the SHF model
were obtained from two, online databases and were used to estimate
mean life expectancy and predicted mortality at 1 year. Patients
were then followed up, at 1 year, to evaluate; 1) all cause mortality,
2) place of death, and 3) the sensitivity and specificity of the GSF
and SHF to predict death at 1 year.
Results 138 NYHA III-IV patients were identified from a total of
368 patients currently managed within the specialist nurse service;
66% were male, and the mean age was 77 years. GSF criteria,
A53
BCS Abstracts 2011
identified 119/138 (86%) patients that met the minimum requirement for palliative care input. However, the SHF model predicted
that only 6/138 patients (4.3%) had a predicted life expectancy of
less than 1 year. Patients who met GSF criteria for palliative care had
significantly more hospital admissions (p¼0.001) and had significantly lower predicted survival rates at 1 year (p¼0.038) than those
patients that did not meet GSF criteria. At follow-up, 43/138
patients had died (31%). Of these, 58% (25/43) died in hospital,
following an acute admission. The sensitivity and specificity for the
GSF and SHF model were 22%/83% and 98%/12% respectively.
Overall, the patients renal function (eGFR<35 ml/min) was the best
predictor of mortality, (sensitivity/specificity¼82%/56%).
Discussion Neither the GSF nor the SHF were very accurate in
predicting which patients were in the last year of life, in this
selected sample. Despite the increasing drive towards palliation in
heart failure, clinicians are still faced with a substantial prognostic
barrier. Therefore, the progress of palliative care in heart failure
patients may require a shift away from the traditional “end of life”
model developed in cancer treatment, and focus instead on a
patient9 s increasing needs coupled with an understanding that
death, itself, may remain unpredictable.
93
OPTIMAL MEDICAL THERAPY IN HEART FAILURE: IS THERE
SPACE FOR ADDITIONAL HEART RATE CONTROL?
doi:10.1136/heartjnl-2011-300198.93
1
2
3
2
S Russell, M Oliver, H Rose, J Davies, H Llewellyn-Griffiths, 4A Raybould, 2V Sim,
3
Z R Yousef. 1Wales Heart Research Institute, Cardiff, UK; 2University Hospital Llandough, Cardiff, UK; 3University Hospital of Wales, Cardiff, UK; 4Hywel Dda Health
Board, Camarthen, UK
Abstract 93 Figure 1 Heart Failure Patients Potentially Suitable for
Additional Heart Rate Reduction After Optimisation of Standard Medical
Therapy.
Abstract 93 Table 1
Patient Characteristics (nВј172)
4
Introduction Current evidence suggests that heart rate (HR) may
serve both as a modifiable risk factor, and as a disease modifying
variable in patients with impaired left ventricular (LV) systolic
function. The systolic heart failure (HF) treatment with If inhibitor
ivabradine trial (SHIFT) for example recently demonstrated significantly improved outcomes in otherwise optimally treated HF
patients following additional HR reduction with ivabradine. We
therefore estimated the number of patients who after optimisation
of conventional HF medications may be suitable for additional HR
reduction.
Methods We performed a retrospective analysis from two HF clinics
where patients are referred for nurse lead, protocol-guided optimisation of conventional HF therapies. Data on patient demographics and classification of HF including; severity (ejection
fraction>35% vs ejection fraction#35%), functional limitation
(New York Heart Association; NYHA class), and cause (ischaemic vs
non-ischaemic) were recorded. In addition, we collected data on
patient’s resting pulse (absolute value and rhythm: sinus vs atrial
п¬Ѓbrillation), and blood pressure at the п¬Ѓrst and last clinic visits.
Between the two clinic visits, patients underwent protocol-guided
forced up-titration of standard neurohormonal HF therapies. We
also collected data on the maximal tolerated doses of beta blocker
(bB), ACE inhibitor (ACE-I) or angiotensin receptor blocker (ARB),
and the reasons for the inability to achieve target doses of bB.
Results Of 172 consecutive patients referred for optimisation of HF
therapies (age 71613 yrs, 67% male), 71 (41%) were in atrial п¬Ѓbrillation. Of the patients in sinus rhythm, 78% had severe LV systolic
dysfunction (Abstract 93 п¬Ѓgure 1). Overall, 145 of 172 patients
(83%) tolerated bB therapy; of these, 39% achieved the target
maximal dose, 57% at least half target dose, and 4% less than half of
the target dose of bB. Reasons for failure to initiate bB (nВј27, 17%)
included; severe and limiting hypotension (48%), intractable lethargy (26%), and hospitalisation with worsening airways disease
(26%). ACE-I/ARB, aldosterone antagonists, and digoxin were
A54
tolerated in 92%, 30%, and 18% of patients respectively (Abstract 93
table 1). Resting heart rate and blood pressure before and after
optimisation of medical therapy are shown in Abstract 93 table 2.
NYHA Class (%)
I
II
10.5
62.2
III
IV
26.2
1.1
HF aetiology (%)
Ischaemic
57
Non-ischaemic
LV function (%)
43
Ejection Fraction #35%
Ejection Fraction >35%
92.4
7.6
Cardiac rhythm (%)
Sinus
Atrial Fibrillation
58.7
41.3
Medication use (%)
b-blockers
83
ACE-I/ARBs
Aldosterone antagonists
92
30
Digoxin
18
Abstract 93 Table 2 Haemodynamic profiles before and after
optimisation of medication
First Clinic Visit
(pre-optimisation)
Final Clinic Visit
(post-optimisation)
p value
Resting Heart Rate (beats/min)
73.8614.8
67.369.5
<0.001
Systolic Blood Pressure (mm Hg)
Diastolic Blood Pressure (mm Hg)
120619.6
71.7611.6
115.1618.0
67.2610.4
<0.001
<0.001
Conclusions Of 172 unselected patients attending HF clinics for
optimisation of medical therapy, w50% are in sinus rhythm with an
ejection fraction #35%. Despite forced optimisation of medical
therapy, half of these patients have a resting heart rate $70 beats/
minute. Overall, w1 in every 3 patients attending a heart failure
clinic may be suitable for additional heart rate control.
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
94
A COMPARISON OF FUNCTIONAL AND
ECHOCARDIOGRAPHIC OUTCOMES IN NICE COMPLIANT
AND NON-COMPLIANT PATIENTS UNDERGOING CRT IN THE
REAL WORLD
doi:10.1136/heartjnl-2011-300198.94
1
S J Russell, 1I Rees, 2P O’Callaghan, 2Z R Yousef. 1Wales Heart Research Institute,
Cardiff, UK; 2University Hospital of Wales, Cardiff, UK
Introduction The National Institute for Clinical Excellence (NICE)
define a population of patients that are most likely to respond to
cardiac resynchronisation therapy (CRT) and have a favourable
health economic profile. Current NICE criteria (technology
appraisal; TA120) for CRT include: NYHA class III or IV symptoms
despite optimal medical therapy, sinus rhythm, ejection fraction
#35%, and either QRS duration >150 mS alone or 120e149 mS
together with echocardiographic (echo) evidence of mechanical
dyssynchrony. Several randomised clinical trials however have
consistently reported beneficial effects of CRT in patients outside
current NICE guidelines. In our centre, potential CRT patients are
discussed at a multi-disciplinary team (MDT) meeting attended by a
heart failure specialist, electrophysiologist, interventional cardiologist,
cardiac surgeon and hospital manager. CRT is offered where there is
consensus agreement that the individual patient is likely to benefit.
This individualised and evidence based approach provides for a
comparison of outcomes in NICE compliant (NICE:+ve) and NICE:
ГЂve patients (patients with a clinical need and evidence base
supporting CRT, but who do not meet NICE criteria).
Methods Our unit operates an integrated CRT service with preassessment, implantation, and follow-up components. Pre-assessment includes clinical evaluation and baseline echo (EF: ejection
fraction, and ESV: left ventricular end-systolic volume) and func-
tional characterisation: a) Minnesota quality of life score (QoL), b)
6 min walk test (6MWT), and c) peak oxygen consumption on
cardiopulmonary exercise test (VO2). Follow-up at 3 and 6 months
post CRT includes clinical evaluation, device/medical optimisation,
and reassessment of echo and functional outcomes. This study
involves a retrospective analysis of our CRT database and compares
outcomes in NICE:+ve and NICE: ГЂve patients.
Results Between January 2007 and December 2009, 253 patients
received CRT. Complete paired data comparing baseline and
6 month functional and echo data are available for 139 patients; 89
NICE:+ve and 50 NICE: ГЂve (Abstract 94 table 1). Exclusions for
the NICE: ГЂve patients included: atrial п¬Ѓbrillation (nВј19), QRS
120e149 mS without mechanical dyssynchrony (nВј12); QRS
<120 mS (nВј5); pacemaker upgrades (nВј9). An additional 5
patients with right bundle branch block and otherwise NICE CRT
compliance are analysed as NICE: ГЂve in this study. Compared to
baseline, 6-month outcomes were similar and significantly improved
in both NICE:+ve and NICE: ГЂve groups (Abstract 94 table 2).
Conclusions We observed significantly favourable and similar functional and echocardiographic responses to CRT in patients meeting
and not meeting current NICE criteria for CRT. Guidelines should
guide therapy but ultimately each therapy should be individualised
and evidence based.
95
IMPAIRED CARDIAC ENERGETICS IN DILATED
CARDIOMYOPATHY: MAGNETIC RESONANCE
SPECTROSCOPY AT 3T
doi:10.1136/heartjnl-2011-300198.95
1
2
2
2
R M Beadle, L K Williams, M Kuehl, S Bowater, 2K Abozguia, 2F Leyva Leon,
M P Frenneaux. 1University of Aberdeen, Aberdeen, UK; 2University of Birmingham,
Birmingham, UK
1
Abstract 94 Table 1
compliant patients
Characteristics of NICE compliant and nonNICE:+ve
NICE:Lve
Age: years (SD)
65 (11)
66 (11)
Male: %
83
90
Ejection fraction: % (SD)
QRS duration: mS (SD)
22 (7.1)
164 (26)
24 (7.2)
158 (37)
CRT-Defibrillator: %
57
46
Abstract 94 Table 2
patients
Outcomes in NICE compliant and noncompliant
NICE:+ve
(n[89)
QOL (score): baseline (SD)
p value
(baseline v NICE:Lve
6 months) (n[50)
58.2 (23.6)
p value
(baseline v
6 months)
63.5 (31.7)
QOL (score): 6 months (SD)
6MWT (m): baseline (SD)
40.1 (25.0) <0.001
216.4 (118.3)
38.9 (25.6) <0.001
208.5 (131.8)
6MWT (m): 6 months (SD)
V02 (ml/kg/min): baseline (SD)
324.5 (131.2) <0.001
13.2 (5.6)
291.5 (127.5) <0.01
12.3 (4.0)
V02 (ml/kg/min): 6 months (SD)
Ejection fraction- baseline (SD)
14.4 (3.3)
21.5 (7.1)
0.24
12.8 (4.2)
24.3 (7.2)
0.64
Ejection fraction- 6 months (SD)
End-systolic volumebaseline /ml (SD)
End-systolic volume6 months /ml (SD)
30.7 (10.4)
185.1 (79.3)
<0.001
31.4 (6.6)
177.2 (67.2)
<0.001
144.6 (73.5)
0.02
135.2 (57.2)
0.01
Heart June 2011 Vol 97 Suppl 1
Introduction The aim was to measure the cardiac phosphocreatine to
ATP (PCr/ATP) ratio non-invasively in patients with dilated cardiomyopathy and normal controls, and to correlate the patient’s
results to symptom status, ejection fraction (EF) and quality of life
scores. Dilated cardiomyopathy is known to be associated with
cardiac energy deficiency. Magnetic resonance spectroscopy (MRS)
has been proposed as a non-invasive method of assessing cardiac
energetics and as a method of measuring response to therapy.
Interrogation at high п¬Ѓeld strength improves signal to noise ratio.
Methods 32 patients and 22 control subjects were studied using
phosphorus-31 (31P) MRS and patients were classified to NYHA
symptom class. In vivo energetics were measured using a commercially available Philips Achieva 3 Tesla scanner and dedicated 31P coil
with ISIS volume selection. Java Magnetic Resonance User Interface
(jMRUI) was used for analysis. Furthermore, all patients completed
a Minnesota Living with Heart Failure (MLWHF) score and underwent echocardiography. LVEF was measured using biplane Simpson’s method.
Results The PCr/ATP ratio was significantly reduced in patients
(1.3560.31) compared with control subjects (1.9060.40; p<0.005).
The PCr/ATP ratio was correlated with NHYA class (rВјГЂ0.68,
nВј32, p<0.0005). No correlation was found with LVEF or MLWHF
score.
Conclusions This study confirms the presence of energy deficiency in
dilated cardiomyopathy as measured by MRS at 3T. The energy
status correlates strongly with symptom status but not with ejection fraction nor quality of life score. Cardiac energetic status is
directly proportional to symptoms status and therefore any treatments targeted to improve cardiac energetics may improve patient
symptoms in dilated cardiomyopathy.
A55
BCS Abstracts 2011
(1.1260.06). The single-visit RISE95 test incorporating incrementaland step- exercise phases, each to the volitional limit, was well
tolerated by CHF patients: The SE phase was contraindicated in only
3 of the 47 tests. The RISE95 detected VO2max in 14 of 21 patients
with a sensitivity of w10% (ie, similar to healthy subjects), and
without the need for secondary criteria or incidence of false-positive.
In contrast, the end-exercise RER was sensitive to both modality and
ramp rate and provided a false-positive for VO2max attainment in
every incidence. Therefore, the RISE95 protocol provides a robust
measure of VO2max in CHF patients, to within an individuallydefined CI without dependence on secondary criteria.
Abstract 95 Figure 1
97
INCREASING SKELETAL MUSCLE OXYGENATION BY PRIOR
MODERATE-INTENSITY EXERCISE INCREASES AEROBIC
ENERGY PROVISION IN CHRONIC HEART FAILURE
doi:10.1136/heartjnl-2011-300198.97
T S Bowen, D T Cannon, S R Murgatroyd, K K Witte, H B Rossiter. University of Leeds,
Leeds, UK
Abstract 95 Figure 2
96
A TEST TO CONFIRM MAXIMAL OXYGEN UPTAKE IN
CHRONIC HEART FAILURE PATIENTS WITHOUT THE NEED
FOR SECONDARY CRITERIA
doi:10.1136/heartjnl-2011-300198.96
T S Bowen, D T Cannon, G Begg, V Baliga, K K Witte, H B Rossiter. University of
Leeds, Leeds, UK
Cardiopulmonary exercise testing for peak oxygen uptake (VO2peak)
is widely used to evaluate severity, pathophysiology and prognosis in
patients with chronic heart failure (CHF). A VO2peak #14 (or 12 with
b-blocker) ml/kg/min is associated with increased mortality and is a
key criterion for cardiac transplant listing. A symptom-limited
exercise test, however, may elicit a VO2peak lower than the maximum
physiological limit (VO2max); the latter commonly “confirmed” using
the secondary criterion of respiratory exchange ratio (RER) >1.05.
RER, however, is sensitive to the test format. We, therefore, determined if a ramp-incremental (RI) step-exercise (SE) (or RISE) test
could determine VO2max in CHF patients without using RER, by
satisfying the criterion that two different work rates are terminated
at the same VO2peak. Twenty-one male CHF patients (NYHA class I:
n¼3, II: n¼16, and III: n¼1) initially performed a modified Bruce
treadmill test. Patients then completed a symptom-limited RISE95
cycle ergometer test in the format: RI (4e18 W/min; w10 min);
5-min recovery (10 W); SE (95% of peak RI work rate). Thirteen of
these patients also performed RISE95 tests using slow (RI 3e8 W/
min; w15 min) and fast (RI 10e30 W/min; w6 min) ramp rates.
VO2 and RER were measured breath-by-breath by a mass spectrometer and turbine (MSX, NSpire, UK). Peak VO2 and RER were
compared within-subjects, between RI and SE, by unpaired t test of
the п¬Ѓnal 12 breaths of exercise. This approach allowed VO2max and its
associated 95% confidence limits to be estimated. VO2peak was
similar (p>0.05) in treadmill and cycle exercise (mean6SD: 16.262.7
vs 15.063.2 ml/kg/min, nВј20, respectively), despite RER being
greater in cycling (1.0860.12 vs 1.1560.09; p<0.05). As a group,
VO2peak was similar (p>0.05) between RI and SE (mean6SD:
14.663.2 vs 14.963.2 ml/kg/min, nВј21). A within-subject comparison, however, revealed that the VO2max criterion was met in 14 of 21
patients (measurement sensitivity range 0.6e3.8 ml/kg/min),
despite RER being >1.05 in the remaining 7 (1.1660.09). There was
no effect of ramp rate on VO2peak (p>0.05), however RER was greater
(p<0.05) in the fast ramp (1.2460.09) compared to the slow
A56
Rapid adaptation of pulmonary oxygen uptake (VO2) at exercise
onset reduces the reliance on limited anaerobic energy stores and is
associated with increased exercise tolerance. These VO2 kinetics,
however, are slow in patients with chronic heart failure (CHF). This
could be due to limitations in the control of muscle O2 consumption
and/or O2 delivery. Recent evidence in CHF of a transient overshoot
in microvascular deoxygenation at exercise onset supports the latter.
As prior exercise is known to increase muscle blood flow in healthy
individuals, we examined whether it could attenuate the fall in
microvascular deoxygenation and speed VO2 kinetics on transition to
moderate exercise in CHF patients. Thirteen CHF patients (NYHA
class I: nВј3, II: nВј9, and III: nВј1) performed a ramp test on a cycle
ergometer for estimation of lactate threshold (LT) and VO2max.
Patients subsequently repeated two 6-min moderate-intensity exercise
transitions (bout 1, bout 2) from rest to 90%LT, separated by 6-min of
rest. Measurements included breath-by-breath VO2 using a turbine
and mass spectrometer (MSX, NSpire, UK), and tissue oxygenation
index (TOI) of the vastus lateralis by spatially resolved near-infrared
spectroscopy (NIRO200, Hamamatsu, Japan). The exponential timeconstant (s) for TOI and phase II VO2 were estimated using nonlinear least-squares regression. The sVO2/sTOI, or “kinetic index”,
was taken to reflect the relative matching of muscle oxygenation to
its instantaneous requirement. LT and VO2max were 9.961.7
(mean6SD) and 15.063.2 ml/kg/min, respectively. Prior exercise
increased resting TOI by 1063% (p<0.05), attenuated the transient
overshoot in muscle deoxygenation by w50% (p<0.05) and slowed
the rate of deoxygenation in the transient (sTOI: 1061 vs 21613 s;
p<0.05). Both sVO2 (46620 vs 39618 s; p<0.05) and the kinetic
index (4.561.8 vs 2.260.9; p<0.05) were reduced following prior
exercise. sVO2 was well correlated to the kinetic index (R2Вј0.92) in
bout 1. However, although a lower sVO2 was typically reflected in a
reduced kinetic index in bout 2, VO2 kinetics remained slowed in 4
patients. These patients had a higher NYHA class (2.360.5 vs
1.660.5; pВј0.06) and greater initial sVO2 (62617 vs 3369 s; p<0.05)
than the others. In CHF prior moderate-intensity exercise improved
the dynamic matching of muscle oxygenation to its instantaneous
requirement and speeded VO2 kinetics in all patients. This suggests
that slow VO2 kinetics in CHF are due, at least in part, to a dynamic
limitation in O2 delivery. However, this approach revealed an apparent limitation in the control of muscle O2 consumption in the most
severe patients, which was only partly ameliorated by improving O2
delivery. Nevertheless, these п¬Ѓndings suggest that an acute intervention to improve muscle oxygenation can increase aerobic energy
provision on transition to exercise in CHF patients.
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
98
HIGH PREVALENCE OF UNDIAGNOSED CARDIAC
DYSFUNCTION IN THE OLDEST OLD: FINDINGS FROM THE
NEWCASTLE 85+ STUDY
doi:10.1136/heartjnl-2011-300198.98
1
1
2
1
F Yousaf, J Collerton, A Kenny, T Kirkwood, 1C Jagger, 1A Kingston, 3B Keavney.
Institute of Ageing and Health, Newcastle University, Newcastle upon Tyne, UK;
2
Freeman Hospital, Newcastle upon Tyne, UK; 3Institute of Human Genetics,
Newcastle University, Newcastle upon Tyne, UK
1
Background Heart failure prevalence increases sharply at older ages.
The section of the population aged 85 and over represents the most
rapidly increasing demographic worldwide. Previous epidemiological
studies of ventricular dysfunction and heart failure have included
only small numbers of the “oldest old”, and have generally been
conducted in hospital-based settings, potentially introducing ascertainment biases. We conducted a community-based study of the
oldest old using domiciliary echocardiography to estimate the
prevalence of cardiac dysfunction and heart failure. Since in elderly
people with multiple comorbidities, heart failure may more
frequently be incorrectly diagnosed, we cross-referenced our п¬Ѓndings
to preceding diagnoses present in general practice records.
Methods Four hundred and twenty-seven individuals aged
86e89 years (mean age 87.9 years; 39.1% (nВј167) men, 60.9%
(nВј260) women) were visited in their usual place of residence. A full
cardiovascular and medical history, including current medication,
was taken; symptoms were graded using the NYHA classification.
Previous diagnoses of heart failure (HF) were abstracted from the GP
record. Participants underwent 2-D and Doppler echocardiography,
including tissue Doppler measurements of LV long axis velocities,
using a portable instrument (Vivid-I, GE Healthcare). LV systolic
and diastolic dysfunction were graded according to American
Society of Echocardiography guidelines.
Results LV systolic function could be quantified in 93.2% (n¼398)
participants and diastolic function (classified as normal, mild, moderate
or severe dysfunction) in 88.1% (nВј376). 37.2% of participants
(nВј140/376) had normal cardiac function or isolated mild diastolic
dysfunction; 19.6% (nВј78/398) had moderate or severe LV systolic
dysfunction, which was commoner in men (27.4%) than women
(14.5%); and 14.4% (nВј54/376) had isolated moderate or severe
diastolic dysfunction. 65.1% (278/427) of participants had valid data on
previous diagnosis of HF, NYHA class and echocardiographic assessment of cardiac dysfunction. Of these, 37.4% (104/278) had clinical
evidence of HF, which was defined as NYHA class II, III, or IV symptoms with underlying systolic dysfunction (29.5% (82/278)) or isolated
moderate or severe diastolic dysfunction (7.9% (22/278)) on echo. Only
7.6% (21/278) had a previous diagnosis of HF. 33.1% (nВј92/278) had no
previous diagnosis of HF but had clinical evidence of HF and an additional 21.6% (nВј60/278) had no previous diagnosis but evidence of
pre-clinical HF (NYHA class I with systolic or moderate/severe
diastolic dysfunction). Of those with a previous diagnosis of HF, 23.5%
(nВј5/21) had no echocardiographic evidence of cardiac dysfunction.
Conclusions Systolic and diastolic dysfunction and HF were
commoner in our population than previous studies in the “younger
old” have suggested. There are significant levels of both undiagnosed
and misdiagnosed HF in this age group.
99
warranting consideration for transplantation (Circulation 2010;
122:173). We examined whether this variable is a good indicator of
cardiac function in overweight heart failure (HF) patients.
Methods We compared the cardiopulmonary exercise performance
and non-invasive haemodynamics of overweight (BMI >34 kg/m2)
and non-overweight (BMI #30) male heart failure patients in
NYHA Classes II and III, with those of healthy male volunteers
with no known cardiovascular diseases (nВј101, age 43.2618.1
(SD) years, BMI 26.063.1) as controls. Their physical and cardiac
functional reserves were measured during treadmill exercise testing
with standard respiratory gas analyses and rebreathing method of
non-invasively measuring cardiac outputs during peak exercise.
Results Consecutive overweight HF were screened and 24 patients (age
4968(SD) years, BMI 44.966.8, NYHA 2.5060.50) managed to
exercise to acceptable cardiopulmonary limits (peak RERВј1.0160.12),
and achieved Vo2max of 16.864.6 mls/kg/min which was significantly
lower than controls (37.0610.7 mls/kg/min, p<10ГЂ6) and also lower
than those of 30 non-overweight HF counterparts (20.063.7 mls/kg/
min, pВј0.0019, age 49615 years, BMI 25.062.9, NYHA 2.4860.51).
As shown in Abstract 99 п¬Ѓgure 1, the overweight HF patients had
Vo2max values which distributed around the 14 mls/kg/min cut-off
value, and 9 of whom were indeed below this cut-off value. However,
the uncorrected Vo2max were higher than those of non-overweight
counterparts (Overweight: 25756748 vs 15946325 mls/min, p<10ГЂ6),
and its range of 1485e4210 mls/min overlapped with the range of
1244e5774 mls/min in controls. The peak cardiac power output
(CPOmax, 4.561.6 W, minimum 2.7 W) of overweight HF patients
were clearly above those of non-overweight (2.460.6 W, p<10ГЂ6,
Abstract 99 п¬Ѓgure 2) and all above the transplant cut-off value of 1.5 W.
Abstract 99 Figure 1
IS VO2MAX/KG A RELIABLE INDICATOR OF CARDIAC
DYSFUNCTION IN OVERWEIGHT HEART FAILURE
PATIENTS?
doi:10.1136/heartjnl-2011-300198.99
S Chinnappa, N Lewis, D Barker, L B Tan. Leeds Teaching Hospitals NHS Trust, Leeds,
UK
Background Peak O2 consumption (Vo2max) of #14 ml/kg/min has
been widely accepted as being indicative of poor cardiac function
Heart June 2011 Vol 97 Suppl 1
Abstract 99 Figure 2
A57
BCS Abstracts 2011
Conclusion These results indicate that in principle Vo2max in ml/kg/min
as an indirect indicator of cardiac function or for cardiac transplantation selection is unreliable when applied to overweight heart
failure patients. Extending this concept to the entire spectrum of
body weights, the practice of correcting Vo2max by body weight in
cardiological practice would also require urgent reconsideration.
100
PRESSURE VS FLOW AS A GUIDE FOR PACEMAKER
OPTIMISATION? THE ACUTE HAEMODYNAMIC EFFECTS OF
CHANGES TO ATRIOVENTRICULAR DELAY
doi:10.1136/heartjnl-2011-300198.100
C H Manisty, B Unsworth, R Baruah, P Pabari, Z I Whinnett, J Mayet, D P Francis.
Imperial College, St. Marys Hospital, London, UK
Background Non-invasive blood pressure monitoring by continuous
п¬Ѓnger photoplethysmography (Finometer) may have value in pacemaker
optimisation. However, the immediate increment in blood pressure
seems to diminish somewhat in the initial minute: it is unclear
whether this is due to an (undesirable) fall in stroke volume or a
(desirable) compensatory reduction in peripheral resistance.
Methods and Results We studied this question by measuring beat-bybeat stroke volume (flow) using Doppler echocardiography, and
blood pressure using continuous п¬Ѓnger photoplethysmography,
during and after atrioventricular delay adjustment from 40 to
120 ms in 19 subjects with cardiac pacemakers. Quintuplicate
experimental runs were performed. Blood pressure and stroke
volume (flow) both increased immediately (p<0.00001 within one
heartbeat). The immediate pressure increment correlated strongly
with the immediate flow increment (r¼0.74, p¼0.0001). Pressure
showed a partial decline a few seconds later (average rate 0.65 mm
Hg/beat, r¼e0.98, p<0.0001), in contrast, flow did not decline
(p¼NS), Abstract 100 figure 1. Signal-to-noise ratio was significantly
better for pressure than flow (6.363.6 vs 2.161.4, p<0.0001),
Abstract 100 п¬Ѓgure 2.
Conclusions Improving atrioventricular delay immediately increases
blood pressure; however this effect decays slightly over the subsequent minute. This is due to compensatory vasodilatation rather
than a reduction in cardiac function. Pressure changes are simpler to
measure and easier to distinguish from random variation than
Doppler measurements of flow, but are best measured immediately,
before the vascular compensation.
101
WHAT DEGREE OF PULMONARY HYPERTENSION
PREDICTS POOR OUTCOME IN PATIENTS WITH LEFT
VENTRICULAR SYSTOLIC DYSFUNCTION? A 10-YEAR
FOLLOW-UP STUDY
doi:10.1136/heartjnl-2011-300198.101
Abstract 100 Figure 1
1
B R Szwejkowski, 1D H J Elder, 1A M J Choy, 2S D Pringle, 1A D Struthers, 1C C Lang.
University of Dundee, Dundee, UK; 2Department of Cardiology, NHS Tayside, Dundee
1
Abstract 100 Figure 2
A58
Introduction The presence of pulmonary hypertension in left
ventricular systolic dysfunction (LVSD) is an ominous sign. It
remains unclear the level at which pulmonary hypertension conveys
a mortality risk in patients with LVSD.
Methods We performed a record-linkage study in Tayside, UK
(population approximately 400 000) utilising the Tayside echocardiogram database (>100 000 echo’s) maintained by the Health
Informatics Centre (HIC). Datasets from HIC include mortality
data and other health care activities linked anonymously by the
community health index (CHI) number. Patients were included in
the analysis if they had LVSD and had a right ventricular systolic
pressure (RVSP) measurement. Cox proportional hazards regression
analysis was used to examine the effects of different ranges of RVSP
measures on all cause mortality.
Results 2910 patients (mean age, 74.5611.4 years; 43 % male) met
entry criteria. Mean RVSP was 43.3 6 12.7 mm Hg and median
follow was 362 days (IQR 129e850 days). There was a significant
correlation between RVSP and survival (p<0.0001). In quartiles of
RVSP, the HR after adjustment for confounding factors including
LVSD and the presence of chronic obstructive pulmonary disease
(COPD) were: RVSP 35e41 mm Hg, HR 1.12 (95% CI 0.95 to 1.32,
pВј0.175), RVSP 42e50 mm Hg, 1.27 (1.07 to 1.49, p<0.001) and
RVSP 51e106 mm Hg 1.62 (1.38 to 1.1, p<0.001). For each 5 mm
Hg stepwise increase in RVSP the HR for all cause mortality was
1.07 (1.04 to 1.09, p<0.001). Abstract 101 п¬Ѓgure 1 shows the
Kaplan-Meier survival curves for all cause mortality for all patients
expressed as different RVSP quartiles.
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
glyceryltrinitrate- and sodium nitroprusside-mediated (endothelialindependent) response was observed between study groups. In
south Asian subjects, parameters of pulse wave velocity and
augmentation index did not differ between those with HF and those
in control groups. No ethnic differences were detected in pulse wave
velocity. Conclusion: South Asian patients with HF have impaired
micro- and macro-vascular endothelial function, but preserved
arterial elastic properties. Significant ethnic differences in endothelial function are present in patients with HF.
103
SENILE SYSTEMIC AMYLOIDOSIS: A COMMON CAUSE OF
HEART FAILURE IN THE ELDERLY?
doi:10.1136/heartjnl-2011-300198.103
Abstract 101 Figure 1
Survival of RVSP quartile.
Conclusion An RVSP of greater than 42 mm Hg is predictive of
increased mortality in heart failure. This is п¬Ѓnding is independent of
LVSD and COPD.
102
ETHNIC DIFFERENCES IN ENDOTHELIAL FUNCTION IN
CHRONIC HEART FAILURE
doi:10.1136/heartjnl-2011-300198.102
1
E Shantsila, 2P S Gill, 3G Y H Lip. 1University of Birmingham Centre for Cardiovascular
Sciences, City Hospital, Birmingham, UK; 2University of Birmingham, Primary Care and
Populational Sciences, Birmingham, UK; 3University of Birmingham Centre for Cardiovascular Science, Birmingham, UK
Background Endothelial dysfunction is characteristic of patients
with heart failure (HF) and is associated with an increased risk of
future cardiovascular events. However, data on ethnic differences in
endothelial function in HF are scarce. In this study we aimed to
compare parameters of macro- and micro-vascular endothelial
function and arterial elasticity in HF age- and sex-matched patients
of different ethnic origin: (i) white European, (ii) south Asian and
(iii) African-Caribbean. Additionally, SA patients with systolic HF
were compared to two matched control groups: (i) south Asian
patients with coronary artery disease without HF(disease controls)
and (ii) south Asian “healthy controls”.
Methods We recruited 186 age/sex-matched patients with HF (ejection
fraction <40%) of SA (nВј43, age 66.5611.1 years), white (nВј44, age
68.469.4 years) and African-Caribbean (nВј21, age 69.2610.3 years)
origin; as well as 36 disease controls (age 64.0610.6 years) and
40 healthy controls (nВј40, age 63.369.24 years). Macrovascular
endothelial function was assessed as brachial artery flow mediated
dilation in response to hyperaemia (FMD) and glyceryltrinitrate were
assessed by vascular ultrasonography (iE33, Philips, USA). Microvascular endothelial function was evaluated by laser Doppler flowmetry of forearm skin (DRT4, Moor Instruments, UK) after
iontophoresis of acetylcholine and sodium nitroprusside. Arterial
stiffness was quantified by pulse wave velocity and augmentation
index using (Sphygmocor, Australia).
Results Compared to disease controls and healthy controls south
Asian patients with HF had impaired microvascular response to
acetylcholine (3906302%, 5496264%, and 123695.5%, respectively,
p<0.05) and reduced FMD (7.1263.64%, 11.864.66%, and
4.8664.88%, respectively). HF patients of south Asian origin had
impaired microvascular endothelial function (response to
acetylcholine123695.5%) compared to white (258615.6%) and
African-Caribbean (286617.3%) groups (p>0.05). HF patients of
white origin had higher FMD than south Asian (4.8664.88%) and
African-Caribbean (5.3663.24%) patients (p<0.05). No difference in
Heart June 2011 Vol 97 Suppl 1
1
J H Pinney, 2H J Lachmann, 2J D Gillmore, 2A Wechalekar, 3S D J Gibbs,
P Sattianayagam, 4,5S M Banypersad, 6,7J Dungu, 3N Wassef, 3C A McCarthy,
3
P N Hawkins, 3C J Whelan. 1National Amyloidosis Centre and UCL Centre for
Nephrology, UCL Division of Medicine, Royal Free Hospital, London, UK; 2National
Amyloidosis Centre, UCL Division of Medicine, Royal Free Hospital, London, UK;
3
National Amyloidosis Centre, UCL Medical School, Royal Free Hospital, London, UK;
4
National Amyloidosis Centre, London, UK; 5The Heart Hospital, UCL Medical School,
London, UK; 6National Amyloidosis Centre, UCL Medical School, University of London,
London, UK; 7St George’s Hospital, University of London, London, UK
3
Senile systemic amyloidosis (SSA) is a rare cause of heart failure due
to the deposition of wildtype transthyretin. The clinical features
and outcome are ill defined; our aim was to evaluate the natural
history of the disease in the UK in a group of thoroughly characterised patients. The series included all cases of biopsy proven
transthyretin (TTR) amyloidosis with wildtype TTR gene
sequencing who were prospectively followed up between January
2001 and May 2010. Clinical, biochemical, ECG and echocardiographic evaluation were performed at presentation to our centre.
Patient survival was estimated using KaplaneMeier analysis. 55
patients with histologically proven SSA; 36 (65.5%) from cardiac, 14
(25.4%) from GI tract, 3 (5.5%) from bladder, 1 (1.8%) from fat and
1 (1.8%) from carpal tunnel tissue were identified. 49 (89%) were
male. The median age at diagnosis and death were 74 (range 66e89)
and 79 (range 69e84) years respectively. Survival from symptom
onset and diagnosis was 7.04 (range 0.54e8.41) and 4.58 (range
0.07e5.41) years respectively. In recent years more patients have
been diagnosed with 2 (3.6%), 14 (25.5%) and 39 (70.9%) patients
between 2001e2003, 2004e2006 and 2007e2009 respectively. The
most common presentation was with breathlessness in 28 patients
(51%). Twenty-four patients (43.6%) had prior carpal tunnel operations. Twelve (21.8%) patients had a history of ischaemic heart
disease. Fifteen had had a coronary angiogram; 8 were reportedly
normal and 7 required intervention. Arrhythmias were common, 20
patients (36.3%) had a history of atrial п¬Ѓbrillation and 6 (10.9) had
pacemakers in situ. ECG п¬Ѓndings were; 24 (43.6%) in AF, 6 (10.9%)
п¬Ѓrst degree block, 10 (18.2%) left bundle and 6 (10.9%) right bundle
branch block, 27 (49%) Twave changes, 11 (20%) <5 mm complexes
in all inferior leads. Echocardiographic п¬Ѓndings revealed the median
IVSd was 1.7 (range 1.1e2.5) cm, median E/A ratio was 2.7 (range
0.79e5.4), E/E9 15.81 (range 7.5e41.1) and ejection fraction was
45.5 (range 13e83)%. Blood results showed; the median baseline
NT-proBNP was 356.1 (range 5e2611) and troponin T 0.03 (range
0.01e0.28). Twenty-п¬Ѓve patients had a troponin T >0.03 (45%). Ten
patients (18%) had a detectable paraprotein and 2 (3.6%) had bence
jones proteins. SSA is present in >25% of the very elderly at post
mortem but was rarely diagnosed during life. It is becoming more
frequently recognised perhaps due to widespread use of cardiac MRI.
Most patients are male but women can be affected. A history of
carpal tunnel syndrome is common. The diagnosis is often made
after the onset of breathlessness. Systolic and diastolic dysfunction
A59
BCS Abstracts 2011
can be seen on echocardiogram. A positive troponin is a common
п¬Ѓnding with a subsequent normal coronary angiogram. Incidental
paraproteins are prevalent in up to 8% of this population and it is
important to obtain a tissue diagnosis to rule out AL amyloidosis.
With supportive management medium term outcomes are good.
104
PROGNOSTIC UTILITY OF CALCULATED PLASMA VOLUME
STATUS IN CHRONIC HEART FAILURE
doi:10.1136/heartjnl-2011-300198.104
1
H Z Ling, 1N Aung, 1,2J Flint, 1,2S Aggarwal, 1,2S Weissert, 1,2A Cheng, 3D P Francis,
J Mayet, 1,2M Thomas, 1,2S Woldman, 1,2,4D O Okonko. 1University College London
Hospital, London, UK; 2The Heart Hospital, London, UK; 3International Center for
Circulatory Health, NHLI, Imperial College London, London, UK; 4NHLI Imperial College
London, London, UK
3
Background Plasma volume (PV) expansion is a hallmark feature of
worsening heart failure that is notoriously underestimated by clinical examination. While radioisotope assays optimally quantify PV
status, numerous haemodialysis-based equations also exist for its
estimation. The prognostic utility of such formulas in chronic heart
failure (CHF) is unknown.
Methods We analysed the relation between estimated PV status and
mortality in 246 outpatients with CHF (mean (6SD) age 67613 years,
NYHA class 261, LVEF 2868%). PV status was calculated (Hakim
RM, et al) by subtracting the patients actual PV ((1-haematocrit) 3
(a + (b 3 weight)); a and b are gender-specific constants) from their
ideal PV ((c 3 weight); c¼gender-specific constant).
Results Median (6IQR) PV status wasd2616550 ml with 78% and
21% of patients having PV contraction and expansion, respectively.
Patients with PV excess had significantly higher creatinine and lower
albumin levels. Over a median follow-up of 13616 months, 36 (15%)
patients died. PV status predicted mortality (HR 1.001, 95% CI 1.001
to 1.002, pВј0.001) in a graded fashion (Abstract 104 п¬Ѓgure 1A) and did
so independently of NYHA class, LVEF, weight, haematocrit and
creatinine. A PV status #ГЂ178 ml optimally predicted survival (ROC
AUC 0.68, pВј0.0007) and conferred a 75% reduced hazard for death
(HR 0.16, 95% CI 0.07 to 0.37, p<0.0001, Abstract 104 п¬Ѓgure 1B).
2
Department of Respiratory Medicine, York Hospitals NHS Foundation Trust, York, UK;
Department of Echocardiography, York Hospitals NHS Foundation Trust, York, UK;
4
Department of Biochemistry, York Hospitals NHS Foundation Trust, York, UK; 5Leeds
Teaching Hospitals, Leeds, UK; 6Department of Cardiology, York Hospitals NHS
Foundation Trust, York, UK
3
Background Brain natriuretic peptides have been shown to be
reliable indicators of left ventricular failure and markers of risk in
cardiac disease. However, patients with chronic obstructive
pulmonary disease (COPD) are also known to have elevated
concentrations of brain natriuretic peptides in the absence of overt
cardiac disease, likely due to right ventricular strain. This has been
shown to have prognostic value and has a potential role in the
management of the condition; for example, it has been suggested
that it could be used to guide the initiation of non-invasive
ventilation. The aim of this study was to identify clinical and
echocardiographic determinants of the polypeptide N-terminal proBrain Natriuretic Peptide (NT pro-BNP) in patients with stable
COPD.
Method Arterial blood gases, plasma NT pro-BNP and transthoracic
echocardiographic parameters were studied in 140 patients with
stable COPD attending a respiratory outpatient clinic.
Results Of the 140 patients, 65 (46%) were male, 26 (19%) received
home oxygen therapy, 115 (82%) were current smokers, 38 (27%)
were prescribed diuretics and 15 (11%) had a left ventricular ejection
fraction <45%. Patients with cor pulmonale (nВј6) were more likely
to have left ventricular systolic dysfunction (p<0.001), reduced
tricuspid annular plane systolic excursion (pВј0.017) and higher
pulmonary artery systolic pressures (pВј0.01). The median (IQR)
NT pro-BNP concentration was 16.2 (25.4) pmol/l. Concentrations
were significantly higher in those with a dilated left atrium, aortic
stenosis, left ventricular systolic dysfunction, right ventricular
impairment, atrial п¬Ѓbrillation and those prescribed diuretics and
ACE inhibitors. Significant predictors of NT pro-BNP were a dilated
left atrium, aortic stenosis and left ventricular systolic dysfunction.
NT Pro-BNP was an excellent discriminator of RV impairment (C
statisticВј0.90).
Conclusions NT pro-BNP readily identifies patients with stable
COPD who have right ventricular dysfunction. However, several
other clinical variables also associated with increased NT pro-BNP
concentrations are prevalent in this population. This is likely to
confound clinical decision making.
106
CHF PATIENTS ARE VITAMIN D DEFICIENT AND
HYPERPARATHYROID, WITH LEVELS OF EACH RELATED TO
MARKERS OF SEVERITY
doi:10.1136/heartjnl-2011-300198.106
Abstract 104 Figure 1
1
Conclusions Calculating plasma volume status in CHF patients
appears prognostically useful and suggests that dehydration is better
tolerated than volume excess in these individuals and that targeting
therapy to achieve a plasma volume status #178 ml might increment survival.
105
CLINICAL AND ECHOCARDIOGRAPHIC DETERMINANTS OF
N-TERMINAL PRO B-TYPE NATRIURETIC PEPTIDE LEVEL IN
PATIENTS WITH STABLE CHRONIC OBSTRUCTIVE AIRWAYS
DISEASE: A PROSPECTIVE OBSERVATIONAL STUDY OF 140
PATIENTS
doi:10.1136/heartjnl-2011-300198.105
1
6
C P Gale, J White, A Hunter, J Owen, J Watson, 5I R Pearson, 4I Holbrook,
N Durham, 6M Pye. 1Division of Biostatistics, University of Leeds, Leeds, UK;
A60
2
2
3
4
G A Begg, 1L Kearney, 2A C Wheatcroft, 1R Byrom, 1S Barnes, 1J Gierula, 2J Barth,
R Cubbon, 2M T Kearney, 2K K Witte. 1Leeds General Infirmary, Leeds, UK; 2University
of Leeds, Leeds, UK
2
Background The vitamin D-parathyroid (PTH) axis is increasingly
recognised as potentially being involved with many of the features
of the syndrome of CHF. We wanted to explore the relationship
between vitamin D and PTH levels in a group of CHF patients and
relate these to markers of severity.
Methods We analysed serum 25(OH) vitamin D3 levels in 406
consecutive attendees of the Leeds Advanced Heart Failure clinic
(310 men) and correlated these to clinical markers of severity.
Results Mean age (SE) was 69 (3) years, mean left ventricular ejection fraction (LVEF) 31 (2)%, mean serum creatinine 117 mmol/l
(2.4), median vitamin D levels (IQR) 30 (20e43) nmol/l (normal for
skeletal health>75 nmol/l) and median parathyroid levels 8.8
(6.2e13.5) pmol/l (normal<6.5 pmol/l). Aetiology was ischaemic
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
heart disease in 63% and 23% had diabetes mellitus. Patients were
optimally treated (84% on b-blockers, 88% on ACE inhibitors, and
46% on spironolactone). The mean daily dose of furosemide was 60
(3) mg. Very few patients (5%) were sufficient in vitamin D. Patients
with worse symptoms as measured by NYHA status had lower
vitamin D levels and higher PTH levels (Abstract 106 п¬Ѓgures 1 and
2). There was also a negative relationship between furosemide dose
and vitamin D (Abstract 106 п¬Ѓgure 3) and, in an unselected subset of
160 patients (mean peak oxygen uptake (pVo2) 16.6 (0.5) ml/kg/
min), there was a positive relationship between pVo2 and vitamin D
(Abstract 106 п¬Ѓgure 4). Patients with diabetes had lower vitamin D
levels than non-diabetics (p<0.001) and there was a negative
correlation between vitamin D and fasting glucose levels (rВј0.13;
pВј0.02). There was no relationship between vitamin D levels
and age, calcium, creatinine or CRP, and no differences between
those patients taking and those not taking b-blockers and ACE
inhibitors. In 8 unselected patients we found a negative
relationship between tumour necrosis factor-alpha (TNF-a) levels
and vitamin D (rВј0.62; pВј0.05). Although there was no relationship between vitamin D levels and baseline LVEF, in a subgroup of
150 patients followed up one year after titration to optimal CHF
therapy, there was a significant positive relationship between
change in LV dimensions and vitamin D levels at the time of the
baseline scan (p<0.05).
Conclusions The vitamin D-PTH axis is abnormal in CHF, related to
the severity of the condition. Our data suggest that reverse
remodelling in response to optimal drug titration is greater in those
with higher vitamin D levels. Whether vitamin D deficiency is
causally related to CHF remains unknown and requires a long-term,
randomised, placebo-controlled study in CHF patients with efficacy
and mechanistic outcomes, using a dose of vitamin D capable of
normalising both vitamin D and PTH levels.
Abstract 106 Figure 3
Abstract 106 Figure 4
107
EXPANSION OF THE RED CELL DISTRIBUTION WIDTH AND
EVOLVING IRON DEFICIENCY AS PREDICTORS OF POOR
OUTCOME IN CHRONIC HEART FAILURE
doi:10.1136/heartjnl-2011-300198.107
1
N Aung, 1H Z Ling, 1,2S Aggarwal, 1,2J Flint, 1,2S Weissert, 1,2A Cheng, 1T Richards,
D P Francis, 3J Mayet, 1,2M Thomas, 1,2,4D O Okonko. 1University College London
Hospital, London, UK; 2The Heart Hospital, London, UK; 3International Center for
Circulatory Health, NHLI Imperial College London, London, UK; 4NHLI Imperial College,
London, UK
3
Abstract 106 Figure 1
Abstract 106 Figure 2
Heart June 2011 Vol 97 Suppl 1
Background Red cell distribution width (RDW) is a surrogate of
many aberrations (inflammation, malnutrition, iron deficiency (ID))
that may drive chronic heart failure (CHF) progression. While an
elevated RDW and iron deficiency at baseline predict mortality in
CHF, little is known about the prognostic implications of their
temporal trends.
Methods We analysed the relation of red cell indices on п¬Ѓrst
consultation and over time with mortality in 274 outpatients with
CHF (mean (6SD) age 70614 years, LVEF 2868%, NYHA class
261, 54% ischaemic). The combination of a rising RDW and a
falling mean cell volume (MCV) identified evolving ID.
Results On initial consultation, an RDW >15%, Hb<12.5 g/dl, and
MCV <80 fl were evident in 41%, 46%, and 8% of patients. Over a
median (6IQR) follow-up of 15617 months, 60 (22%) patients
died. On Cox proportional hazards analyses, a higher RDW independently predicted increased mortality (HR 1.21, p<0.0001). Over
time, 51%, 58%, 40%, and 23% of patients had a rise in RDW, a fall
in Hb, a fall in MCV, and evolving ID, respectively. A rising RDW
predicted death (HR 1.18, pВј0.002) independently of baseline
RDWs and changes in Hb, with an absolute increase >1% conferring
a twofold escalated risk of mortality (Abstract 107 п¬Ѓgure 1A).
Evolving ID was also associated with poorer survival (HR 2.89,
p<0.0001, Abstract 107 п¬Ѓgure 1B).
A61
BCS Abstracts 2011
Abstract 107 Figure 1
Conclusions An expanding RDW and evolving iron deficiency over
time predict an amplified risk of death in CHF and could be utilised
for risk stratification or therapeutically targeted to improve
outcomes.
108
Results Significant vortical flow in any segment (defined as flow
disturbance occupying more than one half of the aortic lumen) was
present in all patients with MFS, but in only 7/18 controls
(p<0.0005). The severity of flow disturbance was greater in MFS
patients than controls (median severity score 3 for Marfan patients,
1 for controls, p<0.0005). There was marked regional variation in
the prevalence of major flow disturbance (Abstract 108 figure 2),
with the sinuses of Valsalva and proximal descending aorta being
most frequently affected. Prior repaired aortic dissection was associated with marked abnormalities of blood flow (Abstract 108 figure
1C), with corresponding increases in axial WSS within the true
lumen of the dissected aorta (typical axial WSS in the dissected
ascending aorta was +0.9 N/m2, compared to +0.54 N/m2 in
healthy controls). Aortic flow disturbance in MFS was of one of
three types: Type A: flow disturbance confined to the sinuses of
Valsalva, Type B: flow disturbance confined to the proximal
descending aorta, Type C: flow disturbance in both the sinuses of
Valsalva and the proximal descending aorta.
4D-FLOW CMR DEMONSTRATES THE REGIONAL
DISTRIBUTION OF AORTIC FLOW DISTURBANCE IN
MARFAN SYNDROME
doi:10.1136/heartjnl-2011-300198.108
1
1
1
1
A Pitcher, T E Cassar, J Suttie, J M Francis, 2P Leeson, 3E Blair, 4B P Wordsworth,
J C Forfar, 6M Markl, 1S N Neubauer, 7S E Petersen. 1Oxford Centre for Clinical
Magnetic Resonance Imaging, Oxford, UK; 2Department of Cardiovascular Medicine,
University of Oxford, Oxford, UK; 3Department of Clinical Genetics, Churchill Hospital,
Oxford, UK; 4Nuffield Department of Medicine, University of Oxford, Oxford, UK; 5John
Radcliffe Hospital, Oxford, UK; 6University Hospital, Freiburg, Germany; 7Centre for
Advanced Cardiovascular Imaging, William Harvey Research Institute, London, UK
5
Background Marfan syndrome (MFS) commonly leads to progressive aortic dilation, aneurysm formation and aortic dissection,
particularly at the aortic sinuses (w60% of dissections), and
descending thoracic aorta (w30% of dissections). Abnormal aortic
blood flow patterns may contribute to the enlargement and
dissection of an inherently weak aorta, or to late complications after
aortic dissection.
Methods 18 patients with MFS (3 with a prior history of aortic
dissection and aortic root surgery, 15 with no such history) and 18
healthy volunteers matched for age, sex and height underwent CMR
at 3T, using a time-resolved 3-dimensional flow technique. The aorta
was segmented into regions on the basis of anatomic features
(Abstract 108 п¬Ѓgure 1A). Each segment was visualised using
streamlines (Abstract 108 п¬Ѓgure 1B) and particle traces, and was
rated as normal or abnormal, (defined as the presence of turbulent
flow vortices) and, where abnormal, extent of abnormality was
classified on a 4-point scale determined by the extent of radial
involvement of the aortic lumen. Wall shear stress (WSS) quantification was undertaken at predefined aortic locations (Abstract 108
п¬Ѓgure 1A).
Abstract 108 Figure 2 Prevalence of vortical flow disturbance
occupying >50% luminal diameter for each aortic region for Marfan
patients and controls.
Conclusion Patients with MFS commonly show aortic flow
disturbance. The sinuses of Valsalva and proximal descending aorta
are most frequently affected. Flow disturbance can be categorised
into one of three categories, and we anticipate that flow abnormalities within a segment will predict progressive aortic dilation and
dissection in an ongoing follow-up study.
109
3T MRI OF ACUTE ATHEROSCLEROTIC PLAQUE RUPTURE
AND DOWNSTREAM EMBOLIC INJURY
doi:10.1136/heartjnl-2011-300198.109
A C Lindsay, L Biasiolli, J M Lee, I Kylintireas, H Watt, W Kuker, A Handa,
M D Robson, S Neubauer, J Kennedy, R P Choudhury. University of Oxford, Oxford, UK
Abstract 108 Figure 1 A. Planes for aortic segmentation and WSS
quantification. B. Flow visualisation in a healthy volunteer. C. Flow
visualisation in a patient with prior aortic dissection fulfilling the Ghent
Criteria for Marfan syndrome.
A62
Introduction Luminal stenosis is a poor predictor of the risk posed by
any given atherosclerotic plaque, therefore current angiographic
imaging techniques cannot reliably determine which patients are
most likely to suffer future ischaemic events. However, MRI may be
able to detect features of atherosclerotic plaque rupture that have
been associated with an increased risk of recurrent atherothrombosis.
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
Hypothesis 3T MRI of the carotid artery can identify atherosclerotic
plaque rupture in patients presenting with TIA or minor stroke.
Methods 81 patients with carotid artery disease were recruited; 41
presented acutely with TIA or minor stroke and 40 asymptomatic
patients acted as the control group. Median time from symptom
onset to MRI in the symptomatic group was 2.1 days (range
0.17e7.0). All patients underwent T1, T2 and proton densityweighted turbo spin echo MRI to 10 mm either side of the carotid.
As part of a combined scan protocol, study participants then
underwent diffusion-weighted imaging (DWI) and Fluid-Attenuated
Inversion Recovery (FLAIR) imaging of the brain to assess acute and
chronic injury, respectively. If physically able, patients underwent
follow-up scanning a minimum of six weeks later. Plaques were
graded according to the MRI modified American Heart Association
(AHA) system by two independent reviewers blinded to the clinical
status of the patient. Statistical analysis was performed using the
Wilcoxon sign rank test and Fisher9 s exact test to compare plaques,
in addition to the Mann Whitney U test to compare cerebral injury.
Results AHA type VI (ruptured) plaque was seen in 22/41(54%) in the
symptomatic group vs 8/41(20%) in the asymptomatic group
(p<0.05), either due to intra-plaque haemorrhage (34% vs 18%,
pВј0.08; Abstract 109 п¬Ѓgure 1A), surface rupture (24% vs 5%, pВј0.03;
Abstract 109 п¬Ѓgure 1B), or luminal thrombus (7% vs 0%, pВј0.24;
Abstract 109 п¬Ѓgure 1C). Of particular note, 17/30 (57%) cases of AHA
VI (ruptured) plaque were seen to cause <70% stenosis―the current
cut-off for surgical treatment. At follow-up scanning a minimum of
6 weeks later, only two cases of AHA VI plaque showed evidence of
full healing. Of the 41 patients in the acute group, evidence of cerebral
injury on DWI imaging was seen in 32/41 patients; the median
number of lesions per patient was 7 and the median total lesion
volume was 10.62 ml (range 0e522 ml). No significant associations
were noted between AHA plaque type and downstream cerebral
injury, however the presence of plaque surface rupture independently
predicted a higher number of DWI lesions, a higher total DWI burden
at presentation, and higher total cerebral FLAIR signal at follow-up
when compared to all other plaque types (p<0.05).
there was already evidence of early changes in systolic function
related to subclinical atherosclerosis.
Methods We studied 81 individuals (44 females, 37 males) without
cardiovascular risk factors and with a mean age of 28.4265.36 years
(mean6SD). Peak mid-ventricular myocardial circumferential
systolic strain and left ventricular mass adjusted for body surface
area (LVM) were assessed by CMR. Carotid IMT was measured as a
marker of subclinical atherosclerosis using ultrasound. Demographic
and anthropometric characteristics were measured as well as
metabolic parameters and peripheral and central blood pressure.
Results Individuals with reduced peak myocardial circumferential
systolic strain had higher carotid IMT (rВј0.392, p<0.001). Total
cholesterol level and waist to hip ratio were both significantly associated with reduced myocardial strain. Increased LVM, central and
peripheral systolic blood pressure, peripheral pulse pressure, glucose,
triglycerides, age, body mass index and waist to hip ratio, as well as
reduced high-density lipoprotein, were all significantly associated
with increased carotid IMT (p<0.01). Males also had higher carotid
IMT than females (mean6SD Вј 0.5460.068 mm vs 0.4760.042 mm,
p<0.001). The association between carotid IMTand peak myocardial
circumferential systolic strain was independent of gender, smoking,
LVM as well as peripheral and central blood pressure measures.
Conclusions We have shown for the п¬Ѓrst time that subclinical
changes in cardiac function and subclinical atherosclerosis are
closely interrelated in young adults, with associations that extend to
those in the normal range of cardiovascular risk. This study further
establishes the ability of CMR to detect early changes in cardiovascular disease development.
111
SINGLE CENTRE PROSPECTIVE CARDIAC CT STUDY TO
DETERMINE THE PREVALENCE OF PATIENTS WITH
CORONARY ARTERY DISEASE WITH A ZERO CORONARY
ARTERY CALCIUM SCORE AND ASSOCIATED NON-CARDIAC
INCIDENTAL FINDINGS
doi:10.1136/heartjnl-2011-300198.111
A J Shah, D R Obaid, D Gopalan, J Babar, J H F Rudd. Addenbrooke’s Hospital,
Cambridge, UK
Abstract 109 Figure 1
Conclusion Acute atherosclerotic plaque rupture can be visualised
using 3T MRI. In particular, MRI can provide detailed information
on plaque morphology that can predict downstream embolic injury,
independent of the degree of luminal stenosis caused.
110
MYOCARDIAL SYSTOLIC STRAIN AND SUBCLINICAL
ATHEROSCLEROSIS IN YOUNG ADULT LIFE
doi:10.1136/heartjnl-2011-300198.110
A J Lewandowski, M Lazdam, E Davis, R Poole, J Diesch, J Francis, D Augustine,
R Banerjee, J Suttie, S Neubauer, P Leeson. Cardiovascular Medicine, University of
Oxford, Oxford, UK
Background In the elderly, reduced left ventricular function is related
to elevated carotid intima media thickness (IMT), a well-established
subclinical marker of atherosclerosis. Cardiovascular magnetic
resonance (CMR) allows for precise quantification of changes in
myocardial structure and function. We therefore sought to determine if in young adults, without overt cardiovascular risk factors,
Heart June 2011 Vol 97 Suppl 1
Introduction Cardiac CT, incorporating coronary artery calcium
(CAC) scoring and angiography, is being increasingly used to evaluate patients with chest pain and exclude coronary artery disease
(CAD), as recommended in the recent NICE guidelines. Calcification
of the coronary arteries is an excellent marker of underlying atherosclerosis, but a zero CAC score does not completely exclude the
diagnosis as potentially significant non-calcified plaques will not be
detected by CAC scoring. CT imaging may also identify non-cardiac
incidental п¬Ѓndings that can lead to further downstream testing and
medical expense.
Objectives (1) To evaluate the probability of CAD in patients with a
CAC score of zero. (2) To determine the incidence of non-cardiac incidental п¬Ѓndings on cardiac CT and to quantify resulting investigations.
Methods 116 symptomatic patients undergoing cardiac CT to exclude
CAD from November 2009 to October 2010 were prospectively
enrolled. Patients underwent CAC scoring and had contrastenhanced, 128-slice, dual source CT coronary angiography (CTCA―
Siemens Flash). Scans were dual-reported by a cardiac radiologist and a
cardiologist. Statistical analysis was performed using GraphPadPrism.
Results 62/116 patients had a CAC score of zero. Of these, 57 (91.9%)
patients had normal coronary arteries, 4 (6.5%) patients had nonobstructive CAD (stenosis <50%), and 1 patient (1.6%) had significant obstructive CAD (stenosis>50%). This patient with obstructive
CAD had a high grade lesion in the proximal left anterior descending
artery that required intervention. 54/116 had non-zero CAC scores.
Of these, 13 (24%) had obstructive CAD and 41 (76%) nonobstructive CAD. 42/116 (36%) patients had incidental п¬Ѓndings on
A63
BCS Abstracts 2011
cardiac CT that are summarised in Abstract 111 table 1. These incidental п¬Ѓndings resulted in further investigations, documented in
Abstract 111 table 2. The mean radiation dose (6 SEM) for CAC
scoring was 0.6160.03 mSv. The mean radiation dose (6 SEM) for
subsequent CTCA was 2.66 6 0.32 mSv in high pitch “flash” mode
(nВј27), 5.8660.50 mSv in prospective mode (nВј64) and
17.1561.68 mSv in the retrospective mode (nВј25).
if strong clinical suspicion remains in patients with a CAC score of zero
further coronary investigation may be warranted. Incidental п¬Ѓndings
are common, and can result in multiple further investigations for
patients. Further research is needed to evaluate the added cost, clinical
benefits and radiation exposure created by investigation of such incidental findings in the context of cardiac CT.
112
COMPUTED TOMOGRAPHIC CORONARY ANGIOGRAPHY TO
SCREEN FOR ALLOGRAFT VASCULOPATHY AFTER HEART
TRANSPLANTATION
Abstract 111 Table 1
Incidental findings on cardiac CT
Area
Structure
Incidental Finding
n
Chest (nВј27)
Lung parenchyma
Nodule <1 cm
Emphysema
5
3
doi:10.1136/heartjnl-2011-300198.112
Atelectasis
Fibrosis
6
4
M G Panicker, A G Mitchell, N R Banner, T K Mittal. Harefield Hospital, Harefield, UK
Tumour recurrence
Bronchiectasis
1
2
Pleura
Effusion
Calcification
2
2
Lymph node
Liver
Adenopathy
Cyst/Nodules
2
6
Adernal
Adenoma/metastasis
Hiatus Hernia
1
5
Objective To evaluate ComputedTomographic Coronary Angiography (CTA) as an alternative to Invasive Coronary Angiography
(ICA) for the detection of Cardiac Allograft Vasculopathy (CAV).
Background CAV is an important cause of late mortality after heart
transplantation (HT). Because patients are often asymptomatic,
surveillance ICA is performed in our institution. CTA is effective for
the diagnosis of coronary disease in non-transplant patients, but few
studies have been done after HT.
Methods 117 HT patients, 1 to 24 years post transplant (meanВј12
years SD6 6) underwent CT coronary artery calcification (CTCAC)
followed by retrospective ECG gated coronary angiogram on a 64slice scanner without the use of any b-blockers. Majority (89%) of
patients had CTA within 24 h before ICA. The Agatston calcium
score (CS) was calculated for all patients. The CTA images were
systematically analysed for image quality and the presence of CAV
(graded as significant if >50% luminal stenosis) using a fifteen
coronary segments model by an independent investigator blinded to
the results of ICA.
Results CS ranged from 0 to 1681 (MeanВј91.76275). Out of 77
patients with absent CS, 3 had significant CAV on ICA. Despite a
mean resting heart rate of 82 bpm SD613 and body mass index of
27 kg/m2 SD 65, 81% of the CTA images were graded as excellent or
satisfactory. For all the 1755 segments assessed by CTA irrespective
of the image quality, CTA had sensitivity, specificity, positive and
negative predictive values of 71%, 79%, 72% and 78% respectively for
the detection of any CAV found by ICA. On a patient basis, CTA best
performed in diagnosing CAV of more than 25% with sensitivity,
specificity, positive and negative predictive values of 74%, 94%, 79%,
and 92% respectively. None of the 61 patients with completely
normal CTA had CAV on ICA. 83 (92%) out of 90 patients who
responded to a patient survey preferred CTA to ICA as a screening
test for CAV. Non-coronary cardiac and non-cardiac abnormalities
were identified in 18% and 14% patients respectively.
Conclusion The study shows that CTA compares favourably with
ICA in detecting CAV in heart transplant recipients, and may be a
preferable screening technique because of its non-invasive nature,
patient preference and yield of additional information. One has to
exercise caution in just using CS in these patients as significant CAV
can be missed out.
Abdomen (nВј7)
Diaphragm (nВј5)
Vasculature (nВј11)
Aorta
Dilatation
8
Renal
Aneurysm
Stenosis
1
1
Coeliac
Stenosis
1
Abstract 111 Table 2
Cardiac CT
Further investigation of incidental findings on
Investigation
n
Bone scintigraphy
1
Chest clinic referral
CT chest
2
4
DMSA
MR adrenals
1
1
MRA renal
Nephrology clinic referral
1
1
Pleural fluid aspiration
Ultrasound kidneys
1
1
Ultrasound liver
3
Abstract 111 Table 3
incidental findings
Investigations and referrals generated by
Investigations or referrals
Number
Bone scintigraphy
1
Chest clinic referral
CT chest
2
4
DMSA
MR adrenals
1
1
MR cardiac
MRA renal
2
1
Nephrology clinic referral
1
Pleural fluid aspiration
Ultrasound kidneys
1
1
Ultrasound liver
3
Conclusions Despite 62 patients having a reassuring CAC score of zero,
8% of this group had evidence of non-calcified plaque, with one patient
having obstructive CAD that required intervention. We conclude that
A64
113
DUAL ENERGY CT IMPROVES DIFFERENTIATION OF
CORONARY ATHEROSCLEROTIC PLAQUE COMPONENTS
COMPARED TO CONVENTIONAL SINGLE ENERGY CT
doi:10.1136/heartjnl-2011-300198.113
1
1
1
2
D R Obaid, P A Calvert, J H F Rudd, D Gopalan, 1M R Bennett. 1University of
Cambridge, Cambridge, UK; 2Papworth Hospital NHS Trust, Cambridge, UK
Introduction Vulnerable plaques have a relatively high necrotic core
area and low п¬Ѓbrous tissue content. Although CT can identify
plaque components on the basis of their x-ray attenuation, there is
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
significant overlap between their attenuation ranges, most crucially
between necrotic core and п¬Ѓbrous plaque. Recently introduced dual
energy CT (DECT) permits acquisition of 2 different energy data
sets simultaneously, with the change in attenuation of plaque
components to different energies depending upon their material
composition. We therefore examined whether DECT was better
than single energy CT in determining plaque components defined by
virtual histology IVUS.
Methods 20 patients underwent DECT and 3-vessel VH-IVUS. CT
data was obtained at peak voltages of 100 kV and 140 kV. 52 plaques
were chosen with either homogenous fibrous plaque or confluent
areas of calcified plaque or necrotic core as defined by VH-IVUS. VHIVUS images were co-registered and orientated with the corresponding CT images using distance from coronary ostia and fiduciary markers (Abstract 113 figure 1). Multiple regions of interest
(ROI) were placed within the plaque components or in lumen on
cross sectional CT images pre-classified by VH-IVUS (Abstract 113
figure 1). ROI densities were measured (in Hounsfield Units) and
assigned to the plaque component. A dual energy index (DEI) was
created for each component, defined as the ratio of the difference in
attenuation at 2 different energies / sum of attenuation with 1000
added to each attenuation value to avoid negatives.
data sets permitted resolution of necrotic core and п¬Ѓbrous plaque
without overlap (Abstract 113 п¬Ѓgure 2B).
Abstract 113 Figure 2 (A) Defined CT attenuation spectra of
plaque components using a single energy (140kV), calcified plaque
is distinguishable from all others but necrotic core and fibrous
plaque overlap. (B) The use of dual energy index from the attenuation
data at 2 energies (100/140kV) allows significant separation of
necrotic core and fibrous plaque (p<0.05) (Tukeys multiple
comparison test).
Abstract 113 Table 1
Plaque
Component
100 kV mean
HU (SD)
140 kV mean
HU (SD)
Necrotic Core
Fibrous Plaque
57.26 (42.20)
148.30 (49.47)
42.69 (31.51)
84.60 (30.34)
Calcified Plaque
Lumen
733.10 (226.7)
411.5 (82.27)
582.20 (194.9)
282.90 (55.93)
Mean Difference
(100e140 kV)
14.57
63.69
150.9
128.6
Dual Energy
Index (mean)
0.0071
0.0283
0.0450
0.0483
Conclusions The additional attenuation data provided by DECT
improves the differentiation of plaque components when compared
to conventional single energy CT. In particular, DECT may allow
better differentiation of necrotic core and п¬Ѓbrous plaque, a weakness
of conventional cardiac CT, allowing for more accurate non-invasive
identification of vulnerable plaques.
114
RADIATION DOSES TRENDS FROM CARDIAC CT USING A
CARDIAC SPECIFIC CONVERSION FACTOR: SYSTEM
UNDERSTANDING & AN OPTIMISATION STRATEGY
SIGNIFICANTLY REDUCES THE DOSE TO THE PATIENTS IN A
CLINICAL SERVICE
doi:10.1136/heartjnl-2011-300198.114
1
1
1
1
O E Gosling, S Iyengar, R Loader, G Morgan-Hughes, 2W D Strain, 3C Roobottom.
Plymouth Hospitals NHS Trust, Plymouth, UK; 2Peninsula College of Medicine and
Dentistry, Exeter, UK; 3Peninsula College of Medicine and Dentistry, Plymouth, UK
1
Abstract 113 Figure 1 Demonstration of plaque co-registration
between VH-IUS and 140kV/100kV CT data sets. Calcified plaque is
identified 5mm from side branch adjacent to characteristic calcification
(yellow line). Cross section taken through this plaque (blue arrow) and
following orientation with VH-IVUS cross section HU region of interest
sampling is performed in calcified plaque.
Results Attenuation values for 1088 ROIs were measured from 70
paired data sets at 100 kV and 140 kV creating 70 DEIs (12 necrotic
core, 11 fibrous plaque, 29 calcified plaques and 18 lumen). Values
obtained using a single energy data set showed good differentiation
between calcified plaque and all others (p<0.05), but considerable
overlap between necrotic core and п¬Ѓbrous plaque (pВјns) (Abstract
113 п¬Ѓgure 2A) (Abstract 113 table 1). In DECT, lumen (iodinated
contrast) showed the greatest change in attenuation and hence had
the highest DEI. Necrotic core had the lowest DEI and could be
distinguished from all other components (p<000.1) Importantly, in
contrast to the single energy data, DEI derived from both energy
Heart June 2011 Vol 97 Suppl 1
Background CT coronary angiography CTCA now has an established role in the investigation of patients with chest pain. Under
the IRMER regulations radiation doses to patients should be kept as
low as reasonably practical (ALARP). Previous publications have
used a chest conversion factor to calculate the effective dose (mSv)
from CTCA. We have previously demonstrated that chest conversion factors significantly under-estimate the effective dose to the
patient when applied to CTCA and have calculated a cardiac specific
conversion factor of 0.028 mSv (mGy.cm)-1. Our department
follows the ALARP ethos and has implemented new technologies
together with physician training to reduce the radiation dose from
CTCA. We aimed to investigate what impact the implementation of
new technologies has had on the radiation dose of CTCA.
Method All patients who were coded as attending for a cardiac CT
scan on the PACS and CRIS systems were included in the analysis.
Scan indication included: rule out coronary artery disease, CABG
assessment, pre-EP studies and problem solving. CT scanning
A65
BCS Abstracts 2011
between September 2007 and August 2010 was included; the total
dose for the whole examination is used including the scout and nonenhanced scan (calcium score). Scans were performed on a Lightspeed VCT or HD750 (GE Healthcare). To calculate the effective
dose a conversion factor was applied to the dose length product of
each examination. The DLP is the radiation dose in one CT slice
multiplied by the length of the scan. A cardiac specific conversion
factor was used rather than a chest conversion factor (0.014) which
significantly underestimates the effective dose from CTCA. Data
was transformed and expressed as a geometric mean with 99% CI.
For each analysis period all scans were included; retrospective,
prospective, low kV and zero padding.
Results In the 3-year period 1736 scans were performed. The mean
radiation dose in the п¬Ѓrst 6 months of the study (retrospective
gating) was 29.6 mSv; using the accepted conversion factor at the
time the mean dose was 14.9 mSv. In March 2008 prospective ECG
gating was installed; this resulted in a halving of the mean radiation
dose to 13.6 mSv. In March 2009 the scanner parameters was set to
zero padding and 100 KV reducing the dose to 7.4 mSv. For the п¬Ѓnal
6 months the mean radiation dose for a cardiac scan was 5.9 mSv;
this Abstract 114 п¬Ѓgure 1 incorporates scans performed with
standard п¬Ѓltered back projection, iterative reconstruction, high
definition scanning and retrospective ECG gating for a variety of
differing clinical scenarios.
115
ATRIAL HIGH RATE EPISODES AND ATRIAL FIBRILLATION
BURDEN: DO THEY HAVE SIMILAR ASSOCIATION WITH
CARDIAC REMODELLING?
doi:10.1136/heartjnl-2011-300198.115
C W Khoo, S Krishnamoorthy, G Dwivedi, B Balakrishnan, H S Lim, G Y H Lip.
University Department of Medicine Centre for Cardiovascular Sciences, City Hospital,
Birmingham, UK
Background and Objectives Contemporary pacemaker devices allow
quantification of atrial high-rate episodes (AHREs) and atrial fibrillation burden (AFB) accurately. Cumulative ventricular pacing (Vp)
is associated with development of atrial п¬Ѓbrillation, but it is not
clear if AHREs and AFB share similar pathophysiologic associations
with left atrium (LA) and ventricle (LV) function and remodelling.
Methods In total, 87 patients with dual-chamber pacemaker
underwent two-dimension (2D) and tissue Doppler imaging (TDI)
echocardiography. LA volume (LAV) was evaluated by area-length
method and indexed to body surface area. Septal A9 was used to
measured regional LA function. LV systolic and diastolic parameters
were evaluated by mitral inflow velocity (E, A, E/A), LV ejection
fraction (biplane Simpson’s) and septal TDI velocity. The presence
of AHREs (defined by atrial-rate $220 beats/min and $5 minutes)
and AFB were derived from pacemaker diagnostics. Plasma markers
of remodelling, matrix metalloproteinases-1 (MMP1) and tissue
inhibitors of metalloproteinases-1 (TIMP1), were analysed by ELISA.
Results Baseline characteristics and comorbidities were comparable
between groups (Abstract 115 table 1). Patients with AHREs had
significantly larger indexed LAV (p¼0.011) and higher cumulative
Vp (pВј0.012), but this was not associated with elevation of MMP1
and TIMP1. Plasma markers, LV systolic and diastolic parameters
were comparable between groups. In patients with AHREs, the AFB
ranged from 0 to 99% and correlated with E/A (rВј0.966, p<0.001),
and inversely correlated with late acceleration velocity (A)
(rВјГЂ0.612, pВј0.009). On linear regression analysis, A, E/A, septal A9
were independently associated with AFB (all p<0.01).
Conclusion Cumulative Vp and increased LAV are associated with
the development of AHRE, but AFB is independently associated
with changes in LA function and LV diastolic function. This study
suggests AHREs and AFB have dissimilar pathophysiologic associations with left atrium and ventricle remodelling.
Abstract 115 Table 1
Abstract 114 Figure 1
Effective dose (mSv) by protocol period.
Conclusion The introduction of dose saving strategies and appropriate physician training has lead to a significant reduction in the
radiation dose from cardiac CT. As CTCA programmes become
established in hospitals around the UK it is important that clinicians
have the appropriate training and experience to keep the radiation
dose to the patients as low as reasonably practical.
Number of Patients
Mean Effective
Dose (mSv)
CIs (99%) (mSv)
A66
AHRE (n[17)
p Value
71.0611.6
75.468.8
0.1
Body mass index (kg/m2)
Indexed LA volume (ml/m2)
26.464.4
27.467.9
27.664.7
34.869.4
0.38
0.01
LV ejection fraction (%)
E/A
52.8611.9
0.860.2
55.169.2
1.060.6
0.4
0.23
8.962.2
6.661.8
7.962.6
6.561.4
0.16
0.71
Septal A’ (cm/s)
Septal S’ (cm/s)
Septal E/E’
Percentage Vp
116
Abstract 114 Table 1
Scanning protocol
No AHRE (n[70)
Age (years)
Retrospective
Gatingddose
modulation
Prospective
gating
Zero paddingd
100 kV
Final 6
months
150
29.6
489
13.6
636
7.4
461
5.9
33
26.6
14.9
12.5
8
6.8
6.5
5.3
13.766.2
21.9 (1.8e99.0)
14.163.5
98.6 (41.0e99.9)
0.74
0.01
CRT OPTIMISATION: IMPROVING ECHOCARDIOGRAPHIC
TECHNIQUES BY ACCOMMODATING BIOLOGICAL
VARIABILITY WITHIN DIFFERENT ECHOCARDIOGRAPHIC
PARAMETERS
doi:10.1136/heartjnl-2011-300198.116
P A Pabari, A Kyriacou, M Moraldo, B Unsworth, N Sutaria, J Mayet, A D Hughes,
D P Francis. Imperial College London, London, UK
Background In optimisation of CRT (and even selection for implantation) we may have underestimated the impact of beat-to-beat
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
variation on echocardiographic measurements. This can be quantified most clearly in the optimisation process, in which genuine small
changes in cardiac function (signal) must be detected among
potentially large beat-to-beat variation (noise).
Methods and Results In this large study of biological variability, we
performed over 2000 echocardigraphic measurements in 12 patients.
We performed separate, replicate measurements at a series of interventricular delays of each potential optimisation modality at rest.
This included (i) 3D systolic dyssynchrony index, (ii) aortic preejection time, (iii) interventricular mechanical delay, (iv) LVOT VTI
and (v) QRS width. The equivalent of 31 optimisations per patient
were performed. For single measurements at each setting, agreement
between successive optimisations was low, at 39% for SDI, 41% for
aortic pre-ejection time, 32% for IVMD, 54% for LVOT VTI and
58% for QRS width. Agreement between one method and another,
using single replicates, was similarly low, with the average agreement between optima by two methods being only 18% similar to
pure guesswork. The intraclass correlation coefficient was low for all
methods at 0.11, 0.51, 0.30, 0.50 and 0.55 respectively. The intraclass
correlation coefficients improved to 0.19, 0.63, 0.42, 0.54 and 0.66
(pВј0.001) when averages of paired measurements were used. To
optimise within 20 ms or 10 ms of the true optimum, requires a
greater number of measurements, as seen in Abstract 116 п¬Ѓgure 1,
dependant on the intraclass correlation coefficient. The scatter of
optima obtained reduced (improved) significantly when using
averaged pairs of measurements compared to single measurements
from 23 ms to 18 ms (3D SDI), 14 ms to 10 ms (aortic pre-ejection
time), 28 ms to 22 ms (IVMD), 21 ms to 16 ms (LVOT VTI) and
14 ms to 10 ms QRS duration (pВј0.0002).
117
TRICUSPID VALVE ANNULAR DYNAMICS IN NORMAL VS
DILATED RIGHT HEARTS; A 3D TOE STUDY
doi:10.1136/heartjnl-2011-300198.117
L Ring, B Rana, R A Rusk. Papworth Hospital NHS Foundation Trust, Cambridge, UK
Background The tricuspid valve annulus (TVA) is a complex three
dimensional structure that is non-planar, and is incompletely
understood. The dynamics of the normal TVA has not been
described in any significant detail, nor has the impact of abnormal
right hearts on the TVA been described. This study was designed to
assess the feasibility of assessing the TVA throughout the cardiac
cycle using 3D transoesophageal echo (TOE).
Methods 20 patients were included, divided into 2 groups: normal
right hearts (nВј10), and dilated right hearts (nВј10). 3D zoom
images of the TVA were acquired using an iE33 imaging platform
and X7-2t transducer (Phillips, Andover, Massachusetts, USA).
Antero-posterior (AP) diameter, septo-lateral (SL) diameter, area and
height were measured at 6 points of the cardiac cycle adapting
commercially available software designed for assessing the mitral
valve (MVQ, Phillips). The eccentricity ratio was calculated as
AP/SL.
Results TVA area decreases during systole in both groups, and is
greatest in mid-diastole. The area is significantly larger in the
abnormal group (mean 1795 mm2 abnormal vs 1204 mm2 normal;
p<0.01). The SL diameter increased more in the abnormal group,
resulting in a circular orifice and lower eccentricity ratio throughout
the cycle (mean 0.91 abnormal v 1.22 normal; p<0.01, see graph).
Annular height is similar in both groups but has an upward trend in
systole in normals and reduces in abnormals, reaching significance at
end systole (6.7 mm vs 4.9 mm; pВј0.046).
Conclusions In patients with abnormal right hearts, the TVA dilates
in a septo-lateral direction, resulting in a more circular orifice. The
dynamic changes of the TVA are similar in dilated vs normal right
hearts, with the exception of annular height. This pilot study
suggests that 3D TOE provides insight into understanding tricuspid
annular dynamics.
Abstract 116 Figure 1
Conclusions Because of beat-to-beat variability, VV delay optimisation by any of the echocardiographic techniques is not realistic
unless multiple replicates are performed and averaged. Smoothing
biological variation by averaging multiple measurements allows the
full potential of echocardiographic optimisation to be achieved and
improves the consistency of optimisation. Trying to save time by
performing inadequate numbers of replicates is a false economy and
leads to optimisation being a form of randomisation. These observations may also cast light on to why attempts to identify future
responders from CRT has not e when tested in externally monitored randomised trialsdbeen fruitful: dyssynchrony assessment to
select patients for implantation may need averaging too, and of far
more replicate measurements than is current practice. Integration of
this biological insight into technological achievements of clinical
imaging is necessary, if reliable predictors of which patients will
benefit from CRT, are to be developed.
Heart June 2011 Vol 97 Suppl 1
Abstract 117 Figure 1 Eccentricity ratio of the tricuspid valve annulus
during the cardiac cycle: normal vs dilated rated hearts.
A67
BCS Abstracts 2011
118
HIGH-RESOLUTION CARDIAC MAGNETIC RESONANCE
PERFUSION IMAGING VS POSITRON EMISSION
TOMOGRAPHY FOR THE DETECTION AND LOCALISATION OF
CORONARY ARTERY DISEASE
doi:10.1136/heartjnl-2011-300198.118
G D J Morton, M Ishida, A Chiribiri, A Schuster, S Baker, S Hussain, D Perera,
M O’Doherty, S Barrington, E Nagel. King’s College London, London, UK
Background Non-invasive imaging has a key role in the detection of
coronary artery disease (CAD). Its importance has been affirmed by
recent National Institute of Clinical Excellence (NICE) guidelines.
Localisation of ischaemia to a coronary territory is also important in
patient management. Cardiac Magnetic Resonance (CMR) perfusion imaging is a well-established and radiation-free test for these
purposes. However, there are few data comparing perfusion CMR
with Positron Emission Tomography (PET), which is widely
regarded as the non-invasive gold standard. Furthermore novel CMR
methods, including those based on k-t acceleration techniques, allow
myocardial perfusion imaging with unprecedented spatial resolution.
Methods 31 patients with known or suspected CAD referred for
diagnostic x-ray coronary angiography (XCA) underwent both CMR
and PET examinations. Both PET and CMR protocols included
adenosine stress and rest perfusion imaging. CMR perfusion
imaging was performed at 1.5T with a k-t-accelerated steady-state
free-precession sequence. PET imaging was performed with 13NAmmonia. The Abstract 118 п¬Ѓgure 1 shows an example. Experts
blinded to the clinical data analysed the imaging data and experts
blinded to the imaging results visually analysed the XCA data. A
significant coronary artery stenosis was defined as $70% reduction
in diameter or a fractional flow reserve <0.8 where available.
Sensitivity and specificity for PET and CMR vs invasive angiography
were calculated. Localisation of ischaemia was assessed in patients
with CAD by classifying myocardial territories as either supplied by,
or remote from, a stenotic artery.
Abstract 118 Figure 1
Results Patient characteristics are shown in the Abstract 118 table 1.
Mean age 6 SD was 6469 years. One CMR examination was nondiagnostic. The interval between PET and CMR was 266 days (77%
same day), between PET and XCA 22628 days and between CMR
and XCA 22629 days. The prevalence of CAD was 81%. For the
detection of CAD PET sensitivity was 80% (95% CI 59% to 92%)
and specificity was 67% (24% to 94%). CMR sensitivity was 83%
(95% CI 62 to 95%) and specificity was also 83% (36% to 99%). In
patients with CAD ischaemia was localised to 63% of the territories
A68
supplied by stenotic arteries by PET and 76% by CMR. Remote
ischaemia was detected in 24% of territories by PET and 16% by
CMR.
Abstract 118 Table 1
Characteristic
Number (percentage)
of affected patients
Male
25 (81%)
Diabetes
Previous PCI
12 (39%)
10 (32%)
Hypertension
22 (71%)
Conclusions CMR is at least as accurate as PET for the diagnosis of
CAD and also for the localisation of ischaemia to coronary territories. Relatively low numbers mean that CIs are wide and further
work is required. Using an anatomic test as the reference-standard
for functional tests has well-described limitations. Remote
ischaemia is likely to occur for several reasons including underestimation of disease severity at XCA, microvascular disease and also
false positive results.
119
CARDIOVASCULAR MAGNETIC RESONANCE IMAGING
(CMR) DETECTS SUBCLINICAL CARDIOMYOPATHY IN
ASYMPTOMATIC PATIENTS WITH LEFT BUNDLE BRANCH
BLOCK (LBBB) AND NORMAL ECHOCARDIOGRAPHY
doi:10.1136/heartjnl-2011-300198.119
M Mahmod, T D Karamitsos, J J Suttie, S G Myerson, S Neubauer, J M Francis.
University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Oxford, UK
Introduction Asymptomatic left bundle branch block (LBBB) is a
common indication for referral for cardiovascular magnetic resonance (CMR) imaging. However, it is not known whether referral
for LBBB returns a high diagnostic yield. We evaluated the diagnostic
value of CMR in these patients.
Methods All clinical CMR referrals for LBBB from January 2005 to
November 2010 were reviewed by two independent investigators.
Only patients with asymptomatic LBBB and normal echocardiograms (echos) who underwent complete CMR evaluation were
included in the study. Patients were excluded if they had cardiac
symptoms or known coronary artery disease. Anthropometric data,
pre-existing conditions, medications, smoking status, family history
and echocardiographic data were recorded.
Results From January 2005 to November 2010, 63 asymptomatic
patients with LBBB were referred to our institution for CMR from a
total of 3596 CMR referrals. Of these, 34 had normal echos; 20
subjects who had abnormal echos and 9 who had no echos at
presentation were excluded from further analysis. Mean age of the
34 patients with normal echos was 5469 years, and 19 (56%) were
men. Demographic data and left ventricular (LV) measurements are
presented in the Abstract 119 table 1. The most common associated
medical conditions were hypertension (11 patientsd33%) and
hyperlipidaemia (8 patientsd24%). Ten subjects (30%) had a family
history of heart disease. Nine (27%) patients underwent coronary
angiography which was normal. Of the 34 patients, 14 (41%) were
found to have pathological п¬Ѓndings on CMR. The commonest
abnormalities were dilated cardiomyopathy (DCM) (23%), followed
by LV hypertrophy (LVHddefined as LV wall thickness >13 mm)
(9%), arrhythmogenic right ventricular cardiomyopathy (ARVC)
(6%) and Ebstein anomaly (3%). Two patients (6%) had mid wall
late gadolinium enhancement. In the remaining 20 (59%) patients,
no abnormalities on CMR were detected.
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
Abstract 119 Table 1
All patients Normal CMR Abnormal CMR
(n[34)
(n[20)
(n[14)
p value
Age (years (median, IQR))
Male gender (no, %)
54.368.9*
19 (55.8%)
BMI (mean, kg/m2)
LVEDV (ml (median, IQR))
LVESV (ml (median, IQR))
LVEF (ml (mean, SD))
57.5 (19.7)
11 (55.0%)
48.5 (17.0)
8 (57.1%)
0.6
0.59
28.365.6
27.664.9
155.0 (58.0) 133.0 (41.5)
29.366.5
182.5 (60.5)
0.37
0.012
51.0 (26.0)
60.6613.9
48.0 (12.5)
66.165.5
71.5 (39.5)
55.7613.6
0.005
0.004
LV thickness (mm (median, IQR)) 11.0 (7.4)
9.0 (6.1)
LVMI (g/m2 (median, IQR))
72.5618.1* 64.0 (15.0)
12.5 (9.4)
83.0 (14.5)
0.059
0.001
*mean, SD. IQR.
Conclusions There is a high rate of sub-clinical cardiomyopathy
(41%) detected by CMR in asymptomatic patients with LBBB despite
normal echocardiograms. These п¬Ѓndings support the claim that CMR
is a valuable adjunct to conventional investigations in asymptomatic
LBBB. Further studies are needed to evaluate the prognostic implications of CMR abnormalities in this cohort of patients.
The MBH SR curves were п¬Ѓltered with a moving average (MA) to
reduce noise sensitivity, results from a sample width of three and
п¬Ѓve were examined. Differences between SBH and MBH were
assessed using Wilcoxon signed-rank test as not all measures were
normally distributed. Reproducibility assessments were carried out
on all techniques.
Results PeakEcc was significantly higher with MBH vs SBH, but
reproducibility was slightly worse. Results are summarised in
Abstract 120 table 1. Systolic SR was approximately equal with all
techniques although MBH using MA of п¬Ѓve led to a borderline
significant reduction. Diastolic SR was higher when measured with
MBH although only significant using MA of three. Systolic and
diastolic SR measures were more reproducible with MBH compared
with SBH, except for the diastolic SR using MA of three, which was
substantially worse. Strain and SR curves for the same patient are
shown in Abstract 120 п¬Ѓgure 1.
Abstract 120 Table 1
Peak systolic
strain (%)
e13.762.4
e15.163.1
(pВј0.023 vs SBH)
MBH (MA of five)
e15.163.1
(pВј0.023 vs SBH)
SBH reproducibility 0.5061.52; 11.1%;
(MD6SD; CoV; B-A) e2.5 to 3.5
SBH
MBH (MA of three)
Abstract 119 Figure 1 CMR findings in asymptomatic patients with
LBBB and normal echocardiogram.
120
MBH reproducibility
(MA of three)
(MD6SD; CoV; B-A)
MBH reproducibility
(MA of five)
(MD6SD; CoV; B-A)
MD6SDВјmean
difference 6 SD
Peak systolic
strain rate (1/s)
Peak diastolic
strain rate (1/s)
e0.7460.15
e0.7360.11
(pВј0.877 vs SBH)
e0.6960.10
(pВј0.049 vs SBH)
e0.0160.13; 18.1%;
e0.26 to 0.28
0.7560.27
1.1260.54
(pВј0.017 vs SBH)
0.9160.36
(pВј0.535 vs SBH)
e0.0460.16; 21.0%;
e0.36 to 0.27
1.1362.23; 14.7%; 0.0660.04; 5.3%;
e3.3 to 5.6
e0.02 to 0.14
e0.1360.44; 39.0%;
e1.00 to 0.75
1.1362.23; 14.7%; 0.0460.05; 7.8%;
e3.3 to 5.6
e0.07 to 0.15
0.0960.15; 16.9%;
e0.39 to 0.22
CoVВјcoefficient
of variation
BeAВјBlandeAltman
95% limits of agreement
COMPARISON AND REPRODUCIBILITY OF STANDARD AND
HIGH TEMPORAL RESOLUTION MYOCARDIAL TISSUE
TAGGING IN PATIENTS WITH SEVERE AORTIC STENOSIS
doi:10.1136/heartjnl-2011-300198.120
1
C D Steadman, 2N A Razvi, 1K I E Snell, 3J P A Kuijer, 3A C van Rossum,
G P McCann. 1Leicester Cardiovascular Biomedical Research Unit, Leicester, UK;
2
Department of Cardiovascular Sciences, University Hospitals of Leicester, Leicester,
UK; 3Department of Physics and Medical Technology, ICaR-VU, VU University Medical
Center, Amsterdam, The Netherlands; 4University Hospitals of Leicester, Leicester, UK
4
Objectives The aim of this study was to compare and assess the
reproducibility of left ventricular (LV) circumferential peak systolic
strain (PeakEcc) and strain rate (SR) measurements using standard
and high temporal resolution myocardial tissue tagging in patients
with severe aortic stenosis (AS).
Background Myocardial tissue tagging with cardiac magnetic resonance (CMR) can be used to quantify strain and SR, however, there
are little data on the reproducibility. Diastolic SR may be of
particular interest as it may be the most sensitive marker of diastolic
dysfunction often occurring early in the course of disease.
Methods Eight patients with isolated severe AS without obstructive
coronary artery disease were prospectively enrolled. They underwent CMR in a 1.5T scanner (Siemens Avanto) on two separate
occasions, median interval 12 days. Complementary tagged
(CSPAMM) images were acquired with both a single breath-hold
(SBH: temporal resolution 42 ms), and a multiple brief expiration
breath-hold (MBH: high temporal resolution 17 ms) sequence. Midwall PeakEcc was measured in the LV at mid-ventricular level with
HARP Version 2.7 (Diagnosoft, USA). SR was calculated from the
strain data; SRВјEcc2-Ecc1/Time2-Time1. PeakEcc, peak systolic and
diastolic SR were read from curves of strain and SR against time.
Heart June 2011 Vol 97 Suppl 1
Abstract 120 Figure 1
Conclusions It is likely than SBH may be adequate or even superior to
MBH for assessment of PeakEcc. The increased temporal resolution of
MBH may be advantageous for examining systolic and diastolic SR; a
MA of five for diastolic SR may be the preferred method for quantification given the improved reproducibility of this measure.
A69
BCS Abstracts 2011
121
INCIDENTAL EXTRA-CARDIAC FINDINGS ON CLINICAL
CMR; A COMPARISON OF 3 HASTE TECHNIQUES
doi:10.1136/heartjnl-2011-300198.121
1
R B Irwin, 2T Newton, 3C Peebles, 4A Borg, 5D Clark, 4C Miller, 6N Abidin,
M Greaves, 4M Schmitt. 1Wythenshawe Hospital, Manchester, UK; 2Royal Blackburn
Infirmary, Blackburn, UK; 3Southampton General Hospital, Southampton, UK;
4
Wythenshawe Hospital, University Hospitals of South Manchester NHS Trust,
Manchester, UK; 5Alliance Medical, Wythenshawe Hospital CME unit, Manchester,
UK; 6Salford Royal Hospital, Salford, UK
4
Introduction Cardiac magnetic resonance (CMR) is an increasingly
important imaging modality, which by necessity incorporates a
large field of view. Both “localiser ” and multiple slice half-fourier
spin echo (eg, HASTE) sequences provide coverage of the thorax and
upper abdomen. Such imaging may reveal hitherto unexpected
incidental extra-cardiac п¬Ѓndings (IEF). First we sought to assess the
frequency of IEF found on clinically indicated CMR scans. Second
we compared the 3 clinically used HASTE acquisition protocols in
this context. Lastly we determined the impact of the 3 different
protocols on acquisition time and image quality.
Methods Three subsequent groups of 238 patients (714 patients in
total), all referred for clinically indicated CMR, were scanned with
either breath-hold (BH) HASTE (Group 1), free breathing (FB)
HASTE (Group 2) or diaphragmatic navigated (NAV) HASTE
(Group 3). Additionally “localiser” sequences performed in 3 orthogonal planes were analysed. All 714 clinical reports were reviewed
regarding the presence of IEF. These were categorised as either minor,
or major if recommendations for further investigation, follow-up,
and/or clinical correlation were made. Finally, to determine the
impact of each HASTE protocol on acquisition time and image
quality, an additional cohort of 15 patients underwent 3 protocols
back to back in a random fashion. The length of each acquisition was
timed and image quality was reviewed and scored externally.
Results A total of 180 IEF were found in 162 (22.7%) out of 714
patients. There was no significant difference in frequency of IEF
between the 3 HASTE groups. Out of 180 IEF, 88 were considered
minor and 92 major п¬Ѓndings. Of the latter, 8 (1.1%) were considered
highly significant. These included one bronchoalveolar carcinoma
stage 1B requiring lobectomy, 2 cases of florid sarcoidosis in patients
presenting with VT and “structurally normal hearts” on echocardiography, one case of pulmonary aspergillosis, 2 cases of
advanced pulmonary п¬Ѓbrosis, one ascending thoracic aortic
aneurysm and a case of iatrogenic liver haemorrhage following
placement of a pericardial drain. FB HASTE acquisition (6962.5 s)
was significantly faster than BH (10563.8 s) and NAV (12162.7 s),
p<0.001, but also produced the lowest image quality on a 5 point
scale; 3.5 (FB) vs 3.9 (BH) vs 3.8 (NAV), pВј0.08.
Conclusion Overall, IEF are common and lead to follow on investigations in a substantial minority of cases. However, the overall
incidence of highly significant findings in the current study was low
(w1%). There was no difference in the frequency of incidental extracardiac п¬Ѓndings between the 3 HASTE protocols. While the free
breathing HASTE technique is statistically significantly faster than
breath hold and navigated HASTE, the absolute time saving is small
and probably out-weighted by lesser image quality.
122
OBESITY AND PERIVASCULAR ADIPOSITY IN
ATHEROSCLEROSIS
doi:10.1136/heartjnl-2011-300198.122
I Kylintireas, C Shirodaria, O Rider, J M Lee, I Bechar, J Digby, M D Robson,
S Neubuer, R P Choudhury. University of Oxford, Oxford, UK
Introduction It has been proposed that perivascular adipose tissue
(PVAT) contributes to inflammation and advancement of atheroA70
sclerosis via a direct paracrine or vasocrine route. Excess adipose
tissue accumulation leads to adipose tissue dysfunction characterised by a pro-inflammatory and potentially pro-atherogenic
pattern of adipokine secretion. We used MRI for PVAT imaging and
quantification and evaluated the effects of obesity and increased
perivascular adiposity on the relationship of PVATwith the function
and structure of the underlying vessels.
Methods We measured peri-aortic fat, aortic stiffness and atheroma
burden by MRI in 128 cardiovascular patients and in 18 healthy lean
subjects at baseline and in 22 healthy obese subjects (before and
after weight loss intervention (diet or bariatric surgery). Fat around
the brachial artery and FMD of the brachial artery was measured
among 75 cardiovascular patients.
Results There was good inter-observer and intra-observer reproducibility (coefficient of variance (CV) <6% and<5%) and inter-scan
repeatability (CV<8%) of the measurement of PVAT. After adjustment for anthropometric indices, demographics and cardiovascular
risk factors as appropriate: I) A positive independent association
between PVAT and aortic atheroma was detected among obese
participants (BMI$30 kg/m2)(p<0.005) but not among individuals
with intermediate (BMI<30 and $26) and low BMI (BMI<26). II)
Perivascular fat was independently, inversely associated with aortic
stiffness among lean patients (p<0.0005) while the association was
independent and positive for obese participants (p<0.05). III) An
independent, negative linear correlation between peri-brachial fat and
FMD was noted among overweight and obese subjects (BMI$26)
(p<0.001), but not among normal weight participants (BMI<26).
IV) PVAT was an independent negative predictor of aortic elasticity
among healthy obese individuals (BMI$30) (p<0.01) while it was
positively and independently associated with aortic elasticity among
lean healthy controls (BMI#18) (p<0.05). V) Following weight loss
intervention, PVAT reduction was an independent predictor of aortic
elasticity improvement in the obese group (p<0.05).
Conclusions Our results suggest an influence of both generalised and
regional excess adiposity on the functional state and the effects of
perivascular adipose tissue on dysfunction and remodelling of the
underlying vessels.
123
CARDIOVASCULAR RISK IN ASYMPTOMATIC POTENTIAL
SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANT
RECIPIENTS IS DETERMINED BY MYOCARDIAL PERFUSION
SCINTIGRAPHY
doi:10.1136/heartjnl-2011-300198.123
V M S Stoll, N S Sabharwal, O O Ormerod. The John Radcliffe Hospital, Oxford, UK
Introduction More than 50% of renal transplant recipients will die as
a consequence of cardiovascular disease (CVD). Type I diabetics
undergoing simultaneous pancreas-kidney transplantation (SPK) are
at an even greater risk of CVD. Optimising a patient9 s cardiovascular status is necessary before SPK transplant surgery. Patients can
remain on transplant waiting lists for years. There is little evidence
as to how frequently repeat cardiovascular risk assessments are
required in asymptomatic patients. Myocardial perfusion scintigraphy is used in SPK patients to detect any asymptomatic myocardial ischaemia or abnormal left ventricular function. This study
analyses data from a SPK transplant centre with an annual surveillance programme to aim to establish the suitable frequency of MPS.
Methods Potential SPK transplant recipients who had undergone
two perfusion scans were included for analysis. An abnormal MPS
was defined as either showing a regional wall motion abnormality,
inducible ischaemia, or impaired left ventricular function. The scan
results were both documented and compared. Angiography results
from the study period were also recorded.
Results 99 out of 130 patients on the SPK waiting list in November
2009 had undergone two perfusion scans as part of their
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
pre-transplant assessment. The median age was 45 yrs (range
26e63), with 41% female and a median time between scans of
1.4 yrs (range 0.6e3.0). 59 patients (60%) had two consecutive
normal scans. The remaining 40 patients had at least one abnormal
scan. 16% of patients with a normal 1st scan developed an abnormal
2nd scan within a median period of 1.4 years. 28 (70%) of the
patients with an abnormal MPS underwent angiography, of these 12
required revascularisation (either PCI or CABG). Of the remaining
16 patients; 1 died before angiography and the other 15 patients
were treated with medical therapy. Of the 59 patients with two
normal scans; 3 underwent angiography during the study period (for
new symptoms), 1 of these patients required revascularisation after
presenting with an ACS. 2 had minor plaque disease.
Conclusions 40% of SPK patients on the waiting list have an
abnormal MPS. Of the patients with normal scans 5% required an
angiogram because of new symptoms with only 2% requiring
revascularisation. Of the patients undergoing angiography driven by
MPS 43% subsequently underwent revascularisation. The current
screening interval is successfully monitoring changes in the patients’
cardiovascular status with only one patient requiring an intervention which was not predicted by MPS. Therefore a near annual
MPS is a useful, non-invasive means by which to monitor patients
at very high risk of asymptomatic cardiovascular disease while
awaiting a SPK transplant.
124
VALIDATION OF THE BCIS-1 MYOCARDIAL JEOPARDY
SCORE USING CARDIAC MRI
doi:10.1136/heartjnl-2011-300198.124
1
G D J Morton, 2K De Silva, 1M Ishida, 1A Chiribiri, 1A Indermuhle, 1A Schuster,
S Redwood, 1E Nagel, 1D Perera. 1King’s College London, London, UK; 2Guy’s and St
Thomas’ NHS Foundation Trust, London, UK
2
Introduction The recently described angiographic BCIS-1 Myocardial
Jeopardy Score (BCIS JS) was designed to classify the extent of
coronary artery disease (CAD). It provides a semi quantitative
estimate of the amount of myocardium at risk as a result of severe
coronary stenoses (0Вјno jeopardy; 12Вјmaximum jeopardy).
Advantages include ease of use and universal applicability including
classification of left main stem disease and CABG. However
anatomic tests, including the BCIS JS, do not incorporate myocardial ischaemia and scar, which are important for management and
prognosis. Cardiac magnetic resonance (CMR) imaging allows reliable assessments of myocardial ischaemia and scar in a single
examination and was used to examine the functional relevance of
the BCIS JS.
Methods 60 consecutive patients with angina and known or
suspected CAD referred for diagnostic x-ray coronary angiography
underwent CMR examination at a single UK centre. CMR included
standard functional and scar imaging and also high-resolution k-t
accelerated adenosine stress and rest perfusion imaging at 1.5T (40
patients) or 3T (20 patients). Expert observers blinded to the clinical
data analysed the angiographic and CMR data. The BCIS JS was
calculated from visual analysis of the coronary angiogram. CMR
perfusion and scar data were segmented according to the standard
17-segment model excluding the apex. Segments were subdivided
into equal endo- and epicardial sub-segments, each assigned 3% of
the total myocardial volume and classified as normal, ischaemia or
scar. Myocardial ischaemia and scar burden were calculated and
correlated with the BCIS JS individually and as a combined score
(Abstract 124 п¬Ѓgure 1).
Heart June 2011 Vol 97 Suppl 1
Abstract 124 Figure 1
Results Patient characteristics are summarised in the Abstract 124
table 1. 2 patients were excluded (1 claustrophobia; 1 incomplete
imaging data). Mean interval 6 SD between CMR and coronary
angiography was 40647 days. 13 patients (22%) with no history of
myocardial infarction had CMR evidence of prior infarction. There
was a strong correlation between the BCIS JS and myocardial
ischaemic burden: Pearson’s r¼0.75, p<0.00001 (Abstract 124 figure
2). The BCIS JS was also correlated with the combined burden of
scar and ischaemia: r Вј 0.77, p<0.00001. There was no difference
between 3T and 1.5T CMR imaging. Area under the receiver-operating characteristic curve for BCIS JS to detect $10% myocardial
ischaemic burden was 0.87 (95% CI 0.77 to 0.97). BCIS JS $6
predicted $10% myocardial ischaemic burden with sensitivity 68%
and specificity 90%.
Abstract 124 Figure 2
burden and BCIS JS.
Correlation between myocardial ischemic
Conclusions The BCIS JS correlated well with ischaemic burden on
CMR. A BCIS JS $6 predicts the prognostically important
ischaemic threshold of 10% with high specificity. As expected, the
correlation is imperfect which is likely to be a result of difficulty
predicting haemodynamic effects of angiographically moderate
disease, microvascular disease and limitations of CMR imaging.
A71
BCS Abstracts 2011
Abstract 124 Table 1
Characteristic
Number of patients
Age (mean6SD)
65610
Left ventricular ejection fraction (mean6standard deviation)
Male
59614%
48 (83%)
Diabetes
17 (29%)
Previous CABG
Previous percutaneous coronary intervention
13 (22%)
22 (38%)
Previous MI
Hypertension
10 (17%)
38 (66%)
125
ASSESSING PATIENT BENEFIT FROM THE
REVASCULARISATION OF CHRONICALLY OCCLUDED
CORONARY ARTERIES BY ADVANCED CARDIOVASCULAR
MRI TECHNIQUES
doi:10.1136/heartjnl-2011-300198.125
PCI and 3 with CABG). In those with successful revascularisation
by PCI LV volumes reduced (EDV 185 (54) vs 174 (50) p<0.05; ESV
85(60) vs 77(58) p<0.001) and the left ventricular ejection fraction
improved (56.5(12)% vs 58.9(12)% pВј0.01). During adenosine stress
imaging there was a significant improvement in absolute myocardial
blood flow in the revascularised segments (from 1.87(0.51) to 3.77
(0.67) ml/g/min p<0.001) but not in the remote regions (from 3.76
(0.52) to 3.95(0.58) ml/g/min pВјns). LGE was only present in 25
(20%) revascularised segments. In these segments there was a strong
inverse correlation between the extent of scar and improvement in
segmental systolic thickening (rВјГЂ0.736, p<0.001). There was a
weaker association between the segmental response to low dose
dobutamine and the degree of functional improvement following
successful revascularisation (Pearson rВј0.249, p<0.01).
Conclusion Following revascularisation of CTO, myocardial perfusion increases and both regional and global systolic function
improves. While the majority of subjects in this study had no scar
on LGE imaging, when segments are scarred there is a negative
correlation with improvement in regional systolic thickening.
1
N J Artis, 2A Crean, 1A Zaman, 1S Sorbron, 1A N Mather, 1S G Ball, 1S Plein,
J P Greenwood. 1University of Leeds, Leeds, UK; 2Toronto General Hospital, Toronto,
Canada
1
Background Cardiovascular magnetic resonance (CMR) imaging can
provide an array of information about cardiac function and anatomy.
The utility of CMR in the setting of coronary artery chronic total
occlusion (CTO) has not been fully investigated. We set out to
examine the ability of CMR to show regional improvements in left
ventricular (LV) function and perfusion and to investigate if any
features were able to predict those that benefit from revascularisation.
Methods Twenty-seven patients with single vessel CTO were
recruited from clinical waiting lists and underwent a comprehensive
CMR assessment prior to and 6 months following attempted CTO
revascularisation. A multi-parametric CMR protocol was performed
which included cine imaging to assess regional wall thickness/
thickening and global LV function, rest and adenosine stress perfusion imaging (Fermi model), low dose dobutamine stress to assess
inotropic reserve, and late gadolinium enhancement (LGE) imaging
to determine scar location and extent. Using the AHA 16 segment
model only segments supplied by the CTO artery were studied for
functional improvement. Data are presented as mean (SD).
Results Procedural success in terms of revascularisation of the
occluded artery was achieved in 23 of the 27 patients (85%, 20 with
Abstract 125 Figure 2 Relationship of improvement in segmental
systolic thickening against segmental scar (top panel) and change in
thickening with low dose dobutamine (bottom panel).
126
THE IMPACT OF NICE GUIDELINES FOR THE INVESTIGATION
OF CHEST PAIN ON OUTPATIENT CARDIOLOGY SERVICES IN
THE UK
doi:10.1136/heartjnl-2011-300198.126
Abstract 125 Figure 1 Changes observed in the CTO and a remote
territory following attempted revascularisation. (non-revascularisedd
black lines). Adenosine stress increases perfusion only in the CTO
territory with no change in resting perfusion.
A72
1
C Patterson, 2E Nicol, 3L Bryan, 4T Woodcock, 1S Padley, 1D Bell. 1Imperial College,
London, UK; 2Royal Brompton Hospital, London, UK; 3Chelsea and Westminster
Hospital, London, UK; 4NIHR CLAHRC for Northwest London, London, UK
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
Introduction The National Institute for Health and Clinical Excellence
(NICE) have released guidelines for the investigation of chest pain of
recent onset (1). There is concern that the guidelines will increase
the burden on cardiac imaging, requiring service reconfiguration and
investment (2, 3). This study was performed to assess the impact of
the guidelines on outpatient cardiology services in the UK.
Methods 595 consecutive patients attending chest pain clinics at
two hospitals over six months preceding release of the NICE
guidelines (51% male; median age 55 yrs (range 22e94 yrs)) were
risk stratified using NICE criteria. Preliminary cardiac investigations
recommended by NICE were compared with existing clinical practice and the relative costs calculated.
Results NICE would have recommended 443 patients (74%) for
discharge without cardiac investigation, 10 (2%) for cardiac
computed tomography (CCT), 69 (12%) for functional cardiac
imaging and 73 (12%) for invasive coronary angiography (ICA).
Relative to existing practice there would have been a trend towards
reduced functional cardiac imaging (ГЂ24%; pВј0.06) and increased
CCT (+43%; p¼0.436) but a significant increase in ICA (+508%;
p<0.001). The cost of investigations recommended by NICE would
have been ВЈ15 881 greater than existing practice.
Conclusions This study suggests implementation of the NICE guidelines will require investment in cardiology services, particularly ICA. It
will be necessary to establish and maintain CCT for relatively few
patients; also to establish and maintain functional cardiac imaging
even though referrals are likely to decline. Individual hospitals should
assess their local populations prior to service reconfiguration.
Abstract 126 Table 1 Preliminary cardiac investigations undertaken
(pre-NICE) compared with those recommended by NICE (NВј595)
Pre-NICE
NICE
% change
No investigation
Cardiac CT
33
7
443
10
+1242% (p<0.001)
+43% (p 0.436)
Functional cardiac assessment
Invasive angiography
91
12
69
73
127
ГЂ24% (p 0.06)
+508 (p<0.001)
TIMING OF CARDIOVASCULAR MRI AFTER ACUTE
MYOCARDIAL INFARCTION: EFFECT ON ESTIMATES OF
INFARCT CHARACTERISTICS AND PREDICTION OF LATE
VENTRICULAR REMODELLING
doi:10.1136/heartjnl-2011-300198.127
A N Mather, T A Fairbairn, N J Artis, J P Greenwood, S Plein. University of Leeds,
Leeds, UK
Background The pathophysiological remodelling processes associated with acute myocardial infarction (AMI) evolve over time and
the optimal acute imaging time point to predict medium-term
surrogates for outcome has not been established. This study aimed to
define the evolution of infarct characteristics by cardiovascular
magnetic resonance (CMR), and to assess whether CMR data
acquired at “day 2” or at “1 week” post-AMI are stronger predictors of
infarct size and left ventricular (LV) function measured at 3 months.
Methods Fifty-seven patients were recruited with п¬Ѓrst presentation
ST elevation AMI treated successfully with primary percutaneous
coronary intervention. Cine, T2- weighted and late gadolinium
enhancement CMR imaging were performed at days 2, 7, 30 and 90
after index presentation.
Results Infarct size and extent of myocardial oedema decreased
significantly between “day 2” and “1 week” (mean %LV-scar (SD)
27.2 (13.9) vs 21.6 (14.1), p<0.001 and %LV-AAR (Area At Risk)
(SD), 37.9 (15.2) vs 32.3 (14.3), pВј0.003). These changes were
accompanied by a significant improvement in LV ejection fraction
(%LVEF (SD), 41.7 (9.6) vs 44.6 (10.1), p<0.001). CMR data
Heart June 2011 Vol 97 Suppl 1
acquired at “1 week” were better predictors of LVEF and infarct size
at “3 months” than data collected at “day 2”.
Conclusions The extent of myocardial oedema and infarct size
decrease significantly during the first week after reperfusion for AMI
and these changes are associated with a significant improvement in
LVEF over the same interval. These п¬Ѓndings have implications for
the timing of CMR studies in the early post-infarct period. We
found that the percentage myocardial salvage index did not change
significantly between “day 2” and “1 week”. Therefore, accurate
assessment of the efficacy of reperfusion therapy can be made up to
one week after revascularization. In addition, CMR data acquired at
“1 week” were better predictors of CMR endpoints measured at
“3 months”. Thus, we conclude that the optimal time point to
image patients post-reperfusion therapy for AMI is at 1 week.
128
BRIGHT BLOOD T2 WEIGHTED MRI HAS HIGHER
DIAGNOSTIC PRECISION AND ACCURACY THAN DARK
BLOOD STIR MRI FOR ASSESSMENT OF THE ISCHAEMIC
AREA-AT-RISK AND MYOCARDIAL SALVAGE IN ACUTE
MYOCARDIAL INFARCTION
doi:10.1136/heartjnl-2011-300198.128
1
A R Payne, 1M Casey, 1J McClure, 2R McGeoch, 2A Murphy, 2R Woodward, 2A Saul,
J Gilchrist, 2C Clark, 2K G Oldroyd, 1N Tzemos, 1C Berry. 1University of Glasgow,
Glasgow, UK; 2Golden Jubilee National Hospital, Glasgow, UK
2
Background T2-weighted MRI reveals myocardial oedema and enables
estimation of the ischaemic area-at-risk and myocardial salvage in
patients with acute myocardial infarction (MI). We compared the
diagnostic accuracy of a new bright blood T2-weighted with a
standard black blood T2-weighted MRI in patients with acute MI.
Methods A breath hold bright blood T2-weighted ACUTE pulse
sequence with normalisation for coil sensitivity and a breath hold T2
dark blood short s inversion recovery (STIR) sequence were used to
depict the area-at-risk in 54 consecutive acute MI patients. Infarct
size was measured on gadolinium late contrast enhancement images.
Results Compared with dark blood T2-weighted MRI, consensus
agreements between independent observers for identification of
myocardial oedema were higher with bright blood T2 -weighted MRI
when evaluated per patient (p<0.001) and per segment of left
ventricle (p<0.001). Compared to bright blood T2-weighted MRI,
dark blood T2-weighted MRI under-estimated the area-at-risk
compared to infarct size (p<0.001). The 95% limits of agreement for
inter-observer agreements for the ischaemic area-at-risk and myocardial salvage were wider with dark blood T2-weighted MRI than with
bright blood T2-weighted MRI. Bright blood enabled more accurate
identification of the culprit coronary artery with correct identification
in 94% of cases compared to 61% for dark blood (p<0.001).
Conclusion Bright blood T2-weighted MRI has higher diagnostic
accuracy than dark blood T2-weighted MRI. Additionally, dark
blood T2-weighted MRI may underestimate area-at-risk and
myocardial salvage.
129
MYOCARDIAL SALVAGE DURING PRIMARY PCI CAN BE
PREDICTED IN THE CATH LAB
doi:10.1136/heartjnl-2011-300198.129
1
A R Payne, 1C Berry, 1O Doolin, 2M B McEntegart, 2R Woodward, 2A Saul, 2S D Robb,
M C Petrie, 1I Ford, 2K G Oldroyd. 1University of Glasgow, Glasgow, UK; 2Golden
Jubilee National Hospital, Glasgow, UK
2
Objectives This study investigated the relationship between the
index of microcirculatory resistance (IMR) and myocardial salvage
as determined by T2-weighted and contrast-enhanced cardiac
magnetic resonance (CMR) imaging in patients undergoing primary
percutaneous coronary intervention (pPCI) for ST elevation
myocardial infarction (STEMI).
A73
BCS Abstracts 2011
Background IMR is a simple invasive measure of microvascular
function available at the time of pPCI. T2-weighted non-contrast
CMR can reveal myocardial oedema, and in the post-infarct population this represents the ischaemic area at risk (AAR). Contrastenhanced CMR delineates the area of myocardial infarction. The
volume of myocardium within the AAR, but not contained within
the infarct area is salvaged myocardium.
Methods 108 patients with STEMI underwent invasive coronary
physiology measurements during pPCI and had a subsequent CMR
scan at a median of 19 h post pPCI. Short axis non-contrast T2weighted images were acquired and delayed enhancement imaging
was performed following administration of intravenous gadolinium
(0.1 mmol/kg). AAR was determined and myocardial salvage was
calculated as AARdinfarct area.
Results IMR was 29 (21), AAR 32% (13%) and myocardial salvage
6% (9%)dall mean (SD). Spearman rank correlation between IMR
and AAR was 0.27 (p 0.02) and between IMR and salvage was ГЂ0.31
(p 0.01). IMR was also a multivariate predictor of AAR (p 0.01) and
a negative multivariate predictor of myocardial salvage (p 0.02).
Conclusions IMR measured acutely correlates with AAR and correlates negatively with myocardial salvage as determined by MRI.
130
COMPARISON OF HARMONIC PHASE IMAGING WITH
LOCAL SINE WAVE MODELLING FOR THE ASSESSMENT OF
CIRCUMFERENTIAL MYOCARDIAL STRAIN USING TAGGED
CARDIOVASCULAR MAGNETIC RESONANCE IMAGES
doi:10.1136/heartjnl-2011-300198.130
A N Borg, 1C A Miller, 2C D Steadman, 2G P McCann, 1M Schmitt. 1University
Hospital of South Manchester, Manchester; 2NIHR Leicester Cardiovascular Biomedical
Research Unit, Leicester, UK
repeatability co-efficient (RC) 2.14; intra-observer R¼0.99, RC 1.49).
Reproducibility of global ecc measurements by HARP was somewhat lower, but still high (inter-observer RВј0.89, RC 4.80; intraobserver RВј0.98, RC 2.73). There was much greater variability in
segmental ecc measurements using both methods, particularly with
HARP (Abstract 130 п¬Ѓgure 2).
Abstract 130 Figure 1
Abstract 130 Table 1
1
Introduction Assessment of myocardial strain promises to become an
important quantitative tool in early diagnosis of cardiac disease and
treatment monitoring. Advances in image processing software have
facilitated rapid and clinically feasible analysis of strain from tagged
cardiac magnetic resonance (CMR) images. Harmonic Phase Analysis (HARP) or Local Sine Wave Modelling (SinMod) can be used for
automated derivation of strain. We obtained tagged CMR images to
compare measurements of left ventricular (LV) circumferential
strain obtained using a HARP with a SinMod method.
Methods Ten normal controls, 10 hypertrophic and 10 dilated
cardiomyopathy patients (mean age 46.6614.8 years) were
included. Spatial modulation of magnetisation using short-axis LV
slices at mid-ventricular level, with a temporal resolution of
30e50 mS, were obtained using a 1.5 Tesla scanner (Siemens
Avanto) with a 32-channel coil. Global and segmental transmural
peak circumferential strains (ecc) were measured using HARP
(Diagnosoft, USA, version 2.7) and SinMod (InTag, University of
Lyons, France, version 3.6.1). Prior to running the algorithm, both
methods involve manual tracing of the endocardial and epicardial
borders, and localisation of right ventricle-to-septum insertion
points, in one frame. Agreement between HARP and SinMod was
assessed by Spearman’s correlation co-efficient R and Bland Altman
methods. Repeated measurements were carried out on 10 randomly
selected scans to assess reproducibility.
Results There was a high level of agreement between HARP and
SinMod for global ecc (HARPdSinMod mean difference: ГЂ0.12%,
95% limits of agreement: ГЂ5.69% to 5.45%, RВј0.83, p<0.001)
(Abstract 130 п¬Ѓgure 1). Agreement was much lower for segmental
ecc, ranging from very poor in lateral segments to modest in inferoseptal segments (Abstract 130 table 1). Analysis time using SinMod
was significantly shorter than for HARP (84642 vs 2016120 S,
pВј0.02). Inter- and intra-observer reproducibility were extremely
high for SinMod measurements of global ecc (inter-observer RВј0.99,
A74
Analysed segment
for circumferential
strain
HARP vs SinMod
Mean Difference
В± SD (%)
HARP vs SinMod
95% Limits of
agreement (%)
HARP vs
SinMod
Correlation
Coefficient
Anterior
Anterolateral
ГЂ1.6866.38
ГЂ3.1868.07
ГЂ14.18 to 10.82
ГЂ18.99 to 12.64
0.59
0.22
0.001
0.25
1.4868.24
1.3366.17
ГЂ14.67 to 17.62
ГЂ10.76 to 13.42
0.24
0.48
0.21
0.008
Inferoseptal
Anteroseptal
ГЂ1.6665.63
ГЂ2.4766.77
ГЂ12.68 to 9.37
ГЂ15.73 to 10.79
0.59
0.52
0.001
0.007
All 6 segments
pooled
ГЂ0.9967.11
ГЂ14.92 to 12.95
0.43
<0.001
Inferolateral
Inferior
p-value for
correlation
Abstract 130 Figure 2 Inter- and intra observer variability for HARP
local sine wave modelling: repeatability co-efficients.
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
Conclusions HARP and SinMod methods show a high level of
agreement for assessment of global mid-ventricular transmural
circumferential strain, with good reproducibility for both individual
methods. Agreement is much lower for segmental measurements;
poor reproducibility for segmental measurements using both techniques probably reflect user variability in identification of right
ventricular septal insertion points and contour tracing.
131
AETIOLOGICAL ROLE OF FOLATE DEFICIENCY IN
CONGENITAL HEART DISEASE: EVIDENCE FROM
MENDELIAN RANDOMISATION AND META-ANALYSIS
doi:10.1136/heartjnl-2011-300198.131
V Mamasoula, T Pierscionek, D Hall, J Palomino-Doza, A Topf, T Rahman, J Goodship,
B Keavney. Institute of Human Genetics, Newcastle upon Tyne, UK
Background The existence of a causal relationship between lower
levels of plasma folate and congenital heart disease (CHD) remains
contentious. Randomised trials of this question are not possible, in
view of the known protective effect of folate against neural tube
defects (NTDs). Folate fortification of flour is known to reduce the
incidence of NTDs, but it is not known whether there is any effect
on CHD. Clarity regarding the relationship between folate and
CHD could potentially inform the practice of folate fortification. We
present a genetic approach using “Mendelian randomisation” to
determining the causality of folate in CHD risk.
Methods We compared genotype frequencies at the methylene
tetrahydrofolate reductase (MTHFR) C677T single nucleotide
polymorphism (SNP) in 1186 CHD cases and 4168 controls. The TT
genotype at MTHFR C677T is known to be associated with lower
activity of MTHFR and plasma folate, and higher levels of plasma
homocysteine. The effect of TT genotype on plasma folate levels is
greater in conditions of folate deficiency. Thus, if lower plasma
folate had a causal effect on CHD risk, a higher frequency of TT
genotype among CHD cases than among healthy controls would
be anticipated, and this would be expected to be more marked
in conditions of folate deficiency. We placed our results in the
context of a meta-analysis of all previously published studies of this
question (to September 2010), which together included 1883 cases
and 3069 controls in 25 studies. Thus, the combined analyses
included 3069 CHD cases and 7271 controls. We used randomeffects models to combine the data. We conducted sensitivity
analyses to examine folate fortification of flour as a potential source
of heterogeneity.
Results The primary genotyping data in 1186 cases and 4168
controls revealed a trend towards increased risk with the TT
genotype, but this did not reach statistical significance (OR 1.15
(95% CI 0.94 to 1.40)). Combination of our primary data with
previous studies, however, revealed association in the larger dataset
(OR 1.45 (95% CI 1.12 to 1.89); pВј0.005). The population attributable fraction for the TT genotype was 3% of CHD. There was no
evidence of publication bias among the contributing studies. We
discovered folate fortification status to be a significant source of
heterogeneity. Studies conducted in countries with mandatory
folate fortification showed no effect of C677T genotype on CHD
risk (OR 0.96 (95% CI 0.64 to 1.44)), whereas studies conducted in
countries without mandatory fortification showed a significant
effect of genotype (OR 1.63 (95% CI 1.19 to 2.25)). These ORs were
significantly different from each other (p¼0.032).
Conclusions We demonstrate genetic evidence in favour of a causal
relationship between plasma folate and CHD. The absence of a
genetic association in countries practicing folate fortification
suggests that fortification largely abrogates the risk of CHD
attributable to folate deficiency.
Heart June 2011 Vol 97 Suppl 1
132
NON-SYNONYMOUS SMAD6 MUTATIONS IMPAIRED
INHIBITION OF BMP SIGNALLING IN PATIENTS WITH
CONGENITAL CARDIOVASCULAR MALFORMATION
doi:10.1136/heartjnl-2011-300198.132
1
1
1
1
2
H L Tan, E A Glen, A L Topf, D H Hall, J J O’Sullivan, 2L Sneddon, 2C Wren,
P Avery, 4R J Lewis, 5P ten Dijke, 1H M Arthur, 1J A Goodship, 1B D Keavney.
1
Institute of Human Genetics, Newcastle University, Newcastle upon Tyne, UK;
2
Freeman Hospital, Newcastle upon Tyne, UK; 3School of Mathematics & Statistics,
Newcastle University, Newcastle upon Tyne, UK; 4Institute for Cell and Molecular
Biosciences, Newcastle University, Newcastle upon Tyne, UK; 5Department of
Molecular Cell Biology and Center for Biomedical Genetics, Leiden University, Leiden, UK
3
Introduction Congenital cardiovascular malformation (CVM)
exhibits familial predisposition but the specific genetic factors
involved are unknown. Bone morphogenetic proteins (BMPs) regulate many processes during development, including cardiac development. Five genes of the BMP signalling were surveyed for novel
variants predisposing to CVM risk. One of the genes, SMAD6,
functions as an inhibitory SMAD which preferentially inhibits BMP
signalling. The SMAD6 knockout mouse is characterised by cardiac
valve and outflow tract defects, including aortic ossification. We
hypothesised that rare functional variation in SMAD6 could
predispose to congenital cardiovascular malformation (CVM).
Methods The coding regions of BMP2, BMP4, BMPR1A, BMPR2 and
SMAD6 were sequenced in 90 unrelated Caucasian cases of CVM.
The MH2 domain of SMAD6 were further sequenced in additional
346 CVM patients. Functional effects of the wild-type and variant
SMAD6 proteins were expressed in C2C12 cells and their capacity to
inhibit ALK3 activated expression of a BMP-responsive reporter, or
to inhibit osteogenic differentiation (using an alkaline phosphatase
assay) was assessed.
Results We identified two novel non-synonymous variants, P415L
and C484F, that were not present in 1000 ethnically-matched
controls. P415L was identified in a patient with congenital aortic
stenosis and C484F was identified in a patient with coarctation and
calcification of the aorta. Both mutations are in evolutionarily
conserved amino acid residues and are predicted to be damaging by
in silico analysis. This was confirmed in functional assays as both
SMAD6 variants failed to inhibit BMP signalling compared with
wild-type SMAD6. The P415L mutant appeared to be hypomorphic
whereas C484F appeared to be a null allele in the luciferase assay.
The C484F mutant had a significantly (p<0.05) lower capacity to
inhibit alkaline phosphatase generation in response to BMP signalling.
Conclusions This is the п¬Ѓrst time that functional mutations in
SMAD6 have been described in patients with CVM, specifically
those with calcific aortic malformations. Our data suggest that
inadequate inhibition of BMP signalling pathway due to genetic
variation in SMAD6 may be an important factor in CVM.
133
ACTIVITY AND PSYCHOSOCIAL HEALTH IN ADOLESCENTS
WITH CONGENITAL HEART DISEASE (CHD)
doi:10.1136/heartjnl-2011-300198.133
1
1
1,2
M L Morrison, A J Sands, C G McCusker, 2P P McKeown, 1M McMahon,
J Gordon, 1B G Craig, 1,2F A Casey. 1Royal Belfast Hospital for Sick Children, Belfast,
UK; 2The Queen’s University of Belfast, Belfast, UK
1
Many patients with CHD are now adolescents. Like other patients
with chronic illnesses they may be at higher risk of psychological/
emotional problems. Ability to exercise is an important quality of
life measure and indicator of physical health. We aimed to ascertain
if activity and psychosocial health were reduced in adolescents with
major CHD compared to those with a minor diagnosis. Patients
aged 12e20 years were identified using the Northern Ireland
regional database (HeartSuite). Participants were categorised as
having major or minor CHD and divided into four diagnostic
A75
BCS Abstracts 2011
subgroups. Participants completed validated, age-appropriate questionnaires examining standard psychological parameters. Participants also underwent an evaluation of exercise, including formal
exercise stress testing and measurement of free-living activity using
an ActiGraph accelerometer. Results were analysed using parametric
methods. 143 patients (mean age 15.6 years) consented to participate, 86 were male (60%) and 105 had major CHD (73%). Diagnostic subgroups included 39 acyanotic (27.3%), 61 acyanotic
corrected (42.7%), 30 cyanotic corrected (21.0%) and 13 (9%)
cyanotic palliated patients. Beck Youth Inventory demonstrated
that individuals with major CHD, particularly cyanotic palliated
patients, had higher anxiety scores (p value 0.01 (ГЂ8.42, ГЂ1.13)).
There were no significant differences across study groups for selfesteem or other psychological parameters. 134 participants (93.7%)
took part in regular exercise each week. There was no significant
difference in activity score between study groups. On formal exercise testing, more complex patients performed worse at peak exercise. Exercise time for acyanotic group 11.73 mins (sd 3.74)
compared to 8.26 mins (sd 4.08) in cyanotic palliated group, p value
0.002 (1.32, 5.61)). However, patients with major CHD had significantly higher activity counts. Correlation analysis showed that selfesteem and health locus of control were important predictor variables for activity. Self-esteem and mood seem well preserved in
adolescents with CHD as a whole. The majority of young people
with CHD, in this group, take part in regular exercise. Surprisingly,
complex patients rate themselves to be as active as those with minor
CHD. While accelerometer data indicate that the group may be
more active day to day, they are limited in terms of peak exercise
duration. The experience of growing up with a chronic condition
may therefore have a positive effect on psychological health and
interventions targeted around this area may influence activity.
134
MUTATIONS IN THE SARCOMERE PROTEIN GENE MYH7 IN
EBSTEIN’S ANOMALY
doi:10.1136/heartjnl-2011-300198.134
1
T Rahman, 1J Goodship, 2A Postma, 2K Engelen, 2B Mulder, 3S Klaassen, 4B Keavney.
Institute of Human Genetics, Newcastle upon Tyne, UK; 2Academic Medical Centre,
Amsterdam, The Netherlands; 3Max-Delbrueck-Center for Molecular Medicine, Berlin,
Germany; 4Institute of Human Genetics, Newcastle upon Tyne, UK
1
Background Ebstein’s anomaly is a rare congenital heart malformation characterised by adherence of the septal and posterior leaflets of
the tricuspid valve to the underlying myocardium. As there have
been reports of abnormal left ventricular morphology and function
in patients with Ebstein’s anomaly we hypothesised that mutations
in the b-myosin heavy chain (MYH7) may be associated with
Ebstein’s anomaly.
Methods MYH7 mutation analysis was undertaken in 141 unrelated
affected individuals with Ebstein’s anomaly using next-generation
sequencing on the 454 platform. 64 probands had no associated
cardiac anomalies. The most common associated cardiac malformation were atrial septal defect (48 probands) and left ventricular
non-compaction (LVNC) (7 probands). Where mutations were
discovered, family studies were undertaken and the segregation of
the mutation with disease was investigated.
Results Heterozygous mutations were identified in eight of the
probands including six of the seven with LVNC. Two patients had
the same mutation; of the seven distinct mutations, п¬Ѓve were novel
(four missense changes and an in-frame deletion) and two have been
previously reported in patients with hypertrophic cardiomyopathy.
Family studies revealed additional members with LVNC for three of
the probands, one of whom also had a relative with Ebstein’s anomaly.
In these three pedigrees the mutation segregated with disease.
Conclusions Mutations in MYH7 occur relatively frequently in
Ebstein’s anomaly accompanied by LVNC. This study is another
A76
example of mutations in a sarcomere protein causing congenital
heart malformation.
135
GENE SCREENING OF THE SECONDARY HEART FIELD
NETWORK IN TETRALOGY OF FALLOT PATIENTS
doi:10.1136/heartjnl-2011-300198.135
A ToВЁpf, H R Griffin, D H Hall, E Glen, B D Keavney, J A Goodship; The Change Study
Collaborators. Institute of Human Genetics, Newcastle upon Tyne, UK
Background Tetralogy of Fallot (TOF) is the most common cyanotic
heart defect, affecting 3e6 infants for every 10 000 births. TOF is
phenotypically well defined; it consists of four heart abnormalities: a
VSD, an over-riding aorta, a narrowed pulmonary valve and right
ventricular hypertrophy. During heart development two heart п¬Ѓelds
can be distinguished. The п¬Ѓrst one gives origin to the left ventricle
and contributes to the right and left atria. The secondary heart п¬Ѓeld
gives origin to the right ventricle and the outflow tract. Each of
these fields can be identified by the expression of specific markers. As
TOF is a malformation of the outflow tract, we hypothesised genes
involved in the regulatory network of the secondary heart п¬Ѓeld were
particularly good candidates for TOF susceptibility.
Methods We examined by standard Sanger method the full exonic
and intron boundary regions of 14 secondary heart п¬Ѓeld genes,
namely NKX2-5, GATA4, TBX20, MEF2C, BOP, HAND2, FOXC1,
FOXC2, TBX1, FOXA2, FGF10, FGF8, ISL1 and FOXH1, in a panel of
93 TOF patients. All newly discovered rare variants were checked in
a panel of 1000 control chromosomes by multiplex Sequenom
assays. When available, parents of cases were screened to assess
inheritance of the rare variant.
Results We re-sequenced a total of 80 exons and w30 Kb. Among
the 14 genes studied we found a total of 50 new variants, of which
23 were exclusive to the patient population, ie, were absent from
1000 normal chromosomes. Nine of these variants cause change in
the aminoacid sequence. We found a functional 19aa deletion of a
highly conserved region of TBX1. In FOXC1 we found a contraction
of both alanine and glycine tracts. An alanine expansion, usually
known to be deleterious, was found in HAND2. Four non-synonymous changes were found in FOXA2. Most patients presented just
one variant, however 3 patients presented two, and one patient
presented up to 3 variants. All patients were heterozygotes for the
variants, and had inherited them from one of their phenotypically
normal parents (when parental information was available). In
addition, 75% of the variants were inherited from the mother.
Conclusions Although genes of the secondary heart п¬Ѓeld seemed
good candidates for TOF susceptibility, thus far we have not found
any strong indication of unique causal effect, as all variation found
in probands was also present in their unaffected parents. However,
the presence of multiple variants in the same proband may result in
the disruption of gene-gene interactions in the secondary heart п¬Ѓeld
pathway, which in turn may lead to outflow tract defects. Based on
our results, it would seem more likely that susceptibility to TOF be
determined by a larger number of small genetic contributions which
are also modified by environmental factors. It is evident that larger
scale analysis of significant numbers of whole genomes/exomes will
be necessary to better understand the molecular aetiology of TOF.
136
SHOULD FAMILIAL SCREENING BE ROUTINELY OFFERED TO
PATIENTS WITH BICUSPID AORTIC VALVE DISEASE?
doi:10.1136/heartjnl-2011-300198.136
R Panayotova, S Hosmane, A Macnab, P Waterworth. University Hospital of South
Manchester, Manchester, UK
Background Bicuspid aortic valve (BAV) disease is one of the most
common congenital cardiac abnormalities with prevalence in the
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
general population of up to 2%. There has been growing evidence
supporting its familial predisposition with an autosomal dominant
pattern of inheritance. It is often associated with ascending aortic
dilatation and dissection, occurring at a younger age than in patients
with idiopathic aortic aneurysms. BAV disease carries a 6% lifetime
risk of aortic dissection, 9 times higher than that of the general
population. Thus, the presence of BAV and dilatation of the
ascending aorta requires regular monitoring with a view to timely
pre-emptive surgery. Current ACC/AHA guidelines state that
echocardiographic screening of п¬Ѓrst degree relatives of patients with
BAV is recommended. This, however, to our knowledge, is not
routinely done within the UK.
Methodology and Results We set out to explore the practicalities of
running a routine echocardiographic screening programme for п¬Ѓrst
degree relatives of patients with BAV disease. We identified a total of
47 patients who had undergone aortic valve surgery performed by
the same Consultant Cardiothoracic Surgeon in the context of BAV
disease in the period May 2007eSeptember 2009. Screening of п¬Ѓrst
degree relatives was offered to these patients. 24 patients (51%) gave
us information regarding family members who would like to attend
for an echocardiogram. A total of 75 п¬Ѓrst degree relatives were
referredean approximate average of 3 per patient. Out of these, 52
relatives (70%) actually attended for an appointment. The
remainder did not undergo testing with us as they either lived in a
different geographic region or expressed a personal preference not to
be scanned at this time. The incidence of newly diagnosed bicuspid
aortic valve disease in our cohort of п¬Ѓrst degree relatives was 8% (4
out of 52 relatives). One of these asymptomatic individuals had a
significant ascending aortic aneurysm, which required prompt
surgery. Among the relatives of the 24 index patients, there were a
total of 8 cases (3: 1 ratio) of bicuspid aortic valve diseasedeither
known or newly diagnosed via screening.
Conclusions There is a relatively high prevalence and incidence of
bicuspid aortic valve disease among п¬Ѓrst degree relatives of patients
with this common congenital cardiac abnormality. Routine echocardiographic screening should be offered to these families. Implementing such a programme is limited by adequate motivation to
attend for a screening test if well, and by varying clinical practice in
different geographic regions. Patients with bicuspid aortic valve
disease should be made aware of its familial pattern of inheritance
and screening of their п¬Ѓrst degree relatives should be actively
pursued in order to reduce the potential morbidity and mortality
associated with this condition and its related aortopathy.
137
A CITED2->VEGFA PATHWAY COUPLES MYOCARDIAL AND
CORONARY VASCULAR GROWTH IN THE DEVELOPING
MOUSE HEART
doi:10.1136/heartjnl-2011-300198.137
1
S D Bamforth, 1S T MacDonald, 1J Braganca, 1C-M Chen, 1C Broadbent,
J E Schneider, 2R Schwartz, 1S Bhattacharya. 1University of Oxford, Oxford, UK;
2
Texas A&M Health Science Centre, Houston, Texas, USA
1
Introduction Myocardial development is dependent on the concomitant growth of cardiomyocytes and a supporting vascular network.
The coupling of myocardial and coronary vascular development is
mediated in part by VEGFA signalling. Cited2 is a transcriptional cofactor that can inhibit hypoxia-activated transcription and also acts
as a co-activator for transcription factors such as TFAP2. Genetic
evidence indicates that Cited2 is essential for cardiac left-right
patterning via regulation of the Nodal-Pitx2c left-right patterning
pathway. Zygotic and epiblastic deletion of Cited2 results in atrioventricular septation, outflow tract and aortic arch abnormalities, as
well as left-right patterning defects such as right-isomerism. Cited2
is also essential for adrenal, neural crest, liver, lung, lens and
placental development. However, the early requirement of Cited2 in
Heart June 2011 Vol 97 Suppl 1
left-right patterning and placental development makes it difficult to
identify a later specific role for Cited2 in myocardial development. To
overcome this problem we therefore investigated the role of Cited2
in the myocardium by conditional deletion in cardiomyocyte precursors.
Methods Cited2 was selectively deleted from cardiomyocytes by
intercrossing mice transgenic for Cited2 and Nkx2-5Cre. Embryos
were collected and processed for analysis by histology, MRI, X-Gal
staining, quantitative reverse transcriptase PCR (Q-RTPCR), chromatin immunoprecipitation and transient transfection assays.
Results The cardiomyocyte specific knockout of Cited2 results in
abnormal myocardial compact zone growth and ventricular septal
defects. This is associated with a decreased ratio in the number of
small vessels to large vessels, and a reduction in Vegfa expression. We
also show that CITED2 is present at the Vegfa promoter in mouse
embryonic hearts, and that it stimulates human VEGFA promoter
activity in cooperation with TFAP2 transcription factors in transient transfection assays. However, we observed no change in the
myocardial expression of the left-right patterning gene Pitx2c, a
known target of Cited2.
Conclusions The myocardial and capillary defects observed in
myocardial loss of Cited2 are not associated with Pitx2c deficiency
and suggests that Cited2 can cause myocardial and vascular defects
via a mechanism that is distinct from its effect on the left-right
patterning pathway. Our results delineate a novel mechanism of
Vegfa regulation by CITED2 and TFAP2 transcription factors, and
indicate that coupling of myocardial and coronary vascular growth
in the developing mouse heart occurs, at least in part, through a
Cited2->Vegfa pathway. This pathway may be targeted for the
treatment of heart failure resulting from ischaemic heart disease.
138
CELL-SPECIFIC ROLE OF NOX2 NADPH OXIDASE IN
DEVELOPMENT OF ANGIOTENSIN II-INDUCED CARDIAC
FIBROSIS IN VIVO
doi:10.1136/heartjnl-2011-300198.138
1
1
1
1
2
S Chaubey, C E Murdoch, A Ivetic, B Yu, D Vanhoutte, 2S Heymans, 1A Brewer,
A M Shah. 1Kings College London BHF Centre of Excellence, London, UK; 2University
Hospital Maastricht, Maastricht, The Netherlands
1
Introduction Mice globally deficient in Nox2 are protected against
cardiac п¬Ѓbrosis in response to chronic AngII infusion even though
the degree of hypertrophy was unaltered. The selective effect of
Nox2 on fibrosis may reflect its activation in a non-cardiomyocyte
cell type. We hypothesised that Nox2, which is expressed in endothelial cells and inflammatory cells, may be important for cardiac
п¬Ѓbrosis in these cell types.
Methods To investigate the role of Nox2 in inflammatory cells, we
generated chimeric mice by irradiation (10Gy, 15 min) to deplete
resident bone marrow cells, followed by bone marrow (BM) transplantation, using the following permutations: wild-type (WT)
recipient with either KO or WT BM, and KO recipients with WT
BM. To assess the role of endothelial Nox2, we used transgenic mice
with endothelial-specific overexpression of Nox2 (TG) utilising the
tie2 promoter construct.
Result AngII (1.1 mg/kg/day, 14-day) infusion caused similar
increase in systolic hypertension and cardiac hypertrophy in all 3
chimeric groups. However, cardiac п¬Ѓbrosis assessed by Sirius red
staining was significantly lower in KO mice receiving WT BM
(0.560.1%) compared to the WT:WT group (2.760.7%) or in WT
receiving KO BM (2.360.6%). These data suggested that resident
Nox2-expressing cells are responsible for the protective effect
observed in global Nox2 KO mice. TG mice developed the same level
of systolic hypertension and hypertrophy as WT littermates after
AngII infusion. However, the extent of cardiac fibrosis was significantly greater in TG than WT by w2-fold (p<0.05). This was
associated with a greater degree of infiltration by CD45+
A77
BCS Abstracts 2011
inflammatory cells (w1.8-fold, p<0.05) and 30% (p<0.05) more
VCAM-1 positive blood vessels in AngII treated TG hearts.
Furthermore, isolated TG endothelial cells recruited w2-fold
(p<0.05) more leukocytes than WT upon AngII treatment.
Conclusion These results indicate there is a cell-specific role of
endothelial Nox2 in the development of п¬Ѓbrosis. Endothelial Nox2
enhances AngII-induced cardiac п¬Ѓbrosis, possibly by enhancing
inflammatory cell recruitment and influx via VCAM-1 expression.
Although inflammatory cells may be important for the development
of п¬Ѓbrosis, our results indicate that Nox2 in these cells is not
essential for any pro-п¬Ѓbrotic effect.
139
ENDOTHELIAL SPECIFIC INSULIN RESISTANCE PROMOTES
THE DEVELOPMENT OF ATHEROSCLEROSIS
doi:10.1136/heartjnl-2011-300198.139
1
M C Gage, 1N Yuldasheva, 2C Jackson, 1M Kearney, 1H Imrie, 1H Viswambharan,
M Kahn, 1J Smith, 1S Galloway, 1R Cubbon, 1P Sukumar, 1A Aziz, 1S Wheatcroft.
1
Leeds University, Leeds, UK; 2University of Bristol, Bristol, UK
1
Background Global insulin resistance and endothelial dysfunction
have been identified as predisposing factors for atherosclerosis.
However, it is unclear whether selective insulin resistance in endothelial cells alone, is sufficient to promote atherosclerosis. Here we
addressed this question by crossing Endothelial Specific Mutant
Insulin Receptor Over-expressing (ESMIRO) mice with ApoE null
mice. ESMIRO mice over-express a human insulin receptor with
Ala-Thr1134 mutation in the tyrosine kinase domain (which
disrupts insulin signalling) selectively in endothelial cells under the
control of the tie-2 promoter/enhancer.
Methods Male ApoEГЂ/ГЂESMIRO mice were compared with sexmatched littermate ApoEГЂ/ГЂ mice (both on a C57Bl6 background)
after feeding a Western-style diet for 12 weeks.
Results ApoEГЂ/ГЂESMIRO mice were morphologically indistinguishable from ApoEГЂ/ГЂ control littermates, with normal development and no difference between groups in body mass. Heart rate,
systolic blood pressure, glucose tolerance, insulin sensitivity and
fasting glucose levels were similar in ApoE-/-ESMIRO and ApoEГЂ/ГЂ
mice. Aortic lipid deposition, assessed by en-face oil red O staining,
was similar in ApoEГЂ/ГЂESMIRO and ApoEГЂ/ГЂ mice (6.4%60.5% vs
5.8%60.5%; pВј0.39). However, atherosclerotic lesion area in cross
sections of aortic sinus was significantly increased in ApoEÀ/À
ESMIRO mice compared to ApoEГЂ/ГЂ controls (24.8%62.4% vs
16.6%62.4%; p¼0.02). Absolute plaque size was also significantly
increased in ApoEГЂ/ГЂESMIRO mice compared to ApoE controls
(226 448.9616 154 mm2 vs 149 424.41624 221 mm2; pВј0.01).
Conclusions Endothelial specific insulin resistance is sufficient to
promote atherosclerosis and increase lesion area in ApoE null mice.
This suggests that enhancing endothelial insulin sensitivity may be
an appropriate target to prevent atherosclerosis in insulin-resistant
conditions.
140
IN VIVO DEPLETION OF ENDOGLIN RESULTS IN
SIGNIFICANT LEFT VENTRICULAR REMODELLING
doi:10.1136/heartjnl-2011-300198.140
1
1
1
2
B J Davison, R Redgrave, B Keavney, A Blamire, 1H Arthur. 1Institute of Human
Genetics, Newcastle University, Newcastle Upon Tyne, UK; 2Institute of Cellular
Medicine, Newcastle University, Newcastle Upon Tyne, UK
Endoglin, a TGFb co-receptor, is essential for cardiovascular development. However, endoglin also has an important role in п¬Ѓbrosis in
adult life. Endoglin heterozygous mice have been shown to have
reduced fibrosis in response to renal injury. They also have signifiA78
cantly reduced cardiac function following myocardial infarction. In
rat cardiac п¬Ѓbroblasts, endoglin expression is up regulated following
stimulation with angiotensin II and TGFb, resulting in reduced
expression of MMP1 and increased expression of collagen I. These
effects are inhibited by an endoglin specific antibody. Using our
conditional endoglin knockout mice we sought to investigate the
role of endoglin in cardiac healing following myocardial infarction.
Adult Eng fl/fl Rosa26-CreERT2 or control (Eng fl/fl) mice were
treated with intraperitoneal injection of tamoxifen for 5 days to
activate CreERT2 and deplete endoglin by Cre-lox recombination.
Mice then underwent surgical coronary artery ligation or sham
operation. Cine cardiac MRI was performed 28 days after injury.
Measurement of left ventricular (LV) volumes and myocardial mass
were made using ImageJ, and parameters of cardiac function were
calculated. We found that LV volumes and mass were significantly
increased (p<0.001) and ejection fraction significantly reduced
(p¼0.005) in endoglin deficient mice compared to controls.
However, we also noticed LV volume and mass were increased in
sham operated endoglin deficient mice. This led us to investigate the
effect of endoglin knockdown on normal heart structure and function in adult mice. Cine cardiac MRI was therefore performed on
mice without any surgical procedure after endoglin knockdown. We
found that in the endoglin deficient mice, LV volume and mass were
again significantly increased (p<0.03). However, ejection fraction
did not differ significantly from controls. These results demonstrate
that depletion of endoglin results in significant left ventricular
remodelling and suggest that endoglin plays an essential role in the
maintenance of normal cardiac structure. The fact that cardiac
function was preserved indicates that this is not a cardiomyopathic
process and we hypothesise that the increased left ventricular
volume in the endoglin-deficient mice may be the result of alterations in the extracellular matrix. We are currently investigating this
potential molecular mechanism for left ventricular remodelling in
the absence of endoglin.
141
TISSUE FACTOR PATHWAY INHIBITOR REGULATES
VASCULAR DEVELOPMENT IN ZEBRAFISH
doi:10.1136/heartjnl-2011-300198.141
1
2
2
3
E W Holroyd, C K Pierret, V M Bedell, J Townend, 2S C Ekker, 2R D Simari. 1Queen
Elizabeth Hospital, Birmingham, UK; 2Mayo Clinic, Rochester, UK; 3Queen Elizabeth
Hospital, Rochester, UK
Introduction Angiogenesis requires the coordinate regulation of
multiple biological pathways, including haemostasis. Tissue factor
pathway inhibitor (TFPI) is a potent anticoagulant molecule,
inhibiting tissue factor-led coagulation. However, the role of TFPI in
vascular development is unknown. Zebrafish (Danio rerio) provide a
unique model system to study vascular development in vertebrates.
Despite the divergence of jawed п¬Ѓsh (teleosts) over 430 million years
ago, there is notable conservation of the constituent molecules of
the clotting cascade. Multiple features make this vertebrate model
unique, including its genetic accessibility, the ability to titrate the
degree of genetic knock-down, external embryonic development,
and the transparent nature of the embryos.
Methods Using in-situ hybridisation techniques, we demonstrate
TFPI expression during early vertebrate development. We then
utilise transgenic п¬Ѓsh with labelled endothelium (Fli1GFP) and
erythrocytes (GATA1dsRed), to study in real time, concomitant
fluorescent imaging of both structural development and dynamic
blood flow observation, in living zebrafish embryos.
Results TFPI expression was identified at 24 h post fertilisation
(hpf) in the pronephros (Abstract 141 п¬Ѓgure 1ddark blue staining
denotes TFPI expression; none seen in control embryos). Subsequently, TFPI mRNA became more abundant, localising to
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
2EFHIK&L) were seen by 48hpf. TFPI MO induced coagulopathy (a
spontaneous clot or bleed; white arrows Abstract 141 п¬Ѓgure 2GJMP)
in 25.262.3% (p<0.01 cf. uninjected controls) at 3 ng and
23.865.8% (p<0.01) at 9 ng. Control embryos did not demonstrate
significant signs of coagulopathy (3.363.3%). Extra arteries occurred
in 26.462.6% (p<0.001 by ANOVA cf. uninjected controls) of
embryos injected with 3 ng of TFPI MO. To further define the role of
TFPI in vascular function, RNAi-mediated knockdown of TFPI was
performed in human endothelial cells (EC). Knockdown of TFPI
resulted in enhanced EC tube formation on Matrigel and EC
migration in injury model associated with increased phosphorylation of Vascular Endothelial Growth Factor Receptor-2.
Conclusion These data represent the п¬Ѓrst demonstration of TFPI
expression in zebrafish and the first description of a unique phenotype following TFPI knockdown. They support a model in which
TFPI acts a molecular break to angiogenesis both in vivo, during
early vertebrate embryogenesis, and in vitro in mature human
endothelial cells, secondary to constitutive regulation of VEGF
signalling.
142
ATRIAL SOURCES OF REACTIVE OXYGEN SPECIES VARY
WITH THE SUBSTRATE AND DURATION OF ATRIAL
FIBRILLATION: IMPLICATIONS FOR THE ANTIARRHYTHMIC
EFFECT OF STATINS
doi:10.1136/heartjnl-2011-300198.142
1
S Reilly, 1R Jayaram, 2C Anroniades, 3S Verheule, 1K M Channon, 1N J Alp,
U Schotten, 1B Casadei. 1University of Oxford, John Radcliffe Hospital, Oxford, UK;
2
First Department of Cardiology, University of Athens, Athens, Greece; 3Department of
Physiology, University of Maastricht, Maastricht, The Netherlands
3
Abstract 141 Figure 1
developing kidney, gut, and vasculature. Morpholino (MO)-based
knockdown of TFPI resulted in coagulopathy and disordered
vascular development (Abstract 141 п¬Ѓgure 2. left column: green
endothelial Fli1GFP, right column: red erythrocytes. AB: uninjected
controls. CD: MO controls. EeP: TFPI knockdown). Abnormally
targetted (ie, vessels sprouting from normal site but growing in
abnormal direction; grey arrows) and extra vessels (ie, superfluous
vessels not seen in controls; white arrows in Abstract 141 п¬Ѓgure
Abstract 141 Figure 2
Heart June 2011 Vol 97 Suppl 1
Background Atrial п¬Ѓbrillation (AF) is the most common sustained
cardiac arrhythmia and is associated with altered nitric oxide (NO)redox balance. The molecular mechanisms and implications of this
phenomenon in the management of patients with AF are poorly
understood. Statins improve NO-redox imbalance and decrease the
occurrence of postoperative AF but are less effective in the secondary prevention of AF, suggesting that the sources of reactive oxygen
species might vary with the substrate and duration of AF.
Methods and Results We investigated atrial tissue from 130 patients
undergoing cardiac surgery (26 with permanent AF, 32 who developed AF post-operatively and 72 who were in normal sinus rhythm
before and after surgery), and from goats in sinus rhythm (SR,
nВј19) with or without atrial structural remodelling secondary to
surgical AV block (AVB, nВј10) or after 2 weeks (2W, nВј15) or
6 months (6M, nВј10) of pacing-induced AF. Atrial NADPH oxidase
activity (chemiluminescence and 2-OH ethidium, Abstract 142
п¬Ѓgures 1 and 2), NOX2 & p22phox protein level were increased after
2W-AF and in patients who developed AF post-operatively (nВј32).
In contrast, the increased superoxide production in atrial tissue from
goats with AVB or 6M-AF was exclusively driven by mitochondrial
oxidases and uncoupled NOS (secondary to a reduction in atrial BH4
level and an increase in arginase activity). These п¬Ѓndings were
recapitulated in the right atrial appendage of patients. Increase in
basal superoxide production in postoperative AF was associated
with an apocynin-reversible increase in NADPH oxidase activity and
protein level of the NOX2 and p22phox subunits. NOS activity
remained coupled despite the increase in superoxide production. In
line with this, atrial BH4 content was unaltered. In contrast, in
patients with permanent AF, increased superoxide production was
not reversed by apocynin, and was maintained by mitochondrial
oxidases and uncoupled NOS (secondary to BH4 deplition). Ex-vivo
inhibition of HMG-CoA reductase with atorvastatin (20 mMol/l)
inhibited NADPH oxidase activity (via reducing activity of Rac1 and
membrane translocation of cytosolic subunit p47phox and p67phox
of NADPH oxidase) and caused a mevalonate-reversible reduction in
A79
BCS Abstracts 2011
superoxide release in atrial samples of patients with post-operative
AF but had no effect in patients with permanent AF. Similarly,
atorvastatin did not induce a mevalonate-reversible changes in the
atrial BH4 concentration and NOS uncoupling in neither group.
Conclusions Together, these п¬Ѓndings indicate that upregulation of
NOX2-NADPH oxidases is an early but transient event in the
natural history of AF, as mitochondrial oxidases and uncoupled NOS
account for the statin-resistant increase in atrial superoxide
production in permanent AF. Variation in atrial sources of reactive
oxygen species with the duration and substrate of AF may explain
the reported variability in the effectiveness of statins in the
prevention and management of AF.
143
Abstract 143 Figure 1
TISSUE FACTOR PATHWAY INHIBITOR REGULATES
ANGIOGENESIS INDEPENDENTLY OF TISSUE FACTOR VIA
INHIBITION OF VASCULAR ENDOTHELIAL GROWTH FACTOR
SIGNALLING
doi:10.1136/heartjnl-2011-300198.143
1
E W Holroyd, 2K Larsen, 2R G Vile, 2D Mukhopadhyay, 2R D Simari. 1Queen Elizabeth
Hospital, Birmingham, UK; 2Mayo Clinic, Rochester, Minnesota, USA
Introduction The biological systems of coagulation and angiogenesis
show considerable interdependence. Proteases and inhibitors within
the tissue factor (TF) pathway of coagulation have emerged as
potential regulators of angiogenesis. Tissue factor pathway inhibitor
(TFPI), as the primary physiological inhibitor of tissue factor (TF)mediated coagulation, is ideally situated to modulate the proangiogenic effects of TF. However, TFPI may also have effects on
angiogenesis independent of its anti-TF ability.
Methods We determined the effects of altered TFPI expression on
the regulation of angiogenesis in vivo using genetically-modified
murine models of vascular overexpression (SM22ГЎTFPI strain) and
endothelial-specific deletion of the TF-binding domain of TPFI
(Tie2TFPI). We then defined the mechanism of these effects in vitro
using Human Umbilical Vein Endothelial Cells (HUVECs) overexpressing TFPI or via exogenous addition of TFPI-derived peptides
in assays of angiogenesis.
Results Vascular-directed over-expression of TFPI (SM22ГЎTFPI
strain) inhibited angiogenesis in vivo (Abstract 143 п¬Ѓgure 1).
SM22áTFPI showed significantly impaired recovery from ischaemia
in the hindlimb ischaemia model after 3 days (p<0.05, nВј5 per
group), which persisted throughout the experiment. Survival (until
1-cm tumour dimension) of SM22ГЎTFPI mice vs wild-type control
(median survival 14 cf. 10 days) following s.c. B16 melanoma
injection (n¼7 per group, c2¼4.325, *p<0.05). Endothelial-specific
deletion of the TF-binding domain of TFPI failed to reveal a proangiogenic phenotype. This led us to suspect that the anti-angiogenic action of TFPI may be independent of TF. Systemic delivery of
the murine TFPI carboxyl-terminus (mTFPIct) replicated the effects
of endogenous overexpression. In vitro, overexpression of TFPI
inhibited endothelial cell tube formation on Matrigel and migration
using an injury migration model. Human TFPIct (hTFPIct) inhibited
tube formation and migration through inhibition of Vascular
Endothelial Growth Factor Receptor-2 (VEGFR2) tyrosine-951
phosphorylation, a key event in migration. hTFPIct did not inhibit
VEGF121-induced migration, which lacks the heparin-binding
domain of VEGF165. Utilising the chimeric receptor, EGDR, which
contains the extracellular domain of epidermal growth factor (EGF)
and the intracellular domain of VEGFR2/KDR, a direct effect of
TFPIct on the intracellular domain of VEGFR2 was excluded
(Abstract 143 п¬Ѓgure 2) TFPIct did not block phosphorylation of
EGDR when stimulated with EGF.
A80
Abstract 143 Figure 2
Conclusion Angiogeneis is a key biological system in health and
disease; enabling cells in a hypoxic environment to stimulate new
blood vessel growth. These data demonstrate, both in vivo and in
vitro, an inhibitory role for TFPI in angiogenesis that is TF-independent. In addition to it classical role as a TF-antagonist, TFPI, via
TFPIct, interferes with the interaction of VEGF165 with the
extracellular domain of VEGFR2, thereby limiting angiogenesis.
144
A DRUGGABLE INHIBITOR OF CARDIAC HYPERTROPHY
IDENTIFIED THROUGH AN INNOVATIVE CHEMICAL LIBRARY
SCREEN
doi:10.1136/heartjnl-2011-300198.144
R Abou Leisa, T M A Mohamed, D Oceandy, S Prehar, M Zi, F Baudoin, L Neyses,
E J Cartwright. Manchester University, Manchester, UK
Cardiac hypertrophy is a prerequisite for the development of heart
failure. It currently affects almost one million people in the UK. Few
effective anti-hypertrophic agents with druggable properties have
been identified. Recently, our group showed that plasma membrane
calcium ATPase isoform 4 (PMCA4) knockout mice showed a reduced
response to hypertrophic stress prompting us to hypothesise that a
novel PMCA4 specific inhibitor would modify the development of
cardiac hypertrophy. A library of 1280 medically optimised
compounds was screened using a novel in vitro assay which measures
the Ca2+ dependent ATPase activity of PMCA4. The compound AP2
was identified, which inhibited PMCA4 activity with high affinity
(IC50Вј300 nM) but not other PMCAs (PMCA1, PMCA2 and PMCA3)
or related ATPases which are expressed in the heart including the
sarcoplasmic reticulum calcium ATPase and Na/K ATPase. In isolated
neonatal rat cardiomyocytes (NRCM), AP2 showed dose dependent
inhibition of phenylephrine-induced hypertrophy, indicated by an
85% reduction in cell surface area as well as in BNP activity. In vivo
studies showed that AP2 (5 mg/kg body weight/day IP) significantly
reduced pressure-overload induced hypertrophy following 2 weeks
transverse aortic constriction (TAC) (heart weight/tibia length (mg/
mm): sham, 5.560.3, vehicle treated TAC mice, 8.7 60.2, AP2 treated
TAC mice, 7.0 60.5, nВј10 in each group, p<0.01). AP2 treated TAC
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
mice showed a significant reduction in the cardiomyocyte cross
sectional area (sham, 26763.4 mm2, vehicle treated TAC mice,
48065.8 mm2, AP2 treated TAC mice, 31963.9 mm2). A significant
reduction in the expression of the hypertrophic marker ANP and BNP
and in the percentage of п¬Ѓbrosis was also observed in these mice
compared with vehicle treated TAC mice. AP2 treatment led to a
significant reduction in the expression of the bona fide calcineurin
target RCAN1.4 and a reduction in the NFAT phosphorylation level in
vivo and the NFAT transcriptional activity in vitro. In conclusion, we
have identified AP2 as a novel PMCA4 specific inhibitor and shown its
potential to modify the development of cardiac hypertrophy likely
through inhibition of calcineurin/NFAT signalling. This compound
has drug-like properties and thus lays the basis for a novel approach for
treating cardiac hypertrophy and failure through PMCA4 inhibition.
145
CHARACTERISATION OF FRACTIONATED ATRIAL
ELECTROGRAMS CRITICAL FOR MAINTENANCE OF AF: A
RANDOMISED CONTROLLED TRIAL OF ABLATION
STRATEGIES (THE CFAE AF TRIAL)
doi:10.1136/heartjnl-2011-300198.145
R J Hunter, I Diab, M Tayebjee, L Richmond, S Sporton, M J Earley, R J Schilling. Barts
and The London NHS Trust, London
Introduction Targeting complex fractionated atrial electrograms
(CFAE) in the ablation of atrial п¬Ѓbrillation (AF) may improve
outcomes, although whether this is by eliminating focal drivers or
simply de-bulking atrial tissue is unclear. It is also uncertain what
electrogram morphology should be ablated. This randomised study
aimed to determine the impact of ablating different CFAE
morphologies compared to normal electrograms (ie, de-bulking
normal tissue) on the cycle length of persistent AF (AFCL).
Methods After pulmonary vein isolation CFAE were targeted
systematically throughout the left then right atrium, until termination of AF or abolition of CFAE prior to DC cardioversion. 10 s
electrograms were classified by visual inspection according to a validated scale, with Grade 1 being most fractionated and grade 5 normal.
Patients were randomised to have CFAE grades eliminated sequentially,
from grade 1 to 5 (group 1) or grade 5 to 1 (group 2). Because grade 5
electrograms were considered normal, only 5 were ablated. Mean
AFCL was determined manually over 30 cycles from bipolar electrograms recorded at the left and right atrial appendages before and after
each CFAE was targeted. Lesions were regarded as individual observations, and a resultant increase in mean AFCL $5 ms was regarded as
significant. The randomised strategy first controlled for any cumulative effect of ablation on AFCL, and second allowed assessment of
the order of ablation on the number of CFAE lesions required.
Results 20 patients were randomised. The CFAE grade determined by
rapid visual inspection for the 968 electrograms targeted agreed with
that at off-line manual measurement in 92.7% (lВј0.91). AFCL
increased after targeting 49.5% of grade 1 CFAE, 33.6% of grade 2,
12.8% of grade 3, 33.0% of grade 4, and 8.2% of grade 5 CFAE
(p<0.0001 for grades 1, 2, and 4 vs 5, 3 vs 5 not significant). Binary
logistic regression confirmed the effect of CFAE grade, but showed no
effect of electrogram amplitude, location in the left or right atrium, or
the order in which CFAE were targeted. There was no difference
between groups in the number of grade 1 or 2 CFAE encountered, but
there were fewer grade 3 and 4 CFAE in group 2 than group 1 (both
p<0.01), translating to fewer CFAE targeted per patient in group 1
compared to group 2 (37614 and 58618 respectively; pВј0.015).
Conclusion Targeting CFAE is not simply atrial de-bulking. Ablating
certain grades of CFAE caused AFCL prolongation, suggesting they
are more important in maintaining AF. Targeting these CFAE may
reduce unnecessary left atrial destruction. (ClinicalTrials.gov
number, NCT00894400).
Heart June 2011 Vol 97 Suppl 1
Abstract 145 Figure 1 Impact of CFAE grade on the proportion of
lesions causing AF cycle length prolongation.
146
IS THERE AN ASSOCIATION BETWEEN THROMBOGENESIS
MARKERS AND ATRIAL FIBRILLATION BURDEN IN
PACEMAKER POPULATION?
doi:10.1136/heartjnl-2011-300198.146
C W Khoo, S Krishnamoorthy, G Dwivedi, B Balakrishnan, HS Lim, G Y H Lip. University
Department of Medicine Centre for Cardiovascular Sciences, City Hospital,
Birmingham, UK
Background and Objectives Contemporary pacemaker devices are
able to quantify atrial high-rate episodes (AHREs) and atrial п¬Ѓbrillation burden (AFB) accurately. In this study, we aim to assess the
relationship of thrombogenesis markers in association with AHREs
and AFB.
Methods We studied 87 patients with dual-chamber pacemaker.
Patients on warfarin were excluded. AHREs were defined as atrialrate $220 beats/min and $5 minutes. AFB and percentage of
cumulative pacing were derived from pacemaker diagnostics. Plasma
levels of von Willebrand factor (vWf), tissue factor (TF), soluble
P-selectin (P-sel) and D-dimer (DDM) were analysed using ELISA.
Results Baseline characteristics and co-morbidities were comparable
between groups (Abstract 146 table 1). Patients with AHREs had
significantly higher cumulative percentage ventricular pacing
(p¼0.012). There were no significant differences in levels of vWf, TF,
P-sel and DDM between patients with and without AHREs. The
AFB ranged from 0 to 99% in AHRE group. TF (rВј0.516, pВј0.086),
P-sel (rВј0.795, p<0.001) and DDM (rВј0.643, pВј0.045) correlated
with AFB. On linear regression analysis, both P-sel and DDM were
independently associated with AFB (p<0.05).
Abstract 146 Table 1
No AHRE (n[70)
AHRE (n[17)
p value
Age, years
71.0611.6
75.468.8
0.096
Hypertension, (%)
Antiplatelet, (%)
38, (54)
53, (76)
12, (71)
14, (82)
0.116
0.739
Percentage atrial pacing
Percentage ventricular pacing
34.6 (6.8e81.5)
21.9 (1.8e99.0)
22.1 (6.9e65.0)
98.6 (41.0e99.9)
0.414
0.012
vWf, IU/dl
TF, ng/ml
94.2616.2
0.2 (0.1e0.3)
93.9633.7
0.1 (0.0e0.2)
0.977
0.105
P-sel, ng/ml
DDM, ng/ml
47.6615.8
180.0 (82.0e390.0)
63.4629.7
152.5 (82.5e307.5)
0.055
0.553
A81
BCS Abstracts 2011
Conclusion AFB is independently associated with increased indices
of P-sel and D-dimer which indicate platelet activation and thrombosis respectively.
147
THROMBOEMBOLIC RISK STRATIFICATION, ANTITHROMBOTIC AND ANTICOAGULATION USE FOR PATIENTS
WITH ATRIAL FIBRILLATION, A CLINICAL AUDIT
Abstract 147 Table 2
CHADS2 Score
None (%)
Aspirin (%)
Zero
27.0
70.3
Aspirin or Warfarin (%)
1.3
Warfarin (%)
1.3
One
Two
4.7
0.0
45.1
7.8
43.2
32.2
7.0
60.0
Three
0.0
0.8
11.5
87.7
Four
Five
0.0
0.0
0.0
0.0
5.3
2.9
94.7
97.1
Six
0.0
0.0
2.9
97.1
doi:10.1136/heartjnl-2011-300198.147
R A Veasey, R Kulanthaivelu, P Patel, D W Harrington. Kent and Sussex Hospital,
Tunbridge Wells, UK
Introduction Atrial п¬Ѓbrillation (AF) is the most prevalent arrhythmia
in primary and secondary healthcare settings. Thromboembolic (TE)
risk assessment and initiation of anti-thrombotic or anticoagulation
(AT/AC) therapy, according to level of risk, is recommended in both
national and international guidelines. NICE guidance stratifies
patients with AF in to low, moderate or high risk categories and
recommends “aspirin”, “aspirin or warfarin” or “warfarin” therapy
respectively. ACC/ESC guidance endorses use of the CHADS2
scoring system and for scores of 0, 1, or $2 recommends “aspirin”,
“aspirin or warfarin” or “warfarin” therapy respectively. In addition,
it is recommended that AF episode frequency or subtype (paroxysmal (PAF), persistent (PersAF) or chronic (CAF)) does not influence TE risk assessment. We audited UK cardiologists and general
practitioners (GPs) to assess adherence to these guidelines.
Methods We designed an audit questionnaire assessing: (1) use of
risk stratification tools, (2) choice of AT/AC for increasing levels of
risk, and (3) choice of therapy for a number of hypothetical patients
with variable TE risk and variable AF subtype. The questionnaire
was distributed by electronic or postal mail to 1176 cardiologists and
621 randomly selected GPs.
Results In total, 421 responses were received (306 cardiologists, 115
GPs). Overall, 91.4% of responders reported use of TE risk stratification tools (97.1% cardiologists, 76.5% GPs, p<0.001). NICE risk
assessment is used by 26.6% of responders (24.5% cardiologists,
32.2% GPs, pВј0.14), CHADS2 by 79.3% (90.2% cardiologists, 50.0%
GPs, p<0.001). The frequency of reported use of AT/AC for each risk
level of the NICE assessment and CHADS2 score are shown in
Abstract 147 tables 1 and 2 respectively. Type of AF (PAF/PersAF/
CAF) reportedly influences the use of AT/AC for 34.3% or
responders (24.2% cardiologists, 46.3% GPs, pВј0.001). Abstract 147
п¬Ѓgure 1 demonstrates AT/AC usage for each of the following
hypothetical patients: 1. 61 year old, hypertension, PAF episodes
twice a year lasting 1e2 h (NICE risk: mod, CHADS2 score 1/6). 2.
43 year old, diabetes, PAF episodes weekly lasting 10e12 h (NICE
risk: mod, CHADS2 score 1/6). 3. 53 year old, hypertension, CAF
(NICE risk: mod, CHADS2 score 1/6). 4. 78 year old, no other risk
factors, CAF (NICE risk: mod, CHADS2 score 1/6). 5. 76 year old,
hypertension, diabetes, PAF episodes 3e4 times per year lasting
<1 hour (NICE risk: high, CHADS2 score 3/6). 6. 77 year old,
hypertension, diabetes, PAF episodes occurring weekly and lasting
several hours (NICE risk: high, CHADS2 score 3/6). 7. 80 year old,
previous TIA, CAF (NICE risk: high, CHADS2 score 3/6).
Abstract 147 Table 1
NICE Risk
None (%)
Aspirin (%)
Low
16.7
78.3
2.9
2.1
0.6
0.0
3.5
0.0
66.9
4.4
28.7
95.6
Moderate
High
A82
Aspirin or Warfarin (%)
Warfarin (%)
Abstract 147 Figure 1
Conclusions TE risk stratification tools are reportedly widely used in
UK clinical practice. AT/AC use for NICE and CHADS2 risk levels
are mostly appropriate, although warfarin is under recommended
for patients with a CHADS2 score of 2/6. In addition, the use of AT/
AC is influenced, inappropriately, by AF episode frequency and
subtype.
148
THE ASSESSMENT OF TRANSIENT LOSS OF
CONSCIOUSNESS: WE’RE STILL NOT ASKING THE RIGHT
QUESTIONS
doi:10.1136/heartjnl-2011-300198.148
A E Bewick, A Gasson, L Ala, R A Bleasdale. Royal Glamorgan Hospital, Cardiff, UK
Accurately diagnosing patients with TLOC can be achieved in most
cases with a detailed clinical history. We set out to assess how
patients were assessed in the setting of a district general hospital
(DGH) with 570 beds, receiving an unselected intake via general
practice and an A&E. Using the ESC guidelines of 2009 we generated
a 22-question study proforma for a retrospective review of the
medical records. We identified 322 cases for possible inclusion over a
4 month period. 26 of the case notes were not available to analyse, 8
had insufficient details to identify the relevant patient. Therefore in
total 288 notes were reviewed. Inclusion required the TLOC to be
complete, of rapid onset and short duration with spontaneous
complete recovery. A further 123 patients were therefore excluded.
This left 165 data sets (58% male). The age distribution was a
typical bimodal distribution with 16% between 10 and 29 years of
age and 48% over the age of 70 years. 73% were assessed in A&E,
18% were assessed in the Acute Medical Unit (AMU) and 7% were
assessed in rapid access ambulatory clinics. Only 4% of the initial
assessments were undertaken by consultants, 12% by a Specialist
Registrar (SpR), 21% by a year 1 foundation program (FP1) doctor
and the majority was assessed by FP 2 or core medical trainees
(CMT). Key diagnostic elements of the history are still being
neglected. For example, the symptoms at the onset of the TLOC
were documented in only 58% of cases; the recovery symptom
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
profile was reported in only 37%. Only 47% (n¼78) of records
described a witness account. Within the witness accounts that were
recorded, key elements remained un-reported for example skin
complexion was only reported in 35% of the 78. The duration of the
TLOC was recorded in only 44%, Tongue biting in 27% and the
presence or absence of abnormal movements was recorded in only
12% of this 78 patients. The presence or absence of a family history
of sudden cardiac death was only reported in 2% cases. The family
history of a cardiomyopathy was only recorded in 1% and a family
history of TLOC was recorded in 1%. A patient past history of
cardiac disease was asked about in 40% of cases while a past history
of TLOC was only asked about in 35%. In this majority elderly
study population, a recent change in drug therapy was only asked
about in 2% of cases. This study highlights that in a DGH environment, the initial assessment of patients with TLOC is undertaken by junior medical staff who often do not document key
diagnostically differentiating elements of the history and examination indicating an ongoing lack of adequate training regarding the
most appropriate and accurate techniques for differentiating the
causes of TLOC.
149
Abstract 149 Figure 1 Comparison of pre-ablation and post-ablation %
scar using fixed threshold.
AUTOMATED ANALYSIS OF ATRIAL ABLATION-SCAR USING
DELAYED-ENHANCED CARDIAC MRI
doi:10.1136/heartjnl-2011-300198.149
1
1
2
2
L Malcolme-Lawes, R Karim, C Juli, P B Lim, 2T V Salukhe, 2D W Davies,
D Rueckert, 1N S Peters, 2P Kanagaratnam. 1Imperial College London, London, UK;
2
Imperial College Healthcare, London, UK
1
Introduction Visualisation of the ablation-related atrial scar using
delayed-enhanced MRI (DE-MRI) may reveal important underlying
causes for atrial п¬Ѓbrillation (AF) recurrence following ablation. In
order to develop and objective method for delineating ablation-scar
we compared pre and post DE-MRI after Cryo-balloon lesion on the
basis that a more predictable lesion set would be created for
validation.
Methods and Results 12 patients undergoing cryoablation for PAF
were enrolled in the study, and underwent pre-ablation DE-MRI
scans. Pulmonary vein isolation (PVI) was confirmed in all patients
at the end of the cryoablation procedure using a circular mapping
catheter. Additional ablation by RF or Freezer Max was required to
achieve PVI in 59%. No ablation was performed in any region other
than the PV ostia. Post-ablation DE-MRI was performed at
3 months. An automatic segmentation of the LA was produced with
custom software from the MRA sequence. The preablation and
postablation free breathing late gadolinium enhanced sequence was
registered to the MRA and the maximum intensity within the LA
wall was projected onto the post ablation LA surface. The blood
pool was identified automatically using custom software as the
region 1 cm inside the wall of the LA, and its mean (BPM) and SD
used as a baseline. To identify a universal threshold for scar, regions
of brightest myocardium were initially selected in pre and post
ablation MRIs. The brightest regions were 1.961.2 vs 8.763.1 SDs
above the BPM in pre-and post-ablation MRIs respectively
(pВј0.001). A threshold of 5 SDs above the BPM was therefore
programmed into our custom software to identify regions of scar for
all patients. The ostial regions were defined as extending 1 cm both
proximal and distal to the PVeLA junction, and selected manually
for left and right sided veins prior to scar projection. (See Abstract
149 п¬Ѓgure 1). The scar proportion within these regions was calculated using commercially available software ITK-SNAP. Total LA
scar proportion was 0.260.02% vs 6.360.75% in pre and post
ablation scans respectively. The increase in scar seen in the PV ostia
was 24.661.38% compared with 2.661.28% in the rest of the LA
(pВј0.01) (See Abstract 149 п¬Ѓgure 2).
Heart June 2011 Vol 97 Suppl 1
Abstract 149 Figure 2
Conclusion We have demonstrated the feasibility an objective,
automated method of DE-MRI analysis of left atrial ablation-scar.
This technique will now need to be validated against clinical
outcomes.
150
IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR
LEAD COMPLICATIONS AND CLINICAL EFFECTIVENESS
IN PATIENTS WITH INHERITED CARDIAC
CONDITIONS
doi:10.1136/heartjnl-2011-300198.150
1,2
R Bastiaenen, 1S Ben-Nathan, 2S Jones, 2D Ward, 2M Gallagher, 1,2S Sharma,
E R Behr. 1St George’s University of London, London, UK; 2St George’s Hospital,
London, UK
1,2
Background Implantable cardioverter-defibrillator (ICD) therapy can
reduce sudden death due to ventricular arrhythmia (VT/VF) but is
not without complication, particularly in young patients who live
for many years with a device in situ. We aimed to determine the
ICD complication rate in our inherited cardiac condition (ICC)
population compared with international reports. Particular importance was given to inappropriate shock therapy due to lead failure as
there are new ICD technologies available.
Methods Patients with ICCs who had ICD implantation or box
change between January 2006 and September 2009 were included.
Data on clinical characteristics, complications and ICD therapies
were obtained from pacing and hospital records. We compared our
data with several ICD studies of patients with specific ICCs
(Abstract 150 table 1).
A83
BCS Abstracts 2011
Abstract 150 Table 1
Long QT
SGH ICC Syndrome HCM
ARVC
patients patients
patients patients
(n[101) (n[51)
(n[506) (n[106)
Follow-up (months; mean6SD) 74653
Appropriate therapy (%)
26
87
24
44633
20
Inappropriate therapy (%)
Lead failure (%)
18
21
29
25
Complication rate excluding
lead failure (%)
26
31
Brugada
Syndrome
patients
(n[220)
58635
24
38627
8
27
7
19
2
20
9
n/a
34
20
Results 101 patients (mean age 44.1614.8 years; 59 male) were
included (idiopathic VF 15%; DCM 17%; ARVC 22%; HCM 21%;
long QT syndrome 17%; Brugada syndrome 6%; others 2%). During
a mean follow-up of 74.0653.2 months 2 patients died (1 inappropriate shocks; 1 stroke). Indications were secondary prevention in
71.3% of patients. ICD types were 56.4% single chamber; 39.6%
dual chamber; 4.0% biventricular. Appropriate therapy successfully
terminated VT/VF in 27 (26.7%) patients 34.7% of secondary and
6.9% of primary prevention patients received appropriate therapy.
Inappropriate therapy occurred in 18 (17.8%) patients and lead
failure (noise/wear/fracture) in 22 (20.8%) patients (Abstract 150
table 2). 12 out of 18 inappropriate shocks were due to lead failure, 5
sensing errors (1 T-wave oversensing; 4 AF), 1 generator fault. 10/22
leads that failed were Medtronic Sprint Fidelis and these were
responsible for 8/12 patients receiving inappropriate shocks
including one death due to lead fracture. Comparison with other
studies indicates a high lead failure rate due to the long follow-up
period, similar to the LQT Study which reports 25% lead failure over
87 months (Abstract 150 table 1). With lead failure excluded the
complication rate is comparable to shorter follow-up studies. Inappropriate and appropriate therapy rates are similar among all studies.
Abstract 150 Table 2
Complication
Number of patients
% of patients
Lead failure
Inappropriate shock
21
18
20.8
17.8
Lead displacement
Infection
5
5
4.9
4.9
Pneumothorax/Haemothorax
5
4.9
Box/Wound/Other revision procedure
Thrombosis (venous/lead)
7
2
6.9
1.9
Haematoma
Chronic abdominal cavity postexplant
5
1
4.9
0.9
Conclusions There is a significant rate of ICD lead failure in patients
with ICCs, which may be expected given the high frequency of
Sprint Fidelis leads implanted during this period and the long followup. Our results compare favourably to other similar studies. The
high rate of appropriate therapy highlights the clinical effectiveness
of ICD intervention in secondary prevention. Lead complications
may be lower with the use of new ICD technology in selected patients.
151
RISK OF RECURRENCE FOLLOWING EXTRACTION OF CARDIAC
IMPLANTABLE ELECTRONIC DEVICES FOR INFECTION: WHEN
SHOULD A NEW DEVICE BE RE-IMPLANTED?
doi:10.1136/heartjnl-2011-300198.151
H E Thomas, M Das, D Twomey, C J Plummer, E J Shepherd. Freeman Hospital,
Newcastle upon Tyne, UK
Background The recommended management of cardiac implantable electronic device (CIED) infection is complete system
A84
extraction. There are limited clinical data on the optimal time for
device re-implantation. A small series reported good results with
simultaneous contralateral implantation. We evaluated this
approach in our institution for patients without signs of systemic
sepsis. We present clinical outcomes and completeness of extraction.
Methods The clinical records of all patients undergoing lead
extraction in our institution since January 2008 were reviewed.
Results 68 patients underwent CIED extraction for infection during
this time period (see Abstract 151 table 1). In 34 cases, the device
was removed with simple traction, 9 with locking stylet, 22 with
locking stylet and laser sheath, 1 with locking stylet and mechanical
sheath and 2 with femoral snare. There was complete hardware
removal in 64 cases (94%). One patient with lead related endocarditis required a subsequent surgical procedure to remove a lead
fragment and in 4 other patients who had erosion, pocket infection
or threatened erosion, a small fragment of lead remained. 18/68
patients were re-implanted with a new device on the contralateral
side on the same day as the extraction. 28/68 patients received a
new device between 1 and 227 days later and 22/68 have not
undergone reimplantation. An active п¬Ѓxation bipolar TPW
(temporary pacing wire) was used in 6 patients for a mean
7.862.7 days. 3 patients had a further device related procedure
during a mean follow-up of 4456304 days: 1 lead reposition, 1
pocket washout and 1 extraction. Of the 2 procedures carried out for
recurrent infection, 1 was managed with a TPW for 7 days prior to
reimplantation and 1 underwent reimplantation at 14 days without
TPW. In addition, the patient requiring pocket washout had a
fragment of lead remaining following their initial extraction.
Abstract 151 Table 1
Indication for device extraction
Number of patients, n[80 (%)
Erosion
Pocket infection
31 (39)
25 (31)
Lead infection
Threatened erosion
7 (9)
4 (5)
Pain
1 (1)
Conclusion We report low rates of recurrent infections following
CIED extraction. None of the 18 individuals simultaneously reimplanted with a new device on the contralateral side needed any
further procedures during the follow-up period. This approach may be
appropriate, particularly in pacing dependant patients who would
otherwise require a TPW with its associated risks. In those individuals
who required a TPW, the risk of recurrent infection in our series was
17% despite our use of an active п¬Ѓxation pacing lead and externalised
pulse generator which has a lower reported complication rate. Only
one of the 4 patients with a residual lead fragment required reintervention for recurrent infection. This provides some supportive
evidence that in patients with high surgical risk and pocket abnormalities, if fragments of lead may remain, the patient may be treated
conservatively and monitored for signs of recurrent CIED infection.
152
REAL-TIME CARDIAC MR ANATOMY AND DYSSYNCHRONY
OVERLAY TO GUIDE LEFT VENTRICULAR LEAD PLACEMENT
IN CRT
doi:10.1136/heartjnl-2011-300198.152
1,2
1,2
1,2
1,2
A Shetty, S Duckett, M Ginks, Y Ma, 1,2M Sohal, 1,2P Mehta, 1,2S Hamid,
J Bostock, 1,2G Carr-White, 1,2K Rhode, 1,2R Razavi, 1,2C A Rinaldi. 1Guys and St
Thomas’ Hospital NHS Foundation Trust, London, UK; 2King’s College London, London, UK
1,2
Introduction Optimal left ventricular (LV) lead placement via the
coronary sinus (CS) is a critical factor in defining response to cardiac
resynchronisation therapy (CRT). Using novel semi-automated
image acquisition, segmentation, overlay and registration software
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
we set out to guide lead placement by avoiding scar and targeting
the region of the LV with the latest mechanical activation.
Methods 17 patients underwent cardiac magnetic resonance (CMR)
scans. 3D whole heart images were segmented to produce high п¬Ѓdelity
anatomical models of the cardiac chambers and coronary veins. 2, 3, 4
chamber and short axis cine images were processed using Tomtec
software to give a 16 segment time volume-dyssynchrony map. In
patients with myocardial scar the late gadolinium enhancement
images were manually segmented and registered to the anatomical
model along with the dyssynchrony map. The 3 latest mechanically
activated segments with <50% scar were identified and this information was overlaid at CRT implant on to live fluoroscopic images
using a prototype version of the Philips EP Navigator software.
Subsequently, the x-ray C-arm and table could be moved freely while
automatically maintaining a registered roadmap. We used a high
п¬Ѓdelity pressure wire to assess the acute haemodynamic response to
pacing in different regions of the overlaid 16 segment model. All dP/dt
measurements were compared to baseline AAI or VVI (for those
patients in AF) pacing at 5e10 beats/min above intrinsic rate.
Results 15 of the 17 patients underwent successful placement of a LV
pacing lead via the CS with satisfactory pacing parameters and no
phrenic nerve stimulation at implant. The mean time from insertion
of the CS guide catheter into the venous sheath to successful
cannulation of the CS was 1.361.0 min. In 2 patients we were unable
to place a LV lead successfully in any branch of the CS. We paced in at
least one of our 3 target segments in 11 patients. 67% of patients were
responders as defined by a 10% increase in +dP/dt over baseline. The
mean change in +dP/dt for the best lead position vs baseline+dP/dt
was 15.9611.3% for DDDLV pacing. This compares to a mean
change in+dP/dt of 14.9612.3% when the CMR dyssynchrony-map
defined target region was paced DDDLV. The region of best+dP/dt
response was postero-lateral, lateral or posterior in all cases.
Conclusion We have shown it is feasible to acquire, overlay and
accurately register cardiac MR data on to fluoroscopic images at the
time of CRT implant. Our data suggest that it is also possible to
identify and place the LV lead in at least one target region in most
patients. This appears to give close to the best acute haemodynamic
response that can be achieved in any branch of the CS. The initial
results of this pilot study suggest that a MR dyssynchrony guided
approach to LV lead placement may allow ideal LV lead positioning
(Abstract 152 п¬Ѓgures 1 and 2).
Abstract 152 Figure 1
Heart June 2011 Vol 97 Suppl 1
Abstract 152 Figure 2
153
VENTRICULAR PACING ALONG INDIVIDUAL BRANCHES OF
THE CORONARY SINUS USING A QUADRIPOLAR LV PACING
LEAD
doi:10.1136/heartjnl-2011-300198.153
1,2
A K Shetty, 1,2P Mehta, 1,2S Duckett, 1,2J Bostock, 1,2M Ginks, 1,2S Hamid,
M Sohal, 1,2R Razavi, 1,2Y Ma, 1,2K Rhode, 1,2A Arujuna, 1,2C A Rinaldi. 1Guys and St
Thomas’ Hospital NHS Foundation Trust; 2King’s College London, London, UK
1,2
Introduction Cardiac resynchronisation therapy (CRT) usually
involves placing the left ventricular (LV) pacing lead in the posterolateral or lateral region of the LV epicardial surface as this is thought
likely to re-coordinate myocardial contraction most effectively. The
LV lead is standardly placed in a position with the best pacing
parameters and satisfactory stability. It is not known, however,
whether there is a significant difference in haemodynamic response to
LV pacing in different regions of the same coronary sinus (CS) vein. In
this study we aimed to evaluate the difference in acute haemodynamic response to pacing along individual branches of the CS.
Methods 16 patients underwent an acute haemodynamic study
during their CRT-defibrillator implant. We used a high fidelity
pressure wire to assess the acute haemodynamic response (AHR) to
pacing in different branches of the coronary sinus. We used a novel
quadripolar lead (Quartet, St Jude Medical, Sylmar, California, USA)
that has four poles on the LV lead―distal tip and 3 ring electrodes.
The 3 ring electrodes are spaced 20 mm, 30 mm and 47 mm from
the distal tip electrode and the four poles allow bipolar pacing
between them. It was thus possible for us to test pacing parameters
and AHR along a significant proportion of a CS branch without
having to reposition the LV lead.
Results DDDLV pacing was attempted in as many different CS
branches as possible in each patient (total 56 different positions
used). The mean overall percentage difference in AHR (measured by
change in +dP/dt compared to baseline AAI pacing or VVI pacing in
AF patients) between an individual CS branch bipole with the
lowest +dP/dt and that with the highest was 6.665.6%. Much
larger differences in change in +dP/dt were seen, however, between
different branches of the CS in the same patient with a mean
difference in change in +dP/dt in the best CS vein compared to the
worst CS vein of 16.766.3%. Although the difference in AHR seen
between different bipoles within the same vein were not large, we
did п¬Ѓnd that in some cases no pacing capture was found with one
A85
BCS Abstracts 2011
bipole but was found with another. Furthermore, differences in
whether phrenic nerve stimulation (PNS) occurred were seen when
using different LV lead bipoles within the same branch of the CS.
Conclusion Our data suggest that only a small difference in AHR is
seen when pacing along the same branch of the CS compared to
pacing within different branches of the CS within the same patient.
This means that although the site of LV lead placement is important, a proximal or distal position within a CS branch is much less
important than choosing the right branch in terms of acute
haemodynamic response. A choice of bipoles on the LV lead may
mean, however, that problems with capture thresholds or PNS can
be overcome without the need to reposition the LV lead.
154
2
G A Begg, 1J Gierula, 1Z L Waldron, 2K K Witte. 1Leeds General Infirmary, Leeds, UK;
University of Leeds, Leeds, UK
Background Right ventricular (RV) pacing is an accepted treatment
for symptomatic bradycardia. However, long-term RV pacing is
increasingly recognised to be detrimental to left ventricular (LV)
systolic function. We wanted to establish the prevalence, associated
features and predictors of LV systolic dysfunction (LVSD) and
outcome in a contemporary group of patients with longeterm RV
pacemakers.
Methods We prospectively recruited consecutive patients listed for
PGR between 2008 and 2010 at Leeds General Infirmary. We
performed echocardiography, exercise testing and recorded indications for pacing, pacing variables and duration of pacing, comorbidities, current medication and renal function.
Results Of 399 PGR procedures 342 subjects (86%), 184 men,
attended. Non-attendees had similar pacing variables and were of
similar age as attendees. Mean age (SE) was 76 (1), and mean
duration of pacing was 10 (0.3) years. Comorbidites were common:
diabetes mellitus in 11%, previous myocardial infarction in 15%,
previous cardiac surgery in 26% and atrial п¬Ѓbrillation (AF) in 26%.
Medical therapy included b-blockers in 60% and ACE inhibitors in
70%. Dual chamber devices were implanted in 77% (45% of all
patients had rate responsive (RR) pacing programmed). Mean
percentage of ventricular pacing (%VP) was 61 (2)%. Mean left
ventricular ejection fraction (LVEF) was 49 (1)%, (44% had an LVEF
<50%). Mean peak oxygen uptake (pVo2) (in 107 subjects) was 17
(1) ml/kg/min and mean creatinine was 108 (3) mmol/l. There was
an inverse relationship between LVEF and %VP (0.42; p<0.0001),
and years since п¬Ѓrst implanted (pВј0.09) but there was no effect on
LVEF of age, the presence of AF and the pacing mode. In single
chamber devices, RR pacing was associated with higher %VP
(pВј0.01), and a trend to worse LVEF (pВј0.09). These differences
were not seen in RR programmed dual chamber devices. There was a
negative relationship between pVo2 and %VP (rВј0.21; p<0.03). Even
with a short follow-up period of 16 (0.5) months, 23 (7%) patients
are dead. Patients dead at the censor date were older at the time of
the assessment (p<0.005), had a higher %VP (p<0.03) and worse
renal function (p<0.001), but did not have significantly worse LVEF
or pVo2. The presence of a single chamber device was associated
with a poorer outcome (p<0.002) despite patients with a single
chamber device being of similar age as those with a dual chamber
device.
Conclusions Patients receiving standard pacemaker generator
replacements frequently have cardiovascular comorbidities, left
ventricular dysfunction and impaired pVo2 and suffer a high
A86
155
INCIDENCE SCREENING OF PATIENTS FOLLOWING ST
ELEVATION MYOCARDIAL INFARCTION FOR PRIMARY
PREVENTION IMPLANTABLE CARDIOVERTER
DEFIBRILLATOR (ICD) IMPLANTATION HAS A LOW
THERAPEUTIC YIELD
doi:10.1136/heartjnl-2011-300198.155
PATIENTS RECEIVING STANDARD PACEMAKER
GENERATOR REPLACEMENTS FREQUENTLY HAVE
IMPAIRED LEFT VENTRICULAR FUNCTION AND EXERCISE
INTOLERANCE, RELATED TO THE PERCENTAGE OF RIGHT
VENTRICULAR PACING
doi:10.1136/heartjnl-2011-300198.154
1
mortality rate. In an unselected population of patients with pacemakers, we have established that the amount of RV pacing is related
not only to important surrogate measures of outcome such as
exercise tolerance and LVEF but also mortality. Whether an aggressive policy of limiting RV pacing in patients at risk reduces mortality
is unknown.
E L Berry, H C Padgett, A J Ahsan, A D Staniforth. Nottingham University Hospitals
NHS Trust, Nottingham, UK
Introduction The ICD implant rate for the United Kingdom is low
compared with the European Union and United States of America.
National Institute of Clinical Excellence guidance TAO95 (NICE
2006) makes recommendations for primary prevention ICD
implantation. Our study investigated the feasibility of systematically screening patients following an acute ST elevation myocardial
infarction (STEMI) to improve local ICD implant rates.
Method A prospective single centre study was performed over 14months, in tertiary centre setting. All patients with a diagnosis of an
acute STEMI had an echocardiogram at 6 weeks to assess left
ventricular ejection fraction (LVEF). Patients with impaired LVEF
then underwent screening for primary prevention ICD as per TA095
recommendations (Abstract 155 п¬Ѓgure 1).
Abstract 155 Figure 1
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
Results 326 STEMI patients were identified. Of these 12(3.7%)
declined investigation. 25(7.8%) died during the investigation period
(22 died during their initial acute event, 3 died of non cardiac causes
following discharge). 10(3.1%) requested follow-up in another
geographical area. 26(8%) patients were identified as LVEF<35%;
2(0.6%) patients were assessed as not clinically suitable for further
investigation. 2(0.6%) had LVEF<30% and QRS>120 ms, both
proceeded to have a primary prevention ICD implanted. 24(7.4%)
patients had Holter monitors; 2(0.6%) were identified as having
episodes of NSVT. Both patients had EPS; 1(0.3%) had inducible VT
and proceeded to have a primary prevention ICD implanted.
1 patient (0.3%) self presented with a cardiac arrest before
completion of their screening tests and received a secondary
prevention ICD. In total, 3(0.9%) primary prevention ICDs were
implanted (Abstract 155 п¬Ѓgure 2).
patients had associated symptoms of hyperadrenergic surges. Holter
monitoring prior to treatment demonstrated sinus tachycardia.
Resting pre-treatment mean 24 h HR was 94610 (range 75e100)
and mean HR on minimal exertion was 157620 (range 130e176).
All patients had a structurally normal heart on echocardiogram. Tilt
table testing was considered in 3 patients due to their symptoms
and it excluded postural orthostatic tachycardia syndrome. Pretreatment with b-blockers had been unsuccessful in 5/6 patients.
The remaining patient had symptomatic asthma and was therefore
unable to tolerate b-blockers. Ivabradine was exclusively used in 3
patients and clonidine in 2. 1 patient was started with Ivabradine
but later switched over to clonidine as it was ineffective. All 4
patients taking Ivabradine failed to gain symptom relief with no
significant reduction in mean 24-h HR parameters. Mean resting HR
after 3 months of Ivabradine therapy was 9569 (range 88e105) and
mean HR on exertion was 159623 (range 128e180). 2/4 patients
subsequently had complete sinus node ablation and AAIR pacemaker. In contrast, the 3 patients on clonidine had greater symptom
resolution and fall in resting and exercise heart rates at 3 months
follow-up. Resting mean HR was 8163 (range 78e83) and mean HR
with exertion was 144618 (range 132e164). The HR variability pre
and post treatment is shown in Abstract 156 п¬Ѓgure 1.
Abstract 155 Figure 2
Conclusion The yield from this study was low; 3 patients (0.9%)
proceeded to primary prevention ICD. It should also be noted that the
methodology resultant from TA095 guidelines was labour and resource
intensive. An alternative approach of opportunistic screening in
patient groups with a high prevalence of impaired LV function might
give a higher yield than our approach looking at disease incidence.
156
A SINGLE CENTRE EXPERIENCE OF IVABRADINE AND
CLONIDINE FOR INAPPROPRIATE SINUS TACHYCARDIA
doi:10.1136/heartjnl-2011-300198.156
P P Sadarmin, T R Betts. John Radcliffe Hospital, Oxford, UK
Introduction Inappropriate sinus tachycardia (IST) is a relatively rare
disease that manifests with resting tachycardia, a rapid increase in
heart rate (HR) with minimal exertion, a normal ECG and absence
of structural heart disease. Treatment options include b-blockade or
sinus node modification which are not 100% successful. Newer
agents like sinus node inhibitor (Ivabradine) or a centrally acting a-2
sympathomimetic (Clonidine) can be used but there is no success
outcome data for either and there is also no evidence that one is
better than the other. We present our experience of managing 6
patients with a diagnosis of IST with either Ivabradine or Clonidine
or both.
Methods We identified 6 patients from 2005 to 2009 with a diagnosis of IST (according to accepted international guidelines) who
had been treated with either Ivabradine or Clonidine or both.
Medical case records were reviewed for each patient.
Results 5 out of 6 patients were women with a mean age of
27.5 years (range 16e40 years). All patients had been symptomatic
for alteast 6 months before presentation to our tertiary centre. 2
Heart June 2011 Vol 97 Suppl 1
Abstract 156 Figure 1
Discussion In our case series of 6 patients, Clonidine was more
effective than Ivabradine both in terms of reducing heart rate and
treating symptoms for patients with inappropriate sinus tachycardia. Patients with coexisting hyperadrenergic symptoms may
benefit the most. A trial of Clonidine can be recommended before
considering sinus node ablation. Formal randomised controlled trials
are needed to confirm our findings.
157
AN INSIGHT INTO IMPLANTERS’ PRACTICES OF ICD
IMPLANTATION: A PHYSICIAN SURVEY
doi:10.1136/heartjnl-2011-300198.157
P P Sadarmin, K C K Wong, K Rajappan, Y Bashir, T R Betts. John Radcliffe Hospital,
Oxford, UK
Introduction The Implantable cardioverter defibrillator (ICD) is the
mainstay of treatment for the prevention of sudden cardiac death
(SCD) and the management of tachyarrhythmias. Informed patient
A87
BCS Abstracts 2011
consent is an essential part of the implant process. Our aim was to
get an insight into implanters’ (Imp) practices prior to an ICD
implantation.
Methods A questionnaire survey was sent to UK ICD Imp to test
their knowledge of the risk and benefits of an ICD in patients who
satisfy trial and national guideline criteria and the incidence of
implant complications. Information of the style and language of
consent was requested. This questionnaire was specifically aimed at
Imp and was part of the larger questionnaire looking at knowledge,
attitudes and factors influencing ICD prescription in the UK.
Results Replies were received from 23 implanters. 35% of the
responders were between the age of 30e39 years and 39% were
between 40 and 49 years. 83% of the responders were Consultants
and 96% were working in an implantating centre. 83% of Imp were
fully aware of Primary Prevention (PP) NICE guidelines while 78%
were fully aware of Secondary Prevention (SP) NICE guidelines.
There was widespread use of information leaflets (87%) and
specialist ICD nurses (83%) to disseminate information to patients.
All responders said they would personally discuss the therapy with
the patient prior to the implantation regardless of the referral
source. A discussion regarding the prevention of SCD, inappropriate
shocks and driving restrictions were performed by 96% of
responders and device infections and lead failures discussed by 91%.
Use of absolute risk reduction in percentages and number needed to
treat while explaining the risks and benefits gained from ICDs were
used by 22% and 26% respectively. There was widespread use of
phrases like “small risk” or “moderate risk” (61%) and life prolongation (eg, lets you live longer by an average of 3 months) (30%).
Replies also indicated that Imp under-estimate overall mortality in
medicallytreated and ICD-treated patients, lead dislodgement
requiring re-positioning and major haematoma requiring reoperation.
Imp overestimate infections leading to device removal and the incidence
of pneumothorax when compared to published trial or study data.
Conclusion The majority of implanters are aware of UK ICD
guidelines. The patient consent process is not universal. Guidelines
and awareness about end-of-life care in ICD patients is needed and
should be part of the initial consent process. Evidence based use of
risk and benefit terminologies like ARR and NNT are needed to
better inform the patient rather than abstract phrases. Increasing
awareness of ICD complication rates can help patients and physicians balance risk against benefit which could lead to improved
patient satisfaction with their therapy.
Abstract 157 Table 1
Estimate of ICD
complications
Death as a complication of
device implant
Lead dislodgement requiring
lead repositioning
Lead failure requiring extraction
or additional lead insertion
Mean %
Published/Trial data %
0.3760.48
0.77% (Circulation.1998;98:663e670);
2.08% (Br Heart J.1995:73:20e24)
5% (PACE.2005; 28:926e932);
10% (Circulation.1998;98:663e670)
3.562.08
5.467.28
2.7263.07
5.8% (JAMA.2006:295:1901e1911)
Device infection requiring
removal/extraction
2.2762.4
0.5% (PACE.2005:28:926e932); 0.77%
(Circulation.1998;98:663e670);0.7%
(MADIT2 trial)
0.2% (PACE.2005;28:926e932);
0.64% (Circulation.1998;98:663e670)
0.761.07
IS IT COST EFFECTIVE TO USE A PLUGGED LV PORT?
doi:10.1136/heartjnl-2011-300198.158
M A Jones, T R Betts, K Rajappan, Y Bashir, K C K Wong, N Qureshi. John Radcliffe
Hospital, Oxford, UK
Background Many patients receiving ICD implants do not meet
criteria for CRT therapy, yet are often felt likely to benefit from CRT
in the future. The reasons for this include less severe NYHA class of
HF symptoms at the time of implant, narrow QRS, and (progressive) atrio-ventricular conduction delay. Management options
include only implanting DDD / VVI devices, and then upgrading to
CRT if required; implanting CRT-D devices but without an LV lead,
with the LV port “plugged”, such that if an upgrade were to become
necessary, only a new LV lead (and implant kit) would be required;
and п¬Ѓnally, implanting CRT-D devices with LV leads in all patients
in the п¬Ѓrst instance, as has been suggested by the recent Madit-CRT
and RAFT studies. It is not clear which of these strategies is superior
in terms of the cost-benefit ratio.
Purpose This study analyses a retrospective cohort of patients who
received CRT-D devices but without LV leads, to examine the cost
implications of this approach, and to compare this cost to that of merely
implanting a DDD device, or implanting a full CRT-D system initially.
Method A retrospective analysis of all patients receiving CRT-ICDs
with plugged LV ports between September 2004 and June 2009 at
our institution. Patient characteristics, indication for a plugged LV
port, subsequent addition of a LV lead and reasons for doing so were
taken from patient records. The total cost (surgery and hardware)
was compared with the estimated cost of initially implanting single
or dual chamber ICDs and upgrading the entire system, and to the
cost of implanting full CRT-D systems up front.
Results 35 patients (27 male) were identified. Mean (SD) age was
6768 years. 26 had ischaemic heart disease and 9 non-ischaemic
dilated cardiomyopathy. All had LV EF<30%. Indications for a plugged
LV port were LBBB and NYHA class I or II symptoms in 29 and
NYHA class I or II with a narrow QRS but a high chance of becoming
pacemaker dependent in 6. During a mean (SD) FU of 40 616
months, 6 (17%) patients had an LV lead added, all for the development of NYHA III symptoms, at 10, 11, 15, 17, 17 and 21 months
respectively. Total cost at end of FU period was ВЈ 654 000. If all
patients had initially been implanted with VVI or DDD ICDs and 6
new CRT systems implanted, the estimated cost would have been ВЈ
598 000. If all patients had received full CRT-D the cost would have
been ВЈ 665 000. Taking into account the time to develop symptoms, it
is predicted that an upgrade rate of 26%e31% would be required
before using a plugged LV port becomes cost-effective. Furthermore,
full CRT-D system implantation is even less cost effective.
Conclusion In this series of ICD patients with potential CRT indications but minimal heart failure symptoms, only a small proportion
subsequently required biventricular pacing. Using a CRT-ICD with a
plugged LV port is not a cost effective strategy (Abstract 158 п¬Ѓgure 1).
4.3% (PACE.2005;28:926e932)
Major haematoma requiring
reoperation
Cardiac tamponade
158
Pneumothorax
1.6861.17
1.1% (PACE.2005; 28:926e932);
0.89% (Circulation.1998;98:663e670)
Inappropriate shocks
14.8610.92
Psychological problems
associated with the device
22.6626.68
12% (PACE.2005; 28:926e932); 14.91%
(Circulation.1998;98:663e670);
18% (Z Kardiol.1996;85:809e819)
13e38% (Clin Cardiol 1999;22:481e9)
Abstract 158 Figure 1
A88
Per cent freedom from upgrade to LV lead.
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
159
PILOT STUDY EXPLORING THE REGIONAL REPOLARISATION
INSTABILITY INDEX IN RELATION TO MYOCARDIAL
HETEROGENEITY AND PREDICTION OF VENTRICULAR
ARRHYTHMIA AND DEATH
doi:10.1136/heartjnl-2011-300198.159
1
W B Nicolson, 1C D Steadman, 1P Brown, 2M Jeilan, 2S Yusuf, 2S Kundu,
A J Sandilands, 2P J Stafford, 1F S Schlindwein, 2G P McCann, 1G A Ng. 1University
of Leicester, Leicester, UK; 2University Hospitals of Leicester NHS Trust, Leicester, UK
2
Introduction There is a need for better sudden cardiac death (SCD)
risk markers. Mounting evidence suggests that the mechanism
underlying risk of ventricular arrhythmia (VA) is increased heterogeneity of electrical restitution. We investigated a novel measure of
action potential duration (APD) restitution heterogeneity: the
Regional Repolarisation Instability Index (R2I2) and correlated it
with peri-infarct zone (PIZ) a cardiac magnetic resonance (CMR)
anatomic marker of VA risk.
Methods Blinded retrospective study of 30 patients with ischaemic
cardiomyopathy assessed for an implantable cardioverter defibrillator. The R2I2 was derived from high resolution 12 lead ECG
recorded during programmed electrical stimulation (PES). ECG
surrogates were used to plot APD as a function of diastolic interval;
the R2I2 was the maximal value of the mean squared residuals of
the mean points for anterior, inferior and lateral leads normalised to
the mean value for the total population. PIZ was measured from late
gadolinium enhanced CMR images using the full width half
maximum technique.
Results Seven patients reached the endpoint of VA/death (median
follow-up 24 months). R2I2 > median was found to be predictive of
VA/death independent of PES result, left ventricular ejection fraction and QRS duration (6/14 vs 1/15 pВј0.031). Modest correlation
was seen between the R2I2 and PIZ (rВј0.41 pВј0.057) (Abstract 159
п¬Ѓgure 1).
Abstract 159 Figure 1
Conclusions In this pilot study of ischaemic cardiomyopathy
patients, the R2I2 was shown to be an electrical measure of VA/
death risk with a moderately strong correlation with an anatomic
measure of arrhythmic substrate, the extent of PIZ. The R2I2 may
add value to existing markers of VA/death and merits further
investigation.
Heart June 2011 Vol 97 Suppl 1
Abstract 159 Table 1
Variable
Whole Group
(n[30)
No VA/death
(n[23)
VA/death
(n[7)
Age (years)
Sex (% male)
6769
97
6569
96
7268
100
0.055
QRSD(ms)
EF(%)
107620
31614
107621
32.4615
106615
2767.5
0.95
0.34
PES result (positive/total)
R2I2>median
12/30
14/29
7/23
8/22
5/7
6/7
0.068
0.031
EDV index (ml/cm)
SV index (ml/cm)
1.4860.41
0.4260.14
1.4960.41
0.4360.14
1.4560.45
0.3960.15
0.84
0.47
Follow-up (months)
PIZ %
24 (18)
7.8 (10.7)
24 (16)
7.5 (8.4)
16 (16)
13.6 (8.5)
0.088
0.093
Scar %
10.9 (16.5)
9.67 (13.5)
21.9 (17.8)
0.16
160
p
HIGH DOSE OCTREOTIDE; A NOVEL THERAPY FOR THE
TREATMENT OF DRUG REFRACTORY POSTURAL
ORTHOSTATIC TACHYCARDIA SYNDROME IN PATIENTS
WITH JOINT HYPERMOBILITY SYNDROME
doi:10.1136/heartjnl-2011-300198.160
A E French, C Shepherd, A Horne, C Parker, J Tagney, J Pitts-Crick, T Johnson,
G Thomas. Bristol Heart Institute, Bristol, UK
Introduction Postural orthostatic tachycardia syndrome (POTS) is
defined as symptomatic orthostatic intolerance with an increase in
heart rate of 30 beats per minute within 10 min of head up tilt
(HUT). This dysautonomia causes wide-ranging symptoms
including palpitations, presyncope, chronic fatigue, headache and
cognitive difficulties. When POTS occurs in patients with preexisting Joint Hypermobility Syndrome (JHS), symptoms begin
approximately a decade earlier than non-JHS patients with a
preponderance of neurological features, secondary to cerebral hypoperfusion. Vascular laxity with splanchnic venous pooling has been
implicated as a causative factor thus measures to expand plasma
volume (thereby increasing mean arterial pressure and restoring
cerebral perfusion) form the mainstay of therapy. Symptomatic
improvements have been previously reported in POTS patients with
the somatostatin analogue Octreotide, a powerful splanchnic vasoconstrictor. We report the п¬Ѓrst UK series of JHS patients with drug
refractory POTS treated with high-dose octreotide.
Methods Six patients (female, aged 21e52) were referred to our
institution. All had known JHS (4 requiring a wheelchair), neurological symptoms (headache and cognitive impairment) and diagnostic tilt-table testing with a mean increase in heart rate of
64 beats/min (range 47e73) with head-up tilt (HUT). All patients
had remained symptomatic despite pre-treatment with a mean of 5
POTS medications (range 5e7) including fludrocortisone, midodrine, propranolol, ivabradine, selective serotonin reuptake inhibitors, gabapentin and erythropoietin. Octreotide was commenced
using a short-acting preparation given 3 times daily (dosage
50e250 mg according to body mass) in conjunction with a longacting (monthly), intramuscular injection (dosage 10e30 mg). The
short-acting preparation was weaned following the second monthly
injection.
Results During follow-up of 3 months (range 1e8), 3 (50%) patients
reported a complete resolution of all postural and neurological
symptoms which corresponded with a normalised response to HUT.
The remaining patients reported a dramatic improvement but
ongoing postural symptoms. No patients developed supine hypertension. Side effects including mild abdominal discomfort and
transient diarrhoea were reported in 3 (50%) patients.
Conclusion Octreotide is increasingly recognised as an effective
therapy in POTS patients. Both short-acting, subcutaneous (0.9 mg/
Kg) and long-acting, intramuscular (10e20 mg) preparations have
A89
BCS Abstracts 2011
previously been reported. We conclude that higher dosages of both
preparations when administered together are effective and well
tolerated in JHS patients with drug refractory POTS.
162
THE CLINICAL MANAGEMENT OF RELATIVES OF YOUNG
SUDDEN ARRHYTHMIC DEATH VICTIMS; ICDS ARE RARELY
INDICATED
doi:10.1136/heartjnl-2011-300198.162
1
1
2
2
J C Caldwell, Z Borbas, N Moreton, N Khan, 2L Kerzin-Storrar, 2K Metcalfe,
W Newman, 1C J Garratt. 1Manchester Heart Centre, Central Manchester University
NHS Foundation Trust, Manchester, UK; 2Department of Clinical Genetics, St Mary9 s
Hospital, Central Manchester University NHS Foundation Trust, Manchester, UK
2
161
CATHETER ABLATION OF ATRIAL FIBRILLATION ON
UNINTERRUPTED WARFARIN USING STANDARD AND DUTY
CYCLED RADIOFREQUENCY ENERGY: SAFE AND EFFECTIVE
doi:10.1136/heartjnl-2011-300198.161
J R J Foley, N C Davidson, B D Brown, D J Fox. University Hospital of South
Manchester, Manchester, UK
Introduction Catheter ablation (CA) for atrial п¬Ѓbrillation (AF) is
growing exponentially. Although ablation for paroxysmal AF (PAF)
is associated with shorter procedure times and less extensive left
atrial ablation vs persistent AF thromboembolic complications can
occur in both sub-groups. Inadequate anticoagulation leads to
thrombotic complications and excessive anticoagulation can lead to
bleeding risks. Many centres adopt a policy of discontinuing
warfarin in the immediate run-up to the procedure, covering the
procedure with unfractionated heparin and “bridging” postoperative
patients with low molecular weight heparins (LMWH) back onto
warfarin. We wished to determine the safety of CA for AF with a
therapeutic INR using both the single transseptal approach and
duty cycled radiofrequency energy (RF) with non irrigated PVAC
catheters and the double transseptal puncture technique using irrigated RF catheters and either CARTO or NAVX electroanatomical
mapping.
Methods A retrospective analysis of 173 patients who underwent
CA for AF while taking uninterrupted warfarin. Procedural target
International Normalised Ratio (INR) was 2e3 with a peri-procedural target ACT of 300e350 s. In sub therapeutic INR patients
weight adjusted LMWH was used post procedure with warfarin
until INR was >2. Standard technique employed was large area
circumferential ablation using conventional RF energy or pulmonary
vein isolation using duty cycled RF energy. Data was gathered for
demographics, procedural INR, total dose of unfractionated heparin,
fluoroscopy time, and type of radiofrequency energy used.
Endpoints were minor bleeding, major bleeding (requiring transfusion), vascular complications, pericardial tamponade and stroke/
TIA within 28 days of the procedure.
Results There were 128/173 male patients, age range between 21
and 73 years (mean 57 years). 122 underwent ablation for PAF and
51 for persistent AF. Mean procedural INR was 2.4 (range 1.7e3.9).
Mean unfractionated heparin dose was 6000 units (range
1000e14 500). Mean fluoroscopy time for the PVAC group was
23.4 mins (range 8.3e50.1 mins). Mean fluoroscopy time for
CARTO/NAVX group was 31mins (range 14.10e58.44 mins). There
were no major bleeding complications. There was 1 minor bleeding
complication with a groin pseudoaneurysm. There were 2 cases of
pericardial tamponade (2/173%e1.2%) both managed with percutaneous pericardial drainage. There were no stroke/TIAs.
Conclusion These data demonstrate that CA for AF by both single
and double transseptal technique using both standard RF and duty
cycled RF while maintaining a therapeutic INR is a safe procedure.
Maintaining a therapeutic INR reduces the risk of embolic events
associated with “bridging” heparin without an increase in bleeding
complications. This technique is convenient for patients and avoids
switching between LMWH and warfarin and ensures patient safety
by maintaining therapeutic anticoagulation before, during and after
the procedure.
A90
Introduction Following National Service Framework guidance on the
management of sudden cardiac death (SCD), regional inherited
cardiac conditions clinics were established to identify and treat those
at increased risk of dying from an arrhythmic condition. Studies have
examined the yield of different diagnostic strategies but the outcome
of management in these patients has not been reported.
Methods We present data on 193 consecutive patients (108 families)
referred to a regional inherited cardiac conditions clinic because of
SCD/aborted cardiac arrest of a relative. The mean age on referral
was 38617 yrs and mean duration of follow-up was 15 months
(range 1 day to 56 months). All individuals underwent clinical
assessment by history, examination, ECG and echo. If treadmill
exercise test had not previously been performed this was undertaken. Further imaging by CMR or contrast echo was performed in
those with structurally abnormal hearts or with T wave inversion in
V2/V3. Ajmaline provocative testing was performed in those with a
history and/or ECG suggestive of Brugada syndrome.
Results Of the 193 patients, 43 individuals (22%) from 36 families
(33%) were diagnosed with an inheritable cause of SCD and 145
patients were clinically normal (see Abstract 162 table 1). Five
patients were found to have other conditions (LV non-compaction,
AVNRT, skeletal myopathy, mild AS and congenital sub-aortic
membrane). Of the 43 patients diagnosed with an inheritable
condition, 21 had medication commenced by the clinic (b-blockers
(21), ACEi/ARB(2), Spironolactone[1]). ICDs were implanted as per
HRUK guidelines, resulting in 4 patients having an ICD inserted on
clinic recommendation (2 HCM, 1 DCM, 1 ARVC). To date no
appropriate therapies have been administered (follow-up 8e29
months) but there was 1 inappropriate shock from a fractured lead.
Three individuals had b-blockade withdrawn after negative genetic
testing for an established familial mutations (2 CPVT, 1 LQT), one
ICD was removed and one deactivated (both negative for CPVT). Of
the 145 patients thought to be clinically normal, 85 were reassured
and discharged, 13 failed to return to clinic and 47 are regular
reviewed as the risk of developing an inheritable condition cannot be
excluded; this includes those with family histories of HCM (7),
ARVC (12), DCM (9), CPVT (5), Brugada (4) and LQT(1). To date
no deaths have occurred in those diagnosed with inherited causes of
SCD (follow-up mean 20, 1e52 range) or those clinically normal
with ongoing review (follow-up mean 22 months, 1e56 range).
Abstract 162 Table 1
Diagnosis of patient
Numbers
Clinically normal
LQTS
145
12
Brugada
CPVT
2
5
ARVC
DCM
7
7
HCM
10
Conclusion A diagnosis of an inheritable cause of SCD was obtained
in 22% of individuals and 33% families with a history of SCD/
aborted cardiac arrest in a relative. The number of ICDs inserted was
very small (2%) and there have been no appropriate therapies in this
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
group. Two ICDs have been removed/deactivated after exclusion of
a known familial mutation.
163
THE UNITED KINGDOM TRANSCATHETER AORTIC VALVE
REGISTRY - OUTCOMES TO DECEMBER 2009 AND UPDATE
doi:10.1136/heartjnl-2011-300198.163
P F Ludman. On Behalf of the UK TAVI Steering Group, Birmingham, UK
Introduction The United Kingdom Transcatheter Aortic Valve (TAVI)
Registry was established to define the clinical and procedural details
of all patients being treated by TAVI, regardless of access route or
technology used, and to assess their outcomes. The registry has
captured all cases in England and Wales.
Methods For every TAVI performed, all centres complete an agreed
dataset. The data are encrypted and sent electronically to servers at
the Central Cardiac Audit Database (CCAD) for analysis. A unique
patient identifier (the NHS number) is used to link with the NHS
Central Register to track mortality. This analysis is based on all
procedures performed up to 31st December 2009.
Results 25 centres in England and Wales performed a total of 877
procedures in 870 patients; 66 in 2007, 273 in 2008 and 538 in 2009.
Median number of cases per centre was 24. Median (IQR) age was
82 (78e87) yrs. 52% were male, and mean logistic Euroscore (LES)
was 22.2%. 68% were transfemoral, the remainder being mainly
transapical. 90% of CoreValve implants and 46% of Edwards used a
transfemoral approach. Patients needing a transapical route had
more comorbid conditions than those treated by a transfemoral
route (LES 25.2% vs 20.9%). Mortality tracking was successful in
100% of patients. Survival at 30 days was 93.1%, 78.9% at 1 year
(443 at risk) and 72.3% at 2 years (114 at risk). Survival was
significantly poorer in those needing non-transfemoral approaches
(1 year survival 73.5% vs 81.4%). Survival was also poorer in those
with poorer LV ejection fraction, with moderate or severe post
procedural aortic regurgitation and with a LES>40. Survival was not
associated with age, NYHA class, or the presence of concomitant
coronary artery disease, and not different between those with a
LES<21 compared with LES 21e40. There was also no difference in
survival between patients treated with CoreValve or Edwards
technologies, or between proctored and non proctored cases. There
was a significant improvement in survival over the 3 years of the
registry, and a change in demographics with the proportion of
patients with prior CABG rising from 16.4% in 2007 to 29.9% in
2009. The total number of cases in the UK TAVI registry has risen to
1490 as of 29 Nov 2010. More details of the 2010 cohort will be
available at the time of presentation (Abstract 163 п¬Ѓgure 1).
Abstract 163 Figure 1
Heart June 2011 Vol 97 Suppl 1
Conclusions The UK TAVI Registry has successfully captured the
entire TAVI activity of England and Wales incorporating the learning
curves of every centre. Outcomes following TAVI are excellent in a
high risk patient population. Outcomes are better in the population
who are suitable for a transfemoral approach (with less comorbidity) than those treated with the transapical approach. These data
suggest that careful proctoring allows the introduction of a new
treatment method without an adverse effect on patient outcome,
and we have demonstrated no systematic difference in outcome
between the two commercially available technologies.
164
EARLY HAEMODYNAMIC CHANGES AND MYOCARDIAL
INJURY AFTER TRANSFEMORAL TRANSCATHETER AORTIC
VALVE IMPLANTATION (TAVI)
doi:10.1136/heartjnl-2011-300198.164
R Dworakowski, A Bhan, B Brickham, O Wendler, M Monaghan, A M Shah,
P MacCarthy. Kings College Hospital, Kings Health Partners, London, UK
Purpose Transfemoral (TF) TAVI is a novel procedure for the
treatment of severe aortic stenosis, without the need for thoracotomy or cardiopulmonary bypass. The procedure results in
almost instantaneous normalisation of transvalvular gradients, but
little is yet known about the periprocedural haemodynamic effects.
We aimed to describe these effects using 3D and tissue Doppler (tD)
transthoracic echocardiography (TTE) and Cardiac Output monitoring.
Methods In 16 patients undergoing TF TAVI haemodynamics were
characterised with a number of tD and 3D TTE measurements.
Abstract 164 Figure 1
A91
BCS Abstracts 2011
These were taken at multiple time points (baseline, 6 and 24 hours
post procedure). Calculated volumetric parameters included 3D enddiastolic volume (EDV) and end-systolic volume (ESV), stroke
volume (SV) and 3D LA volume (LAV). Diastolic function was
monitored using the indices mean E:E9 and systolic function/
contractility was measured with dP/dt max and early peak systolic
velocity (S9 ). The FloTrac system (consisting of the Vigileo monitor
and sensor), uses a clinically validated algorithm to provide
continuous cardiac output (CO), stroke volume (SV) and systemic
vascular resistance in real-time.
Results TAVI resulted in an immediate increase in cardiac output
(3.7 (baseline), 4.6 (6 h) 4.5 l/min (24 h), p<0.5 baseline vs 6 h and
24 h) with no significant change in systemic vascular resistance
(1162, 1292 and 1367 dyn*s/cm5). However, 6 h post-TAVI there
was a significant decrease in systolic function as measured by dP/dt
max/EDV (see Abstract 164 п¬Ѓgure 1A) and co-existent impairment
of diastolic function as indicated by medial E:E9 values (see Abstract
164 п¬Ѓgure 1B), which was associated with an appropriate increase in
LA volume (70.3, 82.6 and 72.8 ml, p<0.05 baseline vs 6 h).
Following this, there was a recovery of both systolic and diastolic
indices. In addition, another marker of systolic function, S9 increased
after 24 h (6.4, 6.6, 8.2 cm/s, p<0.05 baseline vs 24 h and 6 h vs
24 h). Concurrent with this recovery, we observed a significant
decrease in EDV and ESV at 24 h post-TAVI (EDV: 94.9 to 83.4 ml
(p<0.05); ESV 41.9 to 33.5 ml (p<0.05)). These changes in haemodynamics were associated with significant increase of troponin I
levels at 24 h and increase in CK-MB at 6 h after the procedure
(troponin: 0.06 vs 1.19 mg/l, p<0.05; CK-MB 1.6 vs 6.6 mg/l, p<0.05).
Conclusion Successful TF TAVI results in an immediate improvement in cardiac output. However, overlying this, within the п¬Ѓrst
24 h both systolic and diastolic dysfunction occurs. The rise in the
markers of myocardial injury suggest this may be due to myocardial
stunning and/or some periprocedural myocardial damage. Recovery
of contractility is observed after 24 hours.
165
THE OXVALVE STUDY: ECHOCARDIOGRAPHIC SCREENING
FOR VALVULAR HEART DISEASE IN THE COMMUNITY
SETTING: METHODOLOGY, FEASIBILITY AND PRELIMINARY
RESULTS
British Society of Echocardiography guidelines. The threshold for
inclusion in the screen positive group was deliberately low to capture
all manifestations of VHD. Participants were given preliminary
results, before completing a shortened Spielberger STAI questionnaire.
Results Uptake was 46% (age range 65e96 years; male to female
ratio 1:1.1). VHD was detected in 33% of participants and prevalence increased with increasing age (see Abstract 165 п¬Ѓgure 1).
Mitral regurgitation and aortic regurgitation were the most
common lesions detected (present in 17% and 14% respectively).
The majority of VHD was graded as mild (84%); only 1% of VHD
detected was severe. The majority of participants (99%) described
themselves as calm or relaxed at the time of screening; none
expressed significant levels of worry or tension. 98% would be
prepared to undergo repeat echocardiography as screening for VHD.
Abstract 165 Figure 1
Prevalence of VHD in $65s by age group.
Conclusions The prevalence of VHD in adults aged over 65 in the
Oxfordshire population, using a low threshold for detection, is
approximately 33% and increases with age. Mitral regurgitation is
the most common lesion, and the majority of detected VHD is mild.
Echocardiographic screening for VHD is feasible in the primary care
setting and acceptable in this group of patients.
doi:10.1136/heartjnl-2011-300198.165
1
2
3
4
J L d’Arcy, D Ebbs, P Grimwade, A J Farmer, 4D Mant, 1B D Prendergast. 1John
Radcliffe Hospital, Oxford, UK; 2Didcot Health Centre, Oxford, UK; 3Bampton Medical
Practice, Oxford, UK; 4Department of Public Health and Primary Care, University of
Oxford, Oxford, UK
Introduction Valvular heart disease (VHD) is poorly researched in
comparison with other areas of cardiovascular disease. Principle
limitations are the diverse nature of patients with VHD, inability to
identify individuals at the earliest stages of disease and lack of an
appropriate investigational infrastructure. Studies addressing the
contemporary epidemiology and natural history of VHD are scarce
but demonstrate an increasing prevalence in the elderly, associated
with significant morbidity and mortality. Cohort studies in the USA
are ongoing but there are no European or UK studies to date. We
have developed a large scale, prospective community echocardiographic screening study within the adult Oxfordshire population, to
determine the epidemiological characteristics of VHD in the UK for
the п¬Ѓrst time, to assess the acceptability of echocardiographic screening
for VHD, and establish cohorts with well-characterised genetic and
echocardiographic phenotypes for future study. Herein, we present
preliminary data for the п¬Ѓrst 1050 patients, with enrolment ongoing.
Methods Patients >65 years, registered with participating general
practices (GP) and with no known VHD, were invited to attend
their GP surgery where routine demographic and cardiac data were
collected and a focused examination undertaken. Participants underwent a standard transthoracic echocardiogram (TTE) according to
A92
166
CARDIOVASCULAR MAGNETIC RESONANCE (CMR)
TAGGING IDENTIFIES DIFFERENTIAL VENTRICULAR
REMODELLING IN PATIENTS WITH BICUSPID VS TRICUSPID
AORTIC VALVE DISEASE
doi:10.1136/heartjnl-2011-300198.166
S Bull, J Suttie, N Blundell, J M Francis, T D Karamitsos, A Pitcher, J D’Arcy,
B Prendergast, S Neubauer, S G Myerson. John Radcliffe Hospital, Oxford, UK
Background Bicuspid aortic valves (BAV) are a common inherited
abnormality with a very high rate of adverse cardiac events at an
earlier age than tricuspid aortic valves (TAV). Risk stratification for
moderate to severe aortic stenosis, in both bicuspid and tricuspid
disease, remains a significant clinical challenge. It is unknown
whether pathological left ventricular (LV) remodelling, a strong
predictor of adverse cardiac events, differs between patients with
bicuspid and tricuspid valvular disease with comparable transvalvular gradients. Cardiovascular magnetic resonance (CMR)
tagging provides detailed characterisation of global and regional
contractility, and is a powerful investigative tool in the assessment
of myocardial disease. We therefore assessed left ventricular strain
(using CMR tagging), valve morphology and LV hypertrophy in
patients with bicuspid and tricuspid aortic valve disease matched for
transvalvular gradient.
Methods 42 subjects were recruited in total: 24 patients with
moderate to severe BAV (age 55 615 yrs, female 21%, peak transHeart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
aortic velocity 3.160.6/ms, LV mass 172648 g; SBP 127 614 mm
Hg DBP 76 610 mm Hg) and 18 patients with velocity-matched
TAV (age 74 66 years, female 28%, velocity 3.160.6/ ms, LV mass
147627 g; SBP 136617 mm Hg; DBP 7967 mm Hg; Abstract 166
table 1). Patients were scanned using a 1.5 T Avanto scanner (Siemens
Healthcare, Erlangen, Germany) and basal, mid-ventricular and apical
short axis tagging images were acquired. Peak systolic global
circumferential strain was calculated at each ventricular level using
CimTag2D software v.7 (Auckland MRI Research Group, New Zealand).
Abstract 166 Table 1
Bicuspid vs tricuspid aortic valve disease
Morphology
Bicuspid
aortic valve
(BAV)
Tricuspid aortic
valve (TAV)
p Value
Age (yrs)
Female (%)
55615
21
7466
28
<0.01
0.31
Transvalvular velocity (msГЂ1)
Left ventricular mass (g)
3.160.6
172648
3.160.6
147627
0.50
0.04
Systolic blood pressure (SBP)
Diastolic blood pressure (DBP)
127614
76610
136617
7967
0.04
0.15
Basal circumferential systolic strain (%)
Mid ventricular circumferential strain (%)
2063
1962
2263
2162
0.04
0.07
Apical ventricular circumferential strain (%)
1764
1963
0.04
Results Patients with BAV had significantly greater left ventricular
hypertrophy (BAV 172 648 g vs TAV 147627 g; pВј0.04) despite
similar degrees of valve stenosis. Peak systolic circumferential strain
was lower (ie, reduced contractility) in patients with BAV than TAV
(Basal BAV 2063% vs TAV 2263% PВј0.04; Mid BAV 19 6 2% vs
TAV 21 6 2% pВј0.07; apical BAV 1764% vs TAV 1963%; p<0.04),
despite the younger age and lower blood pressure.
Conclusion Ventricular remodelling differs between BAV and TAV
patients with equivalent transvalvular gradients. BAV patients,
despite being younger and having lower systolic blood pressure, have
more severe hypertrophy and lower myocardial contractility. This
п¬Ѓnding may have implications for monitoring disease progression
or more timely medical or surgical intervention in patients with BAV.
Abstract 166 Figure 1 Velocity matched tricuspid and bicuspid aortic
valves showing valve morphology, tagging and cine imaging.
Heart June 2011 Vol 97 Suppl 1
167
AORTIC REGURGITATION QUANTIFICATION WITH
CARDIOVASCULAR MAGNETIC RESONANCE PREDICTS
CLINICAL OUTCOME
doi:10.1136/heartjnl-2011-300198.167
1
1
2
3
S G Myerson, J D’Arcy, R Mohiaddin, J P Greenwood, 1T D Karamitsos,
J M Francis, 1A P Banning, 4J P Christiansen, 1S Neubauer. 1John Radcliffe Hospital &
University of Oxford, Oxford, UK; 2CMR Unit, Royal Brompton Hospital and the National
Heart and Lung Institute, London, UK; 3University of Leeds, Leeds, UK; 4North Shore
Hospital, Auckland, New Zealand
1
Background The timing of valve surgery in asymptomatic patients
with significant aortic regurgitation can be challenging. Current
indications focus on symptoms and left ventricular (LV) dilation/
dysfunction, but prognosis is already reduced by this time. Quantification of the regurgitation has not previously been used to guide
management, likely due to the difficulty of achieving this with
echocardiography. Cardiovascular magnetic resonance (CMR) can
accurately quantify aortic regurgitation and LV volumes, and we
examined whether either could predict symptom development and
the need for aortic valve surgery.
Methods 94 asymptomatic patients with moderate or severe aortic
regurgitation on echocardiography were identified from four high
volume CMR centres. CMR scans were performed to quantify aortic
regurgitation and LV volume indices, and subsequent clinical followup occurred for up to 7 years (mean 2.662.1 years). The best
predictors of progression to symptoms and other conventional
indications for surgery were determined.
Results Aortic regurgitant fraction was the best predictor of clinical
outcome; area under the curve (AUC) on receiver operating characteristics analysis 0.93 (p<0.0001), with a specificity of 93% and
sensitivity of 78% for predicting the progression to symptoms and
surgery. Survival without surgery was 88% for patients with a
regurgitant fraction <37%, compared to 6% for those with a
regurgitant fraction $37% (see Abstract 167 п¬Ѓgure 1). Regurgitant
volume >38 mls and regurgitant volume index >25 ml/m2 were also
good predictors (AUC 0.91 and 0.90 respectively), though regurgitant fraction had significantly greater predictive power (OR 1.26
compared to 1.09 for regurgitant volume). LV volumetric indices also
predicted outcome, but less strongly than measures of regurgitation:
LV end-diastolic volume >267 mls (AUC 0.85), LV end-systolic
volume >88 mls (AUC 0.78). Regurgitant fraction and volume were
the only independent outcome predictors on multiple logistic
regression analysis. The predictive ability of CMR applied to
patients with both moderate and severe aortic regurgitation on
echocardiography. Supporting data also comes from a comparison
Abstract 167 Figure 1 Kaplan-Meier survival curve showing survival
without surgery for conventional indications.
A93
BCS Abstracts 2011
with patients already planning to undergo surgery at the time of
CMR scanning, which showed similar regurgitant fractions in the
surgical group (mean 6SD: 45.4%612.1%) compared to the initially
asymptomatic patients who developed symptoms or other indications for surgery (42.8%610.4%); pВј0.32. Subjects who remained
asymptomatic had a significantly lower regurgitant fraction:
25.368.6% (p<0.0001 vs both the planned surgical group and the
symptom progression group).
Conclusions CMR quantification of aortic regurgitation and LV
volumes accurately predicts the progression to symptoms/surgery.
Its use in patients with aortic regurgitation should be encouraged.
168
b-BLOCKER THERAPY IMPROVES CLINICAL OUTCOMES IN
PATIENTS WITH MODERATE TO SEVERE MITRAL
REGURGITATION
doi:10.1136/heartjnl-2011-300198.168
A Nadir, D H Elder, M G MacArtney, S D Pringle, A M Choy, A D Struthers, C C Lang.
University of Dundee, Dundee, UK
Background Volume overload seen in mitral regurgitation (MR)
leads to neuro-endocrine activation including heightened sympathetic activity. Experimental data have reported protective effects of
beta-blockers (BBs) on myocardial function in MR suggesting that
BB therapy may be beneficial in MR. However, the effect of BB
therapy on clinical outcomes in MR has not been defined. Hence, in
this large observational study we investigated the impact of BB
therapy on clinical outcome in patients with moderate to severe
MR.
Methods The Health Informatics dispensed prescribing, morbidity
and mortality database for the population of Tayside, Scotland was
linked through a unique patient identifier to the Tayside echocardiography database (>110 000 scans). Patients with a diagnosis of
moderate or severe MR from 1993 to 2008 were identified. Cox
regression model (adjusted for age, gender, left ventricular dimensions and function, left atrial diameter, cardiovascular (CV) history
and concurrent CV medications) was used to assess the impact of
BB therapy on all-cause mortality and cardiovascular events (CV
death or hospitalisations).
Results A total of 4437 patients with moderate to severe MR (mean
age 74 Â611 years, 46% males) were identified. MR was categorised
as functional in 2523 (57%) and organic in 1894 (43%) while 1324
(30%) were on BBs. Over a mean follow-up of 3.9 years there were
2287 (51%) all-cause deaths and 2333 (52%) CV events. Those
treated with BBs had a significantly lower all-cause mortality with
an adjusted HR of 0.65 (95% CI 0.56 to 0.75, p<0.0001) and fewer
CV events with an adjusted HR of 0.79 (95% CI 0.69 to 0.90,
p<0.0001).
Conclusions This large observational study suggests that BB therapy
is associated with an improved survival and a lower risk of CV
events in patients with moderate to severe MR. These observations
needs to be confirmed in prospective studies and support the
rationale for undertaking a future randomised clinical trial.
169
MID-WALL FIBROSIS IS AN INDEPENDENT PREDICTOR OF
MORTALITY IN PATIENTS WITH AORTIC STENOSIS
doi:10.1136/heartjnl-2011-300198.169
1,2
1
1
1
1
1
M R Dweck, S Joshi, T Murigu, A Gulati, F Alpendurado, R Mohiaddin,
J Pepper, 1D Pennell, 2D Newby, 1S Prasad. 1Royal Brompton Hospital, London, UK;
2
Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, UK
ciated with an adverse prognosis in a range of other cardiac conditions. Using late gadolinium enhancement, we sought to assess the
prognostic significance of mid-wall and infarct patterns of myocardial fibrosis in aortic stenosis.
Methods Between January 2003 and October 2008, consecutive
patients with moderate or severe aortic stenosis (aortic valve area
<1.5 cm2) underwent cardiovascular magnetic resonance with
assessment of myocardial п¬Ѓbrosis by late gadolinium enhancement.
Patients were categorised into absent, mid-wall or infarct patterns of
late gadolinium enhancement by blinded independent observers.
Patient follow-up was completed using the National Strategic
Tracing Scheme.
Results 143 patients (aged 68614 years; 97 male) were followed up
for 2.061.4 years. 81 patients had coronary artery disease, 72
underwent aortic valve replacement and 27 died. Compared to those
with no late gadolinium enhancement (nВј49), univariate analysis
revealed that patients with mid-wall п¬Ѓbrosis (nВј54) had an eightfold increase in all-cause mortality despite similar aortic stenosis
severity and coronary artery disease burden. Patients with an infarct
pattern (nВј40) had a six-fold increase. Mid-wall п¬Ѓbrosis (HR, 5.35
(95% CI, 1.16 to 24.56); pВј0.03) and ejection fraction (HR 0.96
(95% CI, 0.94 to 0.99); pВј0.01) were independent predictors of all
cause mortality by multivariate analysis. Conclusion: Mid-wall
п¬Ѓbrosis is an independent predictor of mortality in patients with
moderate and severe aortic stenosis. It has incremental prognostic
value to ejection fraction and may provide a useful method of
risk stratification in patients with advanced disease (Abstract 169
п¬Ѓgure 1).
Abstract 169 Figure 1 Kaplan-Meier curves of cardiac mortality (left)
and all cause mortality (right) according to pattern of LGE (AВј No LGE,
BВј Infarct LGE, CВј Mid-wall LGE).
Abstract 169 Table 1
No LGE
Mid-wall LGE
Infarct LGE
p Value
Number of patients
Mean age yrs
49
64616
54
70611
40
70613
e
Documented CAD %
Ejection fraction %
37
69613
42
58621
98
44618
<0.001
<0.001
Aortic valve area
Indexed LV mass g/m2
1.0560.37
92.6*
(86.0, 99.6)
15.7
1.0060.31
113.7*
(104.5, 123.8)
142.7
0.9160.26
97.8*
(90.9, 105.2)
173.7
1
Introduction Predicting adverse clinical outcomes in aortic stenosis is
challenging. Late gadolinium enhancement (LGE) has been asso-
A94
Mortality rate (deaths /
1000 pt years)
0.031
0.111
0.005
* Geometric
mean (95%)
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
170
ETHNIC DIFFERENCES IN PHENOTYPIC EXPRESSION OF
HYPERTROPHIC CARDIOMYOPATHY
doi:10.1136/heartjnl-2011-300198.170
N Sheikh, M Papadakis, N Chandra, H Raju, A Zaidi, S Ghani, M Muggenthaler, S Gati,
S Sharma. St. George’s University of London, London, UK
Purpose Hypertrophic Cardiomyopathy is a heterogeneous condition with variable phenotypic expression. Current studies are based
on predominantly Caucasian cohorts (white patients; WP), therefore the phenotypic manifestations of HCM in individuals of
African/Afro-Caribbean origin (black patients; BP) are not fully
realised. Data in athletes and hypertensive patients indicate that
black ethnicity is associated with a greater prevalence of repolarisation abnormalities on the ECG as well as a greater magnitude of
left ventricular hypertrophy (LVH), highlighting the importance of
defining the HCM phenotype in this ethnic group.
Methods Between 2001 and 2010, 155 consecutive patients with
HCM (52 BP, 103 WP) were assessed in 3 specialist cardiomyopathy
clinics in South London. All individuals underwent comprehensive
Abstract 170 Table 1
Black HCM
(n[52)
Demographics
Age of diagnosis (years)
48.1617.1
white HCM
(n[103)
50.5616.5
p Value
0.552
Gender (males)
FH of HCM/SCD
61.5%
34.6%
62.1%
32.0%
0.942
0.747
NYHA functional class III or IV
Patients on treatment
7.7%
55.8%
7.8%
46.6%
0.987
0.281
B-blockers
Calcium antagonists
28.8%
26.9%
39.1%
12.6%
0.445
0.026
Amiodarone
Diuretics
7.7%
13.5%
1.9%
9.7%
0.080
0.480
3.8%
5.8%
9.7%
5.8%
0.197
0.989
Disopyramide
Intracardiac defibrillator in situ
Echocanliographic characteristics
Ao (mm)
31.363.7
33.265.8
0.123
LA (mm)
LVED (mm)
40.967.3
44.066.1
39.967.3
44.466.1
0.593
0.787
17.364.9
279.66106.5
18.864.1
287.66112.7
0.069
0.767
FS (%)
E wave (m/s)
40.469.1
0.7060.18
39.868.3
0.7460.20
0.641
0.443
A wave (m/s)
E/A
0.6760.18
1.1160.44
0.6660.27
1.2260.58
0.851
0.422
mLVWTd (mm)
LV mass (g)
SAM
LVOT gradient Вј 30 mm Hg
23.1%
23.1%
37.9%
34.0%
0.064
0.163
ASH
Concentric
25%
44.2%
57.3%
30.1%
0.004
Apical
No hypertrophy
28.8%
1.9%
11.7%
1.0%
Echocanliographic characteristics
LVH (Sokolow & Lyon)
53.8%
35.9%
0.033
Left atrial enlargement
Pathological Q waves
44.2%
9.6%
49.5%
23.3%
0.534
0.039
Left axis deviation
Inverted T-waves
11.5%
82.7%
17.2%
69.9%
0.270
0.086
T-wave inversions in V1eV4
T-wave inversions in inferior leads
3.8%
1.9%
3.9%
5.8%
0.991
0.269
T-wave inversions in lateral leads
Deep T-wave inversions
76.9%
69.2%
60.2%
51.5%
0.038
0.035
ST-segment elevation
ST-segment depression
9.6%
50%
9.7%
35.0%
0.985
0.071
LVH pattern
Heart June 2011 Vol 97 Suppl 1
cardiac evaluation including 12-lead ECG and echocardiography.
Patients subject to therapeutic interventions potentially affecting
repolarisation patterns were excluded.
Results Black patients revealed significantly different echocardiographic patterns of LVH, with more concentric (44.2% vs 30.1%)
and apical (28.8% vs 11.7%) hypertrophy compared to WP who
exhibited more asymmetric septal hypertrophy (57.3% vs 25.0%)
(pВј0.004). Black patients exhibited a similar magnitude of LVH
compared to WP (17.364.9 vs 18.864.1 mm, pВј0.069). Relating to
ECG repolarisation abnormalities, BP exhibited more T wave inversions in the lateral leads (76.9% vs 60.2%, pВј0.038) and deep
($ГЂ0.2 mV) T-wave inversions (69.2% vs 51.5%, pВј0.035). Black
patients also tended to display more ST segment depression (50.0%
vs 35.0%, p¼0.071), although this was not statistically significant.
In contrast, WP had significantly more pathological Q waves (23.3%
vs 9.6%, pВј0.039).
Conclusions Ethnicity appears to exert a significant effect on ECG
and echocardiographic patterns in patients with HCM. A significant
proportion of black patients exhibit concentric LVH, highlighting
the diagnostic challenges in distinguishing HCM from hypertensive
heart disease and physiological adaptation to exercise in black
individuals. The greater prevalence of deep T wave inversions and T
wave inversions in the lateral leads underscores the importance of
further evaluation of black individuals with such ECG repolarisation
abnormalities, which may represent the initial expression of HCM.
171
THE RIGHT VENTRICLE OF THE ENDURANCE ATHLETE: THE
RELATIONSHIP BETWEEN MORPHOLOGY AND
DEFORMATION
doi:10.1136/heartjnl-2011-300198.171
1
D Oxborough, 2R Shave, 3G Whyte, 1K Birch, 4N Artis, 3K George, 5S Sharma.
University of Leeds, Leeds, UK; 2UWIC, Cardiff, UK; 3Liverpool John Moores
University, Liverpool, UK; 4Leeds Teaching Hospitals NHS Trust, Leeds, UK; 5St
Georges University Hospital, London, UK
1
Introduction It is well established that endurance exercise results in
cardiac adaptation including eccentric hypertrophy of the left
ventricle which can complicate the differential diagnosis of the
athletic heart from some cardiac pathologies that may pre-dispose to
sudden cardiac death. The impact of physiological conditioning on
RV structure and function, and a similar diagnostic challenge with
arrhythmogenic right ventricular cardiomyopathy (ARVC), has
received less attention. A recent guideline paper from the American
Society of Echocardiography (ASE) has provided a range for normal
RV dimensions and functional deformation. These guidelines
suggest the RV inflow (RVI) should be <42 mm while the proximal
outflow tract (RVOT) <35 mm. A recent paper also suggested that
an RVOT dimension >36 mm or 21 mm/m2 is a major criterion for
the diagnosis of ARVC and furthermore longitudinal RV deformation has been shown to be impaired in these patients. In view of
this, the aims of this study are twofold:
1. To provide a range of absolute values for RV dimensions in
102 endurance athletes as well as providing a range of data
indexed for body surface area (BSA).
2. To provide normal athlete data for indices of RV strain (3) and
strain rate (SR).
Methods and Results One hundred and two (102) endurance athletes
(86 males and 16 females) with a broad age range (mean 6 SD age
(range)Вј36 6 11 (21e71) years) volunteered and were consecutively
enrolled in the study. All subjects were either endurance runners or
cyclists and were scanned at peak condition. Echocardiography
provided measurements of RVI, RV length, RVOT and RV diastolic
area (RVDarea). A 2D strain technique was utilised to provide
indices of RV3 and systolic and diastolic SR. The values for RVI
A95
BCS Abstracts 2011
ranged from 30 to 55 mm with 57% of the population having values
greater than the normal range. Proximal RVOT ranged from 26 to
49 mm with 40% of the population above the normal range. 28% of
the population had RVOT values greater than the proposed “major
criteria” for ARVC. RV length ranged from 70 to 110 mm and
RVDarea from 13 to 38 cm2 with values falling above ASE cut-offs
in 69% and 59% of the population, respectively. When indexed (ratio
scaling) for BSA proximal RVOT ranged from 13 to 25 mm/m2 with
6% of the population meeting the major criteria for ARVC. Peak RV3
ranged from ГЂ18 to ГЂ41% and peak RV SRS9 from ГЂ0.75 to ГЂ2.65 l/s,
consistent with normal ranges proposed by the ASE. RV diastolic
deformation indices displayed marked individual variability with a
dominant SRE9 (mean 6 SDВј2.060.61 l/s) and smaller SRA9
(1.2560.56 l/s).
Conclusion RV dimensions in endurance athletes are higher than
those proposed as “normal” and likewise may be consistent with the
criteria for ARVC. Despite this enlargement, RV function in
endurance athletes is preserved and therefore the role of RV strain
imaging may provide additional diagnostic value in differentiating
physiological from pathological adaptation.
Abstract 171 Table 1
Parameter
Mean В± SD (range)
ASE Normal
Values
Indexed (ratio
scaling) for BSA
RVOT (mm)
RVDI (mm)
3465 (26 to 49)
4465 (30 to 55)
<35
<42
1763 (13 to 25) mm/m2
2263 (15 to 30) mm/m2
RV Length (mm)
RVDarea (cm2)
9269 (70 to 110)
2665 (13 to 38)
<86
<25
4565 (32 to 61) mm/m2
12.862 (8.7 to 17.6)
RV 3 (%)
RVSRS9 (l/s)
ГЂ18 to ГЂ39
0.7 to 2.54
N/A
N/A
RVSRE9 (l/s)
ГЂ2766 (ГЂ18 to ГЂ41)
ГЂ1.5360.43
(ГЂ0.75 to ГЂ2.63)
2.060.61 (0.87 to 3.76)
N/A
N/A
RVSRA9 (l/s)
RVSR E9 /A9
1.2560.56 (0.28 to 2.88)
1.8961.03 (0.49 to 7.25)
N/A
N/A
N/A
N/A
172
INCREASING ANTI-OXIDANT CAPACITY REVERSES IRON
OVERLOAD MEDIATED DYSFUNCTION IN
CARDIOMYOCYTES
doi:10.1136/heartjnl-2011-300198.172
1
F R Millar, 1D T Baptista-Hon, 2S C O9 Neill, 1M E DД±Вґaz. 1University of Edinburgh,
Edinburgh, UK; 2University of Manchester, Manchester, UK
Abstract 171 Figure 1
A96
Introduction Iron overload-cardiomyopathy (IOCM) is an increasing
clinical problem worldwide. 70% of patients who receive compulsory blood transfusion die of IOCM, with increased susceptibility to
arrhythmias and sudden death. We have previously found that iron
exposure impairs cardiomyocyte Ca homeostasis. However, the
cellular mechanisms responsible are unknown. Iron is known to
participate in the Fenton reaction to produce reactive oxygen species
(ROS), which mediate oxidative damage. We therefore tested the
hypothesis that increasing the anti-oxidant capacity of cardiomyocytes, with the ROS scavenger Tempol, could be cardioprotective in
the presence of iron.
Methods Single rat ventricular cardiomyocytes were loaded with
fluo-3 to monitor intracellular Ca changes upon stimulation while
bathed in control Tyrode solution and after adding ferrous iron (iron
II). Sarcoplamic reticulum (SR) Ca load and sarcolemmal Ca
extrusion rates were estimated during exposure to caffeine, which
empties SR Ca stores. The ROS scavenger tempol was used to
dissect ROS-mediated pathways from the direct effects of iron II on
Ca handling. Data are provided as mean6SEM. Significance was
tested using paired student t test and defined as p<0.05.
Results Iron II exposure significantly increases systolic Ca transient
amplitude (mean increase 82.8621.8%, nВј9) and causes spontaneous arrhythmogenic Ca release events (SACRE). These changes
corresponded with increased SR Ca content (mean increase
21.065.7%, nВј8), which is known to impact on systolic Ca release
and spontaneous activity in cardiomyocytes. Sarcolemmal Ca
extrusion rate was also significantly reduced upon iron II exposure
(measured as the rate of fall of the caffeine response; mean decrease
48.765.5%, nВј8), consistent with an overall gain of Ca by the
cardiomyocyte. The onset of these Ca disruptions was significantly
delayed in the presence of the ROS scavenger tempol (p<0.001).
Without tempol, SACRE onset occurred after 6.960.6 min (nВј22)
following iron II exposure. The same manoeuvre in in tempol
delayed the onset of SACRE to 17.861.8 min (nВј7). Furthermore,
increasing ROS scavenging reversed the increase in systolic Ca
transient amplitude, as well as SACRE upon washout of iron II. In
contrast, in cardiomyocytes not exposed to tempol, the effects of
iron II were irreversible.
Conclusions Our data show that iron II disrupts cardiomyocyte Ca
handling. This is mediated via inhibition of sarcolemmal Ca extrusion, leading to SR Ca overload and SACRE. These are the initiators
of most fatal non-reentrant arrhythmias and cardiac sudden death in
Heart June 2011 Vol 97 Suppl 1
BCS Abstracts 2011
experimental models. The observed effects are partly due to iron IImediated oxidative damage. This was confirmed by the presence of a
ROS scavenger delaying the onset of the effects of iron II, and
crucially rendering the effects reversible upon iron-washout. These
effects of tempol suggest a novel therapeutic target for the treatment of IOCM patients.
173
A GENERIC METHOD TO ASSESS THE ADEQUACY OF
INDIVIDUAL MATERNAL CARDIAC RESERVE TO TOLERATE
THE DEMANDS OF PREGNANCY AND LABOUR
doi:10.1136/heartjnl-2011-300198.173
1
D Barker, 2N Lewis, 2G Mason, 2L B Tan. 1Liverpool Heart and Chest Hospital,
Liverpool, UK; 2Leeds General Infirmary, Leeds, UK
Introduction Clinicians often feel apprehensive when managing
pregnant patients with heart disease. To complement current evaluation, we have developed a new method of directly assessing the
individual patient’s cardiac functional reserve through stress testing.
Pregnant mothers with and without heart disease were studied to
test the hypothesis that pregnant cardiac patients who possess
cardiac reserve equivalent to that of controls can tolerate the usual
demands of pregnancy, labour and puerperium.
Methods Fifty-one pregnant women with heart disease (mean age
30.766.5 (range 21e42), mean gestation 25.668.6 weeks) and 102
healthy pregnant women (mean age 31.465.0, (range 19e41), mean
gestation 25.169.2 weeks) underwent maximal symptom-limited
treadmill cardiopulmonary exercise testing. Fifty-nine non-pregnant
women (mean age 32.765.1 (range 20e41) years) were similarly
tested and used as a control group. Cardiac output (CO) was
measured at peak exercise using the CO2 re-breathing method.
Heart June 2011 Vol 97 Suppl 1
Cardiac power output (CPO) was calculated as the product of CO
and mean arterial pressure. A composite endpoint including
maternal death, fetal death, emergency caesarean section for
maternal distress and significant morbidities was determined.
Results All tests were performed without significant complications.
Employing data from a previous study of haemodynamics during
labour in healthy women, the mean CPO required during peak
labour is 2.6 W. This value was adopted for investigation as the
minimum required for an average woman to cope with the circulatory demands of normal labour. The healthy controls had a mean
peak CPO (PkCPO) of 3.7960.6 W and all non-pregnant women had
PkCPO exceeding 2.6 W. The majority of heart disease patients were
able to achieve PkCPO values overlapping their healthy counterparts. Only a small proportion of the cardiac patients had PkCPO
values lower than the 2.6 W cutoff. Women were significantly more
likely to have uncomplicated pregnancy, labour and puerperium if
able to achieve PkCPO>2.6 W (OR 8.1, 95% CI 1.8 to 37.0,
pВј0.023). Pregnant women in NYHA class I had PkCPO values
indistinguishable from controls (mean 3.9860.77 W, NS); whereas
symptomatic pregnant women had significantly lower values (mean
3.1560.71W, p<0.005).
Conclusions Direct measurement of cardiac functional reserve
capacity can be performed by maximal cardiopulmonary exercise
testing with non-invasive assessment of PkCPO, which can be safely
undertaken during pregnancy. A cutoff value of PkCPO 2.6 W was
identified as the lower limit for healthy women, corresponding to
that required for normal labour. Most cardiac patients studied had
PkCPO values comfortably above this cutoff, and all asymptomatic
(NYHA I) and low risk cardiac patients had PkCPO values similar to
controls. Measurement of PkCPO allows pregnant patients to be
further classified into those with adequate vs limited cardiac reserve,
supplementary to existing risk stratification methods.
A97
Author index
The number next to the author indicates the page number, not the abstract number.
Abbas A, A1, A3
Abidin N, A70
Abozguia K, A55
Abu-Own H, A25
Adam Z, A5
Adams PC, A39
Aggarwal R, A22, A30
Aggarwal S, A60, A61
Ahmed R, A43
Ahsan AJ, A86
Aitma TJ, A4
Akhtar M, A9
Al Fakih K, A36
Ala L, A82
Alahmar A, A27
Alamgir MF, A23
Alp NJ, A79
Alpendurada F, A53
Alpendurado F, A94
Amersey R, A15
Anand A, A7
Angelini G, A24
Anroniades C, A79
Antoniou S, A5
Appleby C, A27
Archbold A, A46
Archbold RA, A5
Arthur H, A78
Arthur HM, A75
Artis N, A95
Artis NJ, A72, A73
Arujuna A, A85
Augustine D, A63
Aung N, A60, A61
Austin D, A5
Avery P, A75
Awan M, A5
Ayers L, A50
Aziz A, A78
Babar J, A63
Baker CSR, A18
Baker S, A68
Balakrishnan B, A66, A81
Baliga V, A56
Ball SG, A35, A41, A72
Balmforth AJ, A35, A41
Bamforth SD, A77
Banerjee A, A40
Banerjee G, A7
Banerjee R, A63
Banerjee S, A7
Banner NR, A48, A49, A64
Banning AP, A12, A93
Banypersad SM, A59
Bapat V, A19
Baptista-Hon DT, A96
Barker D, A57, A97
Barker J, A7
Barmby D, A21
Barnes S, A60
Barrington S, A68
Barsan A, A49
Barth J, A60
Barth JH, A8, A17
Baruah R, A51, A58
Basavarajaiah S, A33
Bashir Y, A87, A88
A98
Bastiaenen R, A33, A38, A83
Baudoin F, A80
Baumbach A, A24
Bawamia BR, A10
Beadle RM, A55
Beatt K, A24
Bechar I, A70
Bedell VM, A78
Begg G, A56
Begg GA, A60, A86
Begley D, A50
Behan M, A16
Behar J, A15
Behar JM, A25
Behr E, A38
Behr ER, A33, A83
Bell D, A72
Bell J, A45
Bellamy MF, A18
Ben-Nathan S, A83
Bennett MR, A2, A64
Berry C, A16, A73
Berry EL, A86
Betts TR, A87, A88
Bewick AE, A82
Bhabra M, A19, A40
Bhan A, A91
Bhattacharya S, A77
Biasiolli L, A62
Bijnens BH, A52
Birch K, A95
Blackman DJ, A21
Blair E, A62
Blake J, A11
Blamire A, A78
Bland MB, A37
Blaxill JM, A21
Bleasdale RA, A34, A82
Bloomer LDS, A41
Blundell N, A92
Bonser RS, A36, A48
Borbas Z, A90
Borg A, A70
Borg AN, A74
Bostock J, A52, A84, A85
Boston-Griffiths E, A30
Bowater S, A55
Bowen TS, A56
Braganca J, A77
Braganza D, A2
Braund PS, A41, A42
Brewer A, A77
Brewster S, A46
Brickham B, A91
Broadbent C, A77
Brown AJ, A29
Brown BD, A90
Brown P, A89
Bryan L, A72
Buchanan L, A23
Bull S, A92
Byrom R, A60
Caldwell JC, A90
Calver A, A16
Calvert PA, A2, A64
Camara O, A52
Campbell M, A11
Cannon DT, A56
Caplin JL, A23
Carr-White G, A52, A84
Carre F, A38
Carrick D, A16
Carter J, A5
Cartwright EJ, A41, A80
Casadei B, A79
Casey FA, A75
Casey M, A73
Cassar TE, A62
Chalmers RTA, A3
Chambers J, A43
Chandra N, A33, A38, A95
Channon K, A12
Channon KM, A79
Chaubey S, A77
Chaudhry U, A27
Chen C-M, A77
Cheng A, A60, A61
Chico TJA, A43
Chinchapatnam P, A52
Chinnappa S, A57
Chiribiri A, A68, A71
Chong E, A24
Choudhury RP, A12, A62, A70
Chowienczyk P, A28, A32
Choy AM, A94
Choy AMJ, A58
Christiansen JP, A93
Christie J, A16
Christofidou P, A41
Churchhouse AMD, A7
Clack L, A19
Clapp B, A24, A32
Claridge S, A36
Clark C, A73
Clark D, A70
Clarke B, A26
Clarke SC, A2
Cleary N, A46
Clesham G, A30
Codd V, A42
Collerton J, A57
Connelly K, A22
Connolly S, A7
Cook DG, A41
Cook S, A43
Cook SA, A4
Corbett S, A16
Cotton J, A19
Cowie MR, A53
Cox RD, A41
Craig BG, A75
Crean A, A72
Crossman D, A13
Cruddas E, A24
Cubbon R, A1, A3, A60, A78
Cunliffe E, A52
Curzen N, A16
D’Arcy J, A92, A93
d’Arcy JL, A92
DД±Вґaz ME, A96
Dall’Armellina E, A12
Damm E, A30
Danesh J, A43
Das D, A43
Heart June 2011 Vol 97 Suppl 1
Author index
Das M, A84
Davidson C, A14
Davidson J, A35
Davidson NC, A90
Davies DW, A51, A83
Davies J, A22, A30, A45, A54
Davies JE, A10
Davies MJ, A6
Davis E, A37, A63
Davison BJ, A78
Dawson A, A34
de Belder A, A45
de Belder MA, A5
De Silva K, A24, A28, A71
Deanfield JE, A41
Deaton C, A26
Debiec R, A41
Densem CG, A2
Dent H, A16
Denvir MA, A7, A53
Dhillon OS, A10
Diab I, A81
Dick AJ, A22
Dick KJ, A42
Dickens C, A11
Diesch J, A37, A63
Digby J, A70
Dinh DT, A9
Dixit A, A26
Dixon G, A45
Dobrzynski H, A4
Doherty PD, A37
Donald A, A32
Donald AE, A41
Donin A, A41
Doolin O, A73
Douglas-Hill C, A19
Drury-Smith M, A19
Duckett S, A84, A85
Duckett SG, A52
Dungu J, A18, A59
Durham N, A60
Dutka DP, A50
Dweck M, A3
Dweck MR, A94
Dwivedi G, A66, A81
Dworakowski R, A91
Earley MJ, A81
Ebbs D, A92
Eccleston D, A38
Edmunds L, A45
Edwards R, A10, A29
Eftychiou C, A21
Ekker SC, A78
El-Omar M, A26
Elder DH, A94
Elder DHJ, A34, A58
Ellins E, A41
Emin A, A48
Engelen K, A76
Englyst N, A16
Eve S, A47
Fairbairn TA, A73
Farmer AJ, A92
Fath-Ordoubadi F, A11
Ferguson E, A5
Ferreira V, A12
Finch S, A46
Flather M, A13, A24, A38
Heart June 2011 Vol 97 Suppl 1
Flint J, A60, A61
Foley C, A13
Foley JRJ, A90
Foo F, A16
Ford I, A73
Forfar C, A12
Forfar JC, A62
Fox DJ, A90
Fox K, A13
Fox KAA, A7
Fox KF, A7
Frampton C, A11
Francis DP, A49, A50, A51, A58, A60, A61, A66
Francis J, A37, A63
Francis JM, A12, A62, A68, A92, A93
Frangi AF, A52
Fraser AG, A34
Fraser D, A26
Freemantle N, A49
French AE, A89
Frenneaux MP, A55
Gage M, A1, A3
Gage MC, A78
Gale CP, A8, A17, A60
Gale CPG, A37
Gallagher M, A83
Gallagher S, A15, A31
Gallagher SM, A5
Galloway S, A78
Gamble D, A7
Garden OJ, A3
Garratt CJ, A90
Gasson A, A82
Gati S, A31, A95
George DA, A40
George K, A95
Ghani S, A31, A95
Gholap NN, A6
Gibbins A, A45
Gibbons SM, A41
Gibbs SDJ, A59
Gierula J, A60, A86
Gilchrist J, A73
Gill JS, A52
Gill PS, A59
Gillivray TJMac, A3
Gillmore JD, A59
Ginks M, A52, A84, A85
Glen E, A76
Glen EA, A75
Goodall AH, A42
Goodship J, A75, A76
Goodship JA, A75, A76
Gopalan D, A63, A64
Gordon B, A49
Gordon J, A75
Gosling O, A20
Gosling OE, A65
Graham A, A13, A15
Graham C, A7
Graham TR, A36
Gray C, A3, A43
Gray H, A16
Greaves M, A70
Greenwood JP, A13, A21, A72, A73, A93
Griffin HR, A76
Grimwade P, A92
Guha K, A53
Guilcher A, A28
Gulati A, A94
Gunn J, A13
Guttmann O, A9
Guttmann OP, A31
Haga KK, A53
Hall A, A13
Hall AS, A8, A17, A35, A41
Hall ASH, A37
Hall D, A75
Hall DH, A75, A76
Hall JA, A5
Hall R, A24
Hamid S, A84, A85
Hamid SG, A52
Hancock J, A19
Handa A, A62
Haq IU, A39
Haran H, A19
Hards R, A49
Harrington DW, A82
Harwood SM, A17
Hawkins NM, A30
Hawkins PN, A59
Hayward PA, A9
Hedger M, A49
Hegab Z, A41, A44
Heneghan C, A40
Heymans S, A77
Hobson A, A16
Hodson J, A36
Holbrook I, A60
Holroyd EW, A78, A80
Horne A, A89
Hosmane S, A76
Hoye A, A23
Hughes A, A49
Hughes AD, A50, A66
Hunt J, A32
Hunter A, A60
Hunter RJ, A81
Hussain S, A68
Iles-Smith H, A11
Imrie H, A1, A3, A78
Indermeuhle A, A24
Indermuhle A, A71
Ingram TE, A34
Irwin RB, A70
Ishida M, A68, A71
Ivetic A, A77
Iyengar S, A65
Jackson C, A78
Jagger C, A57
Jain A, A13, A15, A25, A31
Jain AK, A5, A9, A15
James PE, A34
Jamieson S, A10
Jamshidi Y, A4
Jayaram R, A79
Jeilan M, A89
Johnson T, A89
Jones D, A5
Jones DA, A9, A13, A15, A25, A31
Jones JD, A30
Jones MA, A88
Jones S, A83
Joshi NV, A10
Joshi S, A94
Joysurry D, A41
Juli C, A83
Kahn M, A1, A78
A99
Author index
Kahn MB, A3
Kaier T, A39
Kanagaratnam P, A51, A83
Kapetanakis S, A52
Kapur A, A17, A24, A31
Kapur AK, A25
Karamitsos TD, A12, A68, A92, A93
Karia N, A12
Karim R, A83
Kearney L, A60
Kearney M, A1, A78
Kearney MT, A3, A60
Keavney B, A57, A75, A76, A78
Keavney BD, A75, A76
Kellman P, A12
Kelly B, A37
Kelly P, A22, A30
Kemp I, A27
Kemp S, A31
Kennedy J, A62
Kenny A, A57
Kervio G, A38
Kerzin-Storrar L, A90
Kesavan S, A24
Kettle AJ, A11
Khan FZ, A50
Khan MF, A23
Khan N, A90
Khan S, A39
Kharbanda RJ, A12
Khattar R, A26
Khawaja MZ, A19
Khimdas K, A46
Khogali S, A19
Khoo CW, A66, A81
Khunti K, A6
Kilcullen N, A8
Kingston A, A57
Kirkwood T, A57
Klaassen S, A76
Knight C, A5, A9, A13, A15, A25, A31
Knight CJ, A25
Kooner J, A43
Kotecha D, A38
Krishnamoorthy S, A66, A81
Krum H, A38
Kuehl M, A55
Kuijer JPA, A69
Kuker W, A62
Kulanthaivelu R, A82
Kumar D, A46
Kundu S, A89
Kylintireas I, A62, A70
Kyriacou A, A50, A51, A66
Lachmann HJ, A59
Lang CC, A35, A58, A94
Langrish JP, A3
Larsen K, A80
Lazdam M, A37, A63
Leadbeater P, A16
Lee JM, A62, A70
Lee KK, A7
Lees B, A13
Leeson P, A37, A62, A63
Leisa RA, A80
Leon FL, A55
Lewandowski AJ, A37, A63
Lewin BL, A37
Lewinter CL, A37
A100
Lewis N, A57, A97
Lewis RJ, A75
Leyva F, A48
Lim HS, A66, A81
Lim PB, A83
Lindsay A, A12
Lindsay AC, A62
Ling HZ, A60, A61
Lip GYH, A59, A66, A81
Little A, A46
Liu A, A21
Llewellyn-Griffiths H, A54
Loader R, A65
Lockie TPE, A28
Loh PH, A23
Lovell MJ, A5
Lowdell M, A20
Lucas A, A37
Ludman A, A9
Ludman PF, A91
Lundmark P, A42
Ma Y, A84, A85
MacArtney MG, A94
MacCarthy P, A91
MacDonald ST, A77
MacDonald TM, A35
Macgillivray K, A19
Macgilivray TJ, A3
MacGowan G, A48, A49
MacLeod M, A7
Macnab A, A76
Mahadevan V, A26
Maher A, A19
Mahmod M, A68
Majumder B, A20
Makri L, A21
Malcolme-Lawes L, A83
Malik N, A22
Mamas M, A26, A44
Mamas MA, A41
Mamasoula V, A75
Manisty C, A50
Manisty CH, A58
Mant D, A92
Marber M, A28
Margulescu A, A34
Markl M, A62
Marshall CJ, A11
Mascaro J, A36
Masi S, A41
Mason G, A97
Mather AN, A72, A73
Mathur A, A5, A9, A13, A15, A25, A31
Mavroudis C, A27
Mavroudis CA, A20
May S, A13
Mayet J, A50, A51, A58, A60, A61, A66
McCann GP, A69, A74, A89
McCarthy CA, A59
McCarthy MI, A43
Mcclean DR, A11
McClure J, A73
McCormick LM, A29
McCusker CG, A75
McDiarmid A, A49
McDonagh T, A53
McEntegart MB, A73
McGeoch R, A73
McGill LA, A15, A25
McGowan L, A11
Mckenzie JL, A11
McKeown PP, A75
McKillop G, A3
McLenachan JM, A21
McMahon M, A75
McNab D, A2
Mehta P, A84, A85
Mehta RL, A6
Menon A, A36
Metcalfe K, A90
Millar FR, A96
Miller C, A70
Miller CA, A74
Mills NL, A7
Mitchell AG, A64
Mittal TK, A64
Moccata T, A11
Mohamed TMA, A80
Mohammed TMA, A41, A44
Mohiaddin R, A93, A94
Mohiddin S, A5, A9, A13
Mole G, A14
Monaghan M, A91
Moraldo M, A50, A66
Moreton N, A90
Morgan-Hughes G, A65
Morrell C, A8
Morrice D, A40
Morrison ML, A75
Morton AC, A13
Morton G, A24
Morton GDJ, A68, A71
Muckett P, A43
Muckett PJ, A4
Muggenthaler M, A33, A95
Muir DF, A5
Mukhopadhyay D, A80
Mulder B, A76
Mullen LJ, A29
Murdoch CE, A77
Murgatroyd SR, A56
Murigu T, A94
Murphy A, A73
Murray SA, A53
Musameh MD, A35
Myerson SG, A68, A92, A93
Nadir A, A35, A94
Nadra I, A19
Nagel E, A68, A71
Nair S, A26
Nallaratnam M, A11
Narayan HK, A10
Nayar V, A50
Nelson CP, A41, A42
Ness A, A53
Neubauer S, A12, A37, A62,
A63, A68, A92, A93
Neubauer SN, A62
Neubuer S, A70
Nevill AM, A40
New G, A38
Newby D, A94
Newby DE, A3, A7
Newman D, A40
Newman W, A90
Newton T, A70
Neyses L, A26, A41, A44, A80
Ng GA, A89
Heart June 2011 Vol 97 Suppl 1
Author index
Ng LL, A10
Nicol E, A72
Nicolson WB, A89
Nightingale CM, A41
Nijjar M, A30
Nijjer SS, A7, A49
Norrie J, A16
Nyawo B, A29
O’Callaghan P, A55
O’Doherty M, A68
O’Donnell M, A53
O’Sullivan JJ, A75
O’Sullivan M, A2
O9 Neill SC, A96
Obaid DR, A2, A63, A64
Oceandy D, A80
Okonko DO, A60, A61
Oldroyd K, A16
Oldroyd KG, A73
Oliver M, A54
Oliver RM, A23
Ordoubadi F, A26
Oriolo V, A47
Ormerod OO, A70
Owen CG, A41
Owen J, A60
Oxborough D, A95
Pabari P, A49, A51, A58
Pabari PA, A50, A66
Padgett HC, A86
Padley S, A72
Pagano D, A36
Palmieri V, A49
Palomino-Doza J, A75
Panayotova R, A76
Panicker MG, A64
Panoulas V, A33, A38
Papadakis M, A33, A38, A95
Parameshwar J, A48
Parker C, A89
Parry G, A49
Pashaei A, A52
Patel P, A82
Paterson E, A7
Patterson C, A72
Paul GA, A22
Payne AR, A73
Pearson IR, A8, A17, A60
Peebles C, A70
Pennell D, A94
Penswick A, A46
Pepper J, A94
Perera D, A24, A28, A68, A71
Perry R, A30
Perry RA, A27
Peters NS, A4, A51, A83
Petersen SE, A62
Petrie MC, A73
Pettit S, A30
Pierret CK, A78
Pierscionek T, A75
Pinney JH, A59
Pitcher A, A62, A92
Pitts-Crick J, A89
Plein S, A72, A73
Plummer CJ, A84
Poole R, A37, A63
Popov AF, A49
Postma A, A76
Heart June 2011 Vol 97 Suppl 1
Prasad S, A53, A94
Pravanec M, A4
Prehar S, A41, A80
Prendergast B, A12, A92
Prendergast BD, A92
Prescott M, A41
Pretsell G, A45
Pringle SD, A58, A94
Pugh PJ, A50
Pye M, A60
Quinn PA, A10
Qureshi AC, A17
Qureshi N, A88
Rahman T, A75, A76
Rajappan K, A87, A88
Raju H, A31, A33, A38, A95
Rajwani A, A1, A3
Rakhit RD, A20, A27
Rampat R, A17
Rana B, A67
Rapala A, A41
Rashid S, A3
Rathod B, A15, A31
Rathod K, A13, A25, A31
Rathod KR, A15
Rathod KS, A9, A15
Rathod VS, A15
Rawling A, A50
Rawlins J, A33, A38
Ray KK, A2
Raybould A, A54
Razavi R, A84, A85
Razavi RS, A52
Razvi NA, A69
Redgrave R, A78
Redwood S, A19, A24, A28, A71
Rees I, A55
Reid CM, A9
Reid J, A53
Reilly S, A79
Rekhraj S, A35
Rhode K, A84, A85
Richards JMJ, A3
Richards M, A11
Richards T, A61
Richmond L, A81
Rider O, A70
Rinaldi CA, A52, A84, A85
Ring L, A67
Robb SD, A73
Robinson N, A49
Robson MD, A12, A62, A70
Rogers C, A11
Rogers CA, A48
Rogers T, A36
Rolandi C, A28
Roobottom C, A65
Rooney SJ, A36
Rose H, A45, A54
Rossiter HB, A56
Rothman A, A13
Rothman M, A46
Roughton M, A17
Rudd JHF, A63, A64
Rudnicka AR, A41
Rueckert D, A83
Rusk RA, A67
Russell S, A46, A54
Russell SJ, A45, A55
Sabharwal NS, A70
Sadarmin PP, A87
Salaheen D, A43
Salukhe TV, A83
Samani NJ, A35, A41, A42
Sambu N, A16
Sammut E, A15, A25
Sammut EC, A13
Sanderson JE, A48
Sandilands AJ, A89
Sands AJ, A75
Sattianayagam P, A59
Saul A, A73
Sayan S, A51
Sayer J, A22, A30
Schilling RJ, A81
Schlindwein FS, A89
Schmitt M, A70, A74
Schneider JE, A77
Schofield PM, A2
Schotten U, A79
Schueler S, A48, A49
Schuster A, A68, A71
Schwartz R, A77
Sehmi J, A43
Semple SI, A3
Sermesant M, A52
Shah A, A7
Shah AJ, A63
Shah AM, A77, A91
Shah NH, A23
Shantsila E, A59
Shapiro LM, A2
Shardey GC, A9
Sharma R, A53
Sharma S, A31, A33, A38, A83, A95
Shave R, A95
Sheikh N, A31, A38, A95
Shelton RJ, A21
Shepherd C, A89
Shepherd EJ, A84
Shetty A, A52, A84
Shetty AK, A85
Shi WY, A9
Shirodaria C, A70
Shome J, A5
Showkathali R, A22, A30
Sicard P, A24
Siebes M, A28
Sim V, A54
Simari RD, A78, A80
Simon A, A48
Simon AR, A49
Simpson I, A16
Singh R, A19
Singhal A, A37
Sinha M, A47
Sivananthan UM, A8, A17
Skinner JS, A39
Smith EJ, A25
Smith J, A78
Smith JA, A9
Sneddon L, A75
Snell KIE, A69
Sohal M, A84, A85
Somauroo J, A31
Somers K, A21
Sorbron S, A72
Spath N, A33
A101
Author index
Sporton S, A81
Squire IB, A6, A10
Stables RH, A27
Stafford PJ, A89
Staniforth AD, A86
Steadman CD, A69, A74, A89
Stegemann B, A49
Stoll VMS, A70
Strain WD, A65
Strauss BH, A22
Struck J, A10
Struthers AD, A34, A35, A58, A94
Sukumar P, A78
Suresh V, A20
Surr J, A1, A3
Sutaria N, A66
Suttie J, A62, A63, A92
Suttie JJ, A68
Sutton AGC, A5
Swanson NM, A5
SyvaВЁnen AC, A42
Szwejkowski BR, A34, A58
ToВЁpf A, A76
Taggu W, A22
Tagney J, A47, A89
Tai ES, A43
Tan HL, A75
Tan LB, A57, A97
Tan YT, A48
Tayebjee M, A81
Taylor R, A29
Templeton C, A34
ten Dijke P, A75
Thackray S, A23
Thomas G, A89
Thomas HE, A84
Thomas HL, A48
Thomas M, A19, A24, A60, A61
Thompson CA, A25
Tilling LM, A32
Tomaszewski M, A35, A41
Tooze P, A21
Topf A, A75
Topf AL, A75
A102
Townend J, A78
Tsui S, A48
Twomey D, A84
Tzemos N, A73
Ungvari T, A23
Unsworth B, A58, A66
Van den Bruel A, A40
van Eeden FJ, A43
van Rossum AC, A69
Vanhoutte D, A77
Veasey RA, A82
Venables P, A20
Verheule S, A79
Vile RG, A80
Virdee MS, A50
Viswambharan H, A1, A3, A78
Viswanathan K, A8
Waldron ZL, A86
Walker S, A7
Wallace W, A3
Wang WYS, A35
Ward D, A83
Ware JS, A4
Warner T, A16
Wassef N, A59
Waterworth P, A76
Watson D, A14
Watson J, A60
Watson OJ, A43
Watt H, A62
Wechalekar A, A59
Weerackody R, A15, A25, A46
Weissert S, A60, A61
Wells TA, A47
Wendler O, A91
Wenzelburger FWG, A48
West NEJ, A2, A29
Westwood M, A5
Wheatcroft AC, A60
Wheatcroft S, A1, A3, A78
Wheatcroft SB, A21
Whelan CJ, A59
Whincup PH, A41
Whinnett Z, A51
Whinnett ZI, A58
White J, A60
Whyte G, A95
Wicks E, A31
Wilkinson S, A4
Williams C, A34
Williams LK, A55
Williams M, A3
Williams P, A26
Williams R, A28, A39
Willson K, A51
Wilson IC, A36
Wilson K, A19
Wilson SJ, A20
Wiper A, A26
Witte KK, A56, A60, A86
Woldman S, A60
Wong KCK, A87, A88
Woodcock T, A72
Woodward R, A73
Wordsworth BP, A62
Wragg A, A9, A13, A15, A25, A31
Wren C, A75
Wright GA, A22
Wright RA, A5
Wrightson N, A49
Yap CH, A9
Yaqoob MM, A17
Yellowlees D, A53
Yeo Y, A43
Young C, A19
Young S, A45
Yousaf F, A57
Yousef ZR, A45, A46, A54, A55
Yu B, A77
Yuldasheva N, A3, A78
Yusuf S, A89
Zaidi A, A31, A33, A95
Zaman A, A10, A72
Zhang W, A43
Zi M, A41, A80
Zych B, A49
Heart June 2011 Vol 97 Suppl 1