CLINICAL RESEARCH
Europace (2012) 14, 1771–1777
doi:10.1093/europace/eus199
Electrophysiology and ablation
Induction of ventricular tachycardia with the
fourth extrastimulus and its relationship
to risk of arrhythmic events in patients with
post-myocardial infarct left ventricular dysfunction
Sarah Zaman 1,2, Saurabh Kumar 1, Arun Narayan 1, Gopal Sivagangabalan 1,
Aravinda Thiagalingam 1, David L. Ross 1, Stuart P. Thomas 1,2,
and Pramesh Kovoor1,2*
1
Department of Cardiology, Westmead Hospital, Corner Darcy and Hawkesbury Roads, Westmead, Sydney, NSW 2145, Australia; and 2University of Sydney, Australia
Received 4 April 2012; accepted after revision 25 May 2012; online publish-ahead-of-print 22 June 2012
Aims
The prognostic significance of ventricular tachycardia (VT) induced by three extrastimuli (ES) is similar to that of VT
induced by one or two ES in patients with coronary disease and abnormal left ventricular (LV) function. The significance of VT inducible with four ES is unclear. To examine the prognostic significance of VT inducible with the fourth
ES in patients with post-myocardial infarct (MI) LV dysfunction.
.....................................................................................................................................................................................
Methods
Consecutive patients (n ¼ 432) with post-MI LV ejection fraction ≤40% underwent electrophysiological (EP) studies
and results
for risk stratification. Inducible VT ≥ 200 ms cycle length (CL) with one to four ES was considered inducible. The
primary endpoint of arrhythmia (sudden death or spontaneous VT/ventricular fibrillation) was compared among
patients with VT inducible with less than or equal to two, three, and four ES. The incidence of inducible VT was
37.9% (n ¼ 164). In patients with inducible VT, inducibility was with less than or equal to two, three, and four ES
in 24% (n ¼ 39), 46% (n ¼ 75), and 30% (n ¼ 50). Compared to VT induced with less than or equal to three ES,
VT induced with the fourth ES was of shorter CL (218 vs. 256 ms, P ¼ 0.01) and more likely to be haemodynamically
unstable requiring cardioversion (77 vs. 55%, P ¼ 0.05). After 3 years the primary endpoint occurred in 28 + 8,
28 + 6, and 18 + 6% in patients with VT induced with less than or equal to two, three, and four ES, respectively
(P ¼ 0.31) and in 5 + 2% of EP-negative patients (P , 0.01).
.....................................................................................................................................................................................
Conclusion
In patients with post-MI LV dysfunction, VT can be induced in a significant proportion of patients with the fourth ES.
These patients are at comparable risk of arrhythmia to patients with inducible VT with less than or equal to three ES.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Myocardial infarction † Electrophysiology study † Sudden death † Ventricular tachycardia † Primary prevention
† Implantable cardioverter defibrillator
Introduction
Inducible ventricular tachycardia (VT) in patients with coronary
artery disease and left ventricular (LV) dysfunction has been
found to be predictive of spontaneous ventricular arrhythmia.1 – 4
The prognostic value of inducible VT is critically dependent on
the mode of induction.5 – 7 Many believe that VT requiring three
extrastimuli (ES) for induction is less likely to occur spontaneously
and has less predictive value for future risk of ventricular arrhythmia. Piccini et al.8 in an analysis from the MUSTT trial showed that
the prognostic significance of VT induced by three ES is similar to
that of VT induced by one or two ES in patients with coronary
disease and LV dysfunction. It is unclear as to whether inducible
VT with four ES is of clinical significance and whether its induction
* Corresponding author. Tel: +61 2 9845 6030; fax: +61 2 98458323, Email: [email protected]
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2012. For permissions please email: [email protected].
1772
S. Zaman et al.
What’s New?
† This is the first study to assess the role of the fourth ES at
EPS in a contemporary population of STEMI patients treated
with primary PCI.
† This study provides important information regarding the
protocol for EPS in determining who may be at risk of ventricular arrhythmia post-myocardial infarction.
portends any future risk of arrhythmic events. The aim of the
present study was to assess the incidence, clinical and electrophysiological (EP) characteristics, and long-term outcomes of
patients with post-myocardial infarct (MI) LV dysfunction who
had inducible VT with four ES.
Methods
Consecutive eligible survivors of ST elevation myocardial infarction
(STEMI) treated with primary percutaneous coronary intervention
(PCI), lysis, or coronary artery bypass grafting were recruited
(Figure 1). Our approach of post-MI sudden death risk stratification
has been described in detail previously. In brief, patients with STEMI
underwent inpatient assessment of LV function beyond Day 3
post-MI with gated heart pool scan (GHPS) or transthoracic echocardiogram where GHPS is not available. Those with LV ejection fraction
(LVEF) ≤40% underwent inpatient VT stimulation at a mean of 5 days
post-MI. Patients with sustained monomorphic VT of cycle length (CL)
≥200 ms with up to four ES were considered inducible. Inducible VT
had to be at least 30 s in duration if haemodynamically tolerated or at
least 10 s in duration if haemodynamically unstable. The long-term outcomes and predictive value of this approach have been discussed in
detail previously.5,9 – 13 Previous studies published from this institution
assessing the predictive value of electrophysiological study (EPS) have
prospectively recruited patients post-myocardial infarction from 1999
to 200713 and to 2008.12 This analysis looking specifically at the role of
the fourth ES in this cohort recruited only STEMI patients from 1999
to 2010. Inclusion criteria for the present study were commencement
of optimal medical therapy for LV dysfunction including beta-blockers
and angiotensin-converting enzyme-I, absence of ongoing myocardial
ischaemia, absence of spontaneous sustained VT/ventricular fibrillation
(VF). 48 h post-MI, absence of cardiogenic shock, or decompensated
heart failure. Exclusion criteria were patient refusal, advanced age
(.85 years), or co-morbidities with life expectancy limited to ,1
year. The study was approved by the Hospital Ethics Committee and
all patients gave their informed consent.
Electrophysiological study
Electrophysiological study was performed under conscious sedation in
the absence of anti-arrhythmic medication. Beta-blockers apart from
sotalol were not withheld. Programmed stimulation was performed
at twice diastolic threshold at the right ventricular (RV) apex using a
programmable stimulator. A drive train (S1S1) of 8 beats at 400 ms
was followed by up to four ES delivered one at a time. Stimuli were
rectangular pulses of 2 ms duration at twice diastolic threshold with
a 3 s delay between each drive train. The initial ES was delivered at
a coupling interval of 300 ms and then decreased in 10 ms steps to
ventricular refractoriness. If the earliest possible ES (e.g. S1S2) failed
to induce VT, that ES was delivered 10 ms outside the ventricular effective refractory period and an additional ES added (e.g. S2S3) at a
coupling interval of 300 ms. The additional ES was decreased in
10 ms steps in the same manner. Additional ES were added in a
similar manner (always starting with coupling interval of 300 ms)
until either VT or VF was induced or refractoriness of the fourth ES
was reached. There was no set lower limit for the shortest permissible
ES coupling interval. Figures of this protocol have been published previously.12 The endpoint for stimulation was sustained ventricular
tachyarrhythmia. The induced tachyarrhythmia was terminated after
30 s if haemodynamically tolerated, or after 10 s if haemodynamically
compromised. If sustained monomorphic VT with a CL ≥ 200 ms14
1999–2009
STEMI
N = 2188
LVEF >40% D5 post MI
N = 1641 (75%) excluded
LVEF £40% D5 post MI
N = 547(25%)
EPS not performed (n=115)
Patient refusal (n=13)
Transfer out of area (n=7)
Death prior to EP (n=30)
Age>85, limited life expectancy (n=40)
Borderline EF for reassessment (n=25)
EPS D13 post MI
N = 432
EPS Nagative
N = 164 (38%)
EPS Nagative
N = 268 (62%)
EPpositive ES£2
N = 39 (24%)
Figure 1 Selection of patient cohort.
EPpositive ES 3
N = 75 (46%)
EPpositive ES 4
N = 50 (30%)
1773
Induction of VT with the fourth ES
was induced by less than or equal to four ES the EP result was considered positive for inducible VT. Ventricular fibrillation or flutter with a
CL , 200 ms were considered a negative result.9 Stimulation was
repeated a second time from the same site, using the same protocol,
if the initial induction was negative for VT. Isoprenaline infusion was
not utilized to facilitate VT induction. If EPS was positive, pre-discharge
implantable cardioverter defibrillator (ICD) implantation was recommended. If EPS was negative, discharge without an ICD was
recommended.
Implantable cardioverter defibrillator
implant and programming
All devices were pre- or sub-pectoral systems with the manufacturer
and type determined by the hospital device acquisition process. The
devices were programmed as described previously.13 For VF or fast
VT (CL , 250 ms) detection required 18 of 24 beats and, subsequently 12 of 16 beats for re-detection. For VT CL . 250 ms, detection
required 16 beats and, subsequently 12 beats for re-detection. Ventricular arrhythmia that did not reach the set number of detection
intervals was classified as non-sustained. Discriminators for supraventricular tachycardia were standardized based on sudden onset of the
arrhythmia, rate stability, and ventriculoatrial dissociation.
Follow-up
Implantable cardioverter defibrillator recipients were followed at 1, 3,
and 6 months with 6-monthly intervals thereafter. Non-ICD recipients
were followed at 1, 6, and 12 months with yearly follow-up thereafter,
unless symptoms intervened. All patients were followed via telephone
contact, in clinics, and a review of hospital medical records for 2 years.
At each follow-up visit, patients were screened for a history of syncope
or ventricular arrhythmias, hospital re-admissions for documented or
suspected ventricular arrhythmias, ICD therapies, and medications.
Implantable cardioverter defibrillator interrogation included analysis
and recording of device detections and activations with electrogram
verification of CLs of any arrhythmias, mode and success of therapy,
and patient symptoms or complications.
Primary and secondary endpoints
The primary endpoint was the occurrence of any arrhythmic event
defined as either sudden cardiac death (SCD) or spontaneous VT/
VF, whichever occurred first. Secondary endpoints included all-cause
mortality, cardiac death, and sudden death. Adjudication of the cause
of death was made by three local investigators blinded to the
EPS results based on information collected from witnesses, family
members, hospital records, ICD interrogated data, and death certificates from local Registry of Births, Deaths, and Marriages. Arrhythmic
(sudden) death based on a modified Hinkle and Thayer system
included witnessed instantaneous deaths, unwitnessed deaths with
no clear cause identified, non-sudden deaths caused by incessant
tachycardia, deaths considered to be a sequela of cardiac arrest,
deaths resulting from proarrhythmia of anti-arrhythmic drugs, and
deaths caused by complications of implantable defibrillators.15 All electrograms from spontaneous ICD activations were reviewed by two
local electrophysiologists blinded to EPS result. Appropriate ICD activations were defined as ventricular tachyarrhythmia due to VT which
met the ICD treatment criteria (defined above) or VF. Inappropriate
ICD activations including supra-VT, atrial fibrillation or flutter, sinus
tachycardia were excluded.
Statistical analysis
The Statistical Package for the Social Sciences for Windows (SPSS,
release 15.0, Chicago, IL, USA) was used for analysis. To test for associations between categorical variables, x2 tests or Fisher’s exact test
were used. Mean values were compared using the Student’s t-test
with Mann–Whitney or Kruskal – Wallis tests used for continuous variables when normal distribution was not present. The cumulative risks
of primary and secondary endpoints were estimated with use of the
Kaplan –Meier procedure and log rank x2 tests. Cox regression multivariable analysis was used to derive independent predictors of the
primary endpoint using variables in Table 1. P value ,0.05 was
considered significant.
Results
Consecutive STEMI patients (n ¼ 2188) were recruited from 1999
to 2010 with LVEF ≤ 40% in 25% (n ¼ 547) (Figure 1). A total of
432 patients with LVEF ≤ 40% underwent EP study and were followed up for a mean of 43 + 33 months (median 35 months, interquartile range 21 –63 months). Mean LVEF was 31 + 6% at median
5 days post-STEMI. Electrophysiological study was performed at
median 13 days post-STEMI with VT inducible in 38% (EPpositive,
n ¼ 164) and no VT inducible or inducible VF/flutter in 62%
(EPnegative, n ¼ 268). Among inducible patients, 39 (24%) patients
had VT inducible with less than or equal to two ES, 75 (46%)
with three ES, and 50 (30%) with four ES.
In the EP-negative patients (n ¼ 268), no arrhythmia was inducible in 44% while VF or ventricular flutter (CL ≤ 200 ms) was inducible in 56% of patients. The fourth ES was used in 73% (n ¼
196) of patients who had a negative EPS. Of these patients receiving a fourth ES, 42% (n ¼ 82) had inducible VF/flutter requiring
direct cardioversion to terminate the arrhythmia in 94%. The
23% (n ¼ 72) of patients with a negative EPS who did not
receive four ES all had VF/flutter induced by less than or equal
to three ES with the VT protocol stopped early. There were no
complications or deaths associated with EP study.
Patients with VT induced by four ES had a lower incidence of
previous MI. Baseline characteristics were otherwise similar
between the groups (Table 1).
Electrophysiological characteristics
of inducible ventricular tachycardia
Ventricular tachycardia induced by the fourth ES was more likely
to be of shorter CL and of left bundle branch block (LBBB) morphology (Table 2). Mean duration of sustained VT was shorter in
patients with VT induced by the fourth ES as the VT was more
likely to be haemodynamically unstable requiring cardioversion.
Implantable cardioverter defibrillator
implantation
An ICD was implanted in a total of 122 patients with a positive EPS,
and 18 patients with a negative EPS. This included 91 singlechamber and 49 dual-chamber devices, with 85 Medtronic, 51
Guidant, and 4 St Jude devices. An ICD was not implanted in 42
patients with a positive EP study due to patient refusal (n ¼ 2),
intra-venous drug use (n ¼ 1), and EP result considered borderline
by treating physician (n ¼ 39; inducible VT CL 200–230 ms).
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S. Zaman et al.
Table 1 Baseline characteristics of patients with inducible ventricular tachycardia at electrophysiological study
Variable (% unless stated otherwise)
Total (n 5 164)
EPposES ≤ 2 (n 5 39)
EPposES 3 (n 5 75)
EPposES 4 (n 5 50)
P value
...............................................................................................................................................................................
Age, years (mean + SD)
61 + 12
61 + 12
61 + 12
59 + 11
0.56
Male gender
STEMI territory: anterior
86%
87%
74%
88%
78%
82%
92%
0.65
0.06
PCI
Lysis
59%
15%
53%
24%
54%
15%
69%
10%
CABG
STEMI treatment
0.01
7%
13%
7%
2%
Background history
Previous MI
45%
57%
51%
28%
0.01
Hypertension
45%
51%
43%
41%
0.61
Hyperlipidaemia
Diabetes
61%
29%
56%
28%
60%
30%
65%
28%
0.71
0.96
Current or past smoker
51%
41%
54%
53%
0.38
Pharmacotherapy
ACE-I
87%
78%
93%
87%
0.10
Beta-blocker
88%
89%
90%
84%
0.65
Statin
Anti-platelets
96%
99%
95%
100%
95%
98%
97%
97%
0.82
0.64
LVEF (mean + SD)
30 + 6
30 + 6
30 + 6
31 + 6
0.84
ES, extrastimuli; CABG, coronary artery bypass grafting.
Table 2 Characteristics of inducible ventricular tachycardia at electrophysiological study according to number of
extrastimuli required for induction
Characteristic
Total (n 5 164)
EPposES ≤ 2 (n 5 39)
EPposES 3 (n 5 75)
EPposES 4 (n 5 50)
CL of first induced VT, ms (mean + SD)
234 + 44
256 + 60
232 + 41
218 + 23
68%
32%
41%
59%
72%
28%
82%
18%
,0.01
36%
39%
33%
51%
31%
48%
47%
16%
,0.01
Duration, s (mean + SD)
24 + 13
26 + 14
26 + 20
20 + 9
0.04
Mode of termination
Spontaneous
7%
3%
11%
4%
0.05
27%
42%
23%
19%
67%
55%
66%
77%
P value
...............................................................................................................................................................................
0.01
Proportion of
VT CL 200– 230 ms
VT CL . 230 ms
Morphology of VT
LBBB
RBBB
Anti-tachycardia pacing
Cardioversion
LBBB, left bundle branch block; RBBB, right bundle branch block.
An ICD was implanted in 18 patients with a negative EPS due to
protocol violations by treating physicians based on LVEF ≤ 30%
and/or patient preferences.
Primary endpoint
The 3-year Kaplan –Meier estimated arrhythmic event rate (SCD
or VT/VF) was 28 + 8, 28 + 6, and 18 + 6% in patients with VT
induced with less than or equal to two, three, and four ES, respectively (log rank P ¼ 0.31), compared with 5 + 2% in patients with
no inducible VT (log rank P , 0.01) (Figure 2). Patients with inducible VT (n ¼ 164) experienced a total of 49 arrhythmic events
(30%) consisting of 15 SCDs and 34 ICD-treated VT/VF
(Table 3). Of these arrhythmic events 10 of 42 (24%) occurred
in patients with VT inducible with the fourth ES. Implantable cardioverter defibrillator-detected VT/VF in patients with inducible VT
by four ES occurred early in 19% (first 40 days post-MI), was due
to VT in 83%, had a mean CL of 286 + 49 and was terminated by
antitachycardia pacing (ATP) in the majority of episodes. Patients
1775
Arrhythmic Event (Sudden Death or VT/VF) %
Induction of VT with the fourth ES
50
EPpos 3 ES (n=75)
EPpos £2 ES (n=39)
Log rank P<0.01
EPpos 4 ES (n=50)
40
EPnegative (n=268)
30
20
10
0
0
40
10
20
30
Time from Myocardial Infarction (months)
Figure 2 Kaplan– Meier estimates of total arrhythmic events (sudden death or ventricular tachycardia/ventricular fibrillation) according to
electrophysiological study (log rank P , 0.01).
Table 3 Primary and secondary outcomes in electrophysiological positive patients according to number of extrastimuli
required to induce ventricular tachycardia
Outcome (number and %)
Total (n 5 164)
ES ≤ 2
(n 5 39)
ES 3 (n 5 75)
32, 82%
11, 28%
58, 77%
28, 37%
ES 4 (n 5 50)
P value
...............................................................................................................................................................................
ICD implanted, yes
Proportion of patients with ≥1 arrhythmic event
Proportion of patients with ≥1 appropriate ICD activation, due to
123, 75%
49, 30%
34, 21%
33, 65%
10, 20%
0.05
0.24
9, 23%
19, 25%
6, 12%
0.32
VT
VF
56%
44%
89%
11%
83%
17%
0.07
CL
252 + 70
329 + 75
286 + 49
Terminated by
ATP
22%
58%
83%
DC shock
88%
42%
17%
15, 20%
9, 12%
8, 16%
4, 8%
,0.01
0.22
Total mortality
Sudden cardiac death
35, 21%
15, 9%
12, 31%
2, 5%
Non-sudden cardiac death
15, 9%
10, 26%
3, 4%
2, 4%
0.01
0
3, 4%
2, 4%
0.66
Non-cardiac death
5, 3%
DC, direct cardioversion.
with no inducible VT (n ¼ 268) experienced a total of 18 arrhythmic events (6.7%) due to SCD in 12 of 18 and ICD-detected VT/VF
in 6 of 18.
The hazard ratio for an arrhythmic event as compared with
EP-negative patients was 3.6 [confidence interval (CI) 1.7 –7.8]
for VT induced by less than or equal to two ES (P ≤ 0.01), 4.9
(CI 2.7 –9.1) for VT induced by three ES (P≤ 0.01), and 3.0
(CI 1.4 – 6.6) for VT induced by four ES (P ¼ 0.01).
Total mortality
Total mortality and cause of death for patients with inducible VT
are shown in Table 3. The 3-year Kaplan–Meier estimated total
mortality was 27 + 8, 15 + 5, and 12 + 5% for patients with VT
induced by ≤2, 3, and four ES, respectively (log rank P ¼ 0.4)
and 6 + 2% in patients without inducible VT (log rank P ¼ 0.05,
Figure 3). Sudden cardiac death occurred in 15 of 164 (9%) of
EP-positive patients with 9 of 15 (60%) of these in non-protocol
followers without an ICD. Sudden cardiac death occurred in 4 of
50 (8%) of patients with VT induced by the fourth ES, all of
these non-protocol followers without an ICD. The incidence of
non-SCDs was significantly higher in the EP-positive patients
with VT induced by less than or equal to two ES (P ¼ 0.01).
Sudden cardiac death occurred in 12 of 268 (4%) of EP-negative
patients, with 7 of 12 in patients with no inducible arrhythmia and
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S. Zaman et al.
50
EPpos 3 ES (n=75)
EPpos £2 ES (n=39)
Total Mortality (%)
40
EPpos 4 ES (n=50)
EPnegative (n=268)
30
20
10
0
0
40
10
20
30
Time from Myocardial Infarction (months)
Figure 3 Kaplan– Meier estimates of the total cumulative mortality according to electrophysiological study (log rank P ¼ 0.05).
5 of 12 in patients with inducible VF/flutter CL ≤ 200 ms. Total
mortality in EP-negative patients was 10% (27 of 268) with
non-SCD in 2% (6 of 268) and non-cardiac death in 3% (9 of 268).
Discussion
In patients with post-MI LV dysfunction assessed with EPS early
post-MI, a significant proportion (30%) will have inducible VT
with the fourth ES. This VT tends to be of short CL and haemodynamically unstable requiring cardioversion. More importantly,
these patients are at significant risk of spontaneous ventricular
tachyarrhythmia over long-term follow-up with a rates of sudden
death or VT/VF similar to that of patients with inducible VT with
two or three ES.
We sought to examine the clinical significance of the use of the
fourth ES in post-STEMI patients. We found that up to 30% of
patients who were found to be at risk of arrhythmia could be
missed if only three ES were used as a set definition for inducibility.
Piccini et al.8 found a similar rate of spontaneous ventricular arrhythmia or sudden death after 3 years follow-up for VT induced
by 3 compared with one or two ES. Earlier studies at our institution have demonstrated that EPS incorporating the fourth ES is
strongly predictive of future arrhythmic events.5,10,11,16 The
current study further evaluates programmed ventricular stimulation using up to four ES in a contemporary population of
post-STEMI patients treated predominantly with primary PCI.
While EP study post-MI is not routinely used for sudden death
risk stratification, the prognostic utility of such an approach
appears to be critically dependent on the VT inducibility definition.
The results of such an approach await systematic evaluation in a
randomized study.
The characteristics of VT induced by three or four ES appear to
differ from those induced by less ‘aggressive’ methods. We found
that VT induced by the fourth ES had a shorter CL compared
with VT induced by three or less ES. Kumar et al.14 found that
fast inducible VT with CL of 200 –250 ms had predictive value in
post-MI patients. Interestingly, analysis of the MUSTT study also
found that patients requiring three ES to induce VT compared
with those induced with one or two ES had a shorter CL (240
vs. 260 ms). Ventricular tachycardia induced by the fourth ES
was significantly more likely to be of LBBB morphology. The significance of this is uncertain with the origin of LBBB morphology VT
most likely from the inter-ventricular septum.17,18
We performed programmed stimulation from a single ventricular site, the RV apex. However, stimulation from two sites, the RV
apex and RV outflow tract or septum, is often standard practice.6,7,19,20 Previous studies have demonstrated that while stimulation from a second site increases the sensitivity of EPS in patients
with known VT, this practice seldom initiates VT in patients without
documented VT.21,22 In addition, the use of a second site for stimulation is required less frequently when using a greater number of
ES.6,20,23 It is possible that the use of the fourth ES in our
cohort of patients who did not have a history of VT, enhanced
yield of inducible VT without requiring use of different sites of
pacing. However, the comparison of an EP protocol with four ES
at a single site, to that of three ES at two sites, has not been performed previously and was beyond the scope of this study.
While a few studies have found that induction of polymorphic
VT/VF does not increase with the number of ES used,6 the
current study was consistent with the majority of studies demonstrating that the fourth ES increases induction of non-prognostic
VF or flutter.5,7,9,11,16,19,24 Ventricular fibrillation/flutter was
promptly treated in our EP lab without complications or deaths,
demonstrating that EPS is safe even early post-MI when performed
in an experienced centre.
Patients with inducible VT at EPS had significantly higher SCD or
spontaneous VT/VF than patients without inducible VT. Cardiac
mortality was also higher in patients with inducible VT at EP
study. It is possible that use of EP study with four ES without the induction of clinically significant VT selects patients with impaired EF
post-MI who are at low risk of arrhythmia who may not benefit from
ICD prophylaxis. Lack of inducible ventricular arrhythmia at EP
study following VT ablation has been recently associated with
improved survival.25 However, there must be caution with regard
Induction of VT with the fourth ES
to giving too much significance to higher mortality in EP-positive
patients in the current study given the small number of deaths.
This needs further evaluation in a large randomized study.
Conclusion
The prognostic significance of VT induced by four ES is similar to
that of VT induced by less than or equal to three ES in patients
with post-MI LV dysfunction. Limitation of ES to three in our
protocol would have resulted in a third of patients at high arrhythmic risk being classified as EP negative. The use of a fourth ES may
increase the prognostic value of EPS at predicting arrhythmic
events as well as negatively select patients at low risk of SCD
who are safe without an ICD.
Study limitations
While there was consecutive recruitment of patients in a systematic and prospective fashion, this study was limited by its observational nature. As ICDs were not implanted in EP-negative patients
there was an unavoidable bias in the detection of arrhythmic
events and it is uncertain as to what proportion of ICD-detected
tachyarrhythmia would have resulted in SCD. In addition, strict
compliance with study protocol was not followed with a proportion of EP-negative patients receiving ICDs and EP-positive patients
not receiving an ICD. However, as this study aimed to evaluate the
predictive value of fourth ES vs. less than or equal to three ES,
rather than the predictive value of EP in general, this would not
have biased our primary endpoint. Ideally, patients with VT inducible by four ES would be randomized to either an ICD or
non-ICD monitoring (such as a loop recorder) to detect differences in SCD. However, based on our arrhythmia event rate
such a trial would require large numbers (.2000 patients).
Conflict of interest: none declared.
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