European Heart Journal – Cardiovascular Imaging (2013) 14, 790–796
doi:10.1093/ehjci/jes285
Diagnostic performance of ultrasonic tissue
characterization for subendocardial ischaemia
in patients with hypertrophic cardiomyopathy
Tatsuya Kawasaki*, Michiyo Yamano, Chieko Sakai, Kuniyasu Harimoto,
Shigeyuki Miki, Tadaaki Kamitani, and Hiroki Sugihara
Department of Cardiology, Matsushita Memorial Hospital, Sotojima 5-55, Moriguchi, Osaka 570-8540, Japan
Received 9 October 2012; accepted after revision 12 November 2012; online publish-ahead-of-print 7 December 2012
Aims
Hypertrophic cardiomyopathy (HCM) patients often develop left-ventricular subendocardial ischaemia, a cause of
chest symptoms, despite normal epicardial coronary arteries. The aim of this study was to examine whether ultrasonic tissue characterization or late gadolinium enhancement on cardiac magnetic resonance imaging can detect subendocardial ischaemia in patients with HCM.
.....................................................................................................................................................................................
Methods
Subendocardial ischaemia was quantified on exercise Tc-99m tetrofosmin myocardial scintigraphy in 29 non-oband results
structive HCM patients with asymmetric septal hypertrophy. Ultrasonic tissue characterization using cyclic variation
of integrated backscatter (CV-IB) and late gadolinium enhancement on cardiac magnetic resonance imaging were analysed separately in the right halves and the left halves of the ventricular septum in relation to subendocardial ischaemia. Subendocardial ischaemia was identified in 17 (59%) patients. The ratio of CV-IB in the right-to-left halves of the
ventricular septum was significantly higher in patients with subendocardial ischaemia (1.19 + 0.10) than those
without (0.84 + 0.10, P ¼ 0.04). The optimal cutoff for the detection of subendocardial ischaemia was the ratio of
CV-IB .1.0, with a sensitivity of 80%, specificity of 71%, and accuracy of 76%. On the other hand, late gadolinium
enhancement was not associated with subendocardial ischaemia in our cohort.
.....................................................................................................................................................................................
Conclusion
Ultrasonic tissue characterization using CV-IB separately in the right and left halves of the ventricular septum, but not
late gadolinium enhancement on magnetic resonance imaging, provided useful information in detecting subendocardial ischaemia in patients with HCM. Ultrasonic tissue characterization may be useful in selecting patients who will
benefit from medications to relieve chest symptoms.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Hypertrophic cardiomyopathy † Subendocardial ischemia † Myocardial tissue characterization † Integrated
backscatter † Cardiac magnetic resonance
Introduction
Approximately one-third to one-half of patients with hypertrophic
cardiomyopathy (HCM) develop transient left-ventricular (LV)
cavity dilation during stress scintigraphy despite normal epicardial
arteries.1 – 5 Transient LV cavity dilation is considered to reflect
subendocardial ischaemia because this scintigraphic abnormality
is associated with myocardial lactate abnormalities1 and occurs in
the absence of any significant changes in LV cavity size.1,3 Myocardial ischaemia plays an important role in the pathophysiology of
HCM,6,7 but non-invasive imaging techniques except for stress
scintigraphy have yet to be established for the detection of subendocardial ischaemia.
Echocardiography and cardiac magnetic resonance imaging are
useful modalities to assess morphology and function in patients
with HCM. Furthermore, the integrated backscatter (IB) technique
on echocardiography8,9 and late gadolinium enhancement on
cardiac magnetic resonance imaging10,11 have been developed to
non-invasively characterize myocardial tissue in clinical settings. Subendocardial ischaemia may cause changes in tissue characteristics in
* Corresponding author. Tel: +81 66992 1231, Fax: +81 66992 4845, Email: [email protected]
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2012. For permissions please email: [email protected]
791
Ultrasonic tissue characterization and ischaemia in HCM
the subendocardium of the LV, but little data are available regarding
the diagnostic performance of echocardiography and cardiac magnetic resonance imaging. Thus, we examined whether ultrasonic
tissue characterization using the IB technique or late gadolinium enhancement on cardiac magnetic resonance imaging can detect subendocardial ischaemia in patients with HCM.
Methods
Study population
The present study consisted of 29 non-obstructive HCM patients with
asymmetric septal hypertrophy referred to Matsushita Memorial Hospital (16 men; mean age, 60 years). Diagnosis of HCM was based on
conventional echocardiographic demonstration of LV end-diastolic
thickness of ≥15 mm and end-diastolic diameter of ≤55 mm in the
absence of any cardiac or systemic disorder that could cause hypertrophy, such as severe hypertension or aortic stenosis. Asymmetric
septal hypertrophy was defined as an end-diastolic ventricular
septum to LV posterior wall thickness ratio of ≥1.5. Left-ventricular
outflow obstruction was considered absent when the peak jet velocity
,2.5 m/s using the continuous wave Doppler method under resting
conditions or Valsalva manoeuver in the supine position. All patients
were in sinus rhythm and were in clinically stable condition; none of
them had a reduced LV ejection fraction or clinically significant valvular
heart disease. There were no patients treated with permanent mechanical device implantations, septal myectomy, alcohol septal ablation,
or heart transplantation. Coronary heart disease was ruled out in all
patients on the basis of conventional coronary angiography or multidetector computed tomography. Informed consent for this study was
obtained from all patients with HCM.
Exercise scintigraphy
All patients underwent maximal symptom-limited exercise testing with
myocardial scintigraphy. All medications, if any, were withdrawn for at
least five half-lives before exercise testing. The exercise workload
began with 25 W and was increased by 25 W every 2 min using an
electrically operated sitting bicycle ergometer under continuous monitoring with a 12-lead electrocardiogram. Blood pressure was measured using arm-cuff sphygmomanometry every 2 min or more
frequently. The exercise testing was finished at achievement of 85%
of the maximal predicted heart rate, or due to physical exhaustion,
ST-segment depression ≥0.2 mV or elevation ≥0.1 mV, systolic
blood pressure ≥200 mmHg, or significant arrhythmias causing
haemodynamic instability. Every exercise-induced displacement of
the ST-segment was measured at 0.08 s after the J point over three
consecutive beats. Positive ST-segment depression was defined as
horizontal or down sloping depression ≥0.1 mV.
Tc-99m tetrofosmin of 370 or 740 MBq was injected intravenously
1 min before the termination of exercise and 4 h later. Single photon
emission computed tomograms were then obtained after stress and
at rest every 30 min after tracer injections with a digital gamma
camera equipped with a low-energy, high-resolution, parallel-hole collimator (Starcam 3000XC/T, General Electric Medical Systems, WI,
USA). The camera was rotated 1808 from a 458 right anterior
oblique position to a 458 left posterior oblique position. Finally, 32
images were obtained on a matrix of 64 × 64 pixels with a 30 s exposure for each 5.68 interval, and were reconstructed as single photon
emission computed tomograms using a Hanning filter without correction for attenuation or scatter.
Stress and rest images were visually semiquantified in a conventional
17-segment model of the LV, including one apex segment on the vertical long-axis view and 16 segments on three short-axis views, using a
standard 5-point scoring system (0 ¼ normal uptake, 1 ¼ mild reduction in tracer uptake, 2 ¼ moderate reduction, 3 ¼ severe reduction,
4 ¼ absence of detectable tracer uptake). In brief, basal and midsections were divided into six segments (anterior, anteroseptal, inferoseptal, inferior, inferolateral, anterolateral) and the apical section was
divided into four segments (anterior, septal, inferior, lateral). Summed
stress score and summed rest score were calculated by adding the 17
segment scores of the stress and rest images, respectively. The
summed difference score was the sum of the difference between the
stress score and rest score in each segment.
To assess subendocardial ischaemia, e.g. as shown in Figure 1A, transient LV cavity dilation was quantified using software that we had
developed previously3,4 and had appropriately modified.5 Briefly, the
LV was divided into 15 short-axis slices and 100 radii were generated
at 3.68 intervals from the centre of each image. An area surrounded by
100 points each displaying the maximum count on each radius was calculated automatically in the stress and rest images. The transient dilation index was defined as the stress-to-rest ratio in the sum of the 15
surface areas, and a subendocardial perfusion abnormality was considered present if the transient dilation index was .1.07.5
Echocardiography
Conventional echocardiographic examination was performed in all
HCM patients using a SONOS 5500 with a wide-band sector transducer, S4 (Philips Medical Systems, Best, the Netherlands). Echocardiographic indexes were measured as: LV end-diastolic diameter, LV
fractional shortening, ventricular septum and LV posterior wall thickness at the level of the chordae, left atrial end-systolic diameter, the
ratio of the E wave to the A wave, and the deceleration time of the
E wave through a mitral valve. Ultrasonic IB analysis was performed
in 16 patients using the online acoustic densitometry software as previously described.12,13 In brief, IB images were obtained from the parasternal short-axis view at the level of the chordae, and stored on a
magneto-optical disk with maximum dynamic range of 60 dB and 60
image frames corresponding to almost two cardiac cycles. The
maximum circle as the region of interest was put on the whole of
the anterior ventricular septum, the right and left halves of the anterior
ventricular septum, and the whole of the LV posterior wall, excluding
endocardial and epicardial reflectors.14,15 Each region of interest was
manually adjusted on a frame-by-frame basis to keep it inside each
region throughout cardiac cycles, excluding endocardial and epicardial
reflectors. The time-gain compensation levels were all equal and
lateral-gain compensation was not used. The pre-processing, focus
position, persistence, compression, frame rate, and post-processing
were maintained constant in all patients, avoiding the signal saturation
that may cause estimation errors. Based on the time– intensity curves,
we measured the cyclic variation magnitude of IB (CV-IB) defined as
the difference between the minimum and maximum values during
cardiac cycles (Figure 1B). An experienced investigator who was
unaware of scintigraphic findings did CV-IB analysis.
Cardiac magnetic resonance
Gadolinium-enhanced cardiac magnetic resonance imaging was performed in 22 patients with HCM, as shown in Figure 1C. All magnetic resonance images were acquired using a 1.5 T imaging system (Signa HDx,
General Electric Medical Systems, WI, USA). As in the scintigraphic analysis described earlier, three short-axis images at the basal-, mid-, and
apical-LV levels and a long-axis image of the apex segment were obtained
792
T. Kawasaki et al.
Figure 1 A representative case of a 64-year-old man with hypertrophic cardiomyopathy. Exercise-induced transient cavity dilation is apparent
on short-axis slices of Tc-99m tetrofosmin scintigraphy after exercise (A, upper), compared with at rest (lower), features consistent with leftventricular subendocardial ischaemia. Time– intensity curves of integrated backscatter from the parasternal short-axis view at the level of the
chordae show reduced cyclic variation in the left half of the ventricular septum of 3.6 dB (B, middle), when compared with the right half of
6.2 dB (upper) or the whole of left-ventricular posterior wall of 8.2 dB (lower). A short-axis image of magnetic resonance shows no late
gadolinium enhancement (C ).
under serial breath-holds using a 2-dimensional, spoiled, and segmented
inversion recovery and gradient-echo sequence 10 min after an intravenous injection of 0.1 mmol/kg gadopentetate dimeglumine (Magnevist, Schering AG, Berlin, Germany). Inversion time was selected using a
standardized algorithm on the basis of myocardial, blood T1 values,
heart-rate, time of imaging from contrast injection, and dose of contrast
administered. The following scan parameters were used: slice thickness
7 mm, field of view 360 × 360 mm, flip angle 208, spatial resolution
1.6 × 2.3 mm, number of averages, 2. Late gadolinium enhancement in
the whole of the ventricular septum, in the right and left halves of the
ventricular septum, and in the whole of the LV posterior wall were
determined on the basis of a 17-segment model of the LV. The areas
of ventricular septum-free wall junctions, defined to be located
between the two radii each making an angle of 308 with the junction
line on opposite side,16 were excluded from the analysis because junction areas have been reported to be different from the ventricular
septum in terms of histology17 and because we calculated CV-IB in the
segment of the ventricular septum without junction areas. Late gadolinium enhancement was defined as two standard deviations above the
mean signal intensity of apparently normal myocardium.18 Furthermore,
when late gadolinium enhancement was present in the ventricular
septum, it was visually assessed in terms of predominance, i.e. rightdominance or left-dominance. Experienced investigators who were
unaware of the scintigraphic findings analysed gadolinium-enhanced
cardiac magnetic resonance images. Disagreements were resolved by
consensus.
Statistical analysis
Categorical variables were compared by x 2 test or Fisher’s exact test as
appropriate. Continuous variables were expressed as the mean +
standard deviation and compared using the Student’s t-test. Scintigraphic
scores and CV-IB indexes were expressed as the mean + standard error
and compared using the Mann–Whitney U test because of the skewed
distributions. Wilcoxon’s matched pairs signed ranks test was used to
analyse CV-IB indexes within each group. Spearman rank correlation coefficient was used to examine correlations between transient dilation
index on scintigraphy and echocardiographic variables. Receiver operator characteristics curve analysis was performed to determine the
optimal cutoff point. Intraobserver and interobserver reproducibility
for CV-IB were evaluated in two-layer analysis of the ventricular
septum using mean absolute differences in the first 10 HCM patients
enrolled in the present study. A two-sided P-value ,0.05 was considered statistically significant. All calculations were performed using
SPSS version 11.0 (SPSS Inc., IL, USA).
Results
Exercise testing was performed without any complications in all
HCM patients except for one patient who developed transient
atrial fibrillation during the cool-down period after peak exercise.
Maximum workload and maximum rate-pressure product in all
patients ranged widely from 50–125 W(mean, 97 W) and from
14 200 to 39 216 (mean, 25 514), respectively. The average subendocardial ischaemia index was 1.12, ranging from 0.90 to 1.36;
in all, 17 (59%) patients were diagnosed as having subendocardial
ischaemia on the basis of exercise scintigraphy.
Patients with or without subendocardial ischaemia did not significantly differ with respect to baseline characteristics or conventional echocardiographic findings, except that subendocardial
793
Ultrasonic tissue characterization and ischaemia in HCM
Baseline characteristics in patients with and without subendocardial ischaemia
Table 1
Subendocardial ischaemia
P-value
............................................................
With
Without
...............................................................................................................................................................................
62 + 9
58 + 9
0.24
9 (53)
7 (58)
0.77
Symptoms (%)
Chest pain
6 (35)
2 (17)
0.25
Palpitation
2 (12)
1 (8)
0.63
Dyspnoea
4 (24)
1 (8)
0.29
6 (35)
9 (75)
0.04
Left-ventricular end-diastolic diameter (mm)
44 + 4
43 + 5
0.54
Left-ventricular fractional shortening (%)
Ventricular septum thickness (mm)
42 + 8
18 + 4
39 + 5
19 + 5
0.16
0.72
Left-ventricular posterior wall thickness (mm)
11 + 3
11 + 2
0.56
Left-atrial diameter (mm)
E/A
43 + 5
1.0 + 0.5
40 + 3
1.0 + 0.5
0.04
0.78
Deceleration time of E (ms)
236 + 92
227 + 79
0.78
106 + 22
0.10
27 832 + 7196
0.14
Age (years)
Men (%)
a
None
Conventional echocardiography
Exercise scintigraphy
Maximum workload (W)
Maximum rate– pressure product
90 + 30
23 879 + 6281
ST-segment depression .0.1 mV (%)
Summed stress score
4 (24)
4.9 + 1.8
4 (33)
3.4 + 1.6
0.43
0.57
Summed rest score
2.3 + 0.8
2.0 + 1.0
0.94
Summed difference score
2.6 + 1.0
1.4 + 0.6
0.47
Data are means + standard deviation or number (%). Scintigraphic scores are means + standard error.
a
Some patients had more than one symptom.
ischaemia was associated with more symptoms and with larger
left-atrial diameter (Table 1). Transient dilation indexes were correlated with left-atrial diameters (correlation coefficient ¼ 0.67,
P ¼ 0.003), but not with values of LV end-diastolic diameter, LV
fractional shortening, ventricular septum and LV posterior wall
thickness, the ratio of the E wave to the A wave, and the deceleration time of the E wave through a mitral valve (all P . 0.3).
Of all, 16 patients with HCM underwent ultrasonic tissue characterization; CV-IB values in the right and left halves of the anterior ventricular septum, and the whole of the LV posterior wall
were obtained in all 16 patients. CV-IB was significantly lower in
the whole of the ventricular septum (5.4 + 0.5 dB) than those
in the whole of the LV posterior wall (10.2 + 0.8 dB, P , 0.01).
No difference was observed between CV-IB in the right halves
of ventricular septum (7.0 + 0.6 dB) and CV-IB in the left halves
(7.0 + 0.8 dB, P ¼ 0.58), although each value was lower than
those in the whole of the LV posterior wall (both P , 0.01). Of
all 16 patients, 10 (63%) were diagnosed as having subendocardial
ischaemia based on exercise scintigraphy. Heart rate during the
acquisition of IB images was similar between patients with subendocardial ischaemia (66 + 4 bpm) and patients without subendocardial ischaemia (64 + 15 bpm, P ¼ 0.76). CV-IB in the right
halves of the ventricular septum was predominant in patients
with subendocardial ischaemia, whereas a reverse predominance
Table 2 Cyclic variation of integrated backscatter in
patients with and without subendocardial ischaemia
Subendocardial
ischaemia
P-value
...........................
With
Without
................................................................................
Whole ventricular septum
5.6 + 0.6
5.1 + 0.7
0.52
Right half of ventricular septum
7.2 + 0.7
6.6 + 1.0
0.63
Left half of ventricular septum
Whole left ventricular
posterior wall
6.5 + 0.8
10.3 + 1.4
7.7 + 1.6
10.1 + 0.6
0.79
0.71
Data are means + standard error.
of CV-IB was observed in patients without subendocardial ischaemia, with no statistical significance (Table 2). CV-IB in the whole of
the ventricular septum and LV posterior wall were similar
between the two groups. As shown in Figure 2, the ratio of
CV-IB in the right halves to the left halves was significantly
higher in patients with subendocardial ischaemia (1.19 + 0.10)
than those without (0.84 + 0.10, P ¼ 0.04). Similarly, the difference in CV-IB from the right halves to the left halves of the
794
T. Kawasaki et al.
Figure 2 The ratio of cyclic variation of integrated backscatter
(CV-IB) in the right halves to the left halves of the ventricular
septum and the difference in CV-IB from the right halves to the
left halves of ventricular septum were higher in patients with subendocardial ischaemia (solid bars) than those without (open
bars).
Table 3 Late gadolinium enhancement on magnetic
resonance imaging in patients with and without
subendocardial ischaemia
Subendocardial
ischaemia
P-value
......................
With
Without
................................................................................
ischaemia, and right-dominated in two and left-dominated in two
among patients without subendocardial ischaemia (P ¼ 0.64).
Both ultrasonic tissue characterization and gadolinium enhanced
cardiac magnetic resonance imaging were performed in nine
patients with HCM, four of whom were diagnosed as having subendocardial ischaemia on the basis of exercise scintigraphy. Late
gadolinium enhancement was detected in two of the four patients;
one showed late gadolinium enhancement in the right half of the
ventricular septum with a CV-IB of 6.0 dB and 11.8 dB in the left
half, while the other showed late gadolinium enhancement in the
left half of the ventricular septum with a CV-IB of 6.2 dB in the
right half and 5.6 dB in the left half. None of the remaining five
patients without subendocardial ischaemia showed late gadolinium
enhancement.
Receiver operator characteristics curve analysis to detect subendocardial ischaemia showed that the optimal cutoff was 1.0 for the
ratio of CV-IB in the right halves to the left halves and 0 dB of the
difference from the right halves to the left halves (Figure 3). The
ratio of CV-IB .1.0 or the difference in CV-IB .0 dB showed
equally good predictive values in detecting subendocardial ischaemia: a sensitivity of 80%, a specificity of 71%, an accuracy of 76%, a
positive predictive value of 80%, and a negative predictive value of
71% in both cutoffs.
Intraobserver and interobserver variability of CV-IB were good,
with a small difference in mean values in the right halves of ventricular septum (1.0 + 0.4 and 1.6 + 0.5 dB) and in the left
halves (0.4 + 0.4 and 0.5 + 0.4 dB) in 10 HCM patients. Of the
10 patients, four showed a ratio of CV-IB in the right halves to
the left halves .1.0, while four patients showed a difference of
.0 dB, at the initial examination. Intraobserver and interobserver
variability did not lead to any change in classification of the 10
patients according to the cutoff point of the ratio of CV-IB .1.0
or the difference of CV-IB .0 dB.
Whole ventricular septum
5 (45)
3 (27)
0.33
Right half of ventricular septum
Left half of ventricular septum
3 (27)
2 (18)
3 (18)
2 (18)
0.50
0.71
Discussion
Whole left ventricular posterior wall
0
0
—
The present study showed that subendocardial ischaemia was frequently observed in non-obstructive HCM patients with asymmetric septal hypertrophy, and that subendocardial ischaemia was
associated with the predominant CV-IB in the right halves of the
ventricular septum, when compared with the left halves. The
ratio of CV-IB in the right halves to the left halves of the ventricular
septum .1.0 or a difference in CV-IB from the right halves to the
left halves .0 dB showed a good diagnostic performance for the
detection of subendocardial ischaemia in HCM patients. On the
other hand, late gadolinium enhancement on cardiac magnetic resonance imaging was not associated with subendocardial ischaemia
in our cohort.
CV-IB in the right halves and the left halves of the ventricular
septum did not differ significantly in all patients who underwent
ultrasonic tissue characterization. This finding is consistent with
previous studies using CV-IB separately in the right halves and
left halves of the ventricular septum in patients with HCM.14,19
However, in the present study, subgroup analysis dichotomized
by the presence or absence of subendocardial ischaemia revealed
an association between the predominance of CV-IB in the ventricular septum and subendocardial ischaemia in patients with
Data show numbers of patients (%).
ventricular septum was higher in patients with subendocardial ischaemia (1.6 + 0.5 dB) than without subendocardial ischaemia
(21.1 + 1.2 dB, P ¼ 0.05).
Of all 22 patients who underwent cardiac magnetic resonance,
eight (36%) showed late gadolinium enhancement in areas including the ventricular septum or LV posterior wall: eight in the whole
of the ventricular septum; five in the right half of the ventricular
septum; four in the left half of the ventricular septum, but none
in the whole of the LV posterior wall. Of all 22 patients,
11 (50%) were diagnosed as having subendocardial ischaemia on
the basis of exercise scintigraphy. The location of late gadolinium
enhancement did not differ between patients with and without
subendocardial ischaemia (Table 3). Late gadolinium enhancement
of the ventricular septum was right-dominated in three patients
and left-dominated in two among those with subendocardial
795
Ultrasonic tissue characterization and ischaemia in HCM
Figure 3 Receiver operator characteristics curve for the detection of subendocardial ischaemia from cyclic variation of integrated backscatter
(CV-IB) in the right and left halves of the ventricular septum. The ratio of CV-IB in the right halves to the left halves and the difference in CV-IB
from the right halves to the left halves show almost similar area under curve values.
HCM. Pingitore et al.15 examined dipyridamole-induced changes in
CV-IB in patients with HCM, and found that CV-IB during dipyridamole infusion was significantly reduced, when compared with
resting values, in the left halves of the ventricular septum, but
did not change in the right halves of the ventricular septum or
the whole of the LV posterior wall. In our study, the diagnostic performance of CV-IB for subendocardial ischaemia was good even on
resting echocardiography, which is preferable to stress echocardiography because of its simplicity and convenience in clinical
practice.
Myocardial ischaemia has been reported to be a determinant of
IB in experimental studies.20,21 CV-IB in the whole LV wall was
reduced during exercise or rapid pacing in patients with coronary
artery disease.22,23 In addition, chronic myocardial ischaemia seems
to reduce CV-IB not only during stress, but also at rest in patients
with coronary artery disease. Pasquet et al.24 examined CV-IB in
patients with chronic coronary artery disease and LV dysfunction,
and found that CV-IB at rest was low in dysfunctional segments,
when compared with normally contracting segments, in which
CV-IB increased parallel to the contractile reserve during dobutamine echocardiography. Furthermore, in patients receiving angioplasty for chronic coronary artery disease studied by Lin et al.,25
a reduction in CV-IB at rest was identified not only in dysfunctional
segments with a contractile reserve, but also in normally contracting segments with ischaemic burden; the reduction in CV-IB recovered soon after angioplasty in both segments. Thus, we may safely
consider that repetitive subendocardial ischaemia causes the reduction in resting CV-IB in the left halves of the ventricular
septum in patients with HCM, although the mechanisms of subendocardial ischaemia in HCM are, in part, different from myocardial
ischaemia in patients with coronary artery disease.
In the present magnetic resonance study, among 11 HCM
patients with subendocardial ischaemia, only two (18%) showed
late gadolinium enhancement in the left halves of the ventricular
septum. Furthermore, late gadolinium enhancement on cardiac
magnetic resonance imaging was not associated with subendocardial ischaemia. Late gadolinium enhancement has been established
as the most reliable non-invasive imaging method for assessing
myocardial fibrosis.10,11 Thus, our findings indicate that repetitive
subendocardial ischaemia is unlikely to cause replacement myocardial fibrosis in patients with HCM. Recently, cardiac magnetic resonance stress testing, e.g. adenosine stress perfusion imaging or
dobutamine stress wall motion analysis, was reported to demonstrate a high diagnostic accuracy for the detection of significant
coronary artery disease,26 although these techniques have not
been popular in the clinical setting. Further studies are needed
to clarify whether stress cardiac magnetic resonance detects subendocardial ischaemia in patients with HCM.
Clinical implications
Myocardial ischaemia is a major cause of chest symptoms in HCM.6
Inability of the coronary microcirculation to respond to the
increased oxygen demand of the hypertrophied myocardium may
lead to chest symptoms in HCM patients without epicardial coronary artery disease.27 The frequency of symptoms in the present
study was significantly lower in patients without subendocardial ischaemia than in those with subendocardial ischaemia, suggesting
that subendocardial ischaemia can cause some symptoms. Some
calcium antagonists, e.g. verapamil28 and diltiazem,29 have been
reported to have reduced or prevented subendocardial ischaemia,
even in patients with non-obstructive HCM, without negatively
affecting exercise tolerance. Ultrasonic tissue characterization
using CV-IB may be useful in selecting HCM patients who will
benefit from medications to reduce symptoms.
Study limitations
The present study was conducted in a single centre and the size
was not large enough to extrapolate the present result to a
community-based population. Not all patients underwent both
ultrasonic tissue characterization and cardiac magnetic resonance
796
mainly because this study was conducted in routine clinical practice. However, we were able to obtain meaningful data of ultrasonic tissue characterization for detecting subendocardial ischaemia
in patients with HCM.
Conclusion
Ultrasonic tissue characterization using CV-IB separately in the
right and left halves of the ventricular septum, but not late gadolinium enhancement on cardiac magnetic resonance imaging, provided useful information for detecting subendocardial ischaemia
in patients with HCM. Ultrasonic tissue characterization may be
useful in selecting HCM patients who will benefit from medications
to relieve chest symptoms.
Conflict of interest: none declared.
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