Download Left ventricular dyssynergy and dispersion as determinant factors of

European Heart Journal – Cardiovascular Imaging (2016) 17, 334–342
doi:10.1093/ehjci/jev172
Left ventricular dyssynergy and dispersion
as determinant factors of fatal ventricular
arrhythmias in patients with mildly reduced
ejection fraction
Hiroki Matsuzoe, Hidekazu Tanaka*, Kensuke Matsumoto, Hiromi Toki,
Hiroyuki Shimoura, Junichi Ooka, Hiroyuki Sano, Takuma Sawa, Yoshiki Motoji,
Yasuhide Mochizuki, Keiko Ryo, Koji Fukuzawa, Akihiro Yoshida, and Ken-ichi Hirata
Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
Received 31 March 2015; accepted after revision 10 June 2015; online publish-ahead-of-print 9 July 2015
Aims
Current guidelines recommend implantation of prophylactic implantable cardioverter-defibrillators (ICD) in patients
with left ventricular (LV) ejection fraction (EF) ,35%. We explored the prognostic factors of fatal ventricular arrhythmias for heart failure (HF) patients with LVEF ≥35%.
.....................................................................................................................................................................................
Methods
We retrospectively studied 72 patients with LVEF of 52 + 12% (all ≥35%) who had undergone ICD implantation. Hetand results
erogeneity of LV regional myocardial contraction was defined as standard deviation of peak strain (dyssynergy index)
and time-to-peak strain (dispersion index) from 18 LV segments determined by speckle tracking. Fatal ventricular arrhythmias with appropriate ICD therapy occurred in 34 patients (47%) during a median follow-up of 17 months. Receiver operating characteristic curve analysis identified dispersion index ≥101 ms and dyssynergy index ≥6.1% as
predictors of fatal ventricular arrhythmias (P ¼ 0.004 and P ¼ 0.0001, respectively). In addition, the combination of dispersion index ≥101 ms and dyssynergy index ≥6.1% was the most predictive of fatal ventricular arrhythmias with a
sensitivity of 77%, specificity of 79%, and area under the curve of 0.795 (P , 0.0001). A sequential Cox model based
on clinical and conventional echocardiographic variables including age, gender, HF aetiology, and LVEF (x 2 ¼ 4.8) was
improved, but not statistically significant (x 2 ¼ 4.9; P ¼ 0.82), by addition of global longitudinal strain, whereas improvement by the addition of the dispersion index (x 2 ¼ 8.9; P ¼ 0.04) and further improvement by the addition of the dyssynergy index (x 2 ¼ 20.2; P , 0.005).
.....................................................................................................................................................................................
Conclusion
Combined assessment of LV dyssynergy and dispersion can enhance predictive capability for fatal ventricular arrhythmias in patients with LVEF ≥35% and may have potential for better management of such patients.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
echocardiography † ventricular arrhythmia † implantable cardioverter-defibrillator † dyssynergy † dispersion †
mild reduced left ventricular ejection fraction
Introduction
Heart failure (HF) patients with severely reduced left ventricular
(LV) ejection fraction (EF) are at high risk of fatal ventricular arrhythmias, and their condition is associated with worsening of long-term
outcome. Such patients can die suddenly and unpredictably from
malignant arrhythmias despite the use of optimal medical therapies.
Sudden cardiac death is most frequently caused by ventricular tachycardia/ventricular fibrillation and can be prevented by an implantable cardioverter-defibrillator (ICD).1 – 4 In addition, prophylactic
ICD implantation in patients for high risk of fatal ventricular arrhythmias has been shown to be efficient, but predicting fatal ventricular
arrhythmias is challenging. The current indications for prophylactic
ICD implantation in HF patients are based on LVEF with a threshold
* Corresponding author. Tel: +81 78 382 5846; Fax: +81 78 382 5859, E-mail: [email protected]
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
335
LV dyssynergy and dispersion for fatal ventricular arrhythmias
value of ,35%.1 – 3,5,6 However, a number of patients with fatal ventricular arrhythmias have shown LVEF ≥35% in the clinical setting,
so that risk stratification for fatal ventricular arrhythmias in such patients is not fully understood. Since the development of fatal ventricular arrhythmias can be associated with multiple factors, it is
not considered to be homogeneous. Parameters other than LVEF
have therefore been proposed to improve the accuracy of selection
of patients for whom ICD therapy is indicated. It was recently reported that LV mechanical dispersion assessed by two-dimensional
longitudinal speckle-tracking strain, which reflects the heterogeneity
of timing of regional LV myocardial contraction, is an excellent predictor of fatal ventricular arrhythmias in advanced HF patients independently LVEF.7 – 11 In addition, it was reported that LV dispersion
is associated with LV dyssynergy which represents the heterogeneity of LV regional myocardial contraction.12 We therefore speculated that LV dyssynergy as well as LV dispersion have an effect on
inhomogeneous electrical conduction and repolarization, resulting
in a fundamental arrhythmogenic risk. Accordingly, our objective
was to test the hypothesis that the additional assessment of LV dyssynergy enhances the predictive capability of LV mechanical dispersion for fatal ventricular arrhythmias in HF patients with LVEF
≥35%.
Methods
Study populations
We retrospectively analysed 83 consecutive patients who underwent
ICD implantation for primary or secondary prevention at Kobe University Hospital between November 2007 and May 2014. The inclusion criterion was LVEF ≥35%, and the patients excluded from the study were
those with: (i) more than moderate aortic and/or mitral valvular heart
disease; (ii) the presence of significant coronary artery stenosis, determined by means of stress myocardial perfusion scintigraphy or coronary
angiography; (iii) congenital heart disease; (iv) left bundle branch block;
and (v) the occurrence of inappropriate ICD therapies. At the time of
enrollment, all patients were in clinically stable condition. Sixteen patients underwent catheter ablation for ventricular arrhythmias prior
to ICD implantation. The anti-arrhythmic drugs were administrated in
30 patients (Table 1). This protocol was approved by the local ethics
committee and written informed consent was obtained from all
patients.
Echocardiographic examination
All echocardiographic studies were performed at a median of 9 days
(5 – 16 days) before ICD implantation with commercially available
echocardiography systems (Vivid 7 or E9; GE Vingmed Ultrasound
AS, Horten, Norway and Aplio Artida; Toshiba Medical Systems, Tochigi, Japan). Digital routine grey-scale, two-dimensional cinèloops
from three consecutive beats were obtained during end-expiratory apnoea from standard LV parasternal and apical views. Mean frame rate
was 45 frames/s for the standard apical views for grey-scale imaging
used for speckle-tracking analysis. Sector width was optimized for
complete myocardial visualization while maintaining the maximal frame
rate. Standard LV measurements were obtained in accordance with the
current guidelines of the European Association of Cardiovascular
Imaging/the American Society of Echocardiography.13 LV volumes and
LVEF were calculated by using the modified biplane Simpson’s method.
The early diastolic (E) and atrial wave velocities as well as the E-wave
deceleration time were measured on a pulsed-wave Doppler
recording from the apical four-chamber view. Spectral pulsed-wave
Doppler-derived early diastolic velocity (E′ ) was obtained from the
septal mitral annulus, and the E/E′ ratio was calculated to obtain an estimate of LV filling pressure.14 All echocardiographic data were analysed by independent observers blinded to clinical data. For patients
with atrial fibrillation, measurements of standard echocardiographic
and speckle-tracking parameters were obtained as averages of ≥4 cardiac cycles.
Speckle-tracking strain analysis
Speckle-tracking strain analysis was performed for each patient with
the aid of dedicated software (Ultra Extend; Toshiba Medical Systems) to avoid discrepancies among different vendors. Speckletracking longitudinal strain was assessed from the standard three
apical views as previously described in detail.15 – 17 Briefly, a region
of interest was traced counterclockwise on the endocardium starting
from the right-hand mitral annulus at end-diastole of each of the three
apical views using a point-and-click approach. A second larger region
of interest was then generated and manually adjusted near the epicardium. Apical images were divided into six standard segments and six
corresponding time-strain curves were generated. Global longitudinal
strain (GLS) was determined as the average of peak strain values of 18
LV segments.13
Assessment of dispersion and dyssynergy
index
The dispersion and dyssynergy index were assessed by means of longitudinal speckle-tracking strain (Figure 1). The dispersion index was defined as the standard deviation of time-to-peak strain and the
dyssynergy index as the standard deviation of peak strain from 18 LV
segments.
Definitions of endpoints
Pre-defined endpoints were determined as the occurrence of appropriate ICD therapy such as anti-tachycardia pacing and/or shock for ventricular tachycardia and/or ventricular fibrillation. The median
follow-up period was 17 months (range: 0.2– 72.5 months). ICD device
interrogation was scheduled every 3 –6 months after implantation in all
patients.
Statistical analysis
Continuous variables were expressed as mean values and standard deviation for normally distributed data and as the median and inter-quartile
range for non-normally distributed data, while categorical variables
were expressed as frequencies and percentages. The parameters of
the two subgroups were compared by using Student’s t-test or
Mann – Whitney U test as appropriate. Proportional differences were
evaluated by using Fisher’s exact test. Receiver operating characteristic
(ROC) curves were computed to determine optimal cut-off values of
echocardiographic indices for prediction of fatal ventricular arrhythmias
as well as to calculate the area under the curve (AUC) for each of the
indexes to determine prognostic significance. Optimal cut-off values for
dispersion and dyssynergy index were computed based on maximizing
the sum of sensitivity plus specificity. AUCs were compared by means of
logistic analysis. The initial univariate Cox proportional hazards analysis
to identify univariate predictors of fatal ventricular arrhythmias was followed by a multivariate Cox proportional hazards model using stepwise
selection, with the P levels for entry from the model set at ,0.15. Candidate predictors were coronary artery disease, GLS, QRS duration, dispersion index, and dyssynergy index. Sequential Cox models were
performed to determine the prognostic advantages of the dyssynergy
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H. Matsuzoe et al.
Table 1
Baseline characteristics of patients
Variables
All patients
(n 5 72)
Patients with fatal ventricular
arrhythmias (n 5 34)
Patients without fatal ventricular
arrhythmias (n 5 38)
P-value
Age, years
58 + 15
59 + 17
57 + 14
0.429
Gender (male/female)
59/13
25/9
34/4
0.124
Body surface area, m2
Implantation criteria (primary/
secondary)
Catheter ablation before ICD
implantation, n (%)
Systolic blood pressure, mmHg
1.67 + 0.20
15/57
1.64 + 0.18
6/28
1.71 + 0.20
9/29
0.138
0.574
16 (22)
9 (26)
7 (18)
0.571
110 + 14
109 + 13
111 + 15
0.587
Diastolic blood pressure, mmHg
61 + 8
60 + 7
62 + 9
0.300
Heart rate, bpm
QRS duration, ms
65 + 12
113 + 27
63 + 10
119 + 33
66 + 13
108 + 19
0.216
0.094
QTc, ms
440 + 37
444 + 37
436 + 37
0.316
Chronic or paroxysmal atrial
fibrillation, n (%)
15 (21)
6 (18)
9 (24)
0.574
Brain natriuretic peptide, pg/mL
NYHA functional class, n (%)
119 (32– 269)
170 (53– 289)
88 (19– 248)
0.232
...............................................................................................................................................................................
I
39 (54)
16 (47)
23 (61)
0.344
II
III
25 (35)
8 (11)
13 (38)
5 (15)
12 (32)
3 (8)
0.624
0.463
IV
0 (0)
0 (0)
0 (0)
Heart failure aetiology, n (%)
Dilated cardiomyopathy
9 (13)
5 (15)
4 (11)
0.727
Hypertrophic cardiomyopathy
12 (17)
5 (15)
7 (18)
0.758
Cardiac sarcoidosis
Coronary artery disease
6 (8)
23 (32)
5 (15)
9 (26)
1 (3)
14 (37)
0.094
0.449
Old myocardial infarction
17 (24)
7 (21)
10 (26)
0.593
Angina pectoris
Vasospastic angina pectoris
0 (0)
6 (8)
0 (0)
2 (6)
0 (0)
4 (11)
0.677
Brugada syndrome
6 (8)
1 (3)
5 (13)
0.203
Idiopathic ventricular fibrillation
Arrhythmogenic right ventricular
cardiomyopathy
7 (10)
2 (3)
3 (9)
1 (3)
4 (11)
1 (3)
1.000
1.000
7 (10)
5 (15)
2 (5)
0.243
Others
Medications, n (%)
Diuretics
22 (31)
13 (38)
9 (24)
0.208
ACEI/ARB, n (%)
b-Blocker, n (%)
47 (65)
45 (63)
22 (65)
24 (71)
25 (66)
21 (55)
1.000
0.226
Spironolactone
24 (33)
15 (44)
9 (24)
0.083
Calcium channel blocker, n (%)
Phosphodiesterase 3 inhibitors
16 (22)
2 (3)
8 (24)
1 (3)
8 (21)
1 (3)
1.000
1.000
Anti-arrhythmic drugs
30 (42)
15 (44)
15 (39)
0.812
Amiodarone
Sotalol
13 (18)
9 (13)
6 (18)
5 (15)
7 (18)
4 (11)
1.000
0.727
Mexilletine
2 (3)
1 (3)
1 (3)
1.000
Quinidine
Bepridil
2 (3)
1 (1)
1 (3)
0 (0)
1 (3)
1 (3)
1.000
1.000
Disopyramide
1 (1)
0 (0)
1 (3)
1.000
Pilsicainide
Procainamide
1 (1)
1 (1)
1 (3)
1 (3)
0 (0)
0 (0)
0.472
0.472
Continued
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LV dyssynergy and dispersion for fatal ventricular arrhythmias
Table1 Continued
Variables
All patients
(n 5 72)
Patients with fatal ventricular
arrhythmias (n 5 34)
Patients without fatal ventricular
arrhythmias (n 5 38)
P-value
LV ejection fraction, %
52.2 + 12.0
49.6 + 12.1
54.4 + 11.5
0.089
LV end-diastolic volume, mL
LV end-systolic volume, mL
111.1 + 36.6
55.4 + 27.9
115.4 + 31.0
59.9 + 26.3
107.2 + 41.0
51.4 + 29.0
0.343
0.196
E/E′
13.2 + 7.8
14.6 + 8.9
11.9 + 6.5
0.162
GLS, %
Dispersion index, ms
211.2 + 3.4
83.1 + 28.6
210.8 + 3.7
93.3 + 31.3
211.5 + 3.2
73.9 + 22.6
0.382
0.004
Dyssynergy index, %
5.4 + 1.9
6.2 + 2.1
4.7 + 1.4
0.0004
...............................................................................................................................................................................
Echocardiographic parameters
Values are mean + SD for normally distributed data, and median and inter-quartile range for non-normally distributed data or n (%).
NYHA, New York Heart Association; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; LV, left ventricular; E, peak early diastolic mitral flow
velocity; E′ , Spectral pulsed-wave Doppler-derived early diastolic velocity from the septal mitral annulus; GLS, global longitudinal strain.
Figure 1 Assessment of LV dispersion and dyssynergy index.
338
index compared with clinical characteristics, LVEF, GLS, and dispersion
index for the prediction of fatal ventricular arrhythmia. A statistically significant increase in the global log-likelihood x2 of the model was defined
as an enhancement of prognostic value. The inter-observer and
intra-observer reproducibilities for dispersion and dyssynergy index
were determined as both intra-class correlation coefficient and
Bland – Altman analysis from 20 randomly selected patients with the
aid of an identical cine loop for each view. The limits of agreement represented the 1.96 standard deviation of the mean bias. For all steps, a
P-value of ,0.05 was regarded as statistically significant. All analyses
were performed with MedCalc version 14.10.2 (MedCalc software;
Mariakerke, Belgium).
Results
Baseline characteristics of patients
Of the 83 patients who met all inclusion criteria, 9 (11%) with
suboptimal images from poor echocardiographic windows and 2
with all right ventricular back-up pacing of the ICD were excluded
from the study. The 72 remaining patients for whom baseline
echocardiographic and long-term outcome data were available
this constituted the final study group. The baseline characteristics
of the 72 patients are summarized in Table 1. Their mean age was
58 + 15 years, 13 (18%) were female, and mean LVEF was 52 +
12% (all ≥35%). ICD implantation was indicated for primary
prevention in 15 (21%) and in 57 (79%) for secondary prevention.
Prevention of sudden cardiac death was considered as secondary
when symptomatic sustained ventricular tachycardia or resuscitated sudden cardiac arrest occurred, otherwise considered as
primary prevention. All patients for primary prevention were
documented sustained ventricular arrhythmia inducible by an electrophysiological study.
Endpoints, pre-defined as appropriate ICD therapy, applied to 34
patients (47%) during follow-up. There were no differences in baseline clinical characteristics except for significantly higher dispersion
and dyssynergy indices for patients with than for patients without
fatal ventricular arrhythmias (dispersion index: 93.3 + 31.3 vs.
73.9 + 22.6 ms, P , 0.01; dyssynergy index: 6.2 + 2.1 vs. 4.7 +
1.4%, P , 0.001).
The intra-class correlation coefficient for intra-observer reproducibility of the dispersion and dyssynergy indices were 0.940
[95% confidence interval (95% CI): 0.777 – 0.984] and 0.861 (95%
CI: 0.485 –0.963), respectively, with corresponding coefficients for
inter-observer reproducibility of 0.917 (95% CI: 0.693 –0.978) and
0.865 (95% CI: 0.498 – 0.964). Bland and Altman plots for
intra-observer reproducibility of the dispersion and dyssynergy indices were 0.28 ms and 0.55% of bias and 18.2 ms and 2.2% of limits of
agreement, respectively, with corresponding for inter-observer reproducibility of the dispersion and dyssynergy indices were
24.50 ms and 0.49% of bias and 23.5 ms and 2.2% of limits of
agreement.
Predictors of fatal ventricular arrhythmias
ROC curve analysis showed that dispersion index ≥101 ms was
predictive of fatal ventricular arrhythmias with a sensitivity of 38%,
specificity of 92%, and AUC of 0.685 (P ¼ 0.004; Figure 2). Dyssynergy index ≥6.1% was also predictive with a sensitivity of 59%,
H. Matsuzoe et al.
specificity of 84%, and AUC of 0.741 (P ¼ 0.0001; Figure 2). In addition, of patients who underwent ICD implantation for primary prevention (n ¼ 15), dispersion index ≥56.3 ms was also predictive of
fatal ventricular arrhythmias with a sensitivity of 100%, specificity of
56%, and AUC of 0.778 (P ¼ 0.03), and dyssynergy index ≥4.4% had
a trend to be predictive with a sensitivity of 83%, specificity of 56%,
and AUC of 0.556 (P ¼ 0.74), but not statistically significant. On the
other hand, other variables listed in Table 1, such as LVEF and GLS,
were not predictive. In addition, the combination of dispersion index ≥101 ms and dyssynergy index ≥6.1% was the most predictive
of fatal ventricular arrhythmias with a sensitivity of 77%, specificity of
79%, and AUC of 0.795 (P , 0.0001; Figure 2).
Figure 3 shows comparisons of prevalence of patients without
fatal ventricular arrhythmias for the three subgroups on the basis
of the presence or absence of significant LV dispersion and dyssynergy. There were 39 patients with both dispersion index
,101 ms and dyssynergy index ,6.1%, and this pattern was most
closely associated with absence of fatal ventricular arrhythmias for
the three subgroups (77%). Conversely, 10 patients with both dispersion index ≥101 ms and dyssynergy index ≥6.1% showed the
weakest association with absence of fatal ventricular arrhythmias
for the three subgroups (20%).
The hazard ratio (HR) and 95% CI for each variable in univariate
and multivariate Cox proportional hazards analyses are shown in
Table 2. An important finding of the multivariate Cox proportional
hazards analysis was that only dyssynergy index was only independent predictor of fatal ventricular arrhythmias (HR, 1.289; 95% CI:
1.096 –1.519; P ¼ 0.002).
The incremental benefit of using sequential Cox models for the
prediction of fatal ventricular arrhythmia is shown in Figure 4. A
model based on clinical and conventional echocardiographic variables including age, gender, HF aetiology, and LVEF (x 2 ¼ 4.8) was
improved by addition of GLS, but not statistically significant (x 2 ¼
4.9; P ¼ 0.82), whereas improvement by the addition of the dispersion index (x 2 ¼ 8.9; P ¼ 0.04) and further improvement by the
addition of the dyssynergy index (x 2 ¼ 20.2; P , 0.005). Figure 5
shows representative cases of longitudinal speckle-tracking strain
curves from the standard three apical views for patients with and
without ventricular arrhythmia.
Discussion
The findings of our study demonstrated that LV dyssynergy as well
as LV dispersion were strongly associated with the development of
fatal ventricular arrhythmias in patients with LVEF ≥35%. In addition, combined assessment of LV dyssynergy and dispersion can enhance the predictive capability for fatal ventricular arrhythmias in
such patients.
Association of heterogeneity of LV
function with fatal ventricular arrhythmias
Haugaa et al. reported that LV mechanical dispersion assessed by
two-dimensional speckle-tracking strain was strongly associated
with fatal ventricular arrhythmias in HF patients with after acute
myocardial infarction8,9 and non-ischaemic cardiomyopathy7 independently of LVEF. They and Ersbøll et al. 10 also demonstrated
LV dyssynergy and dispersion for fatal ventricular arrhythmias
339
Figure 2 Dispersion index ≥101 ms and dyssynergy index ≥6.1% are predictive of fatal ventricular arrhythmias. In addition, the combination of
these two factors was the most predictive of fatal ventricular arrhythmias.
Figure 3 Patients with both dispersion index ,101 ms and dyssynergy index ,6.1% showed the strongest association with the absence of fatal
ventricular arrhythmias. Conversely, patients with both dispersion index ≥101 ms and dyssynergy index ≥6.1% showed the weakest such
association.
340
Table 2
H. Matsuzoe et al.
Univariate and multivariate cox proportional hazards analysis
Covariate
Univariate analysis
...........................................................
HR
95% CI
P-value
Age
0.984
0.954–1.015
0.311
Gender (male)
1.649
0.605–4.488
0.330
Coronary artery disease
QRS duration
0.472
1.003
0.176–1.265
0.991–1.016
0.137
0.080
LVEF
0.986
0.953–1.021
0.429
GLS
1.160
0.996–1.349
0.057
Dispersion index
Dyssynergy index
1.010
1.369
0.990–1.020
1.060–1.770
0.140
0.017
Multivariate analysis
...........................................................
HR
95% CI
P-value
1.289
1.096–1.519
0.002
...............................................................................................................................................................................
LVEF, left ventricular ejection fraction; GLS, global longitudinal strain; CI, confidence interval; HR, hazard ratio.
Figure 4 The incremental benefit of using sequential Cox models for the prediction of fatal ventricular arrhythmias. A model based on clinical
and conventional echocardiographic variables including age, gender, heart failure aetiology, and LVEF (x 2 ¼ 4.8) was improved by addition of GLS,
but not statistically significant (x2 ¼ 4.9; P ¼ 0.82), whereas improvement by the addition of the dispersion index (x 2 ¼ 8.9; P ¼ 0.04) and further
improvement by the addition of the dyssynergy index (x 2 ¼ 20.2; P , 0.005).
the utility of LV mechanical dispersion for patients with acute myocardial infarction with relatively preserved LVEF of ≥35%.8 In addition, other investigators have reported that LV mechanical
dyssynchrony (i.e. dispersion) improved after cardiac resynchronization therapy, which has been linked to reduction in the development
of fatal ventricular arrhythmias during long-term follow-up in severely depressed HF patients with a wide QRS complex, whereas
baseline LV mechanical dyssynchrony did not.11,18 LV myocardial
scar or fibrosis creates the substrate for ventricular reentrant tachycardia. It has been shown that LV fibrosis is present in HF patients
and that the extent of fibrosis correlates with the risk of arrhythmias. LV electrical and mechanical changes are closely related, and
the regional heterogeneity of LV contraction can be regarded as
the mechanical consequence of electrical changes and tissue abnormalities.19 Moreover, it has been shown that LV longitudinal myocardial function, rather than conventional global LV function,
assessed by speckle-tracking strain can be a more accurate marker
for detection of subtle changes in LV myocardial function as well as a
more accurate prognostic marker.20,21 LV longitudinal myocardial
function may also function as an accurate predictive marker of subtle
341
LV dyssynergy and dispersion for fatal ventricular arrhythmias
Figure 5 Representative cases of longitudinal speckle-tracking strain curves from the standard three apical views for patients with and without
ventricular arrhythmia.
LV fibrosis which can be the substrate of fatal ventricular arrhythmias. On the other hand, LV longitudinal myocardial function that
was determined as GLS was not independent predictor and incremental benefit for predicting fatal ventricular arrhythmias in this
study. Since GLS was candidate predictor of multivariate Cox proportional hazards analysis, it may be due to the low number of
patients compared with previous studies.7,8
In this study, we evaluated the capability to predict fatal ventricular arrhythmias of LV dyssynergy, which represents the heterogeneity of LV regional myocardial contraction, as well as of LV
dispersion, which represents the heterogeneity of timing of LV regional myocardial contraction. We could demonstrate that LV dyssynergy was an additive parameter for predicting fatal ventricular
arrhythmias, and that combined assessment of both LV dyssynergy
and dispersion can enhance predictive capability. Our group previously used three-dimensional speckle-tracking strain to quantify LV
dyssynergy in patients with idiopathic dilated cardiomyopathy and
narrow QRS complex.12 We showed the LV systolic function of
the septal and inferior walls was markedly reduced compared
with that of the free wall, and LV regional heterogeneity of systolic
function was proved to be an independent determinant of LV dyssynergy. We therefore speculated that the regional heterogeneity of
LV function, including both LV mechanical dispersion and dyssynergy, represents a fundamental arrhythmogenic risk due to inhomogeneous electrical conduction and repolarization. In addition
to the fibrotic substrate, electrical dispersion, which is caused by
areas of slow conduction leading to electrical instability, plays an important role in arrhythmogenesis. Moreover, myocardial fibrosis
and areas of slow electrical conduction will result in mechanical
changes in both timing and function of LV.
Clinical implications
Current guidelines recommend primary prevention ICD implantation for patients with LVEF ,35%.1 – 3,5,6 However, a number of
HF patients with LVEF .35% can suffer sudden cardiac death
from fatal ventricular arrhythmia despite the use of optimal medical
therapies. Thus, the selection of patients with mildly reduced LVEF
who are at high risk of fatal ventricular arrhythmias remains challenging, as is the indication of prophylactic ICD implantation for such
patients. We demonstrated the utility of the assessment of LV dyssynergy and dispersion for predicting fatal ventricular arrhythmias in
patients with LVEF ≥35% resulting from various HF aetiologies. Although a majority of the patients (79%) were for secondary prevention in this study, these findings point to the importance of such
evaluation in terms of the impact of risk stratification for such malignant arrhythmias in patients with mildly reduced LVEF.
Study limitations
This study covered a small number of patients in a single-centre
retrospective study, so that future studies of larger patient populations are needed to assess our findings for patients with mildly reduced LVEF. Patients with left bundle branch block and right
ventricular back-up pacing were excluded from the study because
of their major effect on LV dispersion. Although the study population still included patients with other morphologies of a wide QRS
complex such as right bundle branch block and inter-ventricular
conduction delay, overall results were similar even when such patients were excluded from the study. Finally, LV myocardial scar
or fibrosis creates the substrate for ventricular reentrant tachycardia and was associated with LV longitudinal strain.22 However, the
342
proof of the presence of scar and fibrosis by means of cardiac magnetic resonance imaging was not part of this study.
Conclusions
Combined assessment of LV dyssynergy and dispersion can enhance
predictive capability for fatal ventricular arrhythmias in patients with
LVEF ≥35%. These findings may have potential for better management of patients with mildly reduced LVEF.
Conflict of interest: None declared.
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