|Year : 2014 | Volume
| Issue : 2 | Page : 447-452
Relationship between cardiac mechanics evaluated by two-dimensional strain imaging and T-wave alternans in patients with hypertrophic cardiomyopathy
Hala M Badran, Naglaa F Ahmed, Ahmed A Attia
Department of Cardiology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
|Date of Submission||29-Jan-2014|
|Date of Acceptance||16-Feb-2014|
|Date of Web Publication||26-Sep-2014|
Ahmed A Attia
Aga Daqahlia Governorate
Source of Support: None, Conflict of Interest: None
The aim of this study was to assess the relationship between left ventricular (LV) deformational abnormalities, measured by two-dimensional strain imaging, and T-wave alternans (TWA) in hypertrophic cardiomyopathy (HCM).
HCM is a prevalent hereditary cardiac disorder linked to arrhythmia and sudden cardiac death. Microvolt TWA involves periodic beat-to-beat variation in the amplitude or the shape of the T wave in an ECG. In HCM, TWA has been linked to increased LV mass and used previously as noninvasive prognostic tools in the evaluation and patient risk stratification.
Patients and methods
The study group consisted of 40 consecutive HCM patients. The HCM group was compared with 33 age-matched and sex-matched healthy participants. All patients and control participants underwent 12-lead ECG, conventional echocardiographic examination, two-dimensional strain imaging, treadmill exercise test, and measurement of TWA, 24-h Holter monitoring.
Depending on TWA results, the patients were divided into two groups: TWA+ patients, and TWA- patients. There were no significant differences among the most conventional echocardiographic measures between TWA groups. Absolute values of esys, SRsys, SRe, and SRa were significantly smaller in HCM patients than the controls at rest and peak exercise (P < 0.001). LV dyssynchrony was evident in TWA+ patients at rest and amplified at peak stress compared with TWA- patients. TWA was closely correlated with LV dyssynchrony at rest and during exercise, and was inversely related to resting esys, SRsys, SRe, SRa, and the functional systolic and diastolic reserve as estimated by ∆ and percent of change of these variables.
The considerable association of myocardial dysfunction with TWA+ outcome provides important new evidence on arrhythmia vulnerability in HCM.
Keywords: ECG, hypertrophic cardiomyopathy, left ventricular, T-wave alternans
|How to cite this article:|
Badran HM, Ahmed NF, Attia AA. Relationship between cardiac mechanics evaluated by two-dimensional strain imaging and T-wave alternans in patients with hypertrophic cardiomyopathy. Menoufia Med J 2014;27:447-52
|How to cite this URL:|
Badran HM, Ahmed NF, Attia AA. Relationship between cardiac mechanics evaluated by two-dimensional strain imaging and T-wave alternans in patients with hypertrophic cardiomyopathy. Menoufia Med J [serial online] 2014 [cited 2019 Nov 21];27:447-52. Available from: http://www.mmj.eg.net/text.asp?2014/27/2/447/141725
| Introduction|| |
Hypertrophic cardiomyopathy (HCM) is a prevalent hereditary cardiac disorder linked to arrhythmia and sudden cardiac death, although the causes of HCM have been identified as genetic mutations in the cardiac sarcomere . Calcium imaging indicated dysregulation of Ca 2+ cycling and elevation in intracellular Ca 2+ , which are central mechanisms for disease pathogenesis and development of ventricular tachyarrhythmias ,.
Microvolt T-wave alternans (TWA) is thought to represent abnormalities in intracellular calcium handling that may predispose to repolarization alternans as one step to ventricular tachyarrhythmias ,.
In HCM, TWA has been linked to increased left ventricular (LV) mass  and used previously as noninvasive prognostic tools in the evaluation and patient risk stratification ,. However, these studies focused merely on sudden cardiac death as an outcome of electrophysiological instability. To the best of our knowledge, no studies have been applied to examine the relationship of TWA, as a marker of repolarization abnormality, to cardiac mechanical properties in HCM patients. Accordingly, the present study was designed to test whether TWA is related to mechanical dysfunction and LV dyssynchrony, using two-dimensional (2D) strain imaging in patients with HCM.
| Patients and methods|| |
The study group consisted of 40 consecutive HCM patients referred to our echocardiographic laboratories for risk stratification. The HCM group was compared with 33 age-matched and sex-matched healthy participants without detectable cardiovascular risk factor or receiving any medication.
Patients with LV outflow tract obstruction of at least 30 mmHg at rest or provoked during exercise, patients with ejection fraction less than 50%, patients with prior myectomy or alcohol septal ablation, ICD, diabetes mellitus, evidence of coronary artery disease, atrial fibrillation, lung disease, and exercise-limiting diseases were excluded from study .
All patients and control participants underwent 12-lead ECG, conventional echocardiographic examination, 2D strain imaging, treadmill exercise test, and measurement of TWA, 24-h Holter monitoring.
Echocardiographic images were obtained in the parasternal, long-axis and short-axis, apical two-chamber, three-chamber, and four-chamber views. Esaote Mylab Gold ultrasound system (Esaote S.p.A., Florence, Italy) equipped with a 2-3 MHz phased-array transducer was utilized. LV dimensions and wall thickness, ejection fraction, and left atrial (LA) diameter and volume were measured in accordance with the recommendations of the American Society of Echocardiography . Continuous-wave Doppler was used to diagnose LV outflow tract obstruction. Peak early (E) and late (A) transmitral filling velocities were measured. Early diastolic annular (E a ) velocity was obtained by placing a tissue Doppler sample volume at the lateral mitral annulus in the apical four-chamber view. The E/E a ratio was calculated.
Analysis of left ventricular deformation
Strain measurement was based on the vector velocity imaging. The global myocardial deformation was evaluated from standard 2D images at frame rate (70 ± 20 frames/s) at rest and adjusted depending on the heart rate to 92 ± 23 frames/s during exercise. Tracking and strain calculations were performed with the software package Esaote-X-Strain based on previously validated algorithm . Peak longitudinal systolic strain (esys), systolic strain rate (SRsys), early and atrial diastolic strain rate (SRe and SRa) in the basal, mid, and apical segments of septal, lateral, anterior, anteroseptal, and inferior wall were measured and averaged to calculate the global longitudinal deformation. The differences between resting and peak exercise values were analyzed (D) and the functional reserve (% change from rest to stress) is calculated as D/resting value.
To estimate LV mechanical dyssynchrony, time to peak strain (TTP) was measured from regional longitudinal strain curves for each ventricular segment, as time from the beginning of Q wave of ECG to the time to peak esys . LV dyssynchrony was defined as the standard deviation of the averaged time to peak strain (TTP-SD) . The stress echocardiogram images were acquired immediately at peak exercise (within 1 min), and focused on analysis of LV deformation.
Careful skin preparation and high-resolution electrodes were used to minimize noise. ECG leads were placed at the standard 12-lead positions and in an orthogonal X, Y, Z configuration. Multistage symptoms limiting exercise test was conducted on a motorized treadmill (My Formula, RAM model 770M; Esaote S.p.A., Switzerland) according to Bruce protocol. Exercise test was interrupted promptly when age-related maximum heart rate was reached or severe hypertension developed. Exercise capacity is determined by:
- Metabolic equivalent,
- Exercise duration,
- Rate pressure product, which is a measure of myocardial oxygen uptake during clinical exercise testing.
It is estimated by the product of maximal achieved heart rate and systolic blood pressure.
T-wave alternans measurement
TWA measurements were made with the CH2000 system (Cambridge Heart), utilizing a spectral analysis designed to allow detection of fluctuating voltage in every other heart beat in the microvolt range of amplitude.
A TWA+ test was defined when sustained alternans voltage was at least 1.9 mV, with an alternans ratio greater than 3.0 in any orthogonal lead, or two consecutive precordial leads during exercise, with an onset heart rate of less than 110 beats/min for at least 1 min. The test was considered negative if alternans was absent during a sustained interval of exercise at a heart rate of at least 105 beats/min. If the result did not meet the positive or negative criteria, it was considered indeterminate .
At the study entry, all patients underwent routine two-channel (CM1 on channel 1 and V2 on channel 2) 24-h ambulatory ECG monitoring (Marquette Electronics, Milwaukee, Wisconsin, USA). All arrhythmias including supraventricular and ventricular origin were analyzed. Ventricular tachycardias were classified as sustained or nonsustained. Nonsustained ventricular tachycardia (NSVT) was defined as at least three consecutive ventricular beats at a rate of at least 120 beats/min, lasting for less than 30 s.
Statistical analysis was performed using the IBM SPSS Statistics for Mac, version 21.
| Results|| |
Depending on TWA results, the patients were divided into two groups: TWA+: 16 patients (40%) with positive/indeterminate results; and TWA-: 24 patients (60%) with negative results.
There were no significant differences among the most conventional echocardiographic measures between TWA groups. All HCM patients had larger LA volume, smaller LV end-systolic diameter, greater LV wall thickness, LV mass index, and higher E/E a ratio compared with control (P < 0.0001).
Hemodynamics during exercise
The achieved level of exercise was maximal in all control participants and in seven (44%) patients with TWA+ and 16 (67%) patients with TWA- (P < 0.01). More arrhythmias (premature ventricular complexes and NSVT) were provoked and less exercise capacity in TWA+ compared with TWA- during peak stress [Table 1].
During Holter monitoring, ventricular arrhythmias were significantly more common in TWA+ patients [Table 1]. Notably, there was a significantly higher frequency of premature ventricular complexes, NSVT in TWA+ compared with TWA- patients.
Left ventricular deformation at rest and exercise in studied group
Absolute values of esys, SRsys, SRe, and SRa were significantly smaller in HCM patients than controls at rest and peak exercise (P < 0.001). Desys was also less in HCM patients, and the functional reserve (D/rest value) was also reduced. There was more reduction in esys by −27 ± 31% during peak exercise in TWA+ compared with −19 ± 26% in TWA- group and improvement by 17 ± 6% in control participants (P < 0.001) [Table 2].
|Table 2: Left ventricular deformation at rest and exercise in the studied group|
Click here to view
The absolute value of SRsys at peak stress was significantly smaller in HCM patients compared with controls (P < 0.001). Similarly, SRsys was significantly reduced at peak exercise by −13 ± 26% TWA+, whereas increased by 15 ± 23% in TWA- patients. Pertaining to diastolic function, the functional reserve during early diastole as expressed by SRe was significantly reduced in the TWA+ group by -7.7 ± 2% compared with improvement by 20 ± 32% in the TWA- group and 23 ± 7% in controls (P < 0.001). Similarly, there was lower augmentation of SRe in TWA+ by 12 ± 36% compared with increase by 29 ± 41 in TWA- patients and 31 ± 14% in controls (P < 0.001) [Figure 1].
Left ventricular dyssynchrony
LV dyssynchrony was evident in TWA+ patients at rest and amplified at peak stress (TTP-SD: 65 ± 31, 68 ± 40 ms) compared with TWA- patients (TTP-SD: 42 ± 24, 48 ± 35 ms) (P < 0.0001), respectively. If TTP-SD greater than 44 ms (mean+2 SD of age-matched controls) was defined as LV dyssynchrony, upon stress, the prevalence of systolic dyssynchrony was markedly higher in the TWA+ group [10 (62.5%)] compared with [nine (37.5%)] in TWA- group (P < 0.001).
In all the 73 participants, including healthy volunteers, the TWA outcome negatively correlated with age, functional capacity, LV maximal wall thickness, LV mass index, LA volume, and severity of mitral regurge (P < 0.0001) [Table 3]. In addition, TWA was closely correlated with LV dyssynchrony at rest and during exercise and was inversely related to resting esys, SRsys, SRe, SRa, and the functional systolic and diastolic reserve as estimated by ∆ and percent of change of these variables [Table 3]. However, when HCM patients taken separately, TWA was only closely related to EX esys (r = 0.264, P<0.02) and TTP-SD (r = 0.435, P < 0.003) [Figure 2] and [Figure 3]. Variables with significant relation to TWA were used to design a stepwise forward logistic regression model to calculate the independent predictors of TWA greater than 1.9. From all clinical and echocardiographic parameters, exercise strain (esys) (b: 0.456, P = 0.03), and early diastolic strain rate (SRe) (b: 0.441, P < 0.01), are independent predictors for TWA+.
|Table 3: Correlation of clinical and deformation variables to T-wave alternans outcome in the study population|
Click here to view
| Discussion|| |
In the current study, we demonstrate a significant relationship between LV deformational abnormalities measured by 2D strain imaging, and TWA in HCM. TWA+ outcome links with not only mechanical function but also electromechanical incoordination as reflected by LV dyssynchrony and more aggressive phenotype. HCM patients with TWA+ display increased arrhythmic events and remarkably reduce their exercise capacity compared with TWA-, the lower functional capacity was significantly correlated to TWA outcome.
T-wave alternans and hypertrophic cardiomyopathy phenotype
In current study, the extent of hypertrophy, severity of mitral regurgitation, LV outflow tract gradient, and LA volume in HCM are related directly to the TWA, and potentially reflect the arrhythmic susceptibility with aggressive phenotype. Moreover, our results expand on the concept that microvolt TWA has the ability to detect significant heterogeneity in the progression of repolarization, possibly reflecting the underlying structural abnormalities ,.
Puntmann et al.  ascertained the relation between phenotype and patient risk, where regional contribution of hypertrophy in HCM populations adds to arrhythmia susceptibility. In their study, HCM patients with arrhythmic events display remarkably greater overall maximal LVWT, and patients with raised maximal LVWT had significantly increased risk of VTAs. Thus, LVWT provided a meaningful contribution to patient risk, even in the absence of other traditional risk factors.
T-wave alternans and left ventricular mechanics
The role of noninvasive imaging in the identification of high-risk HCM patients remains an evolving field of crucial clinical utility. Using speckle tracking, reduced myocardial contractility has been demonstrated in HCM, and regional heterogeneity of LV function has also been observed in the sizeable series of patients ,.
This study provides important new evidence that reduced esys and SR in the TWA+ group, and diminished functional systolic and diastolic reserve of the hypertrophied myocardium in HCM may represent an electrophysiological substrate for proarrhythmia.
Kon-No et al.  investigated the relation between TWA and myocardial damage in 28 patients with HCM and 29 patients with hypertensive LV hypertrophy. TWA was significantly greater in HCM with severe disarray and fibrosis than in HCM with mild disarray and in hypertensive LV hypertrophy. They concluded that a TWA+ test is probably related to abnormal myocardial arrangement and it may reflect electrical instability of the myocardium.
Kuroda et al.  evaluated the relationship between TWA and histopathologic changes quantitatively and genetic mutation in 22 HCM patients. They reported that HCM with severe histopathologic changes were TWA+, and of the histopathologic changes that they examined disarray closely correlated with TWA.
Maron  and McKenna and Camm  suggested that disorganized cells dispersed throughout the LV wall are predisposed toward disordered electrical depolarization and repolarization, and constitute an arrhythmogenic myocardial substrate.
Relation of T-wave alternans to left ventricular dyssynchrony
In this study, TWA+ outcome, a surrogate marker of arrhythmia vulnerability, links with increased LV dyssynchrony; it further correlated directly to TWA+ in the HCM group.
Kutyifa et al. , evaluated the relationship between LV dyssynchrony and the risk of ventricular tachycardias or VF in patients enrolled in the MADIT-CRT trial. In their study, CRT-induced improvement in LV dyssynchrony was associated with significant reduction in ventricular arrhythmias in heart failure patients with LBBB.
| Conclusion|| |
TWA in HCM is related to underlying mechanical dysfunction, LV dyssynchrony, and more severe phenotype. The considerable association of myocardial dysfunction with TWA+ outcome provides important new evidence on arrhythmia vulnerability in HCM. However, whether decreased LV deformation reflects regional fibrosis and its direct involvement in arrhythmia vulnerability and/or TWA outcomes remains to be ascertained in studies.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]