Optimal role of rest and stress echocardiography in cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) is an effective treatment for patients with advanced heart failure (HF), depressed left ventricular (LV) function and wide QRS complex. CRT improves symptoms, exercise capacity, LV function and reduces HF hospitalization and mortality rates. However, in parallel with the impressive results for CRT in several large trials, a consistent percentage of patients do not respond to CRT when the traditional patient selection criteria are applied. The prevalence of non-responders is about 30% when clinical end-points are considered but it is much higher (≥ 45%) if echocardiographic end-points are used. Reduction of the number of non-responders is currently one of the main challenges in the field of CRT. Response to CRT has been related to the presence of cardiac dyssynchrony prior to implantation. LV dyssynchrony can be evaluated using different echocardiographic methods. When LV dyssynchrony is added to traditional patient selection criteria, the prevalence of non-responders decreases considerably. However, the value of LV dyssynchrony to predict response to CRT has shown some limitations and is possibly not sufficient. CRT response is clearly modulated by several factors. Regional and global myocardial viability are key pieces of the puzzle as well as the presence and severity of mitral regurgitation (MR). Echocardiography thus plays an important role in the care of HF patients treated with cardiac resynchronization therapy and is useful to assess acute and long-term beneficial effects of CRT. Numerous recent published reports have used echocardiographic techniques to potentially help patient selection for CRT prior to implantation and to optimize device settings afterwards. These topics are discussed in this review.     

The role of echocardiography in cardiac resynchronization therapy

Echocardiography is the most important imaging tool for managing heart failure patients. With the advent of cardiac resynchronization therapy (CRT), its role has been broadened by data pertaining to patient selection, optimization of device settings, and outcome assessment. Beyond ejection fraction determination, echocardiographic methods that measure tissue velocity and strain may have the capability to determine degree of mechanical dyssynchrony and possibly predict likelihood of benefit with CRT. After implantation (as the ventricles are fully paced, adjusting the atrioventricular delay [atrioventricular optimization]), the timing of the right ventricular and left ventricular lead stimulation (ventricular-ventricular optimization) to achieve maximal cardiac filling or ejection may be clinically important. Atrioventricular and ventricular-ventricular optimization rely on echocardiography to determine optimal values. In long-term follow-up, serial measurement of left ventricular volume has significant correlation with mortality and is a reasonable measure of successful CRT; echocardiography is uniquely suited for this purpose.     

Three-dimensional echocardiography for optimization of cardiac resynchronization therapy

We read with great interest the nice review by Stanton et al.¹concerning techniques for optimization of cardiac resynchronizationtherapy (CRT). In addition to the methods discussed by     

Myocardial tissue Doppler echocardiography and cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) is a promising technique for patients with end-stage, drug-refractory heart failure. Still 20-30% of the patients treated with CRT do not respond. Accordingly, the current selection criteria need to be refined, and it appears that demonstration of left ventricular dyssynchrony may be mandatory for response to CRT. Novel echocardiographic methods are currently investigated to detect left ventricular dyssynchrony and thereby improve the selection of candidates for CRT. In this brief review, these techniques will be discussed.     

超声心动图在心脏再同步化治疗优化中的应用研究

目的:探讨超声心动图评价和优化心脏再同步化治疗(CRT)的价值,总结超声心动图应用于CRT优化的关键指标及方法学.方法:CRT治疗1～3年患者23例,优化组(17例)设定房室间期(AVD)在80～180ms,以20 ms逐次增减,比较不同AVD下超声心动图指标的即刻差异;6例未优化患者作为对照组.对优化组和对照组优化即刻/首次检查与随访6个月时各项指标进行比较.结果:优化组最佳AVD间期分布在100～140ms,取值跨度为80～160 ms,个体差异明显;优化后获得即刻血流动力学改善:左心室舒张充盈时间(LVFT)、二尖瓣流速时间积分(VTI-MV)、左心室收缩期压力上升速率(dp/dt)增加,二尖瓣反流口面积(MV-EROA)、心功能指数(Tei指数)降低(均P＜0.05).优化组优化后6个月血流动力学和临床指标进一步改善:Tei指数和纽约心功能分级(NYHA)分级降低,dp/dt和6min步行试验增加,与优化即刻比较,均P＜0.05,对照组6个月后仅Tei指数优于首次检查(P＜0.05),其他指标均差异无统计学意义(P＞0.05).结论:超声心动图指导CRT优化可使CRT患者获得即刻和长期的血流动力学和临床状态改善,该方法有可能成为改进CRT疗法的重要手段,有良好应用前景.     

Role of echocardiography to determine candidacy for cardiac resynchronization therapy

PURPOSE OF REVIEW: Cardiac resynchronization therapy is a great benefit to many patients with severe symptomatic heart failure, wide QRS duration, and depressed left ventricular ejection fraction. Although the widened QRS is a surrogate for delayed mechanical activation, known as dyssynchrony, imaging techniques have identified a subset of patients with widened QRS who do not have dyssynchrony and accordingly do not respond to cardiac resynchronization therapy. RECENT FINDINGS: Many echocardiographic techniques have emerged to quantify regional dyssynchrony, in hopes of improving patient selection and response rate to cardiac resynchronization therapy. Principal methods include M-mode septal to posterior wall motion delay, pulsed Doppler measures of left ventricular ejection in relation to right ventricular ejection, diastolic filling time as a ratio of cycle length, and several tissue Doppler imaging techniques to assess intraventricular opposing wall delay or dispersion of time to peak velocities. Although the simple and straightforward methods are easy to reproduce, they are modest in predictive value. In contrast, tissue Doppler imaging and other more recent techniques have higher predictive value, but are technically much more complex and require training and experience. SUMMARY: This field continues to evolve and further data are needed to precisely define the appropriate role of echocardiographic dyssynchrony information in patient selection for cardiac resynchronization therapy.     

Effect of cardiac resynchronization therapy on diastolic dysfunction as assessed by transthoracic two-dimensional Doppler echocardiography

Cardiac resynchronization therapy (CRT) in patients with left ventricular systolic dysfunction and electrical dyssynchrony has been shown to improve morbidity and mortality. Improvement in diastolic dysfunction may contribute to these results. In this retrospective study, the authors assessed the effect of CRT on the E/A ratio and mitral valve deceleration time, which are commonly utilized parameters of left ventricular diastolic function. In 13 patients (aged 62 +/- 11.3 years), the E/A ratio increased from 1.17 +/- 0.58 to 1.49 +/- 0.66 (p = nonsignificant) and the mitral valve deceleration time increased from 178.48+/-57.71 milliseconds to 227.70 +/- 76.18 milliseconds (p = 0.054) post-CRT. In patients without mitral regurgitation, there was a significant increase in E/A ratio, from 1.22 +/- 0.4 to 1.86 +/- 0.47 (p = 0.025), but no significant change in the mitral valve deceleration time post-CRT was observed. These data suggest improvement in diastolic dysfunction as assessed by routine two-dimensional echocardiography in patients who receive CRT devices.     

Myocardial gene expression in heart failure patients treated with cardiac resynchronization therapy responders versus nonresponders.

OBJECTIVES: We studied whether functional improvement after cardiac resynchronization therapy (CRT) is associated with reversal of the heart failure (HF) gene program. BACKGROUND: Cardiac resynchronization therapy improves exercise tolerance and survival in patients with advanced congestive HF and dyssynchrony. METHODS: Twenty-four patients referred for CRT underwent left ventricular (LV) endomyocardial biopsies immediately before CRT implantation (baseline). In addition, 17 of them underwent LV endomyocardial biopsy procurement 4 months later (follow-up). In 6 control patients with normal LV function, LV biopsies were obtained at the time of coronary artery bypass grafting. The LV messenger ribonucleic acid (mRNA) levels of contractile and calcium regulatory genes were measured by quantitative real time polymerase chain reaction and normalized for glyceraldehyde 3-phosphate dehydrogenase (GAPDH). The HF patients showing an improvement in New York Heart Association (NYHA) functional class by >1 score and a relative increase in LV ejection fraction > or =25% at 4 months after CRT were considered as responders. RESULTS: The HF patients were characterized by lower LV mRNA levels of alpha-myosin heavy chain (alpha-MHC), beta-myosin heavy chain (beta-MHC), sarcoplasmic reticulum calcium ATPase 2alpha (SERCA), phospholamban (PLN), and higher brain natriuretic peptide (BNP) mRNA levels as compared with control subjects. Responders to CRT (n = 11) showed an increase in LVEF (p < 0.001), a decrease in left ventricular end-diastolic diameter (p = 0.003), and NYHA functional class (p = 0.002), and a reduction in N-terminal proBNP levels (p = 0.032) as compared with baseline. This was associated with an increase in mRNA levels of alpha-MHC (p = 0.035), SERCA (p = 0.032), a decrease in BNP mRNA levels (p = 0.002), and an increase in the ratio of alpha-/beta-MHC (p = 0.018) and SERCA/PLN (p = 0.012). No significant changes in molecular profile were observed in nonresponders. CONCLUSIONS: In HF patients with electromechanical cardiac dyssynchrony, functional improvement related to CRT is associated with favorable changes in established molecular markers of HF, including genes that regulate contractile function and pathologic hypertrophy.     

Effects of cardiac resynchronization therapy on right ventricular function--evaluation with tissue Doppler echocardiography.

INTRODUCTION AND OBJECTIVE: Ventricular resynchronization therapy improves cardiac function in patients (pts) with dilated cardiomyopathy and intraventricular conduction disturbances. The effects of ventricular resynchronization on right ventricular function have been poorly studied. Tricuspid annular motion can be studied with tissue Doppler echocardiography, which enables quantitative assessment of right ventricular function. The aim of this study was to evaluate the effects of ventricular resynchronization on right ventricular function with pulsed tissue Doppler. PATIENTS: We studied ten pts, eight male, mean age 65 +/- 10 years, with dilated cardiomyopathy, intraventricular conduction disturbances and heart failure, New York Heart Association functional class III or IV. Five pts had coronary artery disease and the others idiopathic dilated cardiomyopathy. All pts had an implanted cardioverter-defibrillator with ventricular resynchronization. METHODS: Before and one month after device implantation right ventricular function was evaluated with pulsed wave tissue Doppler study of tricuspid annular motion. The maximum velocity of the S wave (MV-S), E wave (MV-E), and A wave (MV-A), E/A ratio, isovolumetric contraction time (IVCT) and ejection time (ET) were determined. Right ventricular size and left ventricular ejection fraction (EF) were measured. Functional class before and after implantation was assessed. RESULTS: MV-S, MV-E and MV-A did not change significantly. The E/A ratio decreased significantly (p = 0.017). There were no differences in IVCT and ET, nor in right ventricular size before and after resynchronization. EF improved in all but one patient (p = 0.003). All pts had an improvement in functional class, except the one without increased EF. CONCLUSIONS: Ventricular resynchronization therapy does not appear to have a deleterious effect on right ventricular function in pts with dilated cardiomyopathy and intraventricular conduction disturbances. The main beneficial effect of this type of therapy appears to be improvement in left ventricular function.     

Exercise stress echocardiography is superior to rest echocardiography in predicting left ventricular reverse remodelling and functional improvement after cardiac resynchronization therapy

Aims: Cardiac resynchronization therapy (CRT) improves functionalcapacity and survival in heart failure. However, one-third ofpatients fail to respond to CRT. Resting left ventricular (LV)dyssynchrony assessed by echocardiography (ECHO) showed discordantresults in identifying CRT responders. LV dyssynchrony can totallychange during exercise. Aim of this study was to evaluate whetherexercise dyssynchrony could select responders to CRT. Methods and results: Sixty-four patients scheduled for CRT implantation performedbicycle exercise ECHO in semi-supine position on an exercisetilting table before and 6 months after CRT implantation. TissueDoppler imaging (TDI) was acquired both at rest and during exerciseto detect LV mechanical dyssynchrony. Predictive values forCRT response were 70% for rest TDI and 89% for exercise TDI(P = 0.01). Exercise LV dyssynchrony was the only parameterindependently associated with follow-up improvement of restejection fraction and LV volume during multivariable analysis(P < 0.001). Functional improvement at 6-min walking testwas statistically higher in patients with exercise dyssynchrony(P = 0.005), and not different considering rest dyssynchrony(P = 0.30). Conclusion: Exercise intraventricular dyssynchrony assessed by exerciseTDI ECHO is a strong independent predictor of CRT response.It could be used to select candidates for CRT, thus reducingineffective implantations of biventricular pacemakers.     

超声心动图预测心脏再同步治疗反应性的研究进展

慢性心力衰竭的治疗一直是心脏科医生每天面对的难题,尽管目前药物治疗已经取得了很大进展,仍然有相当多的患者疗效不佳.在这种情况下心脏再同步治疗(cardiac resynchronization therapy,CRT)即左右心室同步起搏,由于其卓越的疗效得到了欧洲和美国心力衰竭治疗指南的一致推荐.     

Left intraventricular myocardial deformation dyssynchrony identifies responders to cardiac resynchronization therapy in patients with heart failure.

AIMS: We tested the hypothesis that dyssynchrony of left ventricular (LV) myocardial deformation evaluated by ultrasound can predict success of cardiac resynchronization therapy (CRT) in patients with heart failure (HF). METHODS AND RESULTS: Thirty-seven patients with dilated cardiomyopathy, New York Heart Association class III-IV, LV ejection fraction (EF) < or =35%, QRS > 120 ms were studied before, at pre-discharge, and after 3 and 6 months of CRT. The M-mode peak septal-to-posterior wall motion and thickening delay (SPWMD and SPWTD, ms) and the standard deviation of the averaged time-to-peak strain (TPS-SD, ms) of 12 middle and basal LV segments obtained from the three standard apical views were calculated. Responders were defined at month 6 by > or =20% EF increase and/or > or =15% end-systolic volume (ESV) decrease with respect to baseline. Baseline SPWTD (not SPWMD) and TPS-SD differentiated responders from non-responders with good accuracy and reproducibility. A value > or =194 ms for SPWTD and > or =60 ms for TPS-SD was significantly associated with responder identification. Baseline dyssynchrony parameters correlated significantly with EF (r = 0.53 for SPWTD and r = 0.86 for TPS-SD) and ESV variations (r = -0.42 for SPWTD and r = -0.73 for TPS-SD). CONCLUSION: Patients with chronic HF should undergo ultrasound evaluation to quantify dyssynchrony of LV myocardial deformation, which would help identifying CRT responders.     

超声心动图预测心脏再同步治疗反应性的研究进展

慢性心力衰竭的治疗一直是心脏科医生每天面对的难题,尽管目前药物治疗已经取得了很大进展,仍然有相当多的患者疗效不佳。在这种情况下心脏再同步治疗（cardiacresynch ronizationtherapy,CRT）即左右心室同步起搏,由于其卓越的疗效得到了欧洲和美国心力衰竭治疗指南的一致推荐。