Cardiac resynchronization with sequential biventricular pacing for the treatment of moderate-to-severe heart failure.

OBJECTIVES: The InSync III study evaluated sequential cardiac resynchronization therapy (CRT) in patients with moderate-to-severe heart failure and prolonged QRS. BACKGROUND: Simultaneous CRT improves hemodynamic and clinical performance in patients with moderate-to-severe heart failure (HF) and a wide QRS. Recent evidence suggests that sequentially stimulating the ventricles might provide additional benefit. METHODS: This multicenter, prospective, nonrandomized, six-month trial enrolled a total of 422 patients to determine the effectiveness of sequential CRT in patients with New York Heart Association (NYHA) functional class III or IV HF and a prolonged QRS. The study evaluated: whether patients receiving sequential CRT for six months experienced improvement in 6-min hall walk (6MHW) distance, NYHA functional class, and quality of life (QoL) over control group patients from the reported Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial; whether sequential CRT increased stroke volume compared to simultaneous CRT; and whether an increase in stroke volume translated into greater clinical improvements compared to patients receiving simultaneous CRT. RESULTS: InSync III patients experienced greater improvement in 6MHW, NYHA functional class, and QoL at six months compared to control (all p < 0.0001). Optimization of the sequential pacing increased (median 7.3%) stroke volume in 77% of patients. No additional improvement in NYHA functional class or QoL was seen compared to the simultaneous CRT group; however, InSync III patients demonstrated greater exercise capacity. CONCLUSIONS: Sequential CRT provided most patients with a modest increase in stroke volume above that achieved during simultaneous CRT. Patients receiving sequential CRT had improved exercise capacity, but no change in functional status or QoL.     

心脏再同步治疗:双心室起搏还是希氏-浦肯野系统起搏?

希氏-浦肯野系统(希浦系统)起搏是近年出现的除传统双心室同步起搏外同样能达到心脏再同步治疗(CRT)的新方法。本文阐述了2种方法达到CRT的途径、机制、临床证据及各自的利弊,并对现阶段CRT方式的选择提出了建议。     

Cardiac resynchronization therapy for heart failure: biventricular pacing and beyond

In the early 1990s, attempts at treating patients with dilated cardiomyopathy and end-stage heart failure by using right-sided, dual-chamber pacing met with equivocal results. Although initially discouraging, this work did provide further insight into the electromechanical consequences of advanced heart failure and suggested that atrial-synchronized biventricular pacing, or cardiac resynchronization therapy, might provide better and more consistent symptomatic and hemodynamic improvement. Several studies have recently validated the safety and efficacy of cardiac resynchronization therapy in advanced heart failure. Data from these studies have shown statistically significant improvements in left ventricular ejection fraction, New York Heart Association class, exercise tolerance, and quality of life. Observed reductions in morbidity and mortality await confirmation from ongoing large-scale outcomes studies. This article reviews the evolution of pacing in heart failure and discusses the underlying mechanisms that are potentially responsible for the improvement seen in patients receiving cardiac resynchronization therapy. In addition, the results of recently completed clinical trials, as well as the status of ongoing clinical trials, are reviewed.     

Interventricular delay interval optimization in cardiac resynchronization therapy guided by echocardiography versus guided by electrocardiographic QRS interval width

Present devices for cardiac resynchronization therapy offer the possibility of tailoring the hemodynamic effect of biventricular pacing by optimization of the interventricular delay (VV) beyond atrioventricular (AV)-interval optimization. It was not yet defined whether a QRS width-based strategy may be a helpful tool for echocardiography for device programming. The aim of the study was to investigate the relation between VV-interval optimization guided by echocardiography and guided by QRS interval width. One hundred six patients with a cardiac resynchronization therapy device for > or =3 months were enrolled. All patients underwent echocardiographic AV and VV delay optimization. The AV interval was optimized according to the E wave-A wave (EA) interval and left ventricular filling time. At the optimal AV delay, VV optimization was performed by measuring the aortic velocity time integral at 5 different settings: simultaneous right and left ventricle output, left ventricle pre-excitation (left ventricle + 40 and 80 ms, respectively), and right ventricle pre-excitation (right ventricle + 40 and 80 ms, respectively). A 12-lead electrocardiogram was recorded and QRS duration was measured in the lead with the greatest QRS width. The electrocardiographic (ECG)-optimized VV interval was defined according to the narrowest achievable QRS interval among 5 VV intervals. The echocardiographic-optimized VV interval was left ventricle + 40 ms in 28 patients, left ventricle + 80 ms in 15 patients, simultaneous in 46 patients, right ventricle + 40 ms in 14 patients, and right ventricle + 80 ms in 3 patients. Significant concordance (kappa = 0.69, p <0.001) was found between the echocardiographic- and ECG-optimized VV interval. In conclusion, significant concordance appeared to exist during biventricular pacing between VV programming based on the shortest QRS interval at 12-lead ECG pacing and echocardiographic-guided VV-interval optimization. A combined ECG- and echocardiographic approach could be a less time-consuming solution in performing this operation.     

Calculation of effective VV interval facilitates optimization of AV delay and VV interval in cardiac resynchronization therapy

BACKGROUND: In hearts with left bundle branch block (LBBB), both atrioventricular (AV) delay and interventricular (VV) interval determine left ventricular (LV) pump function in cardiac resynchronization therapy (CRT). The optimal combination of AV delay and VV interval currently is determined by extensive hemodynamic testing. OBJECTIVES: The purpose of this study was to investigate whether the effective VV interval (VV(eff)) can be used to optimize AV delay and VV interval. METHODS: In eight canine hearts with chronic LBBB, LV pacing was performed at various AV delays as well as biventricular pacing at multiple AV delays and VV intervals. LV pump function was assessed from LVdP/dt(max) and stroke volume (conductance catheter). Interventricular asynchrony was calculated from the timing difference between upslope of LV and RV pressure curves. VV(eff) was defined as the time delay between activation of the RV apex and LV lateral wall, irrespective of the source of RV activation (RV pacing or intrinsic conduction). VV(eff) was determined from pacemaker settings and surface ECGs recorded during biventricular pacing at various AV delays (positive values denote LV preexcitation). RESULTS: For all animals, the relationship between VV(eff) and LVdP/dt(max) as well as LV stroke work was parabolic. Maximal improvement in LVdP/dt(max) was similar during LV pacing, simultaneous biventricular pacing, and sequential biventricular pacing and was obtained at similar values of VV(eff). VV(eff) was strongly correlated with interventricular asynchrony (R = 0.97 +/- 0.03). Optimum LVdP/dt(max) occurred at VV(eff) ranging from -24 to 12 ms (mean -6 +/- 13 ms). For each experiment, the optimal VV(eff) was virtually equal to the value halfway between its minimum (during LV pacing at short AV delay) and maximum (during LBBB) value (R = 0.91). CONCLUSION: Use of VV(eff) facilitates determination of the best combination of AV delay and VV interval during biventricular pacing. For each individual heart, VV(eff), resulting in optimum LV pump function, can be estimated using surface ECGs recorded during biventricular pacing.     

Long-term follow-up of atrioventricular delay optimization in patients with biventricular pacing.

BACKGROUND: Atrioventricular (AV) delay optimization may be important in patients with biventricular pacing and the optimal AV delay can be predicted using Doppler echocardiography and the formula: optimal AV delay = AV delay-the interval between the end of A wave and complete closure of the mitral valve when the AV delay is set at slightly prolonged AV delay. METHODS AND RESULTS: In the present study the efficacy of this method was evaluated in 5 patients (67.4+/-8.0 (SD) years old) with biventricular pacing. Cardiac output (CO) and diastolic filling time were measured by Doppler echocardiography. When the AV delay was set at the predicted optimal AV delay -25 ms, the predicted optimal AV delay (133+/-66 ms) and predicted optimal AV delay + 25 ms, the respective CO were 4.5+/-0.9, 5.3+/-1.0, 4.8+/-1.0 L/min (p<0.05, ANOVA) and the diastolic filling times were 364 +/-100, 373+/-105, 335+/-84 ms (p<0.05, ANOVA). Congestive heart failure improved from New York Heart Association class 3.6+/-0.5 to 1.4+/-0.5 (p<0.001). CONCLUSIONS: AV delay optimization is important in patients with biventricular pacing and can be easily achieved by the new method.     

Triple-site biventricular pacing in patients undergoing cardiac resynchronization therapy: a feasibility study.

AIMS: To evaluate implantation safety and efficiency of triple-site (double left-single right) cardiac resynchronization therapy (CRT) and to assess the outcome of this procedure. METHODS AND RESULTS: Twenty-six patients with New York Heart Association (NYHA) class III-IV, left ventricular ejection fraction (EF) < or = 35%, and QRS > or = 120 ms underwent triple-site CRT. Procedural course and complications were analysed. NYHA class, QRS duration, echocardiographic parameters, peak oxygen consumption (VO(2)max), and 6 min walking distance (6MWD) were assessed at baseline and after 3 months. Responders were defined by survival, by no re-hospitalization for heart failure, and by >10% EF, VO(2)max, and 6MWD increase. Implantation was successful in 22 patients (84.6%). Procedure duration (199.1 min) and fluoroscopy time (38.7 min) were higher than in standard procedures. Two clinically silent coronary sinus dissections occurred intra-operatively; one phrenic nerve stimulation and one pocket infection were observed during follow-up. After 3 months of CRT, a significant reduction (P < 0.05) of NYHA class, increment of VO(2)max, 6MWD, EF, and improvement of indices of dyssynchrony were observed. Response rate in the studied group was 95.4%. CONCLUSION: Triple-site resynchronization appears to be a safe and efficient treatment method, with high response rate. Further studies are needed to evaluate the role of this pacing mode in CRT.     

A comparison of cardiac resynchronization by sequential biventricular pacing and left ventricular pacing to simultaneous biventricular pacing: rationale and design of the DECREASE-HF clinical trial

BACKGROUND: The first generation of cardiac resynchronization therapy (CRT) devices approved for the treatment of heart failure used simultaneous biventricular (BiV) pacing to achieve ventricular resynchronization. Left ventricular pacing alone and sequential BiV pacing also show promise as alternative ways to deliver CRT, but have not been studied together in a large randomized trial. METHODS: The Device Evaluation of CONTAK RENEWAL 2 and EASYTRAK 2: Assessment of Safety and Effectiveness in Heart Failure (DECREASE-HF) Trial is a randomized, double-blind, 3-arm study of patients in New York Heart Association Class III or IV with an ejection fraction of 35% or less and a QRS duration > or =150 ms. Patients are randomized to receive either left ventricular pacing, simultaneous BiV pacing, or sequential BiV pacing. CONCLUSION: The study uses a novel composite endpoint that combines peak oxygen consumption and left ventricular end systolic dimension, thus combining a measure of symptomatic improvement (peak oxygen consumption) with a physiologic measure of ventricular reverse remodeling (left ventricular end systolic dimension) into a single composite score. Additionally, the safety and effectiveness of the CONTAK RENEWAL 2/4/4HE/EASYTRAK 2 system will be evaluated using: heart failure-related adverse events; system-related complications; left ventricular lead-related complications; detection time of induced ventricular fibrillation; and left ventricular lead performance (pacing threshold, pacing impedance, and R-wave amplitude).     

Left ventricular resynchronization predicted by individual performance of right and left univentricular pacing: A study on the impact of sequential biventricular pacing on ventricular dyssynchrony

BACKGROUND: There is increasing evidence that improvement in left ventricular (LV) mechanical dyssynchrony is correlated with LV functional recovery in patients undergoing cardiac resynchronization therapy (CRT). Recent studies have suggested that sequential biventricular pacing may be important for further optimizing parameters of ventricular dyssynchrony. OBJECTIVE: The purpose of this study was to evaluate the acute effect of varying sequential biventricular pacing settings on echocardiographic parameters of ventricular dyssynchrony and to identify predictors of the optimal setting. METHODS: Twenty-nine patients referred for CRT were evaluated with standard echocardiography and tissue Doppler imaging before and after implantation. Indices of interventricular and intraventricular dyssynchrony were assessed for trends during simultaneous and sequential biventricular pacing. RESULTS: Twelve patients (41%) demonstrated linear trends of decreasing systolic dyssynchrony index with increasing LV preactivation. The mean additional decrease in dyssynchrony index at the optimized setting compared with simultaneous biventricular pacing was 26% (P <.04). Twenty-two patients (76%) demonstrated linear trends to decreasing interventricular dyssynchrony with increasing LV preactivation. The trends were strongly correlated with the magnitude of difference of the respective dyssynchrony measures in right ventricular only and LV only univentricular pacing. A significantly, superior capacity of LV only pacing for ventricular resynchronization was found in this subgroup of patients. CONCLUSION: In patients undergoing CRT, differences in the performance of univentricular pacing are associated with linear trends in ventricular dyssynchrony parameters in sequential biventricular pacing. Quantitative differences in LV univentricular pacing impact on the capacity of biventricular pacing to correct ventricular dyssynchrony.     

单左室起搏通过频率适应性房室延迟实现双心室再同步

目的探讨单左室起搏通过频率适应性房室延迟(RAAV)算法跟踪生理性房室延迟(AVD)实现双心室再同步的可行性及治疗慢性充血性心力衰竭(CHF)的效果。方法入选符合心脏再同步化治疗(CRT)Ⅰ类适应证并植入带RAAV功能的三腔或双腔起搏器的CHF患者64例,其中RAAV单左室起搏(LUVP)组(单左室组)32例,以标准双室起搏(BVP)组(标准双室组)32例为对照组。两组给予标准心脏超声优化,比较主动脉前向血流速度时间积分(AVI),左室射血分数(LVEF)、十二节段达峰时间标准差(TS-SD12)、主肺动脉射血前时间差(IVMD)、二尖瓣返流面积(MRA)、EA峰间距(E/A pd)、QRS波时限、年平均治疗费用、NYHA分级、6min步行试验(6MWT)等指标。结果与标准双室组比较,单左室组电池寿命更长[(7.8±0.3)年vs(4.5±0.2)年,P0.001],QRS波时限短[(136±10)ms vs(142±11)ms,P0.05],优化耗时较短[(20±4)min vs(52±8)min,P0.001],MRA更少[(3.1±1.1)cm~2 vs(3.7±1.2)cm2,P0.05],IVMD缩短[(64.2±12.8)ms vs(72.3±13.6)ms,P0.05],年均治疗费用低[(1.3±0.1)万元vs(2.2±0.2)万元,P0.001];AVI增加[(21.8±2.3)cm vs(20.6±2.1)cm,P0.05],余指标两组比较均无统计学意义(P0.05)。结论 RAAV单左室起搏可实现双室再同步,疗效不劣于标准BVP,且更符合生理性并降低治疗费用。     

Simultaneous vs. sequential biventricular pacing in dilated cardiomyopathy: an acute hemodynamic study

AIMS: Simultaneous biventricular pacing improves left ventricular (LV) systolic performance in patients with dilated cardiomyopathy and intraventricular conduction delay. We tested the hypothesis that further improvements can be obtained using sequential biventricular pacing by optimizing both atrioventricular and interventricular delays. METHODS AND RESULTS: In 12 patients, LV pressure, right ventricular (RV) pressure and respective rates of change of pressure (dP/dt) were acutely measured during biventricular pacing with different atrioventricular and interventricular (VVi) intervals ranging from -60 to +40 ms. The average increase vs. baseline in maximum LV dP/dt was higher for sequential than for simultaneous biventricular pacing (VDD mode: 35+/-20 vs. 29+/-18%, P<0.01; DDD mode: 38+/-23 vs. 34+/-25%, P<0.01), with a minority of patients accounting for most of the difference. The mean optimal VVi was -25+/-21 ms in VDD mode and -25+/-26 ms in DDD mode. With these settings, RV dP/dt was not significantly different from baseline. QRS shortening was not predictive of LV dP/dt increase. CONCLUSION: A significant increase of LV dP/dt with no change in RV dP/dt can be obtained by sequential biventricular pacing as compared to simultaneous biventricular pacing. The highest LV dP/dt is achieved when LV is stimulated before RV. The hemodynamic advantage might be of clinical significance in selected cases.     

Electrocardiographic versus echocardiographic optimization of the interventricular pacing delay in patients undergoing cardiac resynchronization therapy

Electrocardiographic VV Optimization. Introduction: Echocardiographic optimization of the VV interval may improve CRT response, but it is time‐consuming and not routinely performed. The aim of this study was to compare the response to cardiac resynchronization therapy (CRT) when the interventricular pacing (VV) interval was optimized by Tissue Doppler Imaging (TDI) to CRT response when it was optimized following QRS width criteria. Methods and Results: The study included 156 consecutive CRT patients with severe heart failure and left bundle‐branch block configuration. Atrioventricular interval was selected according to a pulsed Doppler assessment, and VV optimization was randomly assigned to echocardiography (ECHO group, n = 78) or electrocardiography (ECG group, n = 78). Optimal VV was defined for the ECHO group as producing the best LV intraventricular synchrony according to TDI displacement curves and for the ECG group as resulting in the narrowest QRS measured from the earliest deflection. At 6‐month follow‐up, percentage of echocardiographic responders (defined as neither death nor heart transplantation and a LV end‐systolic volume reduction >10%) was higher in the ECG optimized group (50.0% vs 67.9%; P = 0.023), whereas clinical response (defined as neither death nor heart transplantation and >10% improvement in the 6‐minute walking test) was similar in both groups (71.8% vs 73.1%; P = 0.858). Conclusions: VV optimization based on QRS width obtained a higher percentage of responders in terms of LV reverse remodeling compared to the TDI method. (J Cardiovasc Electrophysiol, Vol. 22, pp. 1129‐1134, October 2011)     

Permanent His-bundle pacing as an alternative to biventricular pacing for cardiac resynchronization therapy: A multicenter experience

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Positioning of left ventricular pacing lead guided by intracardiac echocardiography with vector velocity imaging during cardiac resynchronization therapy procedure

LV Lead Positioning Guided by ICE With Vector Velocity Imaging . Introduction: Intraoperative modality for “real‐time” left ventricular (LV) dyssynchrony quantification and optimal resynchronization is not established. This study determined the feasibility, safety, and efficacy of intracardiac echocardiography (ICE), coupled with vector velocity imaging (VVI), to evaluate LV dyssynchrony and to guide LV lead placement at the time of cardiac resynchronization therapy (CRT) implant. Methods: One hundred and four consecutive heart failure patients undergoing ICE‐guided (Group 1, N = 50) or conventional (Group 2, N = 54) CRT implant were included in the study. For Group 1 patients, LV dyssynchrony and resynchronization were evaluated by VVI including visual algorithms and the maximum differences in time‐to‐peak (MD‐TTP) radial strain. Based on the findings, the final LV lead site was determined and optimal resynchronization was achieved. CRT responders were defined using standard criteria 6 months after implantation. Results: Both groups underwent CRT implant with no complications. In Group 1, intraprocedural optimal resynchronization by VVI including visual algorithms and MD‐TTP was a predictor discriminating CRT response with a sensitivity of 95% and specificity of 89%. Use of ICE/VVI increased number of and predicted CRT responders (82% in Group 1 vs 63% in Group 2; OR = 2.68, 95% CI 1.08–6.65, P = 0.03). Conclusion: ICE can be safely performed during CRT implantation. “Real‐time” VVI appears to be helpful in determining the final LV lead position and pacing mode that allow better intraprocedural resynchronization. VVI‐optimized acute resynchronization predicts CRT response and this approach is associated with higher number of CRT responders. (J Cardiovasc Electrophysiol, Vol. 22, pp. 1034‐1041, September 2011)     

Role of echocardiography in selection of patients for biventricular pacing therapy

Cardiac resynchronization therapy (CRT) has demonstrated improved quality of life, New York Heart Association class, left ventricular ejection fraction, and survival in patients with moderate to severe heart failure, left ventricular ejection fraction less than or equal to 35%, and a prolonged QRS duration. QRS duration remains the primary surrogate for mechanical dyssynchrony, defining the pathophysiology of abnormal regional mechanical activation. Studies have demonstrated that 30% to 40% of patients who meet current criteria for CRT are nonresponders. Therefore, there is great interest in the relationship between electrical and mechanical dyssynchrony, and the ability of each alone or together to predict response remains unknown. Echocardiographic approaches have emerged to quantify mechanical dyssynchrony with greater specificity than QRS duration alone. Although these methods are complex, exciting, and highly accurate for predicting response to CRT in single-center studies, they lack widespread applicability and validation to replace current criteria for device implantation. Use of echocardiography to define dyssynchrony and the impact of promising imaging methods for future patient selection for CRT are discussed.     

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