Optimizing atrioventricular and interventricular intervals following cardiac resynchronization therapy

The number of cardiac resynchronization therapy (CRT) device implantations has been increasing exponentially, with the implant rate doubling over the past few years. While the majority of CRT recipients enjoy symptomatic relief, approximately 30% of individuals reap no benefit and only a minority are rendered completely symptom free. In response, many clinicians engage in the theoretically advantageous process of postimplantation optimization of atrial and ventricular stimulation by altering atrioventricular and interventricular pacing intervals. However, the rationale for routine CRT optimization and the methods of doing so have been the subjects of recent debate. Here, we present an overview of the background, techniques and evidence for CRT optimization.     

Echocardiography-guided biventricular pacemaker optimization: role of echo Doppler in hemodynamic assessment and improvement

In spite of improvements in heart failure management and increasing utilization of cardiac resynchronization therapy (CRT), approximately 30-40% of CRT patients remain nonresponders and 50% or more are echocardiographic nonresponders (defined as less than 15% reduction in left ventricular end systolic volume post-CRT). Optimization guided by echocardiography has been studied as one of the methods to improve the nonresponder rate to CRT. Echo-guided biventricular (Biv) pacemaker optimization has been associated with improvement in acute cardiac hemodynamics and improvement in functional class. In this review, the authors discuss various methods to optimize Biv pacemaker by echocardiography, recent advances in pacemaker optimization and the limitations of echocardiography. The authors also demonstrate complex hemodynamic derangements in heart failure via multiple case examples highlighting the role of comprehensive echo Doppler in elucidating cardiac hemodynamics encountered in CRT nonresponders, as well as tailoring of Biv pacemaker optimization to the underlying physiologic derangement.     

Echocardiography-guided biventricular pacemaker optimization: role of echo Doppler in hemodynamic assessment and improvement

In spite of improvements in heart failure management and increasing utilization of cardiac resynchronization therapy (CRT), approximately 30–40% of CRT patients remain nonresponders and 50% or more are echocardiographic nonresponders (defined as less than 15% reduction in left ventricular end systolic volume post-CRT). Optimization guided by echocardiography has been studied as one of the methods to improve the nonresponder rate to CRT. Echo-guided biventricular (Biv) pacemaker optimization has been associated with improvement in acute cardiac hemodynamics and improvement in functional class. In this review, the authors discuss various methods to optimize Biv pacemaker by echocardiography, recent advances in pacemaker optimization and the limitations of echocardiography. The authors also demonstrate complex hemodynamic derangements in heart failure via multiple case examples highlighting the role of comprehensive echo Doppler in elucidating cardiac hemodynamics encountered in CRT nonresponders, as well as tailoring of Biv pacemaker optimization to the underlying physiologic derangement.     

Continuously adjusting CRT therapy: clinical impact of adaptive cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) is a well-established therapy to reduce morbidity and mortality in patients with moderate and severe symptomatic congestive heart failure. Left ventricular (LV) pacing that fuses with intrinsic right ventricular (RV) conduction results in similar or even better cardiac performance compared to biventricular (Biv) pacing. Optimal programming of the atrio-ventricular (AV) and inter-ventricular (VV) delays is crucial to improve LV performance since suboptimal programming of AV and VV delays affect LV filling as well as cardiac output. CRT optimization using echocardiogram is resource-dependent and time consuming. Adaptive CRT (aCRT) algorithm provides a dynamic, automatic, ambulatory adjustment of CRT pacing configuration (Biv or LV pacing) and optimization of AV and VV delays. aCRT algorithm is safe and efficacious for CRT-indicated patients without permanent atrial fibrillation. It has been shown to improve CRT response and reduce morbidity and mortality for patients with normal AV conduction.     

Optimization of AV and VV Delays in the Real-World CRT Patient Population: An International Survey on Current Clinical Practice

Background: Cardiac resynchronization therapy (CRT) is an effective treatment for patients suffering from advanced heart failure and electrical dyssynchrony. Limited data suggest that patients may benefit from routine optimization of the atrioventricular (AV) and interventricular (VV) delays; however, there is scarce information available on how and when optimization should be performed.
Objective: The objective of this survey was to characterize the current international standard of care for optimization of the AV and VV delays in CRT devices recipients.
Methods: Centers participating in the Frequent Optimization Survey Using the QuickOpt Method (FREEDOM) study completed surveys probing into their optimization of AV and VV delays procedures. Probes focused on the methods used to optimizing the delays, visits at which optimization of the delays was performed, percentage of patients that underwent optimization, and factors that limited centers from optimizing the CRT systems.
Results: Few of the 118 investigators from 16 countries who responded to the survey routinely optimized the delays in all patients. At follow-up visits and during hospitalizations, a trend was observed to optimize the delays more often in nonresponders than in responders to CRT. Standard echocardiography was the most common method of optimization. Time availability and lack of qualified staff were the main factors limiting the optimization of CRT systems.
Conclusions: In real-world practice, AV and VV optimization was not performed in a high proportion of patients. A less time-consuming and easier optimization method might enable a more systematic optimization of the AV and VV delays at routine follow-up visits in all recipients of CRT systems.     

A real-time three-dimensional echocardiographic validation of an intracardiac electrogram-based method for optimizing cardiac resynchronization therapy

INTRODUCTION: Although optimization of atrioventricular and interventricular delays has been demonstrated to improve hemodynamics in patients with cardiac resynchronization therapy (CRT), the required time-consuming procedure discourages its use in clinical practice. Recently, a new method for CRT optimization based on the intracardiac electrogram (IEGM) detected by the implanted leads, has been developed. We evaluated the effectiveness of this method in improving left ventricular (LV) asynchrony and performance using real-time 3D echocardiography (RT3DE). METHODS AND RESULTS: Twenty patients with CRT were prospectively studied. RT3DE was performed before and after IEGM optimization. The standard deviation of the time to the regional LV minimum systolic volume (Tmsv) for all 16 segments (Tmsv 16-SD), six basal and six mid segments (Tmsv 12-SD), and the six basal segments (Tmsv 6-SD) were assessed as a asynchrony indexes. LV end-diastolic and end-systolic volumes (EDV, ESV), stroke volume (SV), ejection fraction (EF), myocardial performance index (MPI), ejection time (ET), and filling time (FT), corrected by R-R interval, were also evaluated. After IEGM optimization, as compared with baseline Tmsv 12-SD and Tmsv 16-SD decreased (P = 0.01, P< 0.001, respectively), EF and SV improved (P < 0.001, P = 0.01 respectively), FT/RR and ET/RR increased (P = 0.02 for both), and MPI improved (P < 0.001). Tmsv 6-SD, EDV and ESV did not change. CONCLUSION: A simple IEGM-based method of CRT optimization decreased LV dyssynchrony and improved systolic function.     

A comparison of acoustic cardiography and echocardiography for optimizing pacemaker settings in cardiac resynchronization therapy

Background: Cardiac resynchronization therapy (CRT) is useful in managing patients with refractory heart failure. To increase efficacy, pacemaker settings are optimized, with Doppler echocardiography being the preferred method. Recently, acoustic cardiography, an automated method that records, analyzes, and displays simultaneous ECG and heart sound data, has been developed. In this study, the suitability of acoustic cardiography as an alternative to Doppler echocardiography in CRT optimization is evaluated.
Methods: We studied 43 CRT patients undergoing optimization. Using Doppler echocardiography, we determined the optimal atrioventricular (AV) delay with a transmitral flow assessment. For optimization of the interventricular (VV) delay, we used the left ventricular outflow tract velocity time integral (VTI). For acoustic cardiography, we used the electromechanical activation time (EMAT, the interval from QRS onset to the S1). Reproducibility of echocardiography and acoustic cardiography was determined by programming 10 different delay settings twice in random order.
Results: All 43 subjects underwent AV optimization, and 14 had CRT devices allowing VV optimization. While the intraobserver variability of EMAT and Doppler echocardiography parameter was similar (9.9% vs 8.5%), the reproducibility of EMAT was the highest (r = 0.91) and VTI was the lowest (r = 0.35). The correlation between the optimal AV delays determined by EMAT versus transmitral flow assessment was 0.86 (P < 0.001). The correlation between the optimal VV delays determined by EMAT versus VTI was 0.58 (P < 0.05), perhaps due to the poor reproducibility of the VTI.
Conclusion: For CRT optimization, acoustic cardiography provides results similar to echocardiography but with improved reproducibility and ease of use.     

The Contemporary Role of Echocardiography in Improving Patient Response to Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT) is an important therapy for heart failure patients with widened electrocardiographic QRS complexes and depressed ejection fractions, however, approximately one-third do not respond. This article presents a practical contemporary approach to the utility of echocardiography to improve CRT patient response by assessing mechanical dyssynchrony, optimizing left ventricular lead positioning, and performing appropriate echo-Doppler optimization, along with future potential roles. Specifically, recent long-term outcome data are presented that demonstrates that baseline dyssynchrony is a powerful marker associated with CRT response, in particular for patients with narrower QRS duration or non left bundle branch block morphology. Advances in speckle tracking echocardiography to tailor delivery of CRT by guiding LV lead position is discussed, including data from randomized clinical trials supporting targeting the LV lead toward the site of latest activation. In addition, an update on the current role of Doppler echocardiographic device optimization after CRT implantation is reviewed.     

Iterative Cardiac Output Measurement for Optimizing Cardiac Resynchronization Therapy: A Randomized,Blinded, Crossover Study

Background: Many invasive and noninvasive methods have been proposed for guiding optimal programming of cardiac resynchronization therapy (CRT) devices. However, results are not satisfying. Preliminary results suggest that cardiac output (CO) measurements using inert gas rebreathing (IGR) might be an eligible method to tailor atrioventricular (AV) and ventriculo‐ventricular (VV) programming. The aims of the present study were: (1) to evaluate whether an optimization of CRT can be obtained by noninvasive CO measurements and (2) to evaluate whether acute hemodynamic improvements obtained by this approach relate into increase in cardiac exercise capacity. Methods: In 24 patients on CRT, iterative VV‐ and AV‐delay optimization was done using the IGR method. This blinded, randomized, crossover study compared the responses to optimization during two periods: a 4‐week optimized and a 4‐week standard programming. Exercise capacity after optimization was assessed after each period by New York Heart Association (NYHA) classification, a 6‐minute walking test, and quality of life (QoL) questionnaire. Results: CO could be determined by IGR in all patients. The NYHA class decreased by 17.8% (2.8 ± 0.3 vs 2.3 ± 0.4, P < 0.001), the mean (± standard deviation) distance walked in 6 minutes was 9.3% greater after optimization (456 ± 140 m vs 417 ± 134 m, P < 0.001), and the QoL improved by 14.5% (41.8 ± 10.4 vs 36.5 ± 9.5, P < 0.001). The portion of responders to CRT increased from 66.5% to 87.5%. Conclusion: CRT optimization by iterative CO measurements leads to an increase in CO and an improvement of exercise capacity. Our results suggest that this method might become an important additive tool to adjust CRT programming. (PACE 2010; 33:1188–1194)     

超声心动图在心脏再同步治疗中应用的初步经验

目的 探讨超声心动图在心脏再同步治疗（CRT）中的初步应用. 方法 随访我院2002年1月至2004年8月11例QRS波宽≥130 ms的心力衰竭患者行双心室起搏CRT前后6 min步行试验、心功能和主要超声心动图参数：左心室舒张末期内径、射血分数、二尖瓣反流程度和Q波至室壁峰值收缩速度时间延迟等的改变.结果 有反应者8例,无反应者3例.有反应者临床症状和超声心动图主要参数改善显著.结论 超声心动图在CRT病例选择、优化治疗和长期随访中具有重要作用.     

Noninvasive Imaging in Cardiac Resynchronization Therapy—Part 2: Follow‐up and Optimization of Settings

Cardiac resynchronization therapy (CRT) has become a therapeutic option for drug‐refractory heart failure. Several noninvasive imaging techniques play an increasingly important role before and after device implantation. This review highlights the acute and long‐term CRT benefits after implantation as assessed with echocardiography and nuclear imaging. Furthermore, optimization of CRT settings, in particular atrioventricular and interventricular delay, will be discussed using echocardiography and other (device‐based) techniques.     

Cardiac resynchronization therapy optimization by ultrasonic cardiac output monitoring (USCOM) device

OBJECTIVES: We investigated the accuracy and feasibility of a 2D echo-independent ultrasonic continuous wave Doppler cardiac output monitoring device (USCOM) operated by trained nurse for the atrio-ventricular interval (AVI) optimization in cardiac resynchronization therapy (CRT). BACKGROUND: CRT is of proven benefit in patients with advanced chronic heart failure and ventricular conduction delay. Appropriate AVI selection is critical to optimize hemodynamic in CRT. Currently, most non-invasive methods for AVI optimization are often complicated and labor-intensive. Methods: USCOM method, Ritter method, and aortic outflow cardiac output method were used to determine the optima AVI in 20 patients with CRT. The accuracy and time for measurement of each method were determined. RESULTS: The optimal AVI determined by USCOM method had good correlation with Ritter's method and aortic outflow estimated cardiac output method (r2= 0.78, P < 0.01 and r2= 0.73, P < 0.01, respectively). The optimal AVI determined USCOM method showed good agreement (within 10 msec range) with Ritter's method (85% patients) and aortic outflow estimated cardiac output method (80%). The mean time for determining AVI using USCOM method was shorter than that with aortic outflow method (7.1 +/- 0.7 min vs 12.7 +/- 1.1 min, P < 0.01), whereas the mean time was shortest for Ritter method (4.7 +/- 1.6 min vs 7.1 +/- 0.7 min, P < 0.01). CONCLUSION: USCOM device operated by trained nurse can provide a simple, accurate, and fast non-invasive method for the AVI optimization in CRT population.     

Intracardiac Echocardiography-Guided Cardiac Resynchronization Therapy: Technique and Clinical Application

Background: We undertook a pilot investigation to evaluate the feasibility of a novel technique using intracardiac echocardiography (ICE) for intraoperative assessment of cardiac resynchronization therapy (CRT).
Methods: We evaluated ICE intraoperative imaging of left ventricular (LV) function and aortic valvular flow as well as safety of implementation. ICE was used to guide CRT system lead placement, assess impact of pacing modes, and optimization of device programming.
Results: Twenty-three patients underwent ICE imaging. ICE showed global hypokinesis in six patients, regional wall motion abnormality only in 10 patients, and both in seven patients. Optimized CRT modes included mean atrioventricular (AV) interval of 170 ms and interventricular timing using simultaneous right ventricular (RV)-LV pacing (five patients), LV pacing only (one patient), and sequential LV to RV stimulation (15 patients) or RV to LV stimulation (two patients). ICE-guided CRT acutely improved mean left ventricular ejection fraction (LVEF) from 24 ± 9% to 41 ± 1% (P < 0.00001). During follow-up of 3–24 (mean 11) months, New York Heart Association class improved in all patients from a mean of 3.2 ± 0.4 at implant to 1.6 ± 0.7 (P < 0.0001), with improvement of LVEF from 19 ± 7% to 34 ± 12% (P = 0.0001). Actuarial survival was 83% at 12 months.
Conclusions: (1) ICE imaging is reliable and safe for continuous intraoperative imaging of LV wall motion, and assesses baseline status and impact of CRT interventions. (2) Intraoperative ICE-guided CRT optimization resulted in an increase in LVEF acutely and consistent improvement in heart failure. (3) Sequential biventricular pacing and longer AV interval programming were more often used in ICE-guided CRT.     

SmartDelay Determined AV Optimization: A Comparison of AV Delay Methods Used in Cardiac Resynchronization Therapy (SMART-AV): Rationale and Design

Background: The clinical benefit of cardiac resynchronization therapy (CRT) for patients with moderate-to-severely symptomatic heart failure, left ventricular systolic dysfunction, and ventricular conduction delay is established. However, some patients do not demonstrate clinical improvement following CRT. It is unclear whether systematic optimization of the programmed atrioventricular (AV) delay improves the rate of clinical response.
Methods: SMART-AV is a randomized, multicenter, double-blinded, three-armed trial that will investigate the effects of optimizing AV delay timing in heart failure patients receiving CRT + defibrillator (CRT-D) therapy. A minimum of 950 patients will be randomized in a 1:1:1 ratio using randomly permuted blocks within each center programmed to either DDD or DDDR with a lower rate of 60. The study will include echocardiographic measurements of volumes and function [e.g., left ventricular end-systolic volume (LVESV)], biochemical measurements of plasma biomarker profiles, and functional measurements (e.g., 6-minute hall walk) in CRT-D patients who are enrolled and randomized to fixed AV delay (i.e., 120 ms), AV delay determined by electrogram-based SmartDelay, or an AV delay determined by echocardiography (i.e., mitral inflow). Patients will be evaluated prior to initiation of CRT, 3 and 6 months post-implant. The primary endpoint is the relative change in LVESV at 6 months between the groups. Patient enrollment commenced in May 2008 and the study is registered at clinicaltrials.gov.
Conclusion: SMART-AV is a randomized, clinical trial designed to evaluate three different methods of AV delay optimization to determine whether systematic AV optimization is beneficial for patients receiving CRT for 6 months post-implant. (PACE 2010; 54–63)     

超声指导下优化心脏再同步化治疗患者AV间期的即刻及短期疗效

目的 观察超声指导下AV间期优化对心脏再同步化治疗(CRT)患者血流动力学变化的影响及短期疗效.方法 24例行CRT的慢性心力衰竭患者随机分成优化组和对照组各12例,术后3个月以上在超声指导下应用Ritter公式法进行AV间期优化,优化结束时对照组恢复初始AV间期.所有患者优化后1个月随访.结果优化组AV间期优化即刻及1个月后随访较优化前左心室充盈时间延长[充盈时间:(453±86.6)ms、(490.5±122.4)ms vs(396.6±126.7)ms,P<0.05],优化后1个月左心室内径进一步减小,收缩功能略提高(67.4±8.28) vs (71.08±8.52)mm,(27.58±6.05)% vs(25.50±6.99)%,P<0.05];对照组AV间期优化即刻较优化前左心室充盈时间延长,恢复初始AV间期后1个月左心室充盈时间、左心室内径及收缩功能较优化前差异没有统计学意义.结论 超声指导下AV间期优化能够改善左心室的收缩和舒张功能,进一步提高CRT疗效.     

Biophysical modeling to simulate the response to multisite left ventricular stimulation using a quadripolar pacing lead

Background: Response to cardiac resynchronization therapy (CRT) is reduced in patients with posterolateral scar. Multipolar pacing leads offer the ability to select desirable pacing sites and/or stimulate from multiple pacing sites concurrently using a single lead position. Despite this potential, the clinical evaluation and identification of metrics for optimization of multisite CRT (MCRT) has not been performed. Methods: The efficacy of MCRT via a quadripolar lead with two left ventricular (LV) pacing sites in conjunction with right ventricular pacing was compared with single‐site LV pacing using a coupled electromechanical biophysical model of the human heart with no, mild, or severe scar in the LV posterolateral wall. Result: The maximum dP/dt_max improvement from baseline was 21%, 23%, and 21% for standard CRT versus 22%, 24%, and 25% for MCRT for no, mild, and severe scar, respectively. In the presence of severe scar, there was an incremental benefit of multisite versus standard CRT (25% vs 21%, 19% relative improvement in response). Minimizing total activation time (analogous to QRS duration) or minimizing the activation time of short‐axis slices of the heart did not correlate with CRT response. The peak electrical activation wave area in the LV corresponded with CRT response with an R² value between 0.42 and 0.75. Conclusion: Biophysical modeling predicts that in the presence of posterolateral scar MCRT offers an improved response over conventional CRT. Maximizing the activation wave area in the LV had the most consistent correlation with CRT response, independent of pacing protocol, scar size, or lead location. (PACE 2012; 35:204–214)     

Cardiac resynchronization therapy and the role of nuclear cardiology

Cardiac resynchronization therapy (CRT) is an accepted treatment modality in patients with endstage heart failure despite optimal pharmacologic therapy. Although considerable benefit of CRT has been demonstrated in large clinical trials, a substantial cohort of patients failed to respond to CRT. Accordingly, studies have focused on potential predictors for CRT response, and the relative merits of left ventricular dyssynchrony, viability, and scar tissue for CRT response have been demonstrated. Nuclear cardiology techniques can provide this information, particularly gated myocardial perfusion single photon emission CT with phase analysis, and this technique can be used to improve selection of CRT candidates. Also, nuclear imaging can be used to evaluate effects of CRT (changes in blood flow, oxidative metabolism, glucose utilization, and sympathetic innervation). The use of nuclear imaging in selection of CRT patients, and evaluation of CRT effects, are reviewed here.     

Cardiac resynchronization therapy optimization using noninvasive cardiac output measurement

Aims: Noninvasive cardiac output (CO) measurement (NICOM) is a novel method to assess ventricular function and offers a potential alternative for optimization of cardiac resynchronization therapy (CRT) devices. We compared the effect of NICOM‐based optimization to no optimization (empiric settings) on CRT outcomes. Methods: Two hundred and three patients undergoing CRT were assessed in two consecutive nonrandomized groups; an empiric group (n = 54) was programmed to “out of the box” settings with a fixed AV delay of 120 ms and a VV delay of 0 ms; and the optimization group (n = 149) underwent adjustments of both the AV and VV delays according to the greatest improvement in resting CO. The primary endpoints were improvements in left ventricular (LV) volumes and function from baseline at 6 months. Secondary endpoints were change in New York Heart Association (NYHA) class, quality of life score, and 6‐minute walk test (6 MWT) performance. Results: After 6 months of CRT, the optimization group had a better clinical response with lower NYHA class (2.1±0.8 vs 2.4 ± 0.8, P = 0.048) and quality of life scores (35 ± 18 vs 42 ± 20, P = 0.045) but no differences in 6‐MWT performance (269 ± 110 vs 277 ± 114 m, P = 0.81). Echocardiographic response was also better in the optimization group with lower LV end systolic volume (108 ± 51 vs 126 ± 60 mL, P = 0.048) and higher ejection fraction (30 ± 7 vs 27 ± 8, P = 0.01) compared to empiric settings. Conclusion: Device optimization using noninvasive measures of CO is associated with better clinical and echocardiographic response compared to empiric settings. (PACE 2011; 34:1527–1536)     

Non-invasive cardiac mapping for non-response in cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) is an effective intervention in selected patients with moderate-to-severe heart failure with reduced ejection fraction and abnormal left ventricular activation time. The non-response rate of approximately 30% has remained nearly unchanged since this therapy was introduced 25 years ago. While intracardiac mapping is widely used for diagnosis and guidance of therapy in patients with tachyarrhythmia, its application in characterization of the electrical substrate to elucidate the mechanisms involved in CRT response remain anecdotal. In the present review, we describe the traditional determinants of CRT response before presenting novel non-invasive techniques used for CRT optimization. We discuss efforts to identify the target electrical substrate to guide the deployment of pacing electrodes during the operative procedure. Non-invasive body surface mapping technologies such as ECG imaging or ECG belt enables prediction of acute and chronic CRT response. While electrical dyssynchrony parameters provide high predictive accuracy for CRT response when obtained during intrinsic conduction, their predictive value is less when acquired during CRT or LV-pacing.

Key messages

• Classic predictors of CRT response are female gender, NYHA class ≤ III, left ventricular ejection fraction ≥25%, QRS duration ≥150 ms and estimated glomerular filtration rate ≥60 mL/min.
• ECG-imaging is a comprehensive non-invasive mapping system which allows to express the amount of electrical asynchrony of a CRT candidate.
• Non-invasive body surface mapping technologies enables excellent prediction of acute and chronic CRT response before implantation.
• When performed during CRT or LV-pacing, the added value of these mapping systems remains unclear.

     

心脏再同步治疗术后程控优化的研究

目的超声心动图指导下程控优化心脏再同步治疗(CRT)。方法8例因心力衰竭接受CRT治疗的患者于术后在超声心动图指导下优化AV间期及VV间期。结果8例患者均先后进行了AV间期优化及VV间期优化,左室射血分数从35%升至42%,QRS波宽度从122.3ms降至110.1ms。窦性心律时AV间期从100ms优化到112ms,VV间期从8.0ms优化到24.0ms。程控优化后心率校正的左心室充盈时间从456.2ms升至550.9ms,二尖瓣返流速度时间积分从9.3cm降至6.3cm,间壁与侧壁达峰时间差从45.3ms降至33.2ms,左室流出道速度时间积分从21.2cm升至28.3cm。结论CRT术后程控个体化可以提高疗效。