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.     

Rate-dependent AV delay optimization in cardiac resynchronization therapy

BACKGROUND: During cardiac resynchronization therapy (CRT), cardiac performance is dependent on an optimized atrioventricular delay (AVD). However, the optimal AVD at different heart rates has not been defined yet during CRT. METHOD: The effects of an increase in heart rate by pacing or physical exercise on optimal AVD were studied in 36 patients with biventricular pacemakers/defibrillators. The velocity time integral (VTI) in the left ventricular outflow tract (LVOT) was measured with pulsed Doppler either at three different paced heart rates in the supine position or in seated position before and after physical exercise. RESULTS: The baseline AVD was optimized to 99 +/- 19 ms in the supine and 84 +/- 22 ms in the seated position. When the heart rate was increased by DDD pacing, there was a positive linear relationship between an increase in heart rate, in AVD and in VTI (LVOT-VTI + 0.047 cm/s per 10 beats per minute (bpm) heart rate increase per 20 ms increase in AVD, P = 0.007). A similar but more pronounced relationship was found after physical exercise in the seated position (LVOT-VTI + 0.146 cm/s per 10 bpm heart rate increase per 20 ms increase of AVD, P = 0.013). This effect was observed in patients with and without AV block and mitral regurgitation. CONCLUSIONS: In conclusion, the systolic performance of the dilated ventricle, which depends on an elevated preload, is critically affected by the appropriate timing of the AVD during exercise. In contrast to normal pacemaker patients, in CRT the relatively short baseline AVD should be prolonged at increased heart rates. Further studies with other means of measuring exercise cardiac performance are needed to confirm these unexpected findings.     

Predictors of a positive response to biventricular pacing in patients with severe heart failure and ventricular conduction delay

BACKGROUND: Cardiac resynchronization therapy (CRT) is recommended in patients with ejection fraction <35%, QRS width> 120 ms, and New York Heart Association (NYHA) functional class III or IV despite optimal medical therapy. We aimed to define demographic, clinical, and electrocardiographic predictors of positive clinical response to CRT. METHODS AND RESULTS: Hundred consecutive patients fulfilling the recommended criteria were implanted with a CRT device. Demographic, clinical, two-dimensional echocardiographic and electrographic parameters were measured at baseline and after 6 months of simultaneous biventricular pacing. A positive response to CRT included an improvement of at least one NYHA functional class associated with an absence of hospitalization for worsening heart failure. At the end of follow-up, 12 patients were dead and 71% of the patients were classified as responders. After 6 months of CRT, the ejection fraction was significantly higher (P = 0.035) in responders versus nonresponders. Multivariate analysis identified three independent predictors of positive response to CRT: an idiopathic origin of the cardiomyopathy (P = 0.043), a wider QRS before implantation (P = 0.017), and a narrowing of the QRS after implantation (P = 0.037). CONCLUSION: An idiopathic origin of the cardiomyopathy, a wider QRS before implantation, and a narrowing of the QRS width after implantation were identified as independent predictors of clinical positive response to CRT.     

The rationale and design of the SMART CRT trial

Aims

The SMART CRT study will assess the efficacy of an atrioventricular optimization algorithm to improve reverse remodeling among patients undergoing cardiac resynchronization therapy (CRT) in the presence of interventricular electrical delay.

Methods and results

The SMART CRT study is a global, multicenter, prospective, randomized study of patients undergoing CRT implantation. The primary endpoint of this trial is response rate to CRT, defined as decrease in left ventricular end‐systolic volume (LVESV) ≥15% at 6 months compared to preimplant baseline. Additional prespecified analyses are: (1) clinical composite endpoint combining all‐cause mortality, heart failure events, New York Heart Association class, and Quality of Life (using a patient global assessment instrument); (2) the individual components of the clinical composite endpoint; (3) 6‐minute walk distance; (4) Kansas City Cardiomyopathy Questionnaire; (5) LVESV as a continuous variable; and (6) absolute left‐ventricular ejection fraction. Subjects with intraventricular delay ≥ 70 ms measured between the right ventricular and left ventricular pacing leads will be randomized in a 1:1 ratio to have either an AV Delay and pacing chamber determined by SmartDelay? or a Fixed AV Delay of 120 ms with biventricular pacing. Enrollment of an estimated 726 of subjects from up to 100 centers worldwide is planned to achieve 436 randomized subjects and 370 complete data sets required to power the primary endpoint.

Conclusions

This trial will provide important data regarding the importance of AV Delay programming in patients with prolonged interventricular delay at the pacing sites.

     

Advantage of Optimizing V‐V Timing in Cardiac Resynchronization Therapy Devices

Background: There is little consensus as to the benefits of interventricular (V‐V) timing optimization in cardiac resynchronization therapy (CRT). A variety of parameters are currently used to optimize device timing. This study was designed to investigate the potential advantage of using 3D ejection fraction (EF) and aortic velocity‐time integral (VTI) as measures of global left ventricular (LV) function to optimize ventricular activation in CRT devices. Methods: Seventy‐four patients seen in the Optimization Clinic with adequate echocardiographic images were included. Three aortic VTI and two 3D EF values were recorded at five V‐V settings and the average value used. Aortic VTI and 3D EF were classified as the best, worst, and simultaneous setting values. Data were analyzed using a two‐tailed paired t‐test. Results: Comparing the best to worst V‐V timing settings, VTI improved by 4.7 ± 7.5 cm (P < 0.0001) and 3D EF by 9.9%± 5.7% (P < 0.0001). Comparing the simultaneous setting to the best V‐V timing setting, VTI improved by 2.4 ± 2.1 cm (P < 0.0001) and 3D EF by 3.8%± 4.9% (P < 0.0001). Aortic VTI improved in 85% of patients and 3D EF improved in 72%. However, only 26% of the patients had the same optimal setting using aortic VTI and 3D EF yielding an r² value of 0.003. Conclusions: Individualized echocardiographic V‐V optimization of CRT devices improves global LV function as measured by aortic VTI and 3D EF. Substantial differences in function were seen over an 80‐ms range of V‐V timing and optimization resulted in improved LV function in the majority of patients. (PACE 2010; 33:1161–1168)     

CRT in a congenital heart disease patient with interventricular dyssynchrony due to an RV conduction delay

We encountered a unique pattern of cardiac dyssynchrony in a patient with complex congenital heart disease (heterotaxy syndrome) with a biventricular physiology and systemic left ventricle (LV). On speckle tracking echocardiography, dyssynchrony was not detected within the LV, but was noted in an interventricular fashion between the LV and right ventricle (RV). An electrophysiologic study revealed a conduction delay in the subpulmonary RV. Cardiac resynchronization therapy provided reverse cardiac remodeling and an excellent result in our patient by placing the pacing leads around the dyssynchronous lesion.     

Pacemaker optimization in nonresponders to cardiac resynchronization therapy: left ventricular pacing as an available option

Background: Echocardiographic (ECHO)‐guided pacemaker optimization (PMO) in cardiac resynchronization therapy (CRT) nonresponders acutely improves left ventricular (LV) function. However, the chronic results of LV pacing in this group are less understood. Methods: We retrospectively studied 28 CRT nonresponders optimized based on ECHO to LV pacing and compared them to 28 age‐ and gender‐matched patients optimized to biventricular (BiV) pacing. ECHOs with tissue Doppler imaging assessed LV hemodynamics before, immediately after, and 29 ± 16 months after PMO. Also, 56 age‐ and gender‐matched CRT responders were included for comparison of clinical outcomes. Results: PMO resulted in acute improvements in longitudinal LV systolic function and several measures of dyssynchrony, with greater improvements in the LV paced group. Chronic improvements in ejection fraction (EF) (3.2 ± 7.7%), and left ventricle end‐systolic volume (LVESV) (?11 ± 36 mL) and one dyssynchrony measure were seen in the combined group. Chronically, both LV and BiV paced patients improved some measures of systolic function and dyssynchrony although response varied between the groups. Survival at 3.5 years was similar (P = 0.973) between the PMO (58%) and nonoptimized groups (58%) but survival free of cardiovascular hospitalization was significantly (P = 0.037) better in the nonoptimized group. Conclusions : CRT nonresponders undergoing PMO to either LV or BiV pacing have acute improvements in longitudinal systolic function and some measures of dyssynchrony. Some benefits are sustained chronically, with improvements in EF, LVESV, and dyssynchrony. A strategy of ECHO‐guided PMO results in survival for CRT nonresponders similar to that of CRT patients not referred for PMO. (PACE 2012; 35:685–694))     

The benefits of biventricular pacing in heart failure patients with narrow QRS, NYHA class II and right ventricular pacing

OBJECTIVE: To identify subgroups of heart failure patients who might benefit from biventricular pacing. BACKGROUND: Cardiac resynchronization therapy (CRT) improves the quality of life, New York Heart Association (NYHA) functional class, and exercise capacity and decreases hospitalizations for heart failure for patients who have severe heart failure and a wide QRS. It is unclear if other populations of heart failure patients would benefit from CRT. METHODS: One hundred forty-four consecutive heart failure patients who underwent CRT and completed 3 months of follow-up were reviewed. Demographic, echocardiographic, electrocardiographic, and clinical outcome data were analyzed to assess the relationship of functional class and QRS duration before device implantation to postimplant outcomes. RESULTS: There were 20, 88, and 36 patients in NYHA functional class II, III, and IV, respectively. Thirty-four patients had right ventricular pacing and another 29 patients had a QRS duration < or = 150 ms. Patients who were in NYHA functional class II at baseline had significant improvement in left ventricular ejection fraction and indices of left ventricular remodeling after CRT. Similar significant findings were seen in the subgroup with right ventricular pacing at baseline after CRT. However, in the subgroup with a narrow QRS duration, there were no significant changes in the indices of left ventricular remodeling or in the NYHA functional class and there was a significant increase in the QRS duration. For the study cohort as a whole, an improvement in NYHA functional class after CRT correlated with a significant decrease in adverse clinical outcomes. CONCLUSIONS: Heart failure patients who were in NYHA functional class II and those with right ventricular pacing appeared to benefit from CRT.     

Performance of left ventricular versus biventricular pacing in chronic heart failure assessed by stress echocardiography

Acute hemodynamic studies suggest that resynchronization therapy using single-site left ventricular pacing (LVP) is equivalent to biventricular pacing (BIVP). The aim of this study was to assess the performance of LVP versus BIVP during exercise by means of stress echocardiography. A total of 28 patients (25 men and 3 women, mean age 60.9 +/- 8 years) with advanced chronic heart failure and impaired ventricular conduction (QRS > 150 ms) were studied. Patients were randomly allocated to either BIVP or LVP mode with a crossover on the next day and cardiac output was estimated at rest and during each stage of bicycle ergometry in supine position by means of velocity time integral formula. Maximum exercise level was comparable for both pacing modes (up to 100 W) and no significant differences were revealed either in heart rate or in blood pressure at rest and during any step of exercise. LVP was associated with significantly higher cardiac output at rest (3.2 +/- 0.5 vs 2.8 +/- 0.6 l/min, P < 0.01) and during low level exercise (4.4 +/- 0.8 vs 3.9 +/- 0.8 l/min at 25 W, P < 0.05) as compared with BIVP. There was a trend towards higher cardiac output for LVP even at higher levels of exercise. These effects were predominantly confined to patients with idiopathic dilated cardiomyopathy. It is concluded that cardiac resynchronization therapy using single-site LVP results in better hemodynamic response as compared with BIVP, both at rest and during physical exercise.     

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)     

Prolonged paced QRS duration as a predictor for congestive heart failure in patients with right ventricular apical pacing

BACKGROUND: The recent studies showed that right ventricular (RV) pacing was associated with worsening of heart failure. The aim of this study is to clarify the clinical significance of paced QRS duration during RV pacing to predict congestive heart failure (CHF) patients. METHODS AND RESULTS: This study enrolled in 92 patients with atrioventricular block who underwent initial pacemaker implantation. The paced QRS duration was automatically obtained by electrocardiography immediately after pacemaker implantation and then by routine attendance at a pacemaker clinic every 3 months. The paced QRS duration was positively correlated with left ventricular end-diastolic dimension (P < 0.05) and left ventricular end-systolic dimension (P < 0.05), and tended to negatively correlate with left ventricular ejection fraction (P = 0.0507). The paced QRS duration immediately after pacemaker implantation was 170.4 +/- 18.9 ms. During a mean follow-up period of 53 +/- 16 months, 16 patients developed CHF. We selected as a cut-off value the nearest whole number (190 ms) that was one standard deviation greater than the mean, and divided into two groups according to baseline paced QRS duration. Patients with a paced QRS duration of <190 ms comprised group A (n = 77, nine of which developed CHF) and the remainder comprised group B (n = 15, seven of which developed CHF). Prolonged paced QRS duration (> or =190 ms) was associated with a significant increase in the overall morbidity of CHF (P < 0.05). Additionally, paced QRS duration significantly prolonged during the follow-up period among group A patients with CHF (P < 0.05), but did not change among patients without CHF. CONCLUSION: We concluded that paced QRS duration can be a useful indicator of impaired left ventricular function in patients with RV pacing. Even in patients whose paced QRS duration is relatively shorter, progressive prolongation of paced QRS duration can predict the development of CHF.     

The deleterious consequences of right ventricular apical pacing: time to seek alternate site pacing

BACKGROUND: The purpose of this article is to critically review the data accumulated to date from studies evaluating the hemodynamic and clinical effects of right ventricular apical pacing during conventional permanent cardiac pacing. The data from studies comparing the effects of right ventricular apical pacing and alternate site ventricular pacing are also reviewed. METHODS: We conducted a MEDLINE and journal search of English-language reports published in the last decade and searched relevant papers. RESULTS: Although intraventricular conduction delay in the form of left bundle branch block (LBBB) has traditionally been viewed as an electrophysiologic abnormality, it has now become abundantly clear that it has profound hemodynamic effects due to ventricular dyssynchrony, especially in patients with heart failure. These deleterious effects can be significantly ameliorated by cardiac resynchronization therapy effected by biventricular or left ventricular pacing. However, not only is spontaneous LBBB harmful, but the iatrogenic variety produced by right ventricular apical pacing in patients with permanent pacemakers may be equally deleterious. In this review new evidence from recent studies is presented, which strongly suggests a harmful effect of our long-standing practice of producing an iatrogenic LBBB by conventional right ventricular apical pacing in patients receiving permanent pacemakers. This emerging strong new evidence about the adverse hemodynamic and clinical effects of right ventricular apical pacing would dictate a reassessment of our traditional approach to permanent cardiac pacing and direct our attention to alternate sites of pacing, such as the left ventricle and/or the right ventricular outflow tract or septum, if not for all patients, at least for those with left ventricular dysfunction. Indeed, current convincing data on alternate site ventricular pacing are encouraging and this approach should be actively pursued and further investigated in future studies. CONCLUSIONS: Not only is spontaneous permanent LBBB harmful to our patients, but the iatrogenic variety produced by right ventricular apical pacing during conventional permanent pacing may also be deleterious to some patients. The compelling evidence presented herein cannot be ignored; it may dictate a change of attitude toward right ventricular apical pacing directing our attention to alternate sites of ventricular pacing and avoidance of the right ventricular apex.     

AV junctional ablation allowing more effective delivery of cardiac resynchronization therapy in patients with intra- and interatrial conduction delay

We report two patients with cardiac resynchronization therapy (CRT) devices and evidence of refractory heart failure in whom impaired intraatrial conduction in one patient, and interatrial conduction in the other, prohibited optimization of the atrioventricular (AV) timing sequence. The patient with intraatrial conduction delay exhibited late right atrial sensing and latency during right atrial pacing that required programming of a short-sensed AV delay and long-paced AV delay (wide differential AV delay). In both patients AV junctional ablation and echocardiography-guided device optimization significantly improved heart failure.     

Biventricular upgrading in patients with conventional pacing system and congestive heart failure: results and response predictors

BACKGROUND: There are few studies on cardiac resynchronization therapy (CRT) in heart failure (HF) patients with preexisting right ventricular (RV) pacing. The purpose of this study was to determine the efficacy of CRT upgrading in RV-paced patients and the predictivity of electromechanical dyssynchrony parameters (EDP) evaluated by standard echocardiography (ECHO) and tissue Doppler imaging (TDI). METHODS: Thirty-eight consecutive patients with HF [New York Heart Association (NYHA) class III or IV, LVEF < 35%], prior continuous RV pacing, and absence of atrial fibrillation were enrolled in the presence of a paced QRS > or = 150 ms and evaluated by ECHO and TDI. A responder was defined as a patient with a favorable change in NYHA class and neither HF hospitalization nor death, plus an absolute increase of LVEF > or = 10 units. RESULTS: At six-months follow-up, the whole study population had significant improvement in symptoms, systolic function, and QRS duration (P < 0.001); 32 (84%) patients had a favorable clinical outcome, 25 (66%) were considered responders according to the previous definition. Postimplant QRS was similarly reduced in both responders and nonresponders, whereas EDP had a significant improvement only in responders (P < 0.05). Using EDP, 23 (79%) patients were responders compared with 2 (22%) patients without mechanical dyssynchrony (P = 0.002). CONCLUSIONS: In HF patients with previous RV pacing, CRT is effective to improve clinical, functional outcome, and LV performance and to reduce electromechanical dyssynchrony in a large proportion of patients. Dyssynchrony evaluated by standard and TDI ECHO can be useful for CRT selection of paced patients.