Elsevier

Heart Rhythm

Volume 10, Issue 8, August 2013, Pages 1136-1143
Heart Rhythm

Atrioventricular delay programming and the benefit of cardiac resynchronization therapy in MADIT-CRT

https://doi.org/10.1016/j.hrthm.2013.04.013Get rights and content

Background

The optimal atrioventricular pacing delay (AVD) in cardiac resynchronization therapy (CRT) remains to be determined.

Objective

To determine whether programming CRT devices to short AVD (S-AVD) will improve clinical response secondary to greater reductions in dyssynchrony.

Methods

The study population comprised 1235 patients with left bundle branch block enrolled in Multicenter Automatic Defibrillator Implantation Trial in Cardiac Resynchronization Therapy (MADIT-CRT). We assessed the relationship between AVD and outcomes. Patients programmed to S-AVD (median value of <120 ms; n = 337) vs long AVD (L-AVD; ≥120 ms; n = 390) were assessed for the end points of heart failure (HF) or death, death alone, and echocardiographic response to the CRT at 1-year follow-up. Outcomes were also compared to the left bundle branch block implantable cardioverter-defibrillator-only group (n = 508).

Results

Multivariate analysis showed that patients programmed to S-AVD experienced a significant 33% (hazard ratio [HR] 0.67; 95% confidence interval [CI] 0.44–0.85; P = .037) reduction in the risk of HF or death and a 47% (HR 0.53; 95% CI 0.29–0.94; P = .031) reduction in death alone as compared with those programmed to L-AVD. Patients with CRT-programmed S-AVD and L-AVD experienced 63% (HR 0.37; 95% CI 0.26–0.53; P < .001) and 46% (HR 0.54; 95% CI 0.31–0.96; P < .001) reduction, respectively, in the risk of HF or death compared to patients with implantable cardioverter-defibrillator alone. At 1 year of follow-up, S-AVD vs L-AVD was associated with a greater reduction in left ventricular end-systolic volume (34.2% vs 30.8%; P = .002) along with a significantly greater improvement in dyssynchrony (22.3% vs 9.4%; P = .036).

Conclusions

Our findings indicate that in MADIT-CRT programming, the CRT AVD <120 ms was associated with a greater clinical and echocardiographic response to CRT.

Introduction

Cardiac resynchronization therapy-defibrillator (CRT-D) has proven beneficial in patients with symptomatic systolic heart failure (HF) and prolonged QRS duration.1, 2, 3, 4, 5, 6 Nevertheless, up to 30% of the patients treated with CRT-D will not experience a favorable response.6 Achieving optimal outcomes from CRT-D have been shown to depend, in part, on programming of the atrioventricular delay (AVD).7, 8 The suboptimal programming of the AVD can lead to persistent atrioventricular dyssynchrony, diastolic mitral regurgitation, and a reduction in cardiac output with attenuated CRT-D efficacy.9, 10

Complicating the matter, the major randomized controlled CRT-D trials have all used different AV optimization techniques with similar CRT-D efficacy and clinical nonresponder rates.1, 2, 3, 4, 5, 6 Multiple studies of variable size and follow-up duration have examined AVD optimization techniques in patients treated with CRT-D with inconsistent results,7, 8, 9, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 whereas the negative SMART-AV trial was the only randomized clinical study to examine the effect of a prespecified AVD programming algorithm.15 Thus, currently the optimal value for AVD programming remains unknown.

Current AVD programming in CRT devices is usually performed at rest and may therefore overestimate the optimal interval for pacing during exercise or sympathetic activation. Thus, programming to a short AVD (S-AVD) may lead to a greater degree of biventricular pacing in a clinical setting. Accordingly, we hypothesized that an S-AVD programming will be associated with improved clinical and echocardiographic response to treatment with CRT-D among patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial in Cardiac Resynchronization Therapy (MADIT-CRT) trial.

Section snippets

Study population

The design and results of the MADIT-CRT trial have been reported previously.1 Briefly, 1820 patients enrolled at 110 centers in the United States, Canada, and Europe who had ischemic or nonischemic cardiomyopathy, an ejection fraction of ≤0.30, and abnormal intraventricular conduction with QRS ≥130 ms were randomized to receive CRT-D or implantable cardioverter-defibrillator (ICD) therapy in a 3:2 ratio. Exclusion criteria included an existing indication for CRT-D, New York Heart Association

Patient characteristics

The clinical characteristics of the 1235 included patients dichotomized by device therapy and AVD programming are displayed in Table 1. Among patients treated with CRT-D, the mean ± SD AVD was 119.8 ± 42.3 ms, with a median of 120 ms (interquartile range [IQR] of 90–130 ms and a range of 40–300 ms). Mean programmed AVD for patients with S-AVD was 90 ms with a range of 40–119 ms (median 90 ms; IQR of 80–105 ms), while patients with L-AVD had a mean AVD of 145 ms and a range of 120–300 ms (median

Discussion

The present study is the first to examine the association between CRT-D AVD programming and long-term clinical outcomes in patients with mildly symptomatic HF. We have shown that S-AVD programming (<120 ms) was independently associated with significant reductions in HF and death compared with L-AVD. In a correlative fashion, we have illustrated the positive relationship between S-AVD programming and greater echocardiographic response to CRT-D.

AVD programming in MADIT-CRT primarily used an

Conclusions and clinical implications

The present study is the first to explore the effect of AVD programming on the long-term risk of HF or death in patients with mildly symptomatic CRT-D HF and with LV dysfunction. We have shown that a short AVD resulted in more profound positive ventricular remodeling, resynchronization, and significant reductions in HF and mortality. Importantly, our findings indicate that AVD programming plays an important role in the long-term efficacy of CRT-D and that S-AVD values are clinically beneficial.

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      A subanalysis of the MADIT-CRT trial included 1,235 patients with mildly symptomatic heart failure and left bundle branch block implanted with CRT with defibrillator or ICD and showed that patients with a short programmed CRT atrioventricular delay (<120 ms) had a lower risk of heart failure or death compared with both those with a long programmed CRT atrioventricular delay (>120 ms) and those in the ICD-only group (97). The effect was independent of baseline PR interval (97). In patients with heart failure and an indication for bradycardia pacing who do not meet CRT eligibility criteria, biventricular pacing is advantageous compared with right ventricular pacing (Class IIa recommendation in the European Society of Cardiology guidelines) (59,98,99).

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      The atrioventricular delay was optimized by using echocardiography. The median value was 100 ms (range 100–120 ms); as proportion of PR interval, ms 57.0% (range, 49.0%–66.7%), which is consistent with experimental studies8 and best clinical outcomes.9 Simultaneous BV pacing was applied in 90.7% and sequential in 9.3%.

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      Acute studies of programming suggest little effect of altering the inter-ventricular (VV) pacing interval on blood pressure or cardiac function in most patients but substantial differences with atrioventricular (AV) programming.45,46 This finding implies that AV resynchronization might be more clinically important than VV resynchronization, as also suggested by a recent analysis of the MADIT-CRT (Multicenter Automatic Defibrillator Implantation with Cardiac Resynchronization Therapy) study.47 If this is true, then CRT may deliver little or even no benefit in the absence of atrial systole.

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    The MADIT-CRT study was supported by a research grant from Boston Scientific, St Paul, Minnesota, to the University of Rochester School of Medicine and Dentistry.

    1

    Dr Barsheshet is a Mirowski-Moss Career Development Award Recipient in Cardiology.

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