AdaptResponse - Adaptive Versus Conventional Cardiac Resynchronization Therapy in Patients With Heart Failure

Oct 16, 2023
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Author/Summarized by Author:
Amit Saha, MD
Summary Reviewer:
Anthony A. Bavry, MD, MPH, FACC
Trial Sponsor:
Medtronic
Date Published:
09/30/2023
Date Updated:
10/16/2023
Original Posted Date:
10/16/2023
References

Contribution To Literature:

The AdaptResponse trial showed that in patients with symptomatic HFrEF and LBBB in whom CRT was indicated, adaptive CRT with isolated LV pacing did not reduce the composite outcome of all-cause death or HF decompensation compared with conventional biventricular CRT.

Description:

The goal of this trial was to determine the clinical impact of adaptive cardiac resynchronization therapy (CRT) compared with conventional biventricular pacing in patients with symptomatic heart failure with reduced ejection fraction (HFrEF) and left bundle branch block (LBBB).

Study Design

  • International, multicenter
  • Randomized
  • Single-blinded

Patients with symptomatic HFrEF and LBBB were randomized in 1:1 fashion to adaptive (n = 1,810) or conventional (n = 1,807) CRT. During normal atrioventricular (AV) conduction, the AdaptivCRT algorithm (Medtronic) provides isolated left ventricular (LV) pacing timed to native right ventricular contraction. The algorithm provides dynamically optimized biventricular pacing in the setting of prolonged AV conduction. The conventional CRT group received only biventricular pacing.

  • Total number of enrollees: 3,617
  • Duration of follow-up: 5 years
  • Mean patient age: 64.9 years
  • Percentage female: 43.4%

Inclusion criteria:

  • Age ≥18 years
  • LVEF <35%
  • New York Heart Association (NYHA) class II-IV symptoms despite optimal medical therapy
  • LBBB, QRS duration ≥140 ms (for men) or ≥130 ms (for women), and native PR interval ≤200 ms

Exclusion criteria:

  • Permanent atrial arrhythmia
  • Previously receiving CRT
  • Acute coronary syndrome or coronary revascularization ≤30 days prior
  • Presence of mechanical tricuspid valve or impending tricuspid valve repair or replacement

Other salient features/characteristics:

  • Mean LVEF: 25%
  • Mean QRS duration: 163 ms
  • Implantation of CRT device with defibrillator: 95%

Principal Findings:

The primary outcome, composite of all-cause death or decompensated HF requiring intervention (intravenous diuretics and/or hospitalization) at 5 years, for adaptive vs. conventional CRT, was: 23.5% vs. 25.7% (p = 0.077).

Secondary outcomes for adaptive vs. conventional CRT:

  • All-cause death: 15.6% vs. 17.4% (p = 0.12)
  • ≥1 episode of decompensated HF requiring intervention: 13.2% vs. 14.5% (p = 0.28)

Post hoc analysis of primary outcome for:

  • ≥85% synchronized LV pacing vs. conventional CRT: hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.59-0.85 (p = 0.0002)
  • <85% synchronized LV pacing vs. conventional CRT: HR 1.02, 95% CI 0.86-1.21 (p = 0.80)

Adverse events for adaptive vs. conventional CRT:

  • Periprocedural: 19.0% vs. 21.0%
  • System-related: 25.0% vs. 24.3%

Interpretation:

The AdaptResponse trial did not demonstrate a difference in the 5-year composite outcome of all-cause death or HF decompensation with adaptive versus conventional CRT. Though the primary outcome was not met, the current data represent the largest cohort of patients with the longest follow-up enrolled in a CRT trial. Moreover, the authors note lower rates of all-cause death and HF decompensation in their study population compared to the CRT cohorts of the original CARE-HF and RAFT trials despite low rates of utilization of more novel guideline-directed medical therapies. This may be due to improved operator experience in LV pacing lead placement as well as the stricter inclusion criteria of the current trial, the population of which is most likely to benefit from CRT.

Adaptive CRT trial (2012) first demonstrated noninferiority of an adaptive CRT strategy compared with conventional biventricular CRT with respect to improvement in clinical composite score. Though the original trial was not powered for this, post hoc and registry analysis suggested improvement in mortality and HF hospitalization with adaptive CRT, particularly in patients with higher frequencies of synchronized LV pacing. This is in line with the current study’s post hoc analysis of the primary composite outcome and its components, which demonstrated significant clinical benefit in patients with a higher burden of synchronized LV pacing. Though exploratory, these findings may support a role for adaptive CRT in a subset of patients who are potentially more likely to gain meaningful clinical benefit.

References:

Wilkoff BL, Filippatos G, Leclercq C, et al. Adaptive Versus Conventional Cardiac Resynchronization Therapy in Patients With Heart Failure (AdaptResponse): A Global, Prospective, Randomized Controlled Trial. Lancet 2023;402:1147-57.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure

Keywords: Arrhythmias, Cardiac, Bundle-Branch Block, Cardiac Resynchronization Therapy, Defibrillators, Implantable, Heart Failure


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