Rate-adaptive atrial pacing does not improve exercise performance in HFpEF

Rate-Adaptive Atrial Pacing for Heart Failure with preserved Ejection Fraction: The RAPID-HF trial

News - Mar. 7, 2023

Presented at the ACC.23 by: Barry Borlaug, MD - Rochester, MN, USA

Introduction and methods

Patients with HFpEF often experience a reduced heart rate during exercise, which is associated with reduced aerobic capacity. It is not clear whether restoring the exertional heart rate with atrial pacing is beneficial and safe in this population. The RAPID-HF (Rate-Adaptive Atrial Pacing In Diastolic Heart Failure) trial was designed to examine whether implantation of pacemaker to to augment exertional heart rate by rate-adaptive atrial pacing can improve exercise performance in HFpEF patients with chronotropic incompetence (i.e., inability to reach expected peak heart rates).

The RAPID-HF trial was a single-center, double-blind, crossover RCT in which 29 patients with symptomatic HFpEF (LVEF ≥40%) and chronotropic incompetence (as defined by low heart-rate reserve) underwent pacemaker implantation. After a 4-week recovery period, they were randomized to atrial rate–responsive pacing or no pacing for 4 weeks, followed by a 4-week washout period. Thereafter, they were crossed over to the other study arm for an additional 4 weeks.

The primary endpoint was oxygen consumption at anaerobic threshold (VO2,AT). Secondary endpoints were peak VO2, ventilatory efficiency (VE/VCO2 slope), patient-reported health status as assessed by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), NT-proBNP level, and safety .

Main results

  • In the absence of pacing, both peak VO2 (r=0.51; P=0.006) and VO2,AT (r=0.46; P=0.02) were correlated with peak exercise heart rate.
  • Atrial pacing increased heart rate during submaximal and peak exercise compared to the pacing-off period(both P<0.0001). However, there was no significant change between the pacing-off and pacing-on phases in VO2,AT (absolute difference: +0.3 mL/kg per min; 95%CI: -0.5 to 1.0; P=0.46), peak VO2 (+0.4 mL/kg per min; 95%CI: -0.4 to 1.2; P=0.27), VE/VCO2 slope (+0.5; 95%CI: -0.6 to 1.6; P=0.34), KCCQ-OSS (-0.9; 95%CI: -11.0 to 9.3; P=0.86), or NT-proBNP level (+53 pg/mL; 95%CI: -117 to 221; P=0.53).
  • Exploratory mechanistic analyses showed that despite the increase in heart rate, atrial pacing had no effect on cardiac output at peak exercise (-0.7 L/min; 95%CI: -1.7 to 0.3; P=0.14). This was related to a decrease in peak exercise stroke volume (-24 mL; 95%CI: -43 to -5; P=0.02).
  • In 6 of the 29patients (21%), adverse events judged to be related to the pacemaker device were observed; 1 serious adverse event (pericardial effusion) was judged to be related to pacemaker implantation. Minor adverse events occurred in 8 patients (28%) during the pacing-off phase and in 7 (24%) during the pacing-on phase.


In 29 HFpEF patients with chronotropic incompetence, rate-adaptive atrial pacing did not improve exercise performance or health status. In addition, pacemaker implantation was associated with more adverse events.

-Our reporting is based on the information provided at the ACC.23-

The results of this study were simultaneously published in JAMA .

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