Atrial Pacing for HFpEF Shows Lack of Benefit on Exercise Capacity

Barry A. Borlaug, MD

Credit: Mayo Clinic

The implantation of pacemakers to enhance exercise heart rate is ineffective at improving exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF) and chronotropic incompetence, according to results from the RAPID-HF randomized clinical trial.¹

The research, presented at the American College of Cardiology (ACC) 2023 Annual Scientific Sessions in New Orleans, Louisiana, suggest a direct relationship between exercise heart rate and capacity during a pacing off phase, but no benefit of pacing on patient-perceived health status or on exercise performance using objectively measured cardiopulmonary exercise metrics.

“Current guideline recommendations for pacing for chronotropic incompetence are largely based on expert opinion, including consideration of pacing in patients with HFpEF and a phenotype with chronotropic incompetence,” wrote the investigative team. “The present data do not support this recommendation.”

Led by Barry A. Borlaug, MD, Mayo Clinic and Foundation, the single-center, double-blinded RAPID-HF trial tested whether implanting pacemakers and increasing exertional heart rate through atrial pacing would improve exercise performance in patients with HFpEF and chronotropic incompetence. In the trial, maximal effort cardiopulmonary exercise testing was performed on a treadmill after 4 weeks of pacing on and after 4 weeks of pacing off to measure volume of oxygen consumed (Vo₂), carbon dioxide produced (Vco₂), breathing frequency, tidal volume, and minute ventilation.

The primary end point was change in Vo₂ at anaerobic threshold (Vo_2AT) determined by the V-slope method as the point of disproportionate rise in Vco₂ relative to Vo₂. Secondary endpoints consisted of peak aerobic capacity determined as the mean of values obtained over the final 30 seconds of exercise, ventilatory efficiency, patient-reported health status by the Kansas City Cardiomyopathy Overall Summary Score (KCCQ-OSS), and N-Terminal Pro-B-Type Natriuretic peptide levels.

A total of 32 patients were eligible for the trial, but 3 patients did not return for follow-up visits after pacemaker implantation, leaving a total of 29 patients who completed the study. Patients were described as older, obese, with high comorbidity burden and elevated NT-proBNP levels and all had HFpEF defined by ejection fraction 50% or greater.

As consistent with prior investigations in patients with HFpEF, there was a significant correlation observed between peak heart rate and Vo_2AT (r = .46. P = .02) and peak Vo₂ during the exercise test performed in the pacing-off phase (r = 0.51; P = .006).

During the exercise testing, investigators observed a significant increase in heart rate during submaximal and peak exercise in the pacing on-period, compared with the pacing-off period. In low-level exercise, mean heart rate was increased by 16/min (95% confidence interval [CI], 10 to 23; P <.001) with pacing on. At peak exercise, the mean heart rate increased by 14/min (95% CI, 7 to 21; P <.001) with pacing on compared with pacing off.

The findings suggest a lack of significant effect of pacing on the primary endpoint of Vo_2AT from pacing-off to pacing-on phases (mean difference, 0.3 mL/kg/min [95% CI, -0.5 to 1.0 m:/kg/min]; P = .46). The results additionally showed no significant difference in the secondary end points of peak Vo₂ (mean difference, 0.4 mL/kg/min) or minute ventilation/carbon dioxide production slope (mean difference, 0.5 mL/kg/min).

Moreover, the results showed no significant difference in the change in NT-proBNP level (mean difference, 53 pg/mL) or in KCCQ-OSS (mean difference, -0.9) during pacing-off compared with pacing on phases. Despite an increase in heart rate, there was no significant effect of pacing on exercise cardiac output (mean difference, -0.7 L/min).

Investigators related the absence of benefit in atrial pacing to a decrease in stroke volume during exercise, which prevented gains in cardiac output from a higher exercise heart rate during pacing. They additionally cited the increased risk of significant, clinically important adverse events during pacemaker implantation.

“There were also adverse events clearly related to pacemaker implantation, as well as an increased incidence of chest pain during pacing phases, which mechanistically could be related to pacing-related discomfort, angina from myocardial supply-demand mismatch, or both,” investigators wrote. “These data do not support use of rate-adaptive atrial pacing to treat patients with HFpEF and chronotropic incompetence.”

References

1. Reddy YNV, Koepp KE, Carter R, et al. Rate-Adaptive Atrial Pacing for Heart Failure With Preserved Ejection Fraction: The RAPID-HF Randomized Clinical Trial. JAMA. Published online March 05, 2023. doi:10.1001/jama.2023.0675