RAPID-HF: Rate-Adaptive Pacing Doesn’t Help in HFpEF

NEW ORLEANS, LA—Rate-adaptive atrial pacing to increase heart rate during exercise is not a useful strategy in patients who have heart failure with preserved ejection fraction (HFpEF) and chronotropic incompetence, the RAPID-HF trial shows.

Although the approach successfully boosted heart rate, that didn’t translate into improvements in exercise performance or health status, Barry Borlaug, MD (Mayo Clinic, Rochester, MN), reported to attendees of the American College of Cardiology/World Congress of Cardiology (ACC/WCC) 2023 meeting via livestream.

“The absence of benefit may relate to a decrease in stroke volume during exercise, which may have prevented gains in cardiac output,” Borlaug said, noting that adverse events linked to the pacemaker implant were “not uncommon.”

The findings, published simultaneously online in JAMA, “do not support the use of rate-adaptive atrial pacing to treat patients with HFpEF and chronotropic incompetence,” he concluded.

Speaking with TCTMD, Dalane Kitzman, MD (Wake Forest University School of Medicine, Winston-Salem, NC), lead author of an accompanying editorial in JAMA, predicted that these findings will change guidelines around who should be treated with rate-adaptive atrial pacing. Although there are no recommendations to use the strategy specifically in the setting of HFpEF, current guidance could be interpreted to mean that it may be considered in the HFpEF subset with chronotropic incompetence, he said.

“This study was very well designed and adequately powered and well conducted, and we believe that it was a strong, perhaps definitive, test of the question at hand,” Kitzman commented. He added that it “should lead to a serious reconsideration of the guidelines perhaps to even include that this technique, this strategy, should not be routinely considered for HFpEF patients.”

The RAPID-HF Trial

Borlaug noted that prior studies have shown that patients with a reduced ability to increase their heart rate during exercise—ie, chronotropic incompetence—have worse exercise capacity. Exercise intolerance marked by dyspnea and fatigue is the main symptom in patients with HFpEF, roughly half of whom have chronotropic incompetence.

In the single-center RAPID-HF trial, the investigators tested whether increasing exertional heart rate during exercise through rate-adaptive pacing would improve exercise performance in patients with HFpEF. They recruited 29 patients with HFpEF (LVEF > 40%), NYHA class II/III symptoms, chronotropic incompetence, and no other indications for pacemaker implantation. Mean patient age was 66, and 45% of participants were women. Average LVEF was about 62%.

After patients had recovered from pacemaker implantation, they were randomized to 4 weeks of having atrial pacing on or off. After a 4-week washout period, they were crossed over to the other pacing status for another 4 weeks.

As intended, rate-adaptive atrial pacing significantly increased heart rate during submaximal and peak exercise compared with having pacing turned off.

That did not, however, lead to an improvement in the primary endpoint of oxygen consumption at the anaerobic threshold, which was 10.4 mL/kg/min in the pacing-on group and 10.7 mL/kg/min in the pacing-off group (P = 0.46).

There also were no benefits observed across several secondary endpoints, including peak oxygen consumption, ventilatory efficiency, change in NT-proBNP levels, and change in health status according to the Kansas City Cardiomyopathy Questionnaire overall summary score.

The investigators found that there was no significant effect on peak exercise cardiac output from atrial pacing, but a significant reduction in peak exercise stroke volume (mean 88 vs 112 mL; P = 0.02). “This is what we expect explains the neutral results,” Borlaug said.

The lack of beneficial effects was accompanied by a rate of pacemaker-related adverse events of 21%. Those included once case each of pericardial effusion requiring drainage, tricuspid regurgitation induced by the pacing lead, and upper-extremity deep venous thrombosis, as well as three incision-site reactions.

Searching for Other Solutions

Kitzman called the completion of RAPID-HF “a remarkable and important accomplishment,” noting that several prior attempts at similar studies have failed.

The findings are not necessarily surprising, he said, because prior studies in other types of patients also have shown that increases in heart rate can be counteracted by decreases in stroke volume.

The study indicates that rate-adaptive atrial pacing doesn’t improve exercise capacity in patients with HFpEF and chronotropic incompetence, but there is an additional lesson to be learned from the effort, Kitzman said—namely, that it’s not just the function of the heart that’s causing symptoms in HFpEF.

“This should remind us that there’s other components that contribute to symptoms in patients with this disorder, including skeletal muscle dysfunction, which has been considerably overlooked,” he said. Abnormalities of skeletal muscle are easier to address—with exercise training, for example—than are abnormalities of heart muscle.

“So the other thing that this study reminds us is that HFpEF, while called heart failure, is actually a systemic disorder and includes important contributions from the heart, the blood vessels, the skeletal muscle, kidneys, lungs, and brain,” Kitzman said. “While continuing to focus on strategies that’ll improve the heart abnormalities, we should not overlook that there’s important opportunities by addressing the other contributors to patient symptoms.”