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At ACC 2023, results from the RAPID-HF trial reported atrial pacing was ineffective at improving exercise capacity in patients with HFpEF and chronotropic incompetence.
Can you briefly describe the key findings from the RAPID-HF trial?1
We know that chronotropic incompetence or inability to increase heart correctly with exercise is common in HFpEF and it’s associated with poor exercise capacity. But, it’s remained unknown whether increasing the heart rate with pacing would improve exercise capacity. To bridge this gap, we carried out this double-blind crossover trial where we implanted patients with HFpEF with a pacemaker.
Then, they had two phases. They had one 4-week phase where they had rate responsive pacing on and one phase where they had the pacing off. At the conclusion of each of these 4-week phases, they had a maximal effort, cardiopulmonary exercise test to measure oxygen consumption at anaerobic threshold and peak oxygen consumption, as well as other measures like ventilatory efficiency.
What we found was that pacing-on increased heart rate, certainly, but despite the fact that it increased heart rate, it did not improve exercise capacity. This was because stroke volume decreased. Cardiac output is equal to stroke volume times heart rate, so the heart rate was going up, but the stroke volume was not being maintained. So, there was no increase in cardiac output. We suspect that is why it didn’t lead to the improvements that we were hoping for in an exercise capacity.
Can you juxtapose your findings with the myPACE Randomized Clinical Trial published in JAMA Cardiology?2
They’re quite different. That was not a trial of rate-responsive atrial pacing, which was setting the resting heart rate to a higher value, based on some parameters like height instead of a blanket lower setting of 50 or 60 beats per minute. That was associated over a year with some favorable effects on quality of life and brain natriuretic peptide (BNP) and things like that.
This was different. We were not targeting resting heart rate at all, we were just trying to enhance exercise heart rate. Things are much different during exercise than they are at rest. Market changes in loading conditions, sympathetic, and parasympathetic innervation. Plus, ventilatory changes, muscle changes, and metabolic changes.
They’re two very different questions, I think. The other trial also was only performed on people that already had pacemakers. Whereas in this study, we were taking people with no pacemaker who would not normally get a pacemaker. Usually, you put pacemakers in for something like high-grade AV block; these patients don’t meet these criteria. That was a little bit of a key difference as well.
Do you think that based on your findings, the current guidelines would change? What is the larger effect of this trial’s findings?
I'm not exactly sure how it will be interpreted. I think that this definitely speaks against pacing for this purpose, for chronotropic incompetence and HFpEF. We were adequately powered to see a clinically significant effect. We didn't see it.
Frankly, it's not performed that often anyway these days. And I think that it's very unlikely that people are going to be using it a lot. So my guess is that the guidelines would come out against this. For lack of benefit, not for safety concerns, but for lack of benefit.
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
2. 2. Infeld M, Wahlberg K, Cicero J, et al. Effect of Personalized Accelerated Pacing on Quality of Life, Physical Activity, and Atrial Fibrillation in Patients With Preclinical and Overt Heart Failure With Preserved Ejection Fraction: The myPACE Randomized Clinical Trial. JAMA Cardiol. Published online February 01, 2023. doi:10.1001/jamacardio.2022.5320