Beta-blocker cessation benefits HFpEF patients with chronotropic incompetence and smaller end-systolic left ventricular volume: JAMA

In the analysis that enrolled 52 patients with HFpEF and chronotropic incompetence taking β-blocker treatment, "lower left ventricular systolic volumes identified patients in which β-blocker cessation was linked with a greater short-term improvement in maximal functional capacity," the researchers reported in JAMA Cardiology.

In patients with HFpEF, chronotropic incompetence has emerged as a relevant pathophysiological mechanism. Specifically, chronotropic incompetence has been associated with worse clinical outcomes and functional capacity. For this reason, increasing the patient's heart rate (HR) has emerged as a promising therapeutic option in HFpEF patients. However, the evidence is conflicting, and there is no clarity on the profile of patients who benefit most from this strategy.

Against the above background, Patricia Palau and colleagues from Spain assessed the association of β-blocker treatment withdrawal with changes in the percentage of predicted peak oxygen consumption (VO2) across indexed left ventricular systolic (iLVESV) and indexed left ventricular diastolic volumes (iLVEDV) and left ventricular ejection fraction (LVEF) in patients with HFpEF and chronotropic incompetence.

For the post hoc analysis, the research team used data from the PRESERVE-HR, an investigator-blinded multicenter, randomized, and crossover clinical trial, that took place from 2018 to 2020, to investigate the short-term effects (2 weeks) of β-blocker withdrawal on peak VO2. It included patients with stable HFpEF (New York Heart Association functional class II to III) receiving treatment with β-blocker and chronotropic incompetence.

PRESERVE-HR trial participants were randomized to withdraw versus continue with β-blocker treatment. Following 2 weeks, they were crossed over to receive the opposite intervention. The crossover randomized clinical trial investigated the short-term effect of β-blocker withdrawal on peak VO2. A total of 52 patients (mean age, 73 years; 60% female) were randomized.

The study's primary outcome was to determine the association between β-blocker withdrawal and short-term changes in the percentage of peak VO2 across iLVESV, iLVEDV, and LVEF in patients with HFpEF and chronotropic incompetence treated with β-blocker.

The researchers reported the following findings:

• The mean resting HR, peak HR, peak VO2, and percentage of peak VO2 were 65 beats per minute (bpm), 97 bpm, 12.4 mL/kg per minute, and 72.4%, respectively.
• The medians (minimum-maximum) of iLVEDV, iLVESV, and LVEF were 44 mL/m2, 15 mL/m2, and 64%, respectively.
• After stopping β-blocker treatment, the median increase in peak HR was plus 30 bpm.
• β-Blocker cessation was differentially associated with a change in the percentage of peak VO2 across the continuum of iLVESV, indicating a greater benefit in those with lower iLVESV.

The findings showed that in patients with HFpEF and chronotropic incompetence receiving β-blocker treatment, lower iLVESV may identify those with a greater short-term improvement in maximal functional capacity after stopping β-blocker treatment.

"Further studies are warranted for further investigation," the research team concluded.

Reference:

Palau P, de la Espriella R, Seller J, et al. β-Blocker Withdrawal and Functional Capacity Improvement in Patients With Heart Failure With Preserved Ejection Fraction. JAMA Cardiol. Published online February 07, 2024. doi:10.1001/jamacardio.2023.5500