medwireNews: A post-hoc analysis of the PRESERVE-HR trial has found that discontinuation of beta-blocker therapy in patients with heart failure with preserved ejection fraction (HFpEF) who have chronotropic incompetence is associated with a significant short-term improvement in maximal functional capacity, particularly among those with lower indexed left ventricular end-systolic volume (iLVESV).
“The current findings align with the notion that higher [heart rates] might be particularly beneficial for patients with HFpEF with smaller LV volumes and hyperdynamic systolic function, which are features observed in individuals with lower iLVESV,” say the investigators.
Julio Núñez (University of Valencia, Spain) and colleagues evaluated the short-term impact of stopping beta-blocker treatment for 2 weeks on peak oxygen consumption (VO2), as a measure of functional capacity, in 52 patients with stable HFpEF (New York Heart Association functional class II to III) who had chronotropic incompetence, defined as a chronotropic index less than 0.62 during a maximal cardiopulmonary exercise test, and were taking beta blockers, predominantly bisoprolol, at a median daily dose of 2.5 mg. The majority (60%) of participants were women and the mean age was 73 years.
The participants (60% women) were taking beta blockers, predominantly bisoprolol, at a median daily dose of 2.5 mg, and had a mean age of 73 years.
The enrolled patients were randomly assigned to continue (n=26) or discontinue (n=26) their beta blocker for 2 weeks, and then crossover to the other intervention. Peak VO2 was assessed through cardiopulmonary exercise testing conducted on a bicycle ergometer and was a mean of 12.4 mL/kg at baseline.
The results published in JAMA Cardiology show that stopping beta-blocker treatment led to a significant increase in peak heart rate of 30 bpm, from a mean 97 bpm at baseline, with consistent effects across various LV volumes and LVEF.
With regard to percentage peak of VO2, the greatest increases following beta-blocker withdrawal were seen among patients with small LV volumes and high LVEF. However, the differential effect was only significant for iLVESV; there was no significant effect for indexed LV end-diastolic volumes (iLVEDV) or LVEF.
The study authors also point out that “[w]hile we did not find a differential association across sex, given the trend of the data there is a possibility that women may experience a greater effect.”
Among individuals with an iLVESV below the median of 14.9 mL/m3, the predicted peak VO2 was 14.5%, which was significantly higher than the 9.8% for those with an iLVESV of 14.9 mL/m3 or above.
Moreover, the increase in heart rate achieved by beta-blocker withdrawal was associated with greater functional improvement if patients had an iLVESV below the median, where a 10 bpm increase in peak heart rate was associated with a significant 1.93% improvement in peak VO2, whereas there was no association among individuals with iLVESV at or above the median. And the change in peak heart rate was not differentially associated with peak VO2 in individuals with iLVEDV or LVEF either above or below the median.
Núñez et al suggest: “[I]n patients with HFpEF and chronotropic incompetence on treatment with β-blocker, lower iLVESV could identify patients in whom β-blocker withdrawal was associated with a greater short-term improvement in maximal functional capacity.”
They conclude: “This hypothesis-generating analysis lays the groundwork for future prospective, well-powered, and controlled studies that assess the increase in [heart rate] as a therapeutic measure in HFpEF, chronotropic incompetence, and small LV dimensions.”
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