Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2024 Apr 1;9(4):392-396.
doi: 10.1001/jamacardio.2023.5500.

β-Blocker Withdrawal and Functional Capacity Improvement in Patients With Heart Failure With Preserved Ejection Fraction

Patricia Palau  1 , Rafael de la Espriella  1 , Julia Seller  2 , Enrique Santas  1 , Eloy Domínguez  1   3 , Vicent Bodí  1   4 , Juan Sanchis  1   4 , Eduardo Núñez  1 , Antoni Bayés-Genís  4   5 , Vicente Bertomeu-González  6 , Markus Meyer  7 , Julio Núñez  1   4
Affiliations
Randomized Controlled Trial

β-Blocker Withdrawal and Functional Capacity Improvement in Patients With Heart Failure With Preserved Ejection Fraction

Patricia Palau et al. JAMA Cardiol. .

Abstract

Importance: Increasing the patient's heart rate (HR) has emerged as a therapeutic option in patients with heart failure with preserved ejection fraction (HFpEF). However, the evidence is conflicting, and the profile of patients who benefit most from this strategy remains unclear.

Objective: To assess the association of β-blocker treatment withdrawal with changes in the percentage of predicted peak oxygen consumption (VO2) across indexed left ventricular diastolic (iLVEDV) and indexed left ventricular systolic volumes (iLVESV), and left ventricular ejection fraction (LVEF) in patients with HFpEF and chronotropic incompetence.

Design, setting, and participants: This post hoc analysis was conducted using data from the investigator-blinded multicenter, randomized, and crossover clinical trial, PRESERVE-HR, that took place from October 1, 2018, through December 31, 2020, to investigate the short-term effects (2 weeks) of β-blocker withdrawal on peak oxygen consumption (peak VO2). Patients with stable HFpEF (New York Heart Association functional class II to III) receiving treatment with β-blocker and chronotropic incompetence were included.

Intervention: Participants in the PRESERVE-HR trial were randomized to withdraw vs continue with β-blocker treatment. After 2 weeks, they were crossed over to receive the opposite intervention. This crossover randomized clinical trial examined the short-term effect of β-blocker withdrawal on peak VO2.

Main outcomes and measures: The primary outcome was to evaluate the association between β-blocker withdrawal and short-term changes in percentage of peak VO2 across iLVEDV, iLVESV, and LVEF in patients with HFpEF and chronotropic incompetence treated with β-blocker.

Results: A total of 52 patients (mean age, 73 [SD, 13] years; 60% female) were randomized. The mean resting HR, peak HR, peak VO2, and percentage of peak VO2 were 65 (SD, 9) beats per minute (bpm), 97 (SD, 15) bpm, 12.4 (SD, 2.9) mL/kg per minute, and 72.4% (SD, 17.7%), respectively. The medians (minimum-maximum) of iLVEDV, iLVESV, and LVEF were 44 mL/m2 (IQR, 19-82), 15 mL/m2 (IQR, 7-32), and 64% (IQR, 52%-78%), respectively. After stopping β-blocker treatment, the median increase in peak HR was plus 30 bpm (95% CI, 25-35; P < .001). β-Blocker cessation was differentially associated with change of percentage of peak VO2 across the continuum of iLVESV (P for interaction = .02), indicating a greater benefit in those with lower iLVESV.

Conclusions and relevance: In this study, results showed that in patients with HFpEF and chronotropic incompetence receiving treatment with β-blocker, 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.

Trial registration: ClinicalTrials.gov (NCT03871803).

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Bayés-Genís reported personal fees from Abbott, AstraZeneca, Boehringer Ingelheim, Novartis, Bayer, Roche Diagnostics, and Vifor outside the submitted work. Dr Bertomeu-Gonzalez reported personal fees from Daiichi, Bayer, Pfizer/Bristol Myers Squibb, and Boehringer Ingelheim, and nonfinancial support from Medtronic, outside the submitted work. Dr Meyer reported grants from Medtronic Research Grant outside the submitted work. Dr J. Núñez reported grants from CIBER Cardiovascular and grants from Carlos III Health Institute: FIS (PI17/01426) during the conduct of the study; personal fees from Alleviant, Bayer, Novartis, AstraZeneca, Boehringer Ingelheim, Rovi, and NovoNordisk outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Effect of β-Blocker Withdrawal on the Percentage of Predicted Peak Oxygen Consumption (VO2) Across the Continuum of Left Ventricular Volumes and Left Ventricular Ejection Fraction
Individual patient data are shown. The orange line indicates the regression lines and the shaded area represents the 95% CIs.
Figure 2.
Figure 2.. Effect of the β-Blocker Withdrawal on Percentage of Predicted Peak Oxygen Consumption (VO2) Across the Median of Left Ventricular (LV) Volumes and Left Ventricular Ejection Fraction (LVEF)
X-axis refers to association with predicted percentage changes in peak VO2 after stopping β-blocker treatment across subgroups (LV volumes and LVEF). iLVEDV indicates indexed left ventricular diastolic volume; iLVESV; indexed left ventricular systolic volume.
See this image and copyright information in PMC

References

    1. Zweerink A, van der Lingen ACJ, Handoko ML, van Rossum AC, Allaart CP. Chronotropic incompetence in chronic heart failure. Circ Heart Fail. 2018;11(8):e004969. doi:10.1161/CIRCHEARTFAILURE.118.004969 - DOI - PubMed
    1. Redfield MM, Borlaug BA. Heart failure with preserved ejection fraction: a review. JAMA. 2023;329(10):827-838. doi:10.1001/jama.2023.2020 - DOI - PubMed
    1. Palau P, Domínguez E, Seller J, et al. . Chronotropic index and long-term outcomes in heart failure with preserved ejection fraction. Rev Esp Cardiol (Engl Ed). 2023;76(7):511-518. doi:10.1016/j.recesp.2022.08.002 - DOI - PubMed
    1. Domínguez E, Palau P, Núñez E, et al. . Heart rate response and functional capacity in patients with chronic heart failure with preserved ejection fraction. ESC Heart Fail. 2018;5(4):579-585. doi:10.1002/ehf2.12281 - DOI - PMC - PubMed
    1. Palau P, Seller J, Domínguez E, et al. . Effect of β-blocker withdrawal on functional capacity in heart failure and preserved ejection fraction. J Am Coll Cardiol. 2021;78(21):2042-2056. doi:10.1016/j.jacc.2021.08.073 - DOI - PubMed

Publication types

Substances

Associated data