ImportanceIncreasing 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.ObjectiveTo 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 ParticipantsThis 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.InterventionParticipants 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 MeasuresThe 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.ResultsA 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 RelevanceIn 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 RegistrationClinicalTrials.gov (NCT03871803)

中文翻译：

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射血分数保留的心力衰竭患者的 β 受体阻滞剂戒断和功能能力改善

重要性提高患者心率 (HR) 已成为射血分数保留 (HFpEF) 心力衰竭患者的一种治疗选择。然而，证据是相互矛盾的，并且从该策略中获益最多的患者的情况仍不清楚。 目的评估 β 受体阻滞剂治疗停药与预测峰值耗氧量 (VO2) 百分比变化的关系2) 涵盖 HFpEF 和变时性功能不全患者的指数左心室舒张压 (iLVEDV) 和指数左心室收缩容积 (iLVESV) 以及左心室射血分数 (LVEF)。 设计、设置和参与者此事后分析是使用来自研究者盲法多中心、随机和交叉临床试验 PRESERVE-HR，于 2018 年 10 月 1 日至 2020 年 12 月 31 日进行，旨在研究 β 受体阻滞剂停药对峰值氧的短期影响（2 周）消耗（峰值摄氧量2）。接受 β 受体阻滞剂治疗且变时功能不全的稳定 HFpEF（纽约心脏协会功能分级 II 至 III）的患者也被纳入其中。 干预 PRESERVE-HR 试验的参与者被随机分配退出或继续接受 β 受体阻滞剂治疗。两周后，他们被交叉接受相反的干预。这项交叉随机临床试验检查了 β 受体阻滞剂停药对峰值摄氧量的短期影响2主要结果和措施主要结果是评估β受体阻滞剂戒断与峰值摄氧量百分比短期变化之间的关联2对接受 β 受体阻滞剂治疗的 HFpEF 和变时性功能不全患者的 iLVEDV、iLVESV 和 LVEF 进行比较。 结果 总共 52 名患者（平均年龄，73 [SD，13] 岁；60% 女性）被随机分组​​。平均静息心率、峰值心率、峰值摄氧量2和峰值 VO 的百分比2分别为每分钟 65 (SD, 9) 次 (bpm)、97 (SD, 15) bpm、每分钟 12.4 (SD, 2.9) mL/kg 和 72.4% (SD, 17.7%)。iLVEDV、iLVESV 和 LVEF 的中位数（最小值 - 最大值）为 44 mL/m2（IQR，19-82），15 毫升/米2分别为 (IQR, 7-32) 和 64% (IQR, 52%-78%)。停止 β 受体阻滞剂治疗后，峰值 HR 的中位增加增加了 30 bpm（95% CI，25-35；磷< .001）。β-受体阻滞剂停用与峰值摄氧量百分比的变化存在差异相关2跨越 iLVESV 的连续体（磷交互作用 = .02)，表明 iLVESV 较低的患者获益更大。结论和相关性在这项研究中，结果表明，在接受 β 受体阻滞剂治疗的 HFpEF 和变时性功能不全的患者中，较低的 iLVESV 可能会识别出那些具有较大短时间功能的患者。停止β受体阻滞剂治疗后最大功能能力的长期改善。需要进一步研究进行进一步调查。试验注册ClinicalTrials.gov（NCT03871803）