FISABIO. Universitat Jaume I, Castellón, Spain.
Cardiology Department, Hospital de Denia, Alicante, Spain.
Clin Cardiol. 2020 May;43(5):423-429. doi: 10.1002/clc.23345. Epub 2020 Feb 19.
The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is complex and multifactorial. Chronotropic incompetence (ChI) has emerged as a crucial pathophysiological mechanism. Beta-blockers, drugs with negative chronotropic effects, are commonly used in HFpEF, although current evidence does not support its routine use in these patients.
We postulate beta-blockers may have deleterious effects in HFpEF and ChI. This work aims to evaluate the short-term effect of beta-blockers withdrawal on functional capacity assessed by the maximal oxygen uptake (peakVO2) in patients with HFpEF and ChI.
This is a prospective, crossover, randomized (1:1) and multicenter study. After randomization, the clinical and cardiac rhythm will be continuously registered for 30 days. PeakVO2 is assessed by cardiopulmonary exercise testing (CPET) at 15 and 30 days in both groups. Secondary endpoints include quality of life, cognitive, and safety assessment. Patients with stable HFpEF, functional class New York Heart Association (NYHA) II-III, chronic treatment with beta-blockers, and ChI will be enrolled. A sample size estimation [alfa: 0.05, power: 90%, a 20% loss rate, and delta change of mean peakVO2: +1.2 mL/kg/min (SD ± 2.0)] of 52 patients is necessary to test our hypothesis.
Patients started enrolling in October 2018. As January 14th, 2020, 28 patients have been enrolled. It is projected to enroll the last patient at the end of July 2020.
Optimizing therapy that improves functional capacity remains an unmeet priority in HFpEF. Deprescribing beta-blockers in patients with HFpEF and ChI seems a plausible intervention to improve functional capacity. This trial is an attempt towards precision medicine in this complex syndrome.
ClinicalTrials.gov: NCT03871803.
射血分数保留的心力衰竭（HFpEF）的病理生理学复杂且多因素。变时性功能不全（ChI）已成为一个关键的病理生理机制。β受体阻滞剂具有负性变时作用，常用于 HFpEF，但目前的证据并不支持在这些患者中常规使用。
我们假设β受体阻滞剂可能对 HFpEF 和 ChI 有不良影响。本研究旨在评估 HFpEF 合并 ChI 患者停用β受体阻滞剂对最大摄氧量（peakVO2）评估的功能能力的短期影响。
这是一项前瞻性、交叉、随机（1:1）和多中心研究。随机分组后，连续 30 天记录临床和心脏节律。两组均在第 15 天和第 30 天进行心肺运动试验（CPET）评估 peakVO2。次要终点包括生活质量、认知和安全性评估。纳入稳定的 HFpEF、纽约心脏协会（NYHA）心功能 II-III 级、慢性β受体阻滞剂治疗且合并 ChI 的患者。假设检验需要 52 例患者的样本量估计[α：0.05，效能：90%，平均 peakVO2 变化值：+1.2 mL/kg/min（标准差±2.0），20%失访率，delta 变化]。
患者于 2018 年 10 月开始入组。截至 2020 年 1 月 14 日，已有 28 例患者入组。预计将于 2020 年 7 月底入组最后一名患者。
优化改善功能能力的治疗方法仍然是 HFpEF 未满足的首要任务。HFpEF 合并 ChI 患者停用β受体阻滞剂似乎是改善功能能力的合理干预措施。本试验是对这一复杂综合征进行精准医学的尝试。
ClinicalTrials.gov：NCT03871803。
