Leeds Institute of Cardiovascular and Metabolic Medicine (J.G., J.E.L., M.F.P., C.A.C., R.B., A.O.K., H.C., L.C.K., S.S., R.M.C., M.T.K., K.K.W.), University of Leeds, United Kingdom.
Faculty of Biological Sciences, School of Medicine (T.S.B.), University of Leeds, United Kingdom.
Circulation. 2020 May 26;141(21):1693-1703. doi: 10.1161/CIRCULATIONAHA.119.045066. Epub 2020 Apr 17.
Heart failure with reduced ejection fraction (HFrEF) is characterized by blunting of the positive relationship between heart rate and left ventricular (LV) contractility known as the force-frequency relationship (FFR). We have previously described that tailoring the rate-response programming of cardiac implantable electronic devices in patients with HFrEF on the basis of individual noninvasive FFR data acutely improves exercise capacity. We aimed to examine whether using FFR data to tailor heart rate response in patients with HFrEF with cardiac implantable electronic devices favorably influences exercise capacity and LV function 6 months later.
We conducted a single-center, double-blind, randomized, parallel-group trial in patients with stable symptomatic HFrEF taking optimal guideline-directed medical therapy and with a cardiac implantable electronic device (cardiac resynchronization therapy or implantable cardioverter-defibrillator). Participants were randomized on a 1:1 basis between tailored rate-response programming on the basis of individual FFR data and conventional age-guided rate-response programming. The primary outcome measure was change in walk time on a treadmill walk test. Secondary outcomes included changes in LV systolic function, peak oxygen consumption, and quality of life.
We randomized 83 patients with a mean±SD age 74.6±8.7 years and LV ejection fraction 35.2±10.5. Mean change in exercise time at 6 months was 75.4 (95% CI, 23.4 to 127.5) seconds for FFR-guided rate-adaptive pacing and 3.1 (95% CI, -44.1 to 50.3) seconds for conventional settings (analysis of covariance; =0.044 between groups) despite lower peak mean±SD heart rates (98.6±19.4 versus 112.0±20.3 beats per minute). FFR-guided heart rate settings had no adverse effect on LV structure or function, whereas conventional settings were associated with a reduction in LV ejection fraction.
In this phase II study, FFR-guided rate-response programming determined using a reproducible, noninvasive method appears to improve exercise time and limit changes to LV function in people with HFrEF and cardiac implantable electronic devices. Work is ongoing to confirm our findings in a multicenter setting and on longer-term clinical outcomes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02964650.
射血分数降低的心力衰竭（HFrEF）的特征是心率与左心室（LV）收缩力之间的正相关关系变钝，即力-频率关系（FFR）。我们之前曾描述过，根据个体的无创 FFR 数据，对 HFrEF 患者的心脏植入式电子设备的率反应编程进行定制，可以在急性情况下改善运动能力。我们旨在研究使用 FFR 数据来定制 HFrEF 患者的心率反应是否会在 6 个月后对运动能力和 LV 功能产生有利影响。
我们在接受最佳指南指导的药物治疗且植入心脏植入式电子设备（心脏再同步治疗或植入式心脏复律除颤器）的稳定症状性 HFrEF 患者中进行了一项单中心、双盲、随机、平行组试验。参与者按 1:1 的比例随机分为基于个体 FFR 数据的定制率反应编程组和传统年龄指导的率反应编程组。主要终点测量指标为跑步机步行测试中行走时间的变化。次要终点包括 LV 收缩功能、峰值耗氧量和生活质量的变化。
我们随机分配了 83 名患者，平均年龄为 74.6±8.7 岁，左心室射血分数为 35.2±10.5。6 个月时运动时间的平均变化为 FFR 指导的率适应性起搏组为 75.4（95%CI，23.4 至 127.5）秒，常规设置组为 3.1（95%CI，-44.1 至 50.3）秒（协方差分析；两组之间的差异为 0.044），尽管平均峰值心率（98.6±19.4 与 112.0±20.3 次/分钟）较低。FFR 指导的心率设置对 LV 结构或功能没有不良影响，而常规设置与 LV 射血分数降低有关。
在这项 II 期研究中，使用可重复、无创的方法确定的 FFR 指导的率反应编程似乎可以改善 HFrEF 和心脏植入式电子设备患者的运动时间并限制 LV 功能的变化。目前正在努力在多中心环境和更长期的临床结局中证实我们的发现。注册：网址：https://www.clinicaltrials.gov；唯一标识符：NCT02964650。
