INSERM, Center of Clinical Investigation-9501, University Hospital Nancy, Lorrain Institute of Heart and Vessels Louis Mathieu, 4, rue du Morvan, 54500 Vandoeuvre-Les-Nancy, France.
Eur Heart J. 2013 Aug;34(29):2271-80. doi: 10.1093/eurheartj/ehs433. Epub 2013 Jan 12.
The aim of this study was to assess the association between resting heart rate (HR), chronotropic index (CI), and clinical outcomes in optimally treated chronic heart failure (HF) patients on β-blocker therapy.
We performed a sub-study in 1118 patients with HF and reduced ejection fraction (EF < 35%) included in the HF-ACTION trial. Patients in sinus rhythm who received a β-blocker and who performed with maximal effort on the exercise test were included. Chronotropic index was calculated as an index of HR reserve achieved, by using the equation (220-age) for estimating maximum HR. A sensitivity analysis using an equation developed for HF patients on β-blockers was also performed. Cox proportional hazards models were fit to assess the association between CI and clinical outcomes. Median (25th, 75th percentiles) follow-up was 32 (21, 44) months. In a multivariable model including resting HR and CI as continuous variables, neither was associated with the primary outcome of all-cause mortality or hospitalization. However, each 0.1 unit decrease in CI <0.6 was associated with 17% increased risk of all-cause mortality (hazard ratio 1.17, 95% confidence interval 1.01-1.36; P = 0.036), and 13% increased risk of cardiovascular mortality or HF hospitalization (hazard ratio 1.13, 1.02-1.26; P = 0.025). Overall, 666 of 1118 (60%) patients had a CI <0.6. Chronotropic index did not retain statistical significance when dichotomized at a value of ≤ 0.62.
In HF patients receiving optimal medical therapy, a decrease in CI <0.6 was associated with adverse clinical outcomes. Obtaining an optimal HR response to exercise, even in patients receiving optimal β-blocker therapy, may be a therapeutic target in the HF population.
本研究旨在评估在接受β受体阻滞剂治疗的最佳慢性心力衰竭（HF）患者中，静息心率（HR）和变时指数（CI）与临床结局的相关性。
我们对 HF-ACTION 试验中纳入的 1118 例射血分数降低（EF < 35%）的 HF 患者进行了亚组研究。该研究纳入了窦性节律且在运动试验中达到最大努力的接受β受体阻滞剂治疗的患者。CI 通过使用（220-年龄）计算得出，作为 HR 储备的指标，用于估计最大 HR。还使用专为接受β受体阻滞剂治疗的 HF 患者开发的方程进行了敏感性分析。使用 Cox 比例风险模型评估 CI 与临床结局之间的相关性。中位（25%，75%）随访时间为 32（21，44）个月。在包括静息 HR 和 CI 作为连续变量的多变量模型中，两者均与全因死亡率或住院的主要结局无关。然而，CI <0.6 每降低 0.1 单位与全因死亡率增加 17%相关（风险比 1.17，95%置信区间 1.01-1.36；P = 0.036），心血管死亡率或 HF 住院风险增加 13%（风险比 1.13，1.02-1.26；P = 0.025）。总体而言，1118 例患者中有 666 例（60%）CI <0.6。CI 分为≤0.62 时，无统计学意义。
在接受最佳药物治疗的 HF 患者中，CI <0.6 与不良临床结局相关。即使在接受最佳β受体阻滞剂治疗的患者中，获得最佳的运动 HR 反应可能也是 HF 人群的治疗目标。
