Lin Ting-Tse, Chen Tzu-Yang, Cheng Jen-Fang, Lin Lian-Yu, Wu Cho-Kai
Division of Cardiology, Department of Internal Medicine National Taiwan University College of Medicine and Hospital Taipei Taiwan.
Department of Internal Medicine, College of Medicine National Taiwan University Taipei Taiwan.
J Am Heart Assoc. 2025 Jul;14(13):e037290. doi: 10.1161/JAHA.124.037290. Epub 2025 Jun 18.
Chronotropic incompetence is common in older people and contributes to heart failure with preserved ejection fraction (HFpEF). This prospective study investigated the impact of chronotropic incompetence on cardiovascular outcomes in patients with HFpEF.
From November 2019 to December 2022, 359 subjects undergoing invasive cardiopulmonary exercise testing for heart failure symptoms were enrolled. After excluding those without HFpEF (resting pulmonary capillary wedge pressure <15 mm Hg or exercise pulmonary capillary wedge pressure <25 mm Hg), 113 patients were followed long term. Outcomes included hospitalization for HF and cardiovascular death. Associations between exercise hemodynamic parameters and outcomes were evaluated using Cox regression analysis. Among the 113 patients, 85 (75.2%) had chronotropic incompetence; these patients were older (71 versus 66 years) and more often female (61% versus 28%) compared with those without chronotropic incompetence. At peak exercise, patients with chronotropic incompetence exhibited lower left atrial (LA) booster strain, impaired right ventricle-arterial coupling, reduced systemic vascular resistance, cardiac output, stroke volume, peak oxygen consumption, and respiratory exchange ratio, along with a steeper minute ventilation/carbon dioxide production slope. They also had higher pulmonary capillary wedge pressure (36±10 versus 26±11mm Hg, =0.012). Over a median follow-up of 22.6 months, 20 patients (17.7%) experienced cardiovascular events. Multivariate analysis identified chronotropic incompetence (hazard ratio [HR], 1.725 [95% CI, 1.212-2.413]) and an elevated pulmonary capillary wedge pressure/cardiac output slope (HR, 1.829 [95% CI, 1.331-2.382]) as predictors of adverse outcomes.
In HFpEF, chronotropic incompetence is associated with elevated filling pressures, impaired ventilatory efficiency, and reduced exercise capacity, contributing to hospitalization for HF and cardiovascular death. Recognizing chronotropic incompetence may help predict poor prognosis in HFpEF.
变时性功能不全在老年人中很常见，并导致射血分数保留的心力衰竭（HFpEF）。这项前瞻性研究调查了变时性功能不全对HFpEF患者心血管结局的影响。
2019年11月至2022年12月，纳入359例因心力衰竭症状接受有创心肺运动试验的受试者。排除无HFpEF者（静息肺毛细血管楔压<15 mmHg或运动时肺毛细血管楔压<25 mmHg）后，对113例患者进行长期随访。结局包括因心力衰竭住院和心血管死亡。采用Cox回归分析评估运动血流动力学参数与结局之间的关联。在这113例患者中，85例（75.2%）有变时性功能不全；与无变时性功能不全者相比，这些患者年龄更大（71岁对66岁），女性更多（61%对28%）。在运动峰值时，变时性功能不全的患者表现出较低的左心房（LA）增强应变、右心室-动脉耦合受损、全身血管阻力降低、心输出量、每搏输出量、峰值耗氧量和呼吸交换率降低，以及分钟通气量/二氧化碳产生斜率更陡。他们的肺毛细血管楔压也更高（36±10对26±11 mmHg，P =0.012）。在中位随访22.6个月期间，20例患者（17.7%）发生心血管事件。多变量分析确定变时性功能不全（风险比[HR]，1.725[95%CI，1.212-2.413]）和升高的肺毛细血管楔压/心输出量斜率（HR，1.829[95%CI，1.331-2.382]）是不良结局的预测因素。
在HFpEF中，变时性功能不全与充盈压升高、通气效率受损和运动能力降低有关，并导致因心力衰竭住院和心血管死亡。认识到变时性功能不全可能有助于预测HFpEF的不良预后。
