Department of Cardiology Alfred Hospital Melbourne Australia.
Heart Failure Research Group Baker Heart and Diabetes Institute Melbourne Australia.
J Am Heart Assoc. 2021 Oct 5;10(19):e021584. doi: 10.1161/JAHA.121.021584. Epub 2021 Sep 25.
Background Although a rapid rise in left atrial pressure during exertion is considered pathognomonic of heart failure with preserved ejection fraction (HFpEF), the fundamental circulatory determinants of this response are not clear, impacting upon the development of more effective therapies. We aimed to comprehensively describe the circulatory mechanics of patients with HFpEF at rest and during exercise in comparison with controls. Methods and Results We performed simultaneous right-heart catheterization and echocardiography at rest and during exercise in 22 healthy control volunteers and 60 patients with confirmed HFpEF. Using detailed individual patient-level hemodynamic and left ventricular ejection fraction data we performed computer simulations to evaluate the circulatory parameters including the estimated stressed blood volumethat contribute to the resting and exercise pulmonary capillary pressure. At rest and during exercise, left ventricular stiffness (V, the end-diastolic pressure-volume relationship at a filling pressure of 30 mm Hg), left ventricular elastance, and arterial elastance were all significantly greater in HFpEF than in controls. Stressed blood volume was significantly greater in HFpEF (26.9±5.4 versus 20.2±4.7 mL/kg, <0.001), becoming even more pronounced during exercise (40.9±3.7 versus 27.5±7.0 mL per 70 kg, <0.001). During exercise, the magnitude of the change in stressed blood volume (=0.67, <0.001) and left ventricular stiffness (=-0.44, <0.001) were key determinants of the rise in pulmonary capillary wedge pressure. Further detailed modeling studies showed that the hemodynamic response to exercise results from a complex non-linear interaction between circulatory parameters. Conclusions The circulatory determinants of HFpEF physiology are complex. We identified stressed blood volume at rest and during exercise is a novel, key factor, therebyrepresenting an important potential therapeutic target.
尽管在运动过程中左心房压力的快速升高被认为是射血分数保留的心力衰竭（HFpEF）的特征性表现，但这种反应的基本循环决定因素尚不清楚，这影响了更有效的治疗方法的发展。我们旨在全面描述与对照组相比，HFpEF 患者在休息和运动时的循环力学。
我们在 22 名健康对照志愿者和 60 名确诊的 HFpEF 患者中进行了同步右心导管检查和超声心动图检查。使用详细的个体患者水平的血流动力学和左心室射血分数数据，我们进行了计算机模拟，以评估循环参数，包括贡献静息和运动肺毛细血管压力的估计应激血容量。在休息和运动时，HFpEF 患者的左心室僵硬度（V，在 30mmHg 充盈压下的舒张末期压力-容积关系）、左心室弹性和动脉弹性均显著大于对照组。HFpEF 患者的应激血容量显著更大（26.9±5.4 与 20.2±4.7mL/kg，<0.001），在运动时甚至更为明显（40.9±3.7 与 27.5±7.0 每 70kg，<0.001）。在运动期间，应激血容量的变化幅度（=0.67，<0.001）和左心室僵硬度（=-0.44，<0.001）是肺毛细血管楔压升高的关键决定因素。进一步的详细模型研究表明，运动时的血液动力学反应是循环参数之间复杂的非线性相互作用的结果。
HFpEF 生理学的循环决定因素很复杂。我们发现休息和运动时的应激血容量是一个新的关键因素，因此代表了一个重要的潜在治疗靶点。
