Department of Cardiology, Copenhagen University Hospital-Herlev and Gentofte, Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Am J Physiol Heart Circ Physiol. 2021 Nov 1;321(5):H865-H880. doi: 10.1152/ajpheart.00442.2021. Epub 2021 Aug 27.
Myocardial function and exercise reserve are important determinants of outcome in pulmonary arterial hypertension (PAH) but are incompletely understood. For this study, we performed subject-specific computer simulations, based on invasive measurements and cardiac magnetic resonance imaging (CMR), to investigate whole circulation properties in PAH at rest and exercise and determinants of exercise reserve. CMR and right heart catheterization were performed in nine patients with idiopathic PAH, and CMR in 10 healthy controls. CMR during exercise was performed in seven patients with PAH. A full-circulation computer model was developed, and model parameters were optimized at the individual level. Patient-specific simulations were used to analyze the effect of right ventricular (RV) inotropic reserve on exercise performance. Simulations achieved a high consistency with observed data. RV contractile force was increased in patients with PAH (127.1 ± 28.7 kPa vs. 70.5 ± 14.5 kPa, < 0.001), whereas left ventricular contractile force was reduced (107.5 ± 17.5 kPa vs. 133.9 ± 10.3 kPa, = 0.002). During exercise, RV contractile force increased by 1.56 ± 0.17, = 0.001. In silico experiments confirmed RV inotropic reserve as the important limiting factor for cardiac output. Subject-specific computer simulation of myocardial mechanics in PAH is feasible and can be used to evaluate myocardial performance. With this method, we demonstrate marked functional myocardial adaptation to PAH in the resting state, primarily composed of increased contractile force development by RV myofibers, and we show the negative impact of reduced RV inotropic reserve on cardiac output during exercise. Computer simulations of the myocardial mechanics and hemodynamics of rest and exercise were performed in nine patients with pulmonary arterial hypertension and 10 control subjects, with the use of data from invasive catheterization and from cardiac magnetic resonance. This approach allowed a detailed analysis of myocardial adaptation to pulmonary arterial hypertension and showed how reduction in right ventricular inotropic reserve is the important limiting factor for an increase in cardiac output during exercise.
心肌功能和运动储备是肺动脉高压 (PAH) 预后的重要决定因素，但了解并不完全。为此，我们进行了基于有创测量和心脏磁共振成像 (CMR) 的特定于患者的计算机模拟，以研究 PAH 患者在静息和运动时的整个循环特性以及运动储备的决定因素。对 9 例特发性 PAH 患者和 10 例健康对照者进行了 CMR 和右心导管检查，对 7 例 PAH 患者进行了 CMR 运动检查。建立了一个完整循环的计算机模型，并在个体水平上对模型参数进行了优化。患者特异性模拟用于分析右心室 (RV) 变力储备对运动表现的影响。模拟结果与观察数据高度一致。PAH 患者的 RV 收缩力增加（127.1 ± 28.7 kPa 比 70.5 ± 14.5 kPa， < 0.001），而左心室收缩力降低（107.5 ± 17.5 kPa 比 133.9 ± 10.3 kPa， = 0.002）。在运动期间，RV 收缩力增加了 1.56 ± 0.17， = 0.001。在计算机模拟实验中，RV 变力储备证实是心输出量的重要限制因素。PAH 心肌力学的特定于患者的计算机模拟是可行的，可以用于评估心肌功能。通过这种方法，我们在静息状态下证明了心肌对 PAH 的明显功能性适应性，主要由 RV 心肌纤维收缩力的增加组成，并且我们显示了 RV 变力储备减少对运动期间心输出量的负面影响。对 9 例 PAH 患者和 10 例对照者进行了静息和运动时心肌力学和血液动力学的计算机模拟，方法是使用有创导管和心脏磁共振数据。这种方法允许对心肌对肺动脉高压的适应性进行详细分析，并显示出 RV 变力储备减少如何成为运动时心输出量增加的重要限制因素。
