Effects of pulmonary hypertension on right ventricular mechanics and coronary perfusion: Insights from computational simulations

Abstract

Pulmonary hypertension (PH), defined by elevated mean pulmonary arterial pressure (mPAP), is a leading cause of right heart failure (RHF). However, the mechanisms linking PH to ventricular dysfunction and coronary ischemia remain unclear. An advanced mechanistic understanding is critical for improving clinical diagnosis and treatment strategies. This study aimed to investigate the impact of acute and chronic PH on biventricular mechanics and coronary perfusion. We developed a computational model that integrates coronary perfusion in the major coronary arteries with a biventricular finite element (FE) model in a closed-loop systemic and pulmonary circulation. Validated against clinical measurements, the computational model was applied to simulate the hemodynamics and myocardial perfusion across coronary territories and myocardial walls under conditions of acute and chronic PH. Model predictions demonstrated that in acute PH, coronary flow in the right ventricular free wall (RVFW) and septum was reduced due to elevated intramyocardial pressure (IMP), especially in the endocardium. In chronic PH, coronary flow was reduced in the RVFW, septum, and left ventricular free wall (LVFW) due to diminished perfusion pressure. These findings are consistent with clinical observations: the right-dominant right coronary artery (RCA) is more vulnerable to ischemia in acute PH, whereas the left-dominant left circumflex artery (LCx) is more vulnerable in chronic PH. In conclusion, chronic PH may contribute to subclinical left ventricular dysfunction and increased ischemic risk through impaired coronary perfusion, highlighting potential targets for therapeutic interventions in PH-related RHF.