Biomechanical Determinants of Right Ventricular Failure in Pulmonary Hypertension

Abstract

Pulmonary hypertension (PH) is a disease characterized by progressive adverse remodeling of the distal pulmonary arteries, resulting in elevated pulmonary vascular resistance and load pressure on the right ventricle (RV), ultimately leading to RV failure. Invasive hemodynamic testing is the gold standard for diagnosing PH and guiding patient therapy. We hypothesized that lumped-parameter and biventricular finite-element (FE) modeling may lead to noninvasive predictions of both PH-related hemodynamic and biomechanical parameters that induce PH. We created patient-specific biventricular FE models that characterize the biomechanical response of the heart and coupled them with a lumped-parameter model that represents the systemic and pulmonic circulation. Simulations were calibrated by adjusting the pulmonary vascular resistance and myocardial contractility parameters through matching imaging data of ventricular chambers. Linear regression analysis demonstrated that the lumped-derived RV cardiac index (CI) was in good agreement with catheterization measurements collected from 10 patients with PH (R-2 = 0.82; p < 0.001). Biventricular FE analysis revealed a paradoxical leftward shift of the interventricular septum, and this correlated with invasive measurements of pulmonary vascular resistances (R = 0.70; p = 0.048) as found by Pearson's coefficient. A significant difference was noted for RV myocardial fiber stress in healthy control patients (4.5 +/- 0.7 kPa) compared with that of patients with PH at either rest (30.1 +/- 12.1 kPa; p = 0.005) or simulated exercise conditions (69.6 +/- 24.8 kPa; p < 0.001), thus suggesting adverse RV remodeling. This approach may become a useful and versatile tool for noninvasively assessing RV impairment induced by PH and realistically predicting ventricular mechanics and interactions for an improved management of patients with PH.