Patient-specific modeling of right coronary circulation vulnerability post-liver transplant in Alagille's syndrome.

Abstract

Cardiac output (CO) response to dobutamine can identify Alagille's syndrome (ALGS) patients at higher risk of cardiovascular complications during liver transplantation. We propose a novel patient-specific computational methodology to estimate the coronary autoregulatory responses during different hemodynamic conditions, including those experienced in a post-reperfusion syndrome (PRS), to aid cardiac risk-assessment. Data (pressure, flow, strain and ventricular volumes) from a 6-year-old ALGS patient undergoing catheter/dobutamine stress MRI (DSMRI) were used to parameterize a closed-loop coupled-multidomain (3D-0D) approach consisting of image-derived vascular models of pulmonary and systemic circulations and a series of 0D-lumped parameter networks (LPN) of the heart chambers and the distal arterial and venous circulations. A coronary microcirculation control model (CMCM) was designed to adjust the coronary resistance to match coronary blood flow (and thus oxygen delivery) with MVO2 requirements during Rest, Stress and a virtual PRS condition. In all three simulated conditions, diastolic dominated right coronary artery (RCA) flow was observed, due to high right ventricle (RV) afterload. Despite a measured 45% increase in CO, impaired coronary flow reserve (CFR) (~1.4) at Stress was estimated by the CMCM. During modeled PRS, a marked vasodilatory response was insufficient to match RV myocardial oxygen requirements. Such exhaustion of the RCA autoregulatory response was not anticipated by the DSMRI study. Impaired CFR undetected by DSMRI resulted in predicted myocardial ischemia in a computational model of PRS. This computational framework may identify ALGS patients at higher risk of complications during liver transplantation due to impaired coronary microvascular responses.