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

ObjectivesCardiac 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.Material and methodsData (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.ResultsIn 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.ConclusionImpaired 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.

**研究目的** 针对多巴酚丁胺的心脏输出量（Cardiac output, CO）反应，可识别肝移植期间心血管并发症风险更高的阿拉基尔综合征（Alagille's syndrome, ALGS）患者。本研究提出一种全新的患者特异性计算方法，用于估算不同血流动力学状态下的冠状动脉自身调节反应——包括再灌注后综合征（post-reperfusion syndrome, PRS）相关状态，以辅助心脏风险评估。**材料与方法** 本研究纳入1例接受导管/多巴酚丁胺负荷磁共振成像（catheter/dobutamine stress MRI, DSMRI）的6岁ALGS患者，采集其压力、流量、应变及心室容积数据，用于参数化构建闭环耦合多域（3D-0D）方法：该方法包含基于影像衍生的肺循环与体循环血管模型，以及一系列描述心腔、远端动脉与静脉循环的0阶集总参数网络（0D-lumped parameter networks, LPN）。本研究设计了冠状动脉微循环控制模型（coronary microcirculation control model, CMCM），用于调整冠状动脉阻力，使冠状动脉血流量（及相应的氧输送量）能够匹配静息、负荷状态及虚拟PRS状态下的心肌氧耗量（MVO2）需求。**结果** 在三种模拟状态下，均观察到以舒张期为主的右冠状动脉（Right coronary artery, RCA）血流，这与右心室（Right ventricle, RV）后负荷升高相关。尽管实测CO升高45%，但CMCM估算得出负荷状态下的冠状动脉血流储备（Coronary flow reserve, CFR）受损（约为1.4）。在模拟PRS状态时，显著的血管舒张反应仍不足以匹配RV心肌氧需求。此类RCA自身调节反应耗竭的情况，未在DSMRI研究中被预判到。**结论** 未被DSMRI检出的CFR受损，在PRS计算模型中预测会引发心肌缺血。本研究提出的计算框架，可通过评估冠状动脉微血管反应受损情况，识别肝移植期间并发症风险更高的ALGS患者。