Abstract
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.
Highlights
Alagille’s syndrome (ALGS) is a rare autosomal dominant multi-systemic vasculopathy, with variable penetrance and expression, and an estimated incidence of 1:30,000 up to 1:50,000 per liver birth [1,2]
Despite a measured 45% increase in Cardiac output (CO), impaired coronary flow reserve (CFR) (~1.4) at Stress was estimated by the coronary microcirculation control model (CMCM)
During modeled post-reperfusion syndrome (PRS), a marked vasodilatory response was insufficient to match right ventricle (RV) myocardial oxygen requirements. Such exhaustion of the right coronary artery (RCA) autoregulatory response was not anticipated by the dobutamine stress Magnetic resonance imaging (MRI) (DSMRI) study
Summary
Alagille’s syndrome (ALGS) is a rare autosomal dominant multi-systemic vasculopathy, with variable penetrance and expression, and an estimated incidence of 1:30,000 up to 1:50,000 per liver birth [1,2]. Several mutations have been reported in genes involved in the Notch signaling pathway that regulate differentiation of cell migration during fetal vascular development [3]. These are thought to be the cause of this polymalformative disorder affecting the liver (paucity of interlobular bile ducts resulting in neonatal cholestasis), heart (peripheral pulmonary stenosis, PPS), eyes (posterior embryotoxon), and skeleton (butterfly-like vertebral arch defects), and associated with a characteristic dysmorphic facies. ALGS typically presents in the first 3 to 6 months of life with cholestasis, coursing in half of the cases with debilitating pruritus, disfiguring xanthomas and failure to thrive due to fat malabsorption [4]. Despite aggressive medical care (e.g. tailored diet with carbohydrate, medium-chain triglycerides and individual fat-soluble vitamins supplementation, bile flow stimulants, bile acid–binding resins and antihistamines), in 20–30% of children liver transplantation (LT) is the only option for end-stage liver failure and the debilitating cholestasis symptoms [5]
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