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

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.

CRIMSON: An Open-Source Software Framework for Cardiovascular Integrated Modelling and Simulation

“…To study this, a subject-specific model of an Alagille syndrome patient was created in CRIMSON, consisting of two (pulmonary and systemic) 3D domains segmented from magnetic resonance images, and a closed-loop circulatory system created using NEBCT (Figure 6). In the present article, we illustrate the difference between the myocardial oxygen supply and demand in one region of the left ventricular myocardium; for further details see Silva Vieira et al 2018. This difference was computed using a model of myocardial oxygen supply and demand (Arthurs et al 2016) and implemented within a coronary boundary condition using the CRIMSON Control Systems Framework.…”

“…A complex, two-domain patient-specific 3D model with full closed-loop boundary condition system created in CRIMSON. This was used in a study of cardiovascular complications during liver transplant (Silva Vieira et al 2018). Image used under CC BY 4.0 license.…”

“…The 0D simulation is presented here so that it is computationally tractable for most readers. Both the 0D and 3D simulations are presented in detail elsewhere (Silva Vieira et al 2018). The closed-loop boundary condition circuit specified in this problem is visualized in Figure 8; guidance on how to perform this visualisation is also provided.…”

Cardiac and Liver Disease in Children: Implications for Management Before and After Liver Transplantation

“…The CO response to dobutamine has been suggested as a way to identify patients at higher risk of cardiovascular complications during LT . A recent study modeled 3 different simulated scenarios using data from a 6‐year‐old child with AS undergoing catheter/dobutamine stress magnetic resonance imaging (DSMRI) and concluded that there was impaired coronary flow reserve, which was undetected by DSMRI and resulted in myocardial ischemia . It is possible that by using computational data, this novel approach to risk stratification could be useful to predict morbidity and mortality after LT in children with congenital cardiac disease or CCM …”

Medical Image-Based Hemodynamic Analyses in a Study of the Pulmonary Artery in Children With Pulmonary Hypertension Related to Congenital Heart Disease

“…The main reason is a lack of understanding of its pathophysiology. PH is a response to abnormal hemodynamics in CHD patients (4)(5)(6), which appear before morphologic remodeling (7). Therefore, knowing the hemodynamic characteristics of the pulmonary artery (PA) may benefit comprehension of pathophysiologic mechanisms and yield more detailed information for the diagnosis and treatment of PH in CHD (PH-CHD).…”