Personalization of Biomechanical Models for Early Detection of Disease in Arrhythmogenic Cardiomyopathy

Arrhythmogenic cardiomyopathy (AC) is an inherited cardiac disease clinically characterized by life-threatening ventricular arrhythmias and progressive cardiac dysfunction. Current electrocardiographic and structural imaging methods fail to detect early-stage AC-related myocardial disease in mutation carriers. Here, we propose a cardiac imaging-based personalized modelling approach that enables the identification and characterization of regional electro-mechanical tissue abnormalities in the vulnerable right ventricular (RV) free wall of AC mutation carriers. RV tissue deformation data from 2 controls and 8 mutation carriers, covering various stages of AC disease, were used to personalize the Circ.Adapt model of the human heart and circulation. This resulted in estimates of contractility and stiffness in the apical, midventricular, and basal segments of the RV. Apex-to-base heterogeneity in tissue properties, with increased stiffness and decreased contractility in the RV basal region, was found in most patients and was largest in late-stage AC disease. Future studies should evaluate whether early-stage tissue heterogeneity is predictive for arrhythmic events or AC disease progression.