Hypertrophic cardiomyopathy (HCM) causes sudden cardiac death (SCD) due to ventricular arrhythmias (VA) manifesting from myocardial fibrosis proliferation. Current clinical risk stratification criteria inadequately identify at-risk patients in need of primary prevention of VA. Here, we use mechanistic computational modeling of the heart to analyze how HCM-specific remodeling of the heart promotes arrhythmogenesis and to develop a personalized strategy to forecast risk of VAs in these patients. We combine contrast-enhanced cardiac magnetic-resonance (CMR) imaging and T1 mapping data to construct digital replicas of HCM patient hearts that represent the patient-specific distribution of focal and diffuse fibrosis and evaluate the substrate propensity to VA. Our analysis indicates that the presence of diffuse fibrosis, which is rarely assessed in these patients, increases arrhythmogenic propensity. In forecasting future VA events in HCM patients, the imaging-based computational heart approach achieved 84.6%, 76.9%, and 80.1% sensitivity, specificity, and accuracy, respectively, and significantly outperformed current clinical risk predictors. This novel VA risk assessment may have the potential to prevent SCD and help deploy primary prevention appropriately in HCM patients.

Left ventricular (LV) volumes from short-axis LGE-CMR scans and post-contrast T1 maps were segmented using CardioViz3D (http://www-sop.inria.fr/asclepios/software/CardioViz3D/). LV segmentations (metaimage files) were semi-automatically generated for each patient included in this dataset.

The segmented MRI images of the LV can be used to generate the finite element meshes used in this study. LGE LV Tag = 1; T1 LV Tag = 255.