Abstract
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.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
This work was supported by NIH grants R01HL142496 and R01HL126802 to N.T., a grant from the Leducq Foundation to N.T., an NIH T32 Fellowship (HL125239) to E.B., and a National Science Foundation Graduate Research Fellowship (DGE-1746891) to R.O.
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Footnotes
Competing Interests: The authors declare that no competing interests exist.
Data Availability
Source data is available where possible. Raw numerical data (Figures 2, 4, and 5) has been provided as supplemental material for peer review and will be made available via figshare prior to publication once the manuscript is accepted. Patient imaging and clinical data used in this article will be available for reuse upon reasonable request to the corresponding author and approval from the Institutional Review Board at Johns Hopkins Hospital.