Personalized computational heart models with T1-mapped fibrotic remodeling predict sudden death risk in patients with hypertrophic cardiomyopathy

Abstract

Hypertrophic cardiomyopathy (HCM) is associated with risk of sudden cardiac death (SCD) due to ventricular arrhythmias (VA) arising from the proliferation of fibrosis in the heart. 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 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.

Diffuse Myocardial Fibrosis on Cardiac Magnetic Resonance Imaging Is Related to Galectin-3 and Predicts Outcome in Heart Failure

“…However, to date, there is no consensus on the CMR mapping technique to be used. In some studies, investigators even developed a personalized T1 mapping approach to determine patient-specific focal and interstitial fibrosis [ 27 ].…”

Homogenisation for the monodomain model in the presence of microscopic fibrotic structures

“…In practice, a modeller will most likely have a coarser-scale (100– ) mesh, regular or irregular and in two or three dimensions, on which they wish to simulate cardiac activity in the presence of cardiac fibrosis. Current non-invasive imaging techniques for fibrosis can be used to inform where to place regions of affliction in computational studies [4] , [32] , and operate at increasingly impressive resolutions [56] . In terms of the placement of finescale collagenous obstructions inside regions of fibrosis, however, this would be achieved in consideration of histological data, or more realistically, using a histologically-informed computational generator of microfibrotic patterns [25] .…”

Updated risk assessments for sudden cardiac death in hypertrophic cardiomyopathy patients with implantable cardioverter-defibrillator

“…In adult patients with HCM, diffuse fibrosis is a predictor of non-sustained VT and aborted SCD [ 23 ]. A computational modeling approach that merges data from LGE-CMR with that from post-contrast T1 mapping is able to reveal extensive diffuse fibrotic remodeling, which is a risk factor for SCD and ventricular tachyarrhythmia in HCM and is associated with the occurrence of new ventricular tachyarrhythmias [ 24 ].…”