Science (New York, N.Y.) · 2026
Deep-learning analysis of 3D microarchitectural remodeling in hypertrophic cardiomyopathy.
СтатьяНазвание и аннотация: Перевод в очереди
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Wei Eric Q, Beyer Martin, Brown Kemar J, Bansbach Alexander J, Gorham Joshua M, McDonough Barbara, Chen Huachen, Khoramjoo Mobin, Zhang Anran, Bishop Brian, Ahmad Ferhaan, Del Rio Carlos, Chang Ching-Pin, Ryba David M, Day Sharlene M, Fatkin Diane, Oudit Gavin Y, Seidman Christine E, Seidman Jonathan G
Аннотация
Hypertrophic cardiomyopathy (HCM), a genetic heart disease defined by unexplained cardiac wall thickening, is a leading cause of sudden death worldwide. However, the three-dimensional organization of cardiac tissue underlying left ventricular hypertrophy remains poorly understood. We developed CaMVIA-3D, a deep-learning volumetric imaging and analysis pipeline to characterize cardiac microarchitecture. Analysis of tissues from HCM hearts revealed genotype-specific differences in cardiomyocyte volume, morphology, and extracellular volume, with pathogenic variants exhibiting greater concentric cellular hypertrophy and disarray and variant-negative cases showing predominant fibrosis. Longitudinal profiling of a pig HCM model revealed early-onset fibrosis preceding cardiomyocyte hypertrophy. Integrating transcriptomic and morphologic changes, we identified genes associated with cellular and extracellular remodeling. These findings define genotype-specific microstructural differences in HCM, offering insights to improve diagnostics and targeted therapies.