Deep-learning analysis of 3D microarchitectural remodeling in hypertrophic cardiomyopathy

• 成果类型: Article
• 署名作者: 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.
• 署名单位: Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; German Centre for Cardiovascular Research; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; University of Alberta; University of Iowa; Bristol-Myers Squibb; University of Pennsylvania; Victor Chang Cardiac Research Institute; University of New South Wales Sydney; NSW Health; St Vincents Hospital Sydney
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.ady6443
• 发表日期: 2026-01-15
• 页码: eady6443
• 关键词: MYOCARDIAL FIBROSIS; cardiac-hypertrophy; heart-failure; expression; gene; identification; association; mutations; variants

摘要

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.