Cardiomyopathies

The grounding supports heterogeneous causes, including inherited genetic factors and specific etiological forms such as alcoholic cardiomyopathy and endocardial fibroelastosis. It also supports transthyretin-related amyloidosis as a cause of cardiomyopathy, arising from misfolded transthyretin protein deposition in the heart. Some cardiomyopathies are linked to monogenic disease, while others reflect shared genetic susceptibility or protein misfolding processes.

The disease process centers on structural and functional impairment of cardiac muscle, with effects on left ventricular function and stroke volume. In transthyretin cardiac amyloidosis, misfolded transthyretin forms amyloid fibrils that deposit in the myocardium, causing cardiac dysfunction, heart failure, conduction block, and arrhythmias. Genetic studies also implicate pathways involved in cardiac development, protein homeostasis, and cellular senescence in cardiomyopathy-related heart failure.

Supported risk factors include inherited variants in cardiomyopathy-related genes and inherited variants in the transthyretin sequence for ATTR cardiomyopathy. Aging is associated with transthyretin amyloid formation, and ATTR cardiac amyloidosis predominantly affects men. The grounding also supports alcohol exposure as a risk factor for alcoholic cardiomyopathy.

Management is described at the level of genetic testing, diagnosis, risk stratification, and therapeutic management for inherited cardiomyopathies. For cardiac amyloidosis, treatment strategies include disease-modifying therapies aimed at reducing amyloid formation and stabilizing the cardiac disease process, with newer agents being developed to promote immune-mediated removal of amyloid fibrils. Multimodality cardiac imaging is used to support diagnosis, quantify disease burden, and monitor response to treatment.