Villatore, Andrea

ABSTRACT Genetic variants that impair cardiac function or predispose individuals to autoimmune diseases can influence both the risk and severity of inflammatory heart diseases, including lymphocytic myocarditis and cardiac sarcoidosis. We review recent clinical and experimental studies that describe the emerging interplay between genetic susceptibility and active myocardial inflammation. We summarize the current perspective on the mechanisms of inflammatory pathways and gene‐immune interactions, and explore the emerging therapeutic approaches aimed at targeting inflammation in genetic cardiomyopathies.

Over recent years, preclinical and clinical evidence has implicated myocardial inflammation (M-Infl) in the pathophysiology and phenotypes of traditionally genetic cardiomyopathies. M-Infl resembling myocarditis on imaging and histology occurs frequently as a clinical manifestation of classically genetic cardiac diseases, including dilated and arrhythmogenic cardiomyopathy. The emerging role of M-Infl in disease pathophysiology is leading to the identification of druggable targets for molecular treatment of the inflammatory process and a new paradigm in the field of cardiomyopathies. Cardiomyopathies constitute a leading cause of heart failure and arrhythmic sudden death in the young population. The aim of this review is to present, from bedside to bench, the current state of the art about the genetic basis of M-Infl in nonischemic cardiomyopathies of the dilated and arrhythmogenic spectrum in order to prompt future research towards the identification of novel mechanisms and treatment targets, with the ultimate goal of lowering disease morbidity and mortality.