The Broad Phenotypic Spectrum of Arrhythmogenic Cardiomyopathy

Abstract Arrhythmogenic cardiomyopathy (ACM) is a rare inherited cardiomyopathy (CMP) characterized by progressive fibro–adipose replacement of the myocardium. It is mainly caused by variants in desmosomal genes with autosomal dominant transmission and incomplete penetrance. Originally, ACM was considered a CMP with main if not exclusive involvement of the right ventricle (RV) and more rarely both ventricles. To date, recent data have also highlighted the possibility of isolated left ventricular (LV) involvement, which often results in a disease with peculiar and distinct features. The case we propose is that of a 70–year–old man with no cardiology history but a family history of cardiomyopathy (brother has unspecified cardiomyopathy and is an ICD carrier). In 2015 due to occasional finding of ventricular extrasystole, the patient underwent CVG which was negative and cardiac MRI which documented an area of late–Gadolinium Enhancement (LGE) of the mid–basal portion of the inferior and lateral wall, with greater involvement of the subepicardial versant of the LV of possible post–myocarditis involvement. In September 2023, he was admitted to our cardiology department following a syncopal episode not preceded by prodromes. The ECG showed poor R–wave progression, low voltages and diffuse repolarization changes. The echocardiogram showed dilated LV with reduced EF(35%). Both CVG and cardiac MRI was repeated. The first was still negative and cardiac MRI showed a considerable progression of LGE areas at the mesomyocardial and subendocardial levels, with an almost ubiquitous distribution in the LV. Additional areas of LGE were also appreciated at the atrioventricular valves, the interatrial septum, and in the RV, but the latter was not dysfunctional. These findings appeared compatible with LV ACM with initial biventricular extension. It was decided to implant ICD in primary prevention and to request genetic analysis, which is still ongoing. Beyond the unusual appearance in extent and locations of areas of LGE on cardiac MRI, our clinical case highlights the close correlation that is often present between left ACM and acute myocarditis. It is not well known whether the inflammation associated with acute myocarditis is a primary injury that results in fibroadipose replacement or whether it is the degeneration of the cardiomyocytes themselves that results in these inflammatory phases (hot–phases) with myocarditis–like expression.