Sudden arrhythmic death and the cardiomyopathies: Molecular genetics and pathology

Cardiovascular disease is a significant cause of sudden death (SD) requiring autopsy investigation. Cardiomyopathies account for about one half of cases encountered, especially in young people <35 years of age. Among them, inherited cardiomyopathies at risk of SD include hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC) as well as primary electrical disorders of the myocardium in the absence of structural abnormalities (channelopathies). The pathologist's task is to make the correct diagnosis and, when dealing with a genetic disease, to trigger widespread cardiological investigation of first-degree family members. This is especially important as SD can be the first and last clinical presentation of the underlying inherited cardiomyopathy and the only medical examination undertaken is that done by the pathologist. An accurate pathological diagnosis, which also includes access to molecular techniques (“molecular autopsy”), will provide vital information for the family in preventing a further tragedy. Therefore proper sampling to allow postmortem DNA analysis as well as accurate morphological evaluation, is mandatory, as recommended in the recently-published guidelines for autopsy investigation of SD from the Association for European Cardiovascular Pathology.