Genetically determined cardiomyopathies at autopsy: the pivotal role of the pathologist in establishing the diagnosis and guiding family screening

Mary N Sheppard, Allard C van der Wal, Jytte Banner, Giulia d’Amati, Monica De Gaspari, Rosa De Gouveia, Cira Di Gioia, Carla Giordano, Maiken Kudahl Larsen, Matthew J Lynch, Joaquin Lucena, Pilar Molina, Sarah Parsons, M Paz Suarez-Mier, Stefania Rizzo, Simon Kim Suvarna, Wouter P Te Rijdt, Gaetano Thiene, Aryan Vink, Joseph Westaby, Katarzyna Michaud, Cristina Basso; Association for European Cardiovascular Pathology (AECVP). Virchows Archiv : an international journal of pathology. 2023 Apr. Read the paper here

Cardiomyopathies (CMP) comprise a heterogenous group of diseases affecting primarily the myocardium, either genetic and/or acquired in origin. While many classification systems have been proposed in the clinical setting, there is no internationally agreed pathological consensus concerning the diagnostic approach to inherited CMP at autopsy. A document on autopsy diagnosis of CMP is needed because the complexity of the pathologic backgrounds requires proper insight and expertise. In cases presenting with cardiac hypertrophy and/or dilatation/scarring with normal coronary arteries, a suspicion of inherited CMP must be considered, and a histological examination is essential. Establishing the actual cause of the disease may require a number of tissue-based and/or fluid-based investigations, be it histological, ultrastructural, or molecular. A history of illicit drug use must be looked for. Sudden death is frequently the first manifestation of disease in case of CMP, especially in the young. Also, during routine clinical or forensic autopsies, a suspicion of CMP may arise based on clinical data or pathological findings at autopsy. It is thus a challenge to make a diagnosis of a CMP at autopsy. The pathology report should provide the relevant data and a cardiac diagnosis which can help the family in furthering investigations, including genetic testing in case of genetic forms of CMP. With the explosion in molecular testing and the concept of the molecular autopsy, the pathologist should use strict criteria in the diagnosis of CMP, and helpful for clinical geneticists and cardiologists who advise the family as to the possibility of a genetic disease.