Arrhythmogenic Cardiomyopathy: Genetic Pathology, Inflammatory Syndrome, or both?

Abstract

Arrhythmogenic cardiomyopathy (ACM) affects mainly young athletes <35 years old and has a potential risk of malignant arrhythmias and sudden death. Different post-mortem and clinical studies have been conducted in North America, Asia, and Europe, with sharp differences in incidence and sex-associated pattern. Alterations in desmosome proteins, such as desmoglein, plakophilin, ion channels, or intracellular calcium handling proteins, have been highlighted as the principal cause of ACM, but the pathology has shown more complexity than initially described. This short review summarises the principal and more recent findings about ACM, mainly those related to inflammatory phenomena reported in the literature. Viral infections, especially enterovirus, have been associated with ACM and may be implicated in myocardial apoptosis, structural cardiac changes, and sudden death. Bartonella henselae and Sarcocystis infection have additionally been reported in ACM patients. Information regarding the role of proinflammatory cytokine or T cell infiltration and their possible role in sudden death is scarce, with increasing evidence of proinflammatory infiltrate associated with fibro-fatty ventricular patches related to biventricular affectation and worse outcomes. Nevertheless, findings taken from other sudden death-causing cardiomyopathies, such as viral myocarditis and Chagas disease, allow us to propose proinflammatory cytokines, such as tumour necrosis factor and interleukins 17 and 2, as possible serological markers of sudden death and/or ventricular dysfunction in order to conduct further research and identify diagnosis/prognosis markers for ACM.