Journal Article

Inflammation and Genetics in Myo-Pericardial Diseases: Insights from the Italian Study Group on Cardiomyopathies and Pericardial Diseases

Castelletti, Silvia, Sinagra, Gianfranco, Marzo, Francesca, Bassetto, Giulia, Pedrinelli, Roberto, Biagini, Elena, Musumeci, Beatrice, Imazio, Massimo, Merlo, Marco, D'Ascenzi, Flavio, Cannatà, Antonio, Filardi, Pasquale Perrone, Autore, Camillo, de Gregorio, Cesare, Aimo, Alberto, Limongelli, Giuseppe, Bauce, Barbara, Cappelli, Francesco, Tini, Giacomo

2025

Overview

Abstract In the past decade, advancements in knowledge on the immune system have partially unveiled the complex interplay between the heart and the immune system. This new branch of cardiology is now called cardio-immunology. It encompasses different areas from preclinical to translational and purely clinical research aiming to identify the relationship between the immune system and different cardiovascular diseases. Inflammatory cardiomyopathies are a heterogeneous subgroup of non-ischaemic cardiomyopathies characterized by left ventricular, or biventricular, dysfunction after an inflammatory insult. Recently, genetic testing allowed to identify specific genotype–phenotype correlation in the diagnosis and, mostly, in the prognosis of different cardiomyopathies. Some pathogenic variants might lead to a clinical phenotype in overlap with inflammatory myocardial diseases and inflammation can be found in cardiac magnetic resonance or endomyocardial biopsies of different cardiomyopathies. Although prognostic predictors of adverse events and indication to immunosuppressive therapies have been identified in myocarditis, data are lacking in the context of genetic cardiomyopathies presenting myocardial inflammation. As for pericardial diseases, genetic variants in immune-related genes, such as IL1B have been described, specifically in recurrent pericarditis. A growing body of evidence starting form genetics and cardio-immunology are trying to elucidate the basic mechanisms of the disease and may play a significant role in the understanding the pathophysiology and potentially the treatment of patients. Some examples are represented by arrhythmogenic cardiomyopathy presenting with hot-phases or biopsy-proven myocarditis presenting genetic mutations in specific genes as TTN or DSP. The aim of this review paper is to highlight the current knowledge and the unmet clinical needs, providing a practical and concise guidance for specific areas of research and management of patients affected by myo-pericardial diseases with overlap between genetics and inflammation, ranging from genetic testing to medical and device therapy. Proposed management of myo-pericardial diseases. A systematic interdisciplinary approach to myo-pericardial disease is essential to reach a correct diagnosis, starting from multiparametric characterization including EKG, echocardiography with GLS, laboratory exams and CMR or, in case of electric or haemodynamic instability, EMB. In the presence of red flags suggestive of cardiomyopathy, additional exams such as genetic testing, FDG-PET and, in selected cases, EMB is suggested (see main text).

• Publisher: Oxford University Press,Wiley
• Subject: acute myocarditis / Antigens / Bone marrow / Cardiomyocytes / Cardiomyopathies - genetics / Cardiomyopathy / Cardiovascular disease / cardio‐immunology / Chemokines / Cytokines / Dendritic cells / Ejection fraction / Genetic testing / Genetics / Heart failure / Humans / Immune response / Immune system / Immunity (Disease) / Immunology / Inflammation / Inflammation - genetics / inflammatory cardiomyopathies / Italy - epidemiology / Kinases / Lymphocytes / Myocarditis / Myocarditis - genetics / pericarditis / Pericarditis - genetics / Review / Viral infections