Myocardial Injury in Rheumatic Diseases: Immune and Microcirculatory and Molecular Mechanisms of Cardiomyopathies

Immune-mediated myocardial injury is an important yet underrecognized manifestation of systemic rheumatic diseases and represents a biologically heterogeneous process extending beyond traditional cardiovascular complications such as pericardial disease or accelerated atherosclerosis. This review aimed to summarize current evidence regarding the molecular mechanisms underlying autoimmune myocardial injury and propose an integrated pathogenic framework. A structured narrative review of the literature was performed, focusing on molecular and cellular mechanisms, disease-specific pathogenic pathways, advances in cardio-immunology, and contemporary diagnostic approaches in autoimmune myocardial disease. Current evidence indicates that myocardial injury in rheumatic diseases results from complex interactions involving autoantibody-mediated injury, immune complex deposition, endothelial dysfunction, coronary microvascular dysfunction, dysregulated innate and adaptive immunity, oxidative stress, mitochondrial dysfunction, immunometabolic reprogramming, and regulated cardiomyocyte death. These mechanisms contribute to heterogeneous clinical manifestations, including myocarditis, arrhythmias, inflammatory cardiomyopathy, and heart failure. An integrated immune–microvascular–immunometabolic framework may represent a central mechanism driving myocardial injury and progression to inflammatory cardiomyopathy, supporting earlier diagnosis, improved risk stratification, and the development of precision therapeutic strategies.