Infectious agents in dilated cardiomyopathy: Genetic interactions, autoimmunity, mechanisms, and therapeutic approaches

Dilated cardiomyopathy (DCM) is a heterogeneous myocardial disorder characterized by left ventricular dilation and systolic dysfunction in the absence of ischemic, hypertensive, or valvular heart disease. Although its precise etiology remains unclear, it is widely recognized as a multifactorial disease arising from complex interactions between genetic predisposition and environmental triggers. Among these, infectious agents have been implicated in the pathogenesis of various subtypes, particularly inflammatory and idiopathic DCM. These agents can contribute to disease onset and progression through direct cardiomyocyte injury, immune-mediated chronic inflammation, and other yet-to-be-defined mechanisms. Infection-driven autoimmune activation is another potential key contributor to DCM, potentially linking infectious exposure to sustained myocardial damage. However, the precise role of various infectious agents in DCM initiation and progression, as well as their interactions with genetic predisposition and autoimmune activation, is inadequately understood. Improving understanding of infection-related etiologies could facilitate development of targeted therapeutic strategies; however, significant challenges persist in identifying causative and novel pathogens, and translating this into clinical practice. Therefore, this review explores the complex interactions between infectious agents, genetic predisposition, and autoimmune responses in DCM pathogenesis. We summarize current evidence on the role of infectious agents in DCM and emerging therapeutic strategies aimed at treating infection-related DCM. Finally, we outline future research directions to advance understanding of infection-associated DCM and improve patient outcomes. We reveal that a deeper understanding of host-microbe interactions, immune pathways, and genetic predisposition is essential for advancing DCM research. Furthermore, integrating genomics, metagenomics, and antibody and immunological profiling is crucial for developing personalized therapeutic strategies for this complex disease.