Emerging Mechanisms and Therapeutic Strategies in Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) is a leading cause of heart failure and heart transplantation and is characterized by marked clinical and etiological heterogeneity. Recent studies have expanded the understanding of DCM from a predominantly monogenic disorder to a multifactorial disease shaped by genetic susceptibility and acquired or environmental “second hits”. Beyond rare pathogenic variants, emerging evidence highlights the contribution of clonal hematopoiesis of indeterminate potential to inflammation-driven adverse cardiac remodeling and disease progression. These secondary modifiers interact with pre-existing genetic backgrounds to amplify shared downstream pathways. In parallel, advances in mechanism-informed therapies are increasingly translating these insights into clinical practice. Beyond guideline-directed medical and device therapy, emerging approaches targeting specific molecular pathways, including sarcomeric modulators, inflammatory signaling, and gene- or cell-based interventions, illustrate a shift toward more personalized and stage-specific management of DCM and heart failure. This review aims to provide an updated overview of recent advances in the molecular mechanisms and diagnosis underlying DCM and discuss their implications for current and emerging therapeutic strategies.