Beyond genomics-technological advances improving the molecular characterization and precision treatment of heart failure.

Dilated cardiomyopathy (DCM) is a major cause of heart failure and cardiovascular mortality. In the past 20 years, there has been an overwhelming focus on developing therapeutics that target common downstream disease pathways thought to be involved in all forms of heart failure independent of the initial etiology. While this strategy is effective at the population level, individual responses vary tremendously and only approximately one third of patients receive benefit from modern heart failure treatments. In this perspective, we propose that DCM should be considered as a collection of diseases with a common phenotype of left ventricular dilation and systolic dysfunction rather than a single disease entity, and that mechanism-based classification of disease subtypes will revolutionize our understanding and clinical approach towards DCM. We discuss how these efforts are central to realizing the potential of precision medicine and how they are empowered by the development of new tools that allow investigators to strategically employ genomic and transcriptomic information. Finally, we outline an investigational strategy to (1) define DCM at the patient level, (2) develop new tools to model and mechanistically dissect subtypes of human heart failure, and (3) harness these insights for the development of precision therapeutics.