Heart failure (HF) is a worldwide epidemic with treatments costing tens of billions of dollars every year. Despite this investment, HF therapies have limited efficacy in reducing disease progression. Recent insights in fundamental myocyte biology, HF etiologies and pathogenic mechanisms are propelling new strategies to treat and prevent HF. This meeting will explore biologic and technical advances that inform the genetic architecture, molecular pathogenesis and innovative approaches to treat HF. This comes at a time when very large human HF datasets are available and can be interrogated using advanced computational and bioinformatic approaches. Specific aims are to: 1) Consider genes, molecules, signaling pathways and biomarkers involved in systolic and diastolic HF in humans; 2) Explore disease mechanisms underlying HF in model systems; 3) Understand the role of epigenetics, miRNAs and lncRNAs in HF pathogenesis; and 4) Review translational programs in genomic, pharmacologic and cell-based therapeutics to treat HF. The outcomes of this meeting should be far-reaching for basic, translational and clinical communities. The meeting should also provide an excellent training program for junior scientists and serve as a catalyst for collaboration among research, clinical and industrial participants. This meeting is being held in conjunction with the “Cardiac Development, Regeneration and Repair” meeting that provides an outstanding opportunity for joint sessions in genetics, iPSC disease modeling, stem cell therapeutics and epigenetics.