Abstract
The number of therapies for heart failure (HF) with reduced ejection fraction has nearly doubled in the past decade. In addition, new therapies for HF caused by hypertrophic and infiltrative disease are emerging rapidly. Indeed, we are on the verge of a new era in HF in which insights into the biology of myocardial disease can be matched to an understanding of the genetic predisposition in an individual patient to inform precision approaches to therapy. In this Review, we summarize the biology of HF, emphasizing the causal relationships between genetic contributors and traditional structure-based remodelling outcomes, and highlight the mechanisms of action of traditional and novel therapeutics. We discuss the latest advances in our understanding of both the Mendelian genetics of cardiomyopathy and the complex genetics of the clinical syndrome presenting as HF. In the phenotypic domain, we discuss applications of machine learning for the subcategorization of HF in ways that might inform rational prescribing of medications. We aim to bridge the gap between the biology of the failing heart, its diverse clinical presentations and the range of medications that we can now use to treat it. We present a roadmap for the future of precision medicine in HF.