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.

在过去十年中，射血分数降低的心力衰竭 (HF) 疗法的数量几乎翻了一番。此外，由肥厚性和浸润性疾病引起的 HF 的新疗法正在迅速出现。事实上，我们正处于 HF 新时代的边缘，在这个时代，对心肌疾病生物学的洞察可以与对个体患者遗传易感性的理解相匹配，从而为精确的治疗方法提供信息。在这篇综述中，我们总结了 HF 的生物学，强调了遗传因素与传统的基于结构的重塑结果之间的因果关系，并强调了传统疗法和新型疗法的作用机制。我们讨论了我们对心肌病的孟德尔遗传学和表现为 HF 的临床综合征的复杂遗传学的理解的最新进展。在表型领域，我们讨论了机器学习在 HF 子分类中的应用，这些方法可能为合理的药物处方提供信息。我们的目标是弥合衰竭心脏的生物学特性、其多样化的临床表现和我们现在可以用来治疗它的药物范围之间的差距。我们提出了 HF 精准医学未来的路线图。它多样化的临床表现和我们现在可以用来治疗它的药物范围。我们提出了 HF 精准医学未来的路线图。它多样化的临床表现和我们现在可以用来治疗它的药物范围。我们提出了 HF 精准医学未来的路线图。