Dilated cardiomyopathy (DCM) is a complex disease with multiple causes and various pathogenic mechanisms. Despite improvements in the prognosis of patients with DCM in the past decade, this condition remains a leading cause of heart failure and premature death. Conventional treatment for DCM is based on the foundational therapies for heart failure with reduced ejection fraction. However, increasingly, attention is being directed towards individualized treatments and precision medicine. The ability to confirm genetic causality is gradually being complemented by an increased understanding of genotype–phenotype correlations. Non-genetic factors also influence the onset of DCM, and growing evidence links genetic background with concomitant non-genetic triggers or precipitating factors, increasing the extreme complexity of the pathophysiology of DCM. This Review covers the spectrum of pathophysiological mechanisms in DCM, from monogenic causes to the coexistence of genetic abnormalities and triggering environmental factors (the ‘two-hit’ hypothesis). The roles of common genetic variants in the general population and of gene modifiers in disease onset and progression are also discussed. Finally, areas for future research are highlighted, particularly novel therapies, such as small molecules, RNA and gene therapy, and measures for the prevention of arrhythmic death.

扩张型心肌病 （DCM） 是一种复杂的疾病，具有多种病因和多种致病机制。尽管在过去十年中 DCM 患者的预后有所改善，但这种情况仍然是心力衰竭和过早死亡的主要原因。DCM 的常规治疗基于射血分数降低的心力衰竭的基础疗法。然而，人们越来越多地关注个体化治疗和精准医疗。确认遗传因果关系的能力正逐渐得到对基因型-表型相关性理解的补充。非遗传因素也会影响 DCM 的发作，越来越多的证据表明遗传背景与伴随的非遗传触发因素或诱发因素有关，从而增加了 DCM 病理生理学的极端复杂性。本综述涵盖了 DCM 的病理生理机制范围，从单基因原因到遗传异常和触发环境因素的共存（“两击”假说）。还讨论了一般人群中常见遗传变异和基因修饰因子在疾病发生和进展中的作用。最后，强调了未来研究的领域，特别是新疗法，如小分子、RNA 和基因治疗，以及预防心律失常死亡的措施。