Gigli Marta, Stolfo Davide, Merlo Marco, Sinagra Gianfranco, Taylor Matthew R G, Mestroni Luisa
Cardiothoracovascular Department, Centre for Diagnosis and Treatment of Cardiomyopathies, European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI) and University of Trieste, Trieste, Italy.
Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Nat Rev Cardiol. 2025 Mar;22(3):183-198. doi: 10.1038/s41569-024-01074-2. Epub 2024 Oct 11.
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）是一种病因多样、致病机制复杂的疾病。尽管在过去十年中DCM患者的预后有所改善，但这种疾病仍然是心力衰竭和过早死亡的主要原因。DCM的传统治疗基于射血分数降低的心力衰竭的基础治疗方法。然而，人们越来越关注个体化治疗和精准医学。确认遗传因果关系的能力正逐渐通过对基因型-表型相关性的深入理解得到补充。非遗传因素也会影响DCM的发病，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，这增加了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，从单基因病因到遗传异常与触发环境因素的共存（“两次打击”假说）。还讨论了常见遗传变异在普通人群中的作用以及基因修饰因子在疾病发生和发展中的作用。最后，强调了未来的研究领域，特别是小分子、RNA和基因治疗等新型疗法，以及预防心律失常性死亡的措施。
