Arrhythmogenic cardiomyopathy (ACM) is a life-threatening cardiac disease caused by mutations in genes predominantly encoding for desmosomal proteins that lead to alterations in the molecular composition of the intercalated disc. ACM is characterized by progressive replacement of cardiomyocytes by fibrofatty tissue, ventricular dilatation, cardiac dysfunction, and heart failure but mostly dominated by the occurrence of life-threatening arrhythmias and sudden cardiac death (SCD). As SCD appears mostly in apparently healthy young individuals, there is a demand for better risk stratification of suspected ACM mutation carriers. Moreover, disease severity, progression, and outcome are highly variable in patients with ACM. In this review, we discuss the aetiology of ACM with a focus on pro-arrhythmic disease mechanisms in the early concealed phase of the disease. We summarize potential new biomarkers which might be useful for risk stratification and prediction of disease course. Finally, we explore novel therapeutic strategies to prevent arrhythmias and SCD in the early stages of ACM.

中文翻译：

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致心律失常性心肌病：发病机制、促心律失常重塑和风险分层和治疗的新方法。

致心律失常性心肌病 (ACM) 是一种危及生命的心脏病，由主要编码桥粒蛋白的基因突变引起，导致插入的椎间盘的分子组成发生变化。ACM 的特征是心肌细胞逐渐被纤维脂肪组织替代、心室扩张、心功能不全和心力衰竭，但主要以危及生命的心律失常和心源性猝死 (SCD) 的发生为主。由于 SCD 主要出现在明显健康的年轻个体中，因此需要对疑似 ACM 突变携带者进行更好的风险分层。此外，ACM 患者的疾病严重程度、进展和结果差异很大。在这次审查中，我们讨论了 ACM 的病因，重点是疾病早期隐匿阶段的促心律失常疾病机制。我们总结了可能对风险分层和病程预测有用的潜在新生物标志物。最后，我们探索了预防 ACM 早期心律失常和 SCD 的新治疗策略。