Division of Heart and Lungs, Department of Medical Physiology, University Medical Center Utrecht, PO Box 85060, Utrecht 3508 AB, The Netherlands.
Division of Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, PO Box 85060, Utrecht 3508 AB, The Netherlands.
Cardiovasc Res. 2020 Jul 15;116(9):1571-1584. doi: 10.1093/cvr/cvaa084.
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.
致心律失常性心肌病（ACM）是一种危及生命的心脏疾病，由主要编码桥粒蛋白的基因突变引起，导致连接蛋白分子组成的改变。ACM 的特征是进行性的心肌细胞被纤维脂肪组织取代、心室扩张、心功能障碍和心力衰竭，但主要由危及生命的心律失常和心脏性猝死（SCD）的发生所主导。由于 SCD 主要发生在看似健康的年轻个体中，因此需要更好地对疑似 ACM 突变携带者进行风险分层。此外，ACM 患者的疾病严重程度、进展和结局具有高度的可变性。在这篇综述中，我们讨论了 ACM 的病因，重点是疾病早期隐匿阶段的致心律失常疾病机制。我们总结了可能有助于风险分层和预测疾病进程的潜在新生物标志物。最后，我们探讨了预防 ACM 早期心律失常和 SCD 的新治疗策略。
