Engel Morgan, Shiel Emily A, Chelko Stephen P
Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL, United States of America; Department of Medicine, University of Central Florida College of Medicine, Orlando, FL, United States of America.
Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL, United States of America.
Int J Cardiol. 2024 Feb 15;397:131602. doi: 10.1016/j.ijcard.2023.131602. Epub 2023 Nov 17.
Arrhythmogenic cardiomyopathy (ACM) is a familial, nonischemic heart disease typically inherited via an autosomal dominant pattern (Nava et al., [1]; Wlodarska et al., [2]). Often affecting the young and athletes, early diagnosis of ACM can be complicated as incomplete penetrance with variable expressivity are common characteristics (Wlodarska et al., [2]; Corrado et al., [3]). That said, of the five desmosomal genes implicated in ACM, pathogenic variants in desmocollin-2 (DSC2) and desmoglein-2 (DSG2) have been discovered in both an autosomal-recessive and autosomal-dominant pattern (Wong et al., [4]; Qadri et al., [5]; Chen et al., [6]). Originally known as arrhythmogenic right ventricular dysplasia (ARVD), due to its RV prevalence and manifesting in the young, the disease was first described in 1736 by Giovanni Maria Lancisi in his book "De Motu Cordis et Aneurysmatibus" (Lancisi [7]). However, the first comprehensive clinical description and recognition of this dreadful disease was by Guy Fontaine and Frank Marcus in 1982 (Marcus et al., [8]). These two esteemed pathologists evaluated twenty-two (n = 22/24) young adult patients with recurrent ventricular tachycardia (VT) and RV dysplasia (Marcus et al., [8]). Initially, ARVD was thought to be the result of partial or complete congenital absence of ventricular myocardium during embryonic development (Nava et al., [9]). However, further research into the clinical and pathological manifestations revealed acquired progressive fibrofatty replacement of the myocardium (McKenna et al., [10]); and, in 1995, ARVD was classified as a primary cardiomyopathy by the World Health Organization (Richardson et al., [11]). Thus, now classifying ACM as a cardiomyopathy (i.e., ARVC) rather than a dysplasia (i.e., ARVD). Even more recently, ARVC has shifted from its recognition as a primarily RV disease (i.e., ARVC) to include left-dominant (i.e., ALVC) and biventricular subtypes (i.e., ACM) as well (Saguner et al., [12]), prompting the use of the more general term arrhythmogenic cardiomyopathy (ACM). This review aims to discuss pathogenesis, clinical and pathological phenotypes, basic and translational research on the role of inflammation, and clinical trials aimed to prevent disease onset and progression.
致心律失常性心肌病（ACM）是一种家族性非缺血性心脏病，通常通过常染色体显性模式遗传（纳瓦等人，[1]；沃洛达尔斯卡等人，[2]）。ACM常影响年轻人和运动员，由于不完全外显率和可变表达率是其常见特征，因此ACM的早期诊断可能较为复杂（沃洛达尔斯卡等人，[2]；科拉多等人，[3]）。也就是说，在与ACM相关的五个桥粒基因中，桥粒芯蛋白-2（DSC2）和桥粒芯胶粘蛋白-2（DSG2）的致病变异已在常染色体隐性和常染色体显性模式中均被发现（黄等人，[4]；卡德里等人，[5]；陈等人，[6]）。该疾病最初被称为致心律失常性右心室发育不良（ARVD），因其右心室患病率高且在年轻人中发病，1736年乔瓦尼·玛丽亚·兰奇西在其著作《De Motu Cordis et Aneurysmatibus》中首次对其进行了描述（兰奇西[7]）。然而，对这种可怕疾病的首次全面临床描述和认识是由盖伊·方丹和弗兰克·马库斯在1982年完成的（马库斯等人，[8]）。这两位杰出的病理学家评估了22例（n = 22/24）患有复发性室性心动过速（VT）和右心室发育不良的年轻成年患者（马库斯等人，[8]）。最初，ARVD被认为是胚胎发育过程中部分或完全先天性心室心肌缺失的结果（纳瓦等人，[9]）。然而，对临床和病理表现的进一步研究揭示了心肌的后天性进行性纤维脂肪替代（麦肯纳等人，[10]）；1995年，ARVD被世界卫生组织列为原发性心肌病（理查森等人，[11]）。因此，现在将ACM归类为心肌病（即ARVC）而非发育不良（即ARVD）。更近一些时候，ARVC已从其最初被认为主要是右心室疾病（即ARVC）转变为包括左心室为主型（即ALVC）和双心室亚型（即ACM）（萨古纳等人，[12]），这促使人们使用更通用的术语致心律失常性心肌病（ACM）。本综述旨在讨论其发病机制、临床和病理表型、炎症作用的基础研究和转化研究，以及旨在预防疾病发生和进展的临床试验。
