ABC | Volume 112, Nº1, January 2019

Review Article Arrythmogenic Right Ventricular Cardiomiopathy/Dysplasia (ARVC/D) - What We Have Learned after 40 Years of the Diagnosis of This Clinical Entity Jorge Elias Neto, 1 Joelci Tonet, 2 Robert Frank, 2 Guy Fontaine 2 Vitória Apart Hospital - Serviço de Eletrofisiologia, 1 Serra, ES – Brazil ‘Unité de Rythmologie de l’Institut de Cardiologie de l’Hôpital Pitié-Salpêtrière, 2 Paris – France Mailing Address: Jorge Elias Neto • Vitoria Apart Hospital - Serviço de Eletrofisiologia - Rodovia BR-101 Norte, Km 2,38, s/n. Postal Code 29161-900, Boa Vista II, Serra, ES – Brazil E-mail: jeliasneto@gmail.com Manuscript received August 14, 2018, revised manuscript September 12, 2018, accepted September 12, 2018 Keywords Arrhythmogenic Right Ventricular Dysplasia/physiopathology; Arrhythmias, Cardiac/diagnostic imaging; Catheter Ablation; Defibrillators, Implantable; Magnetic Resonance Imaging. DOI: 10.5935/abc.20180266 Abstract Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) was initially recognized as a clinical entity by Fontaine and Marcus, who evaluated a group of patients with ventricular tachyarrhythmia from a structurally impaired right ventricle (RV). Since then, there have been significant advances in the understanding of the pathophysiology, manifestation and clinical progression, and prognosis of the pathology. The identification of genetic mutations impairing cardiac desmosomes led to the inclusion of this entity in the classification of cardiomyopathies. Classically, ARVC/D is an inherited disease characterized by ventricular arrhythmias, right and / or left ventricular dysfunction; and fibro-fatty substitution of cardiomyocytes; its identification can often be challenging, due to heterogeneous clinical presentation, highly variable intra- and inter-family expressiveness, and incomplete penetrance. In the absence of a gold standard that allows the diagnosis of ARVC/D, several diagnostic categories were combined and recently reviewed for a higher diagnostic sensitivity, without compromising the specificity. The finding that electrical abnormalities, particularly ventricular arrhythmias, usually precede structural abnormalities is extremely important for risk stratification in positive genetic members. Among the complementary exams, cardiac magnetic resonance imaging (CMR) allows the early diagnosis of left ventricular impairment, even before morpho-functional abnormalities. Risk stratification remains a major clinical challenge, and antiarrhythmic drugs, catheter ablation and implantable cardioverter defibrillator are the currently available therapeutic tools. The disqualification of the sport prevents cases of sudden death because the effort can trigger not only the electrical instability, but also the onset and progression of the disease. Introduction ARVC/D is an inherited disease of the heart muscle that predominantly affects the right ventricle (RV). It is characterized by the progressive loss of the right ventricular myocardial tissue and its replacement for fibrous and fatty tissue. 1,2 Originally described by Fontaine and Marcus in 1982, ARVC/D is one of the leading causes of sudden arrhythmic death (SAD) in young people and athletes. 3 Recently, there have been substantial advances in the understanding of its pathogenesis, clinical manifestations and long-term progression. 4 The disease was initially referred to as dysplasia because it was thought to be a congenital defect of the RV myocardial development. The subsequent finding that the disease is caused by a genetic defect in cardiac desmosomes allowed its description as cardiomyopathy, and its inclusion in the classification of cardiomyopathies by the American Heart Association (AHA). 4-7 Etiopathogenesis Histopathological characteristics The characteristic histopathological finding of ARVC/D is the progressive loss of RV myocardial tissue that is replaced by fibrous and fatty tissue. The presence of irregular mononuclear inflammatory infiltrate (predominantly lymphocytic) is common, suggesting that the process may have an immunological mediation. 8 It has been proposed that the inflammatory infiltrate can extend the lesion to previously healthy regions, a process associated with worsening of the electrocardiographic abnormalities with consequent increase in symptomatic arrhythmias. This type of progression may be confused with acute myocarditis. 8 Contrary to what was observed in several forms of heart disease, in which there was a predominance of subendocardial muscle involvement, in the ARVC/D the greatest impairment is evident in the subepicardial region of the RV free wall. In addition, segments of the RV free wall that experience the greatest mechanical stress during the cardiac cycle are more impaired. In general, the trabecular muscles of the RV endocardial region and the interventricular septum (relevant aspect when differentiating from sarcoidosis) are spared. When the left ventricle (LV) is involved, myocardial degeneration and fibrosis are more visible in the subepicardium and in the middle myocardium of the lateral wall. 1,8 1