ABC | Volume 112, Nº1, January 2019

Elias Nero et al ARVC/D - Diagnosis and treatment Arq Bras Cardiol. 2019; 112(1):91-103 Review Article • Biventricular failure: In an advanced stage of the disease, the interventricular septum is involved causing congestive heart failure. At this stage, mural thrombosis may occur, especially in aneurysms that form in the RV or in the presence of atrial fibrillation. The phenotype may mimic advanced dilated cardiomyopathy, hindering the differential diagnosis in the more advanced stages of the disease. 16 Recently, Calkins et al. 6 reported the clinical follow-up of a cohort of 102 patients diagnosed with ARVC/D after 50 years of age. The authors observed that, although SVT is also frequent in this age group, the incidence of syncope, typical electrocardiographic changes, ventricular ectopy to the Holter, and pathogenic mutation were less prevalent than in the younger age groups. 6 A later manifestation of ARVC/D does not translate into a better prognosis of survival free of high-risk arrhythmic events. 14 Clinical diagnosis In general, the diagnosis of ARVC/D should be considered in any young or middle-aged individual presenting: (1) frequent ventricular ectopies; (2) ventricular tachycardia with LBBB morphology with superior or multiple QRS morphologies; and (3) SAD. This hypothesis is reinforced in cases of arrhythmic events that occur during exercise in individuals with inverted T-waves in right precordial leads. 7 Although these clinical indicators lead to the diagnostic hypothesis, the definitive diagnosis of ARVC/D remains a challenge because it is a disease with a low prevalence that lacks a single conclusive diagnostic test. 17 To standardize the clinical diagnosis of ARVC/D, in 1994 an international task force (TFC 94) proposed guidelines in the form of a qualitative scoring system with major and minor criteria. 1,4 In 2010, the task force reviewed the guidelines for improving diagnostic sensitivity, especially for family members (TFC 2010), 18 providing quantitative criteria for the diagnosis of RV abnormalities and aggregating molecular genetic criteria (Table 1). 4,16 Although it is the current gold standard, TFC 2010 does not apply to the predominant forms of involvement of the left chambers 19 that may be included in future reviews. 4,20 Patients are diagnosed as having ARVC/D if they present a total of 4 points considering that the major criterion value is 2 points; and the minor criterion, 1 point. Patients who reach the “3-point” score are classified as probable ARVC/D carriers, while those with 1 or 2 points are classified as not meeting the criteria for ARVC/D. 6,18 The initial evaluation consists of non-invasive examinations (ECG, ECG-HR, echocardiogram (ECHO) and/or CMR, 24‑hour Holter and genetic analysis), while invasive examinations (right ventriculography and endomyocardial biopsy) are recommended only for individuals with high risk of the disease. 1,5 The tissue criteria used in TFC 2010, obtained by endomyocardial biopsy, focused on the severity of myocyte loss and the quantification of fibrosis. 21 However, endomyocardial biopsy is invasive and its diagnostic sensitivity may be limited due to the heterogeneous and variable distribution of the disease. Although RV free wall is often affected, biopsy is usually performed on the septum due to the fear of perforation, which further compromises its sensitivity. 22 Rarely, outside the US, its value in the diagnosis of ARVC/D lies mainly on the differential diagnosis with other cardiomyopathies, myocarditis and sarcoidosis. 4 Electrocardiogram Sinus rhythm The 12-lead ECG usually presents abnormalities in most patients with ARVC/D, indicating that electrocardiographic changes may precede the development of malignant ventricular arrhythmias (Figure 1). Thus, knowing the common manifestations of ARVC/D in the 12-lead ECG, the exercise test, and the 24-hour Holter test may be useful in increasing the diagnostic accuracy when generating the clinical suspicion. 7 In addition, it can help with the identification of relatives affected. 6,9 However, although ECG analysis is crucial to initial stratification, about 12% of patients with ARVC/D may present with a normal ECG, which reinforces the need for clinical evaluation that is based on the criteria proposed by TFC 2010. 9 In addition to electrocardiographic changes classically described in ARVC/D, other alterations can be identified in the baseline ECG: sinus bradycardia, P wave abnormalities (secondary to atrial involvement), and AV conduction disorder (more often first-degree AVB). The occurrence of severe atrioventricular conduction disturbance in ARVC/D is rare. 9 Several multicenter studies have shown that T-wave inversion in V1-3 is the most common ECG finding in ARVC/D. As a result, in TFC 2010, this T wave alteration was considered a major criterion for its diagnosis. The presence of inversion of the T wave only in V1 and V2 is a minor criterion. The inversion of T is secondary to the structural alterations of the RV. The observation of inversion beyond V3 translates a very advanced stage of the disease with severe RV dilation and possible LV involvement and can therefore be considered as indicative of worse prognosis (Figure 1A). 5,6,9 One of the common findings of ARVC/D is complete or incomplete right bundle branch block (RBBB), especially in patients with severe structural impairment, and its presence may compromise the interpretation of ventricular depolarization abnormalities. 6 RBBB in ARVC/D may have the following characteristics: (1) low amplitude of R wave and QRS in V1-2; (2) low R’/S ratio in V1-2; (3) inversion of the T wave in V1-3 or in the other leads of the frontal plane. Epicardial and histopathological mapping studies have demonstrated that RBBB in ARVC/D is not due to a proximal right bundle branch block, but represents the result of the distal changes inherent in delayed stimulus propagation in the regions of fibrous‑fatty transformation. 9 Epsilon wave, a low-frequency deflection that occurs at the end of the QRS and before the T wave (Figure 1), although uncommon, is a sign of the presence of an advanced stage of 3