Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia (ARVC/D) - What We Have Learned after 40 Years of the Diagnosis of This Clinical Entity

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.

Figure 1

Evolution example of ARVC/D. Patient diagnosed with ARVC/D at age 32, after recovery from SAD during sports practice. He underwent implantation of ventricular ICD with multiple episodes of VF in clinical progression. At age 50, he developed sinus dysfunction and episodes of atrial fibrillation with a need for exchange for bicameral ICD. A) 12-lead ECG at diagnosis. Presence of T-wave inversion of V1-V6. Epsilon wave present in all precordial leads and final duration of QRS ≥ 55 ms. B) ECG with atrial fibrillation. C) inappropriate therapy due to atrial fibrillation.

Figure 2

Two examples of voltage mapping for ventricular tachycardia ablation in patients with ARVC/D. 1A) Mapping of epicardial voltage showing (in red) areas of scar in the outflow tract and basal region of the RV. 1B) Mapping of endocardial voltage showing the presence of more extensive scar areas in the same region. 1C) Perspective showing the correlation of the scar areas with the coronary tree. 2A and 2B) Voltage mapping used for substrate ablation in a patient with ICD with multiple therapies. Radiofrequency applications (white and red circles) distributed in the endocardial and epicardial regions. 3C) Mapping image showing scar presence affecting the LV.

Figure 3

Proposed scheme for the prognostic stratification of patients with ARVC/D, according to the clinical presentation. The risk subgroups shown in the figure were defined based on the estimated probability of a major arrhythmic event (sudden cardiac death, cardiac arrest due to ventricular fibrillation, ventricular tachycardia or an event requiring ICD intervention) during follow-up, in relation to arrhythmic events or previous risk factors. An estimated annual risk of more than 10% defines the high-risk group; a risk between 1% and 10% defines the intermediate risk group; and a risk below 1% defines the low-risk group. VEx: ventricular extrasystoles; ARVC/D: cardiomyopathy/right ventricular arrhythmogenic dysplasia. Adapted from Corrado et al., 2017.

Figure 4

Flowchart of indications for implantation of ICD in ARVC/D. The flowchart is based on available data on annual mortality rates associated with specific risk factors. High risk of major arrhythmic events: > 10%/year; intermediate risk: 1% to 10%/year and low risk: < 1%/year. The indications for ICD implantation were determined by consensus, taking not only the statistical risk into account, but also the general health status, socioeconomic factors, psychological impact and adverse effects of the device. SCD: sudden cardiac death; VF: ventricular fibrillation; VT: ventricular tachycardia; RV: right ventricle; LV: left ventricle. *See the text for the distinction between major and minor risk factors. Adapted from Corrado et al., 2017.