Risk Stratification in Arrhythmogenic Right Ventricular Cardiomyopathy

Abstract

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by ventricular arrhythmias and an increased risk of sudden cardiac death. Although structural abnormalities of the right ventricle predominate, it is well recognized that left ventricular involvement is common, particularly in advanced disease, and that left-dominant forms occur. The pathological characteristic of ARVC is myocyte loss with fibrofatty replacement. Since the first detailed clinical description of the disorder in 1982, significant advances have been made in understanding this disease. Once the diagnosis of ARVC is established, the single most important clinical decision is whether a particular patient's sudden cardiac death risk is sufficient to justify placement of an implantable cardioverter-defibrillator. The importance of this decision reflects the fact that ARVC is a common cause of sudden death in young people and that sudden death may be the first manifestation of the disease. This decision is particularly important because these are often young patients who are expected to live for many years. Although an implantable cardioverter-defibrillator can save lives in individuals with this disease, it is also well recognized that implantable cardioverter-defibrillator therapy is associated with both short- and long-term complications. Decisions about the placement of an implantable cardioverter-defibrillator are based on an estimate of a patient's risk of sudden cardiac death, as well as their preferences and values. The primary purpose of this article is to provide a review of the literature that concerns risk stratification in patients with ARVC and to place this literature in the framework of the 3 authors' considerable lifetime experiences in caring for patients with ARVC. The most important parameters to consider when determining arrhythmic risk include electric instability, including the frequency of premature ventricular contractions and sustained ventricular arrhythmia; proband status; extent of structural disease; cardiac syncope; male sex; the presence of multiple mutations or a mutation in TMEM43; and the patient's willingness to restrict exercise and to eliminate participation in competitive or endurance exercise.

Keywords: arrhythmogenic right ventricular dysplasia; death, sudden, cardiac; defibrillators, implantable; risk assessment; syncope.

Figure 1

Schematic representation of the presentation, clinical course and outcome in patients with Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) (14). The majority presented with sustained ventricular arrhythmias (VA) and received an implantable cardioverter-defibrillator (ICD) during follow-up. Printed from Groeneweg et al (14)

Figure 2

A and B. Survival free from any Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) related symptoms, sustained ventricular arrhythmias (VA), cardiac death and cardiac transplantation in ARVD/C index-patients with (2A) pathogenic mutations and (2B) without identified mutations. Symptoms (p=0.005) and sustained VA (p=0.020) occurred more often at younger age in index-patients with mutations. Survival free from cardiac death (p=0.644) and transplantation (p=0.704) was similar in both groups. Reprinted from Groeneweg et al (14)

Figure 2

A and B. Survival free from any Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) related symptoms, sustained ventricular arrhythmias (VA), cardiac death and cardiac transplantation in ARVD/C index-patients with (2A) pathogenic mutations and (2B) without identified mutations. Symptoms (p=0.005) and sustained VA (p=0.020) occurred more often at younger age in index-patients with mutations. Survival free from cardiac death (p=0.644) and transplantation (p=0.704) was similar in both groups. Reprinted from Groeneweg et al (14)

Figure 3

A–F. Cumulative survival from first appropriate ICD intervention (VT/VF) stratified by inducibility on EPS (A), sex (B), number of T-wave inversions (C), PVCs on Holter monitor (D), history of VT at presentation (E), and primary versus secondary prevention (VT/VF) (F) Reprinted from Orgeron et al (41).

Figure 4

A–F. Cumulative survival from ICD intervention for VF/VFL (CL ≤240ms) stratified by sex (A), PVCs on Holter monitor (B), syncope (C), age at presentation (D), history of VT at presentation (E), and primary versus secondary prevention (VT/VF) (F). Reprinted from Orgeron et al (41).

Figure 5

A–D. Incidence of sustained ventricular arrhythmias in patients with ARVD/C receiving an ICD for primary prevention based on 4 variables: Inducibility of VT at EPS (A), nonsustained VT (B) PVC frequency (C), and proband status (D). Reprinted from Bhonsale et al (39).

Figure 6

Flow chart of risk stratification and indications to ICD implantation in ARVC/D. VT, ventricular tachycardia. RV, right ventricle. LV, left ventricle. Major risk factors include syncope, nonsustained VT, and moderate ventricular dysfunction, either RV (RVEF 36% – 46%, or LV (LVEF 36% – 45%). Minor risk factors* include: complex genotype, male gender, proband, positive EP study, T wave inversion in 2 of 3 inferior leads, T wave inversion ≥ 3 precordial leads. Modified from Corrado et al. (7).