Incidence and predictors of sudden cardiac death in arrhythmogenic right ventricular cardiomyopathy: a pooled analysis

Abstract

Aims Arrhythmogenic right ventricular cardiomyopathy (ARVC), an inherited heart muscle abnormality, is a major cause of sudden cardiac death (SCD). However, the burden of SCD and risk factors in ARVC are not clearly described. Thus, we estimated the rates and predictors of SCD in ARVC in a meta-analysis. Methods and results PubMed, Embase, and Web of Science were searched through 7 April 2021. Prospective studies reporting SCD from ARVC cohorts were included. Data were independently extracted by two reviewers and pooled in a random-effects meta-analysis. Fifty-two studies (n = 5485 patients) with moderate-to-low risk of bias were included. The pooled annualized rates of SCD were 0.65 per 1000 [95% confidence interval 0.00–6.43, I2 0.00%] in those with an implantable cardioverter-defibrillator (ICD) and 7.21 (2.38–13.79, I2 0.0%) in non-ICD cohorts: 7.14 in probands and 8.44 for 2010 Task Force Criteria (TFC). Multivariable predictors of life-threatening arrhythmic events including SCD were: age at presentation [adjusted hazard ratio 0.98 (0.97–0.99)], male sex [2.08 (1.29–3.36)], right ventricular (RV) dysfunction [6.99 (2.17–22.49)], QRS fragmentation [6.55 (3.33–12.90)], T-wave inversion [1.12 (1.02–1.24)], syncope at presentation [2.83 (2.40–4.08)], previous non-sustained ventricular tachyarrhythmia [2.53 (1.44–4.45)], and the TFC score [1.96 (1.02–3.76)], (P < 0.05). Predictors of appropriate ICD therapy were RV dysfunction, syncope, and inducible ventricular arrhythmia (P < 0.01). Conclusion This meta-analysis demonstrates a high burden of SCD in ARVC patients, especially among probands and ARVC defined by the modified TFC. Better strategies are required to improve patient management and prevent SCD in ARVC. PROSPERO ID: CRD42020211761.

State‐of‐the‐art document on optimal contemporary management of cardiomyopathies

“…RV fractional area change <23%), male sex, T-wave inversion, QRS dispersion, non-sustained VT and LV dysfunction have been associated with an increased risk of life-threatening ventricular arrhythmias and SCD. 221,222 Risk assessment models have been proposed for predicting the risk of life-threatening ventricular arrhythmias (including SCD), 223,224 however their practical use requires further validation. 225 Recently, a risk prediction model to estimates the 5-year risk of incident ventricular arrhythmias in ARVC has been developed (ARVCrisk.…”

“…Unexplained (arrhythmic) syncope, 218,220 severe RV dysfunction (e.g. RV fractional area change <23%), male sex, T‐wave inversion, QRS dispersion, non‐sustained VT and LV dysfunction have been associated with an increased risk of life‐threatening ventricular arrhythmias and SCD 221,222 . Risk assessment models have been proposed for predicting the risk of life‐threatening ventricular arrhythmias (including SCD), 223,224 however their practical use requires further validation 225 .…”

Incidence, risk assessment and prevention of sudden cardiac death in cardiomyopathies

“…111,112 A meta-analysis of 52 cohort studies (total of 5485 ARVC patients) reported the incidence of SCD of ∼0.7% per year in ARVC patients without ICD, and a significantly lower SCD incidence (0.65 per 1000 patients per year) in ICD recipients. 113…”

“…Disease penetrance in family members is ∼30% and positive genetic testing identifies individuals at higher risk of developing ventricular arrhythmias 125 . However, there are conflicting data on an independent predictive value of genetic basis for SCD in ARVC 113 . It is noteworthy that certain non‐desmosomal mutations (e.g.…”

“…125 However, there are conflicting data on an independent predictive value of genetic basis for SCD in ARVC. 113 It is noteworthy that certain non-desmosomal mutations (e.g. TMEM43, LMNA, PLN) are associated with a particularly high risk of SCD.…”