Programmed Ventricular Stimulation as an Additional Primary Prevention Risk Stratification Tool in Arrhythmogenic Right Ventricular Cardiomyopathy: A Multinational Study

Abstract

BACKGROUND: A novel risk calculator based on clinical characteristics and noninvasive tests that predicts the onset of clinical sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been proposed and validated by recent studies. It remains unknown whether programmed ventricular stimulation (PVS) provides additional prognostic value. METHODS: All patients with a definite ARVC diagnosis, no history of sustained VAs at diagnosis, and PVS performed at baseline were extracted from 6 international ARVC registries. The calculator-predicted risk for sustained VA (sustained or implantable cardioverter defibrillator treated ventricular tachycardia [VT] or fibrillation, [aborted] sudden cardiac arrest) was assessed in all patients. Independent and combined performance of the risk calculator and PVS on sustained VA were assessed during a 5-year follow-up period. RESULTS: Two hundred eighty-eight patients (41.0±14.5 years, 55.9% male, right ventricular ejection fraction 42.5±11.1%) were enrolled. At PVS, 137 (47.6%) patients had inducible ventricular tachycardia. During a median of 5.31 [2.89–10.17] years of follow-up, 83 (60.6%) patients with a positive PVS and 37 (24.5%) with a negative PVS experienced sustained VA ( P <0.001). Inducible ventricular tachycardia predicted clinical sustained VA during the 5-year follow-up and remained an independent predictor after accounting for the calculator-predicted risk (HR, 2.52 [1.58–4.02]; P <0.001). Compared with ARVC risk calculator predictions in isolation (C-statistic 0.72), addition of PVS inducibility showed improved prediction of VA events (C-statistic 0.75) (log-likelihood ratio for nested models, P <0.001). PVS inducibility had a 76% [67–84] sensitivity and 68% [61–74] specificity, corresponding to log-likelihood ratios (LR) of 2.3 and 0.36 for inducible (LR+) and noninducible (LR–) patients, respectively. In patients with a ARVC risk calculator–predicted risk of clinical VA events <25% during 5 years (ie, low/intermediate subgroup), PVS had a 92.6% negative predictive value. CONCLUSIONS: PVS significantly improved risk stratification above and beyond the calculator-predicted risk of VA in a primary prevention cohort of patients with ARVC, mainly for patients considered to be at low and intermediate risk by the clinical risk calculator.

AAV-Mediated Delivery of Plakophilin-2a Arrests Progression of Arrhythmogenic Right Ventricular Cardiomyopathy in Murine Hearts: Preclinical Evidence Supporting Gene Therapy in Humans

“…ARVC is a disease with incomplete penetrance. 2 While significant progress has been made in risk stratification of patients suspect of ARVC, [30][31][32] it remains unpredictable whether or when the disease will present in an asymptomatic gene carrier. 2 As such, any future implementation of gene therapy in PKP2 pathogenic variant carriers will likely not be in an asymptomatic individual as a preventive measure, but as a therapeutic procedure for a patient with an overt disease.…”

Imagenetics for Precision Medicine in Dilated Cardiomyopathy

“…12,31 Similarly, P/LP genetic variants in FLNC or desmosomal genes (eg, DSP, DES [desmin]) may carry an increased risk for arrhythmias and/or heart failure development. 40,58 Imaging can offer important information on DCM prognosis. LVEF is an established determinant of the clinical outcome of DCM patients.…”

“…12,31 Similarly, P/LP genetic variants in FLNC or desmosomal genes (eg, DSP, DES [desmin]) may carry an increased risk for arrhythmias and/or heart failure development. 40,58…”

Letter by Doundoulakis et al Regarding Article, “Programmed Ventricular Stimulation as Additional Primary Prevention Risk Stratification Tool in Arrhythmogenic Right Ventricular Cardiomyopathy”

“…We read with great interest the article from Gasperetti et al showing that programmed ventricular stimulation significantly improved risk stratification above and beyond the calculator-predicted risk of ventricular arrhythmias in a primary prevention cohort of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). 1 Ventricular tachycardia or ventricular fibrillation are significant mechanisms of sudden cardiac death to which a major proportion of cardiac mortality in patients with ARVC is attributed. Indeed, the presence of complex arrhythmias of right ventricular origin characterize this disease.…”