TY - JOUR
T1 - Programmed Ventricular Stimulation as an Additional Primary Prevention Risk Stratification Tool in Arrhythmogenic Right Ventricular Cardiomyopathy
T2 - A Multinational Study
AU - Gasperetti, Alessio
AU - Carrick, Richard T.
AU - Costa, Sarah
AU - Compagnucci, Paolo
AU - Bosman, Laurens P.
AU - Chivulescu, Monica
AU - Tichnell, Crystal
AU - Murray, Brittney
AU - Tandri, Harikrishna
AU - Tadros, Rafik
AU - Rivard, Lena
AU - van den Berg, Maarten P.
AU - Zeppenfeld, Katja
AU - Wilde, Arthur A. M.
AU - Pompilio, Giulio
AU - Carbucicchio, Corrado
AU - Dello Russo, Antonio
AU - Casella, Michela
AU - Svensson, Anneli
AU - Brunckhorst, Corinna B.
AU - van Tintelen, J. Peter
AU - Platonov, Pyotr G.
AU - Haugaa, Kristina H.
AU - Duru, Firat
AU - te Riele, Anneline S. J. M.
AU - Khairy, Paul
AU - Tondo, Claudio
AU - Calkins, Hugh
AU - James, Cynthia A.
AU - Saguner, Ardan M.
AU - Cadrin-Tourigny, Julia
N1 - Funding Information: The Johns Hopkins Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) Program is supported by the Leonie-Wild Foundation, the Leyla Erkan Family Fund for ARVD Research, the Hugh Calkins, Marvin H. Weiner, and Jacqueline J. Bernstein Cardiac Arrhythmia Center, the Dr. Francis P. Chiramonte Private Foundation, the Dr. Satish, Rupal, and Robin Shah ARVD Fund at Johns Hopkins, the Bogle Foundation, the Healing Hearts Foundation, the Campanella Family, the Patrick J. Harrison Family, the Peter French Memorial Foundation, the Wilmerding Endowments, Fondation Leducq, and UL1TR001079 (National Center for Advancing Translational Sciences). This work was performed during Dr Gasperetti’s tenure as the Wilton W. Webster Fellowship in Clinical Cardiac Catheter Ablation Fellow of the Heart Rhythm Society; Dr Cadrin-Tourigny’s work is supported by the Philippa and Marvin Carsley cardiology research chair and the Montreal Heart Institute Foundation. The Zurich ARVC Program is supported by the Georg und Bertha Schwyzer-Winiker Foundation, Baugarten Foundation, Leonie-Wild Foundation, Swiss Heart Foundation grants FF17019 and FF21073‚ and Swiss National Science Foundation grant 160327. Dr Platonov’s work in the Nordic ARVC Registry is supported by the Swedish Heart Lung Foundation (grant 20200674), and support from the Swedish state under the Avtal om läkarutbildning och forsknin (ALF)-agreement. The Dutch ARVC registry (Drs van Tintelen, and Wilde, and te Riele) is funded by the Netherlands Cardiovascular Research Initiative, with support of the Dutch Heart Foundation (grant CVON2015-12/2018-30 eDETECT/PREDICT2). Publisher Copyright: © 2021 American Heart Association, Inc.
PY - 2022/11/8
Y1 - 2022/11/8
N2 - 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 of 2.3 and 0.36 for inducible (likelihood ratio+) and noninducible (likelihood ratio-) 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.
AB - 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 of 2.3 and 0.36 for inducible (likelihood ratio+) and noninducible (likelihood ratio-) 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.
KW - arrhythmogenic right ventricular cardiomyopathy
KW - defibrillator, implantable
KW - electrophysiological techniques, cardiac
KW - risk assessment
KW - sudden cardiac death
UR - http://www.scopus.com/inward/record.url?scp=85141893034&partnerID=8YFLogxK
U2 - https://doi.org/10.1161/CIRCULATIONAHA.122.060866
DO - https://doi.org/10.1161/CIRCULATIONAHA.122.060866
M3 - Article
C2 - 36205131
SN - 0009-7322
VL - 146
SP - 1434
EP - 1443
JO - Circulation
JF - Circulation
IS - 19
ER -