Prediction of ventricular arrhythmia in phospholamban p.Arg14del mutation carriers-reaching the frontiers of individual risk prediction
Verstraelen, Tom E; van Lint, Freyja H M; Bosman, Laurens P; de Brouwer, Remco; Proost, Virginnio M; Abeln, Bob G S; Taha, Karim; Zwinderman, Aeilko H; Dickhoff, Cathelijne; Oomen, Toon; Schoonderwoerd, Bas A; Kimman, Gerardus P; Houweling, Arjan C; Gimeno-Blanes, Juan R; Asselbergs, Folkert W; van der Zwaag, Paul A; de Boer, Rudolf A; van den Berg, Maarten P; van Tintelen, J Peter; Wilde, Arthur A M
(2021) European heart journal, volume 42, issue 29, pp. 2842 - 2850
(Article)
Abstract
AIMS: This study aims to improve risk stratification for primary prevention implantable cardioverter defibrillator (ICD) implantation by developing a new mutation-specific prediction model for malignant ventricular arrhythmia (VA) in phospholamban (PLN) p.Arg14del mutation carriers. The proposed model is compared to an existing PLN risk model. METHODS AND RESULTS: Data were
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collected from PLN p.Arg14del mutation carriers with no history of malignant VA at baseline, identified between 2009 and 2020. Malignant VA was defined as sustained VA, appropriate ICD intervention, or (aborted) sudden cardiac death. A prediction model was developed using Cox regression. The study cohort consisted of 679 PLN p.Arg14del mutation carriers, with a minority of index patients (17%) and male sex (43%), and a median age of 42 years [interquartile range (IQR) 27-55]. During a median follow-up of 4.3 years (IQR 1.7-7.4), 72 (10.6%) carriers experienced malignant VA. Significant predictors were left ventricular ejection fraction, premature ventricular contraction count/24 h, amount of negative T waves, and presence of low-voltage electrocardiogram. The multivariable model had an excellent discriminative ability {C-statistic 0.83 [95% confidence interval (CI) 0.78-0.88]}. Applying the existing PLN risk model to the complete cohort yielded a C-statistic of 0.68 (95% CI 0.61-0.75). CONCLUSION: This new mutation-specific prediction model for individual VA risk in PLN p.Arg14del mutation carriers is superior to the existing PLN risk model, suggesting that risk prediction using mutation-specific phenotypic features can improve accuracy compared to a more generic approach.
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Keywords: Cardiomyopathy, Implantable cardioverter defibrillator, Phospholamban, Risk stratification, Sudden cardiac death, Cardiology and Cardiovascular Medicine, Journal Article
ISSN: 0195-668X
Publisher: Oxford University Press
Note: Funding Information: This work was supported by the PLN Foundation (www.plnheart.org) and the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation (2015-12eDETECT; 2018-30 PREDICT2) and a Fondation Leducq Transatlantic Network of Excellence (Cure-PLaN). Publisher Copyright: © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.
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