Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies
Authors: Karim Wahbi, Rabah Ben Yaou, Estelle Gandjbakhch, Frédéric Anselme, Thomas Gossios, Neal K. Lakdawala, Caroline Stalens, Frédéric Sacher, Dominique Babuty, Jean-Noel Trochu, Ghassan Moubarak, Kostantinos Savvatis, Raphaël Porcher, Pascal Laforêt, Abdallah Fayssoil, Eloi Marijon, Tanya Stojkovic, Anthony Béhin, Sarah Leonard-Louis, Guilhem Sole, Fabien Labombarda, Pascale Richard, Corinne Metay, Susana Quijano-Roy, Ivana Dabaj, Didier Klug, Marie-Christine Vantyghem, Philippe Chevalier, Pierre Ambrosi, Emmanuelle Salort, Nicolas Sadoul, Xavier Waintraub, Khadija Chikhaoui, Philippe Mabo, Nicolas Combes, Philippe Maury, Jean-Marc Sellal, Usha B. Tedrow, Jonathan M. Kalman, Jitendra Vohra, Alexander F.A. Androulakis, Katja Zeppenfeld, Tina Thompson, Christine Barnerias, Henri-Marc Bécane, Eric Bieth, Franck Boccara, Damien Bonnet, Françoise Bouhour, Stéphane Boulé, Anne-Claire Brehin, Françoise Chapon, Pascal Cintas, Jean-Marie Cuisset, Jean-Marc Davy, Annachiara De Sandre-Giovannoli, Florence Demurger, Isabelle Desguerre, Klaus Dieterich, Julien Durigneux, Andoni Echaniz-Laguna, Romain Eschalier, Ana Ferreiro, Xavier Ferrer, Christine Francannet, Mélanie Fradin, Bénédicte Gaborit, Arnaud Gay, Albert Hagège, Arnaud Isapof, Isabelle Jeru, Raul Juntas Morales, Emmanuelle Lagrue, Nicolas Lamblin, Olivier Lascols, Vincent Laugel, Arnaud Lazarus, France Leturcq, Nicolas Levy, Armelle Magot, Véronique Manel, Raphaël Martins, Michèle Mayer, Sandra Mercier, Christophe Meune, Maud Michaud, Marie-Christine Minot-Myhié, Antoine Muchir, Aleksandra Nadaj-Pakleza, Yann Péréon, Philippe Petiot, Florence Petit, Julien Praline, Anne Rollin, Pascal Sabouraud, Catherine Sarret, Stéphane Schaeffer, Frederic Taithe, Céline Tard, Vincent Tiffreau, Annick Toutain, Camille Vatier, Ulrike Walther-Louvier, Bruno Eymard, Philippe Charron, Corinne Vigouroux, Gisèle Bonne, Saurabh Kumar, Perry Elliott, Denis Duboc
Journal: Circulation (2019)

Background: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation. Methods: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator–treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range]. Results: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0–7.2] and 5.1 [2.0–9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711–0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642–0.959), and the calibration slope was 1.082 (95% CI, 0.643–1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach. Conclusions: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03058185.