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Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies

Karim Wahbi 1, * Rabah Ben Yaou 2 Estelle Gandjbakhch 3 Frédéric Anselme 4 Thomas Gossios Neal Lakdawala Caroline Stalens Frederic Sacher 5 Dominique Babuty 6 Jean-Noel Trochu 7 Ghassan Moubarak 8 Kostantinos Savvatis Raphaël Porcher 9 Pascal Laforet 10 Abdallah Fayssoil 11 Eloi Marijon 12 Tanya Stojkovic 10 Anthony Behin 13 Sarah Léonard-Louis Guilhem Sole 14 Fabien Labombarda 15 Pascal Richard 16 Corinne Metay 17 Susana Quijano-Roy 18 Ivana Dabaj Didier Klug 19 Marie-Christine Vantyghem 20 Philippe Chevalier 21 Pierre Ambrosi 22 Emmanuelle Salort-Campana 23, 24 Nicolas Sadoul 25 Xavier Waintraub 26 Khadija Chikhaoui Philippe Mabo 8, 27, 28 Nicolas Combes 29 Philippe Maury 30 Jean-Marc Sellal 5 Usha Tedrow Jonathan Kalman Jitendra Vohra Alexander F.A. Androulakis Katja Zeppenfeld Tina Thompson Christine Barnerias 31 Henri-Marc Becane 32 Eric Bieth 33 Pierre Boccara Damien Bonnet 34 Françoise Bouhour 35 Stéphane Boulé 36 Anne-Claire Bréhin Françoise Chapon 37, 38 Pascal Cintas 30 Jean-Marie Cuisset 39 Jean-Marc Davy 40 Annachiara de Sandre-Giovannoli 23, 41 Florence Demurger 42, 28 Isabelle Desguerre 43 Klaus Dieterich 44 Julien Durigneux Andoni Echaniz-Laguna 45 Pascal Eschalier Ana Ferreiro 46 Xavier Ferrer 47 Christine Francannet 48 Mélanie Fradin 49 Bénédicte Gaborit 50 Arnaud Gay Albert Hagège 51 Arnaud Isapof 52 Isabelle Jéru 53 Raul Juntas Morales Emmanuelle Lagrue 54 Nicolas Lamblin 55 Olivier Lascols 53 Vincent Laugel 56 Arnaud Lazarus 57 France Leturcq 58 Nicolas Lévy 23, 24 Véronique Manel 59 Raphaël Mabo France Mayer Sandra Mercier 60 France Meune Maud Michaud 61 Marie-Christine Minot-Myhié 28 Antoine Muchir 62 Aleksandra Nadaj-Pakleza 63 France Magot Philippe Petiot 64 Florence Petit 65 Julien Praline 54 Anne Rollin 66 Pascal Sabouraud 67 Catherine Sarret 68 Stéphane Schaeffer Frederic Taithe 69 Celine Tard 70 Vincent Tiffreau 71 Annick Toutain 72 France Vatier Ulrike Walther-Louvier 40 Bruno Eymard 73 Philippe Charron 74 Corinne Vatier Gisèle Bonne 18 Saurabh Kumar 75 Perry Elliott 76 Denis Duboc 58, 77
* Corresponding author
41 CRB TAC - Centre de ressources biologiques Tissus ADN Cellules [Hôpital de la Timone - APHM]
Département de génétique médicale [Hôpital de la Timone - APHM], APHM - Assistance Publique - Hôpitaux de Marseille, TIMONE - Hôpital de la Timone [CHU - APHM]
44 INSERM U836, équipe 4, Muscles et pathologies
GIN - Grenoble Institut des Neurosciences
Abstract : 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.
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Last modification on : Wednesday, February 24, 2021 - 4:16:03 PM
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Karim Wahbi, Rabah Ben Yaou, Estelle Gandjbakhch, Frédéric Anselme, Thomas Gossios, et al.. Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies. Circulation, American Heart Association, 2019, 140 (4), pp.293-302. ⟨10.1161/CIRCULATIONAHA.118.039410⟩. ⟨hal-02237297⟩

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