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 14 Guilhem Sole 15 Fabien Labombarda 16 Pascal Richard 17 Corinne Metay 18 Susana Quijano-Roy 19 Ivana Dabaj Didier Klug 20 Marie-Christine Vantyghem 21 Philippe Chevalier 22 Pierre Ambrosi 23 Emmanuelle Salort-Campana 24, 25 Nicolas Sadoul 26 Xavier Waintraub 27 Khadija Chikhaoui Philippe Mabo 8 Nicolas Combes 28 Philippe Maury 29 Jean-Marc Sellal 5 Usha Tedrow Jonathan Kalman Jitendra Vohra Alexander F.A. Androulakis Katja Zeppenfeld Tina Thompson Christine Barnerias 30 Henri-Marc Becane 31 Eric Bieth 32 Pierre Boccara Damien Bonnet 33 Françoise Bouhour 34 Stéphane Boulé 35 Anne-Claire Bréhin Françoise Chapon 36 Pascal Cintas 29 Jean-Marie Cuisset 37 Jean-Marc Davy 38 Annachiara de Sandre-Giovannoli 24, 39 Florence Demurger 40 Isabelle Desguerre 41 Klaus Dieterich 42 Julien Durigneux Andoni Echaniz-Laguna 43 Pascal Eschalier Ana Ferreiro 44 Xavier Ferrer 45 Christine Francannet 46 Mélanie Fradin 47 Bénédicte Gaborit 48 Arnaud Gay Albert Hagège 49 Arnaud Isapof 50 Isabelle Jéru 51 Raul Juntas Morales Emmanuelle Lagrue 52 Nicolas Lamblin 53 Olivier Lascols 51 Vincent Laugel 54 Arnaud Lazarus 55 France Leturcq 56 Nicolas Lévy 24, 25 Véronique Manel 57 Raphaël Mabo France Mayer Sandra Mercier 58 France Meune Maud Michaud 59 Marie-Christine Minot-Myhié 60 Antoine Muchir 61 Aleksandra Nadaj-Pakleza 62 France Magot Philippe Petiot 63 Florence Petit 64 Julien Praline 52 Anne Rollin 65 Pascal Sabouraud 66 Catherine Sarret 67 Stéphane Schaeffer Frederic Taithe 68 Celine Tard 69 Vincent Tiffreau 70 Annick Toutain 71 France Vatier Ulrike Walther-Louvier 38 Bruno Eymard 72 Philippe Charron 73 Corinne Vatier Gisèle Bonne 19 Saurabh Kumar 74 Perry Elliott 75 France Duboc
39 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]
42 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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https://hal.archives-ouvertes.fr/hal-02237297
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Submitted on : Thursday, August 1, 2019 - 12:24:09 PM
Last modification on : Tuesday, August 6, 2019 - 1:15:24 AM

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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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