Risk Factors for Malignant Ventricular Arrhythmias in Lamin A/C Mutation Carriers A European Cohort Study

Ingrid A. W. van Rijsingen, Eloisa Arbustini, Perry M. Elliott, Jens Mogensen, Johanna F. Hermans-van Ast, Anneke J. van der Kooi, J. Peter van Tintelen, Maarten P. van den Berg, Andrea Pilotto, Michele Pasotti, Sharon Jenkins, Camilla Rowland, Uzma Aslam, Arthur A. M. Wilde, Andreas Perrot, Sabine Pankuweit, Aeilko H. Zwinderman, Philippe Charron, Yigal M. Pinto

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Abstract

Objectives The purpose of this study was to determine risk factors that predict malignant ventricular arrhythmias (MVA) in Lamin A/C (LMNA) mutation carriers. Background LMNA mutations cause a variety of clinical phenotypes, including dilated cardiomyopathy and conduction disease. Many LMNA mutation carriers have a poor prognosis, because of a high frequency of MVA and progression to end-stage heart failure. However, it is unclear how to identify mutation carriers that are at risk for MVA. Methods In this multicenter cohort of 269 LMNA mutation carriers, we evaluated risk factors for MVA, defined as sudden cardiac death, resuscitation, and appropriate implantable cardioverter-defibrillator (ICD) treatment. Results In a median follow-up period of 43 months (interquartile range: 17 to 101 months), 48 (18%) persons experienced a first episode of MVA: 11 persons received successful cardiopulmonary resuscitation, 25 received appropriate ICD treatment, and 12 persons died suddenly. Independent risk factors for MVA were nonsustained ventricular tachycardia, left ventricular ejection fraction <45% at the first clinical contact, male sex, and non-missense mutations (insdel/truncating or mutations affecting splicing). MVA occurred only in persons with at least 2 of these risk factors. There was a cumulative risk for MVA per additional risk factor. Conclusions Carriers of LMNA mutations with a high risk of MVA can be identified using these risk factors. This facilitates selection of LMNA mutation carriers who are most likely to benefit from an ICD. (J Am Coll Cardiol 2012; 59: 493-500) (C) 2012 by the American College of Cardiology Foundation
Original languageEnglish
Pages (from-to)493-500
JournalJournal of the American College of Cardiology
Volume59
Issue number5
DOIs
Publication statusPublished - 2012

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