title: Risk factors for malignant ventricular arrhythmias in lamin a/c mutation carriers a European cohort study.
abstract: OBJECTIVE
  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 (ins-del/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.
authors.affiliation: Department of Cardiology, Heart Failure Research Center, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Ingrid A W
authors.initials: IA
authors.lastname: van Rijsingen
authors.forename: Eloisa
authors.initials: E
authors.lastname: Arbustini
authors.forename: Perry M
authors.initials: PM
authors.lastname: Elliott
authors.forename: Jens
authors.initials: J
authors.lastname: Mogensen
authors.forename: Johanna F
authors.initials: JF
authors.lastname: Hermans-van Ast
authors.forename: Anneke J
authors.initials: AJ
authors.lastname: van der Kooi
authors.forename: J Peter
authors.initials: JP
authors.lastname: van Tintelen
authors.forename: Maarten P
authors.initials: MP
authors.lastname: van den Berg
authors.forename: Andrea
authors.initials: A
authors.lastname: Pilotto
authors.forename: Michele
authors.initials: M
authors.lastname: Pasotti
authors.forename: Sharon
authors.initials: S
authors.lastname: Jenkins
authors.forename: Camilla
authors.initials: C
authors.lastname: Rowland
authors.forename: Uzma
authors.initials: U
authors.lastname: Aslam
authors.forename: Arthur A M
authors.initials: AA
authors.lastname: Wilde
authors.forename: Andreas
authors.initials: A
authors.lastname: Perrot
authors.forename: Sabine
authors.initials: S
authors.lastname: Pankuweit
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: Philippe
authors.initials: P
authors.lastname: Charron
authors.forename: Yigal M
authors.initials: YM
authors.lastname: Pinto
mesh_terms: D000328:Adult; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D034904:Lamin Type A / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D017180:Tachycardia, Ventricular / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A; D004247:DNA