title: High risk of severe cardiac adverse events in patients with mitochondrial m.3243A>G mutation.
abstract: OBJECTIVE
  To determine the long-term incidence of cardiac life-threatening complications and death in patients with the m.3243A>G mutation, and to identify cardiac prognostic factors.
  
  
  METHODS
  We retrospectively included patients carrying the m.3243A>G mutation who were admitted to the Neuromuscular Disease Clinic of Pitié Salpêtrière Hospital between January 1992 and December 2010. We collected information relative to their yearly neurologic and cardiac investigations, their mutation load in blood, urine, and muscle at initial admission, and the occurrence of cardiac life-threatening adverse events and death during follow-up.
  
  
  RESULTS
  Forty-one patients (median age = 47 years [36-55 years], men = 13) were included, of whom 38 had clinical manifestations of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and 3 were asymptomatic. One patient had a personal history of cardiac transplantation. Cardiac investigations displayed left ventricular hypertrophy, left ventricular dysfunction, or both abnormalities in 18 patients, along with Wolff-Parkinson-White syndrome in 7, conduction system disease in 4, and atrial fibrillation in 1. Over a median 5-year (3-9 years) follow-up period, 11 patients died, including 3 due to heart failure; 7 had life-threatening adverse events, including 6 hospitalizations for severe heart failure and 1 resuscitated cardiac arrest. By multivariate analysis, left ventricular hypertrophy was the only parameter independently associated with occurrence of cardiac adverse events.
  
  
  CONCLUSIONS
  Patients with the m.3243A>G mutation have a high incidence of cardiac death and life-threatening adverse events. Left ventricular hypertrophy was the only parameter independently associated with occurrence of these events.
authors.affiliation: AP-HP, Pitié-Salpêtrière Hospital, Reference Center for Muscle Diseases Paris-Est, Myology Institute, Paris, France.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Malfatti
authors.forename: Pascal
authors.initials: P
authors.lastname: Laforêt
authors.forename: Claude
authors.initials: C
authors.lastname: Jardel
authors.forename: Tanya
authors.initials: T
authors.lastname: Stojkovic
authors.forename: Anthony
authors.initials: A
authors.lastname: Behin
authors.forename: Bruno
authors.initials: B
authors.lastname: Eymard
authors.forename: Anne
authors.initials: A
authors.lastname: Lombès
authors.forename: Amria
authors.initials: A
authors.lastname: Benmalek
authors.forename: Henri-Marc
authors.initials: HM
authors.lastname: Bécane
authors.forename: Nawal
authors.initials: N
authors.lastname: Berber
authors.forename: Christophe
authors.initials: C
authors.lastname: Meune
authors.forename: Denis
authors.initials: D
authors.lastname: Duboc
authors.forename: Karim
authors.initials: K
authors.lastname: Wahbi
mesh_terms: D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D006331:Heart Diseases / Q000150:complications / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality*; D006801:Humans; D017241:MELAS Syndrome / Q000150:complications / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D012356:RNA, Transfer, Leu / Q000235:genetics*
chemical_list: D012356:RNA, Transfer, Leu