High risk of severe cardiac adverse events in patients with mitochondrial m.3243A>G mutation

Neurology. 2013 Jan 1;80(1):100-5. doi: 10.1212/WNL.0b013e31827b1a2f. Epub 2012 Dec 12.


Objectives: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Genetic Predisposition to Disease
  • Heart Diseases / complications
  • Heart Diseases / diagnosis*
  • Heart Diseases / genetics*
  • Heart Diseases / mortality*
  • Humans
  • MELAS Syndrome / complications
  • MELAS Syndrome / diagnosis*
  • MELAS Syndrome / genetics*
  • MELAS Syndrome / mortality*
  • Male
  • Middle Aged
  • Mitochondria / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Prognosis
  • RNA, Transfer, Leu / genetics*


  • RNA, Transfer, Leu