title: Long-term cardiac prognosis and risk stratification in 260 adults presenting with mitochondrial diseases.
abstract: OBJECTIVE
  The aim of this study is to assess the long-term cardiac prognosis of adults with mitochondrial diseases.
  
  
  RESULTS
  Between January 2000 and May 2014, we retrospectively included in this study 260 consecutive patients (60% women) ≥18 years (interquartile range 31-54), with genetically proven mitochondrial diseases, including 109 with mitochondrial DNA (mtDNA) single large-scale deletions, 64 with the m.3243A>G mutation in MT-TL1, 51 with other mtDNA point mutations, and 36 patients with nuclear gene mutations. Cardiac involvement was present at baseline in 81 patients (30%). Single and multiple variable analyses were performed in search of predictors of major adverse cardiac events (MACEs), and hazard ratios (HRs) and 95% confidence intervals (CI) were calculated. Over a median follow-up of 7 years (3.6-11.7), 27 patients (10%) suffered a MACE, defined as sudden death, death due to heart failure (HF), resuscitated cardiac arrest, third-degree atrioventricular block, sinus node dysfunction, cardiac transplantation, or hospitalization for management of HF. Patients with single large-scale mtDNA deletions or m.3243A>G mutations had the highest incidence of MACE. By multiple variable analysis, intraventricular conduction block (HR = 16.9; 95% CI: 7.2-39.4), diabetes (HR = 7.0; 95% CI: 2.9-16.7), premature ventricular complexes (HR = 3.6; 95% CI: 1.4-9.2), and left ventricular (LV) hypertrophy (HR = 2.5; 95% CI: 1.1-5.8) were independent predictors of MACEs. In patients with zero, one, and two or more risk factors, the incidences of MACE were 1.7, 15 and 42%, respectively.
  
  
  CONCLUSIONS
  Patients with mitochondrial diseases are at high risk of MACE, independently predicted by intraventricular conduction block, diabetes, ventricular prematurity, and LV hypertrophy.
authors.affiliation: Cardiology Department, AP-HP, Cochin Hospital, 27 rue du Faubourg Saint Jacques, 75679 Paris Cedex 14, France Université Paris Descartes-Sorbonne Paris Cité, Paris, France AP-HP, Pitié-Salpêtrière Hospital, Reference Center for Muscle Diseases Paris-Est, Myology Institute, 75651 Paris Cedex 13, France INSERM, UMRS 974, Paris 75013, France karim.wahbi@cch.aphp.fr.
authors.forename: Karim
authors.initials: K
authors.lastname: Wahbi
authors.affiliation: Université Paris Descartes-Sorbonne Paris Cité, Paris, France INSERM Unit 970, Paris Cardiovascular Research Centre (PARCC), Paris, France Medical Intensive Care Unit, AP-HP, Cochin Hospital, Paris Cedex 14, France.
authors.forename: Wulfran
authors.initials: W
authors.lastname: Bougouin
authors.affiliation: AP-HP, Pitié-Salpêtrière Hospital, Reference Center for Muscle Diseases Paris-Est, Myology Institute, 75651 Paris Cedex 13, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Béhin
authors.affiliation: AP-HP, Pitié-Salpêtrière Hospital, Reference Center for Muscle Diseases Paris-Est, Myology Institute, 75651 Paris Cedex 13, France.
authors.forename: Tanya
authors.initials: T
authors.lastname: Stojkovic
authors.affiliation: AP-HP, Pitié-Salpêtrière Hospital, Reference Center for Muscle Diseases Paris-Est, Myology Institute, 75651 Paris Cedex 13, France.
authors.forename: Henri Marc
authors.initials: HM
authors.lastname: Bécane
authors.affiliation: AP-HP, Biochemistry Department, Pitié-Salpêtrière Hospital, 75651 Paris Cedex 13, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Jardel
authors.affiliation: AP-HP, Pitié-Salpêtrière Hospital, Reference Center for Muscle Diseases Paris-Est, Myology Institute, 75651 Paris Cedex 13, France.
authors.forename: Nawal
authors.initials: N
authors.lastname: Berber
authors.affiliation: Genetics Department, INSERM UMR S975, CNRS UMR7225, ICM, AP-HP, Pitié-Salpêtrière Hospital, 75651 Paris Cedex 13, France Pierre et Marie Curie-Paris 6 University, Myology Institute, Pitié-Salpêtrière Hospital, Paris 75013, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Mochel
authors.affiliation: INSERM, UMRS 975, Cochin Hospital, AP-HP, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Lombès
authors.affiliation: AP-HP, Pitié-Salpêtrière Hospital, Reference Center for Muscle Diseases Paris-Est, Myology Institute, 75651 Paris Cedex 13, France Pierre et Marie Curie-Paris 6 University, Myology Institute, Pitié-Salpêtrière Hospital, Paris 75013, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Eymard
authors.affiliation: Cardiology Department, AP-HP, Cochin Hospital, 27 rue du Faubourg Saint Jacques, 75679 Paris Cedex 14, France Université Paris Descartes-Sorbonne Paris Cité, Paris, France AP-HP, Pitié-Salpêtrière Hospital, Reference Center for Muscle Diseases Paris-Est, Myology Institute, 75651 Paris Cedex 13, France INSERM, UMRS 974, Paris 75013, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Duboc
authors.affiliation: AP-HP, Pitié-Salpêtrière Hospital, Reference Center for Muscle Diseases Paris-Est, Myology Institute, 75651 Paris Cedex 13, France Pierre et Marie Curie-Paris 6 University, Myology Institute, Pitié-Salpêtrière Hospital, Paris 75013, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Laforêt
mesh_terms: D000328:Adult; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006331:Heart Diseases / Q000235:genetics* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000235:genetics*; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000401:mortality; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors
chemical_list: D004272:DNA, Mitochondrial
keywords: Genetic cardiac disease; Genetic cardiomyopathy; Genetic conduction system disease; Mitochondrial cardiomyopathy; Mitochondrial disease