Long-term cardiac prognosis and risk stratification in 260 adults presenting with mitochondrial diseases

Karim Wahbi; Wulfran Bougouin; Anthony Béhin; Tanya Stojkovic; Henri Marc Bécane; Claude Jardel; Nawal Berber; Fanny Mochel; Anne Lombès; Bruno Eymard; Denis Duboc; Pascal Laforêt

doi:10.1093/eurheartj/ehv307

Long-term cardiac prognosis and risk stratification in 260 adults presenting with mitochondrial diseases

Eur Heart J. 2015 Nov 7;36(42):2886-93. doi: 10.1093/eurheartj/ehv307. Epub 2015 Jul 29.

Authors

Affiliations

¹ 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.
² 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.
³ AP-HP, Pitié-Salpêtrière Hospital, Reference Center for Muscle Diseases Paris-Est, Myology Institute, 75651 Paris Cedex 13, France.
⁴ AP-HP, Biochemistry Department, Pitié-Salpêtrière Hospital, 75651 Paris Cedex 13, France.
⁵ 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.
⁶ INSERM, UMRS 975, Cochin Hospital, AP-HP, Paris, France.
⁷ 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.
⁸ 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.

PMID: 26224072
DOI: 10.1093/eurheartj/ehv307

Abstract

Aims: The aim of this study is to assess the long-term cardiac prognosis of adults with mitochondrial diseases.

Methods and 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.

Conclusion: Patients with mitochondrial diseases are at high risk of MACE, independently predicted by intraventricular conduction block, diabetes, ventricular prematurity, and LV hypertrophy.

Keywords: Genetic cardiac disease; Genetic cardiomyopathy; Genetic conduction system disease; Mitochondrial cardiomyopathy; Mitochondrial disease.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
DNA, Mitochondrial / genetics*
Female
Gene Deletion
Heart Diseases / genetics*
Heart Diseases / mortality
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Mitochondria, Heart / genetics*
Mitochondrial Diseases / genetics*
Mitochondrial Diseases / mortality
Mutation / genetics*
Prognosis
Retrospective Studies
Risk Assessment / methods
Risk Factors

Substances

DNA, Mitochondrial