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

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.

• Authors: 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
• Journal: European heart journal (Eur Heart J) Vol. 36 Issue 42 Pg. 2886-93 (Nov 07 2015) ISSN: 1522-9645 [Electronic] England
• PMID: 26224072 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)
• Copyright: Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: [email protected].

Chemical References

• DNA, Mitochondrial

Topics

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