Karim Wahbi1, Wulfran Bougouin2, Anthony Béhin3, Tanya Stojkovic3, Henri Marc Bécane3, Claude Jardel4, Nawal Berber3, Fanny Mochel5, Anne Lombès6, Bruno Eymard7, Denis Duboc8, Pascal Laforêt7. 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.
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. Published on behalf of the European Society of Cardiology. All rights reserved.
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. Published on behalf of the European Society of Cardiology. All rights reserved.
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