Cardiac Outcomes in Adults With Mitochondrial Diseases,Journal of the American College of Cardiology

当前位置： X-MOL 学术 › J. Am. Coll. Cardiol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Cardiac Outcomes in Adults With Mitochondrial Diseases
Journal of the American College of Cardiology ( IF 21.7 ) Pub Date : 2022-10-03 , DOI: 10.1016/j.jacc.2022.08.716
Konstantinos Savvatis ₁ , Christoffer Rasmus Vissing ₂ , Lori Klouvi ₃ , Anca Florian ₄ , Mehjabin Rahman ₅ , Anthony Béhin ₆ , Abdallah Fayssoil ₇ , Marion Masingue ₆ , Tanya Stojkovic ₆ , Henri Marc Bécane ₆ , Nawal Berber ₆ , Fanny Mochel ₈ , Denis Duboc ₉ , Bertrand Fontaine ₁₀ , Bjørg Krett ₁₁ , Caroline Stalens ₃ , Julie Lejeune ₃ , Robert D S Pitceathly ₁₂ , Luis Lopes ₁₃ , Malika Saadi ₁₄ , Thomas Gossios ₁₅ , Vincent Procaccio ₁₆ , Marco Spinazzi ₁₇ , Céline Tard ₁₈ , Pascal De Groote ₁₉ , Claire-Marie Dhaenens ₂₀ , Claire Douillard ₂₁ , Andoni Echaniz-Laguna ₂₂ , Ros Quinlivan ₁₂ , Michael G Hanna ₁₂ , Ali Yilmaz ₄ , John Vissing ₁₁ , Pascal Laforêt ₂₃ , Perry Elliott ₁₃ , Karim Wahbi ₂₄

Affiliation

Inherited Cardiac Conditions Unit, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom; William Harvey Research Institute, Queen Mary University London, London, United Kingdom; Centre for Heart Muscle Disease, Institute for Cardiovascular Science, University College London, London, United Kingdom.
Copenhagen Neuromuscular Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; The Capital Region's Unit for Inherited Cardiac Diseases, Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
AFM Telethon, Evry, France.
Department of Cardiology I, Division of Cardiovascular Imaging, University Hospital Münster, Münster, Germany.
Centre for Heart Muscle Disease, Institute for Cardiovascular Science, University College London, London, United Kingdom.
AP-HP, Pitié-Salpêtrière Hospital, Reference Center for Muscle Diseases Paris-Est, Myology Institute, Paris, France.
AP-HP, Raymond Poincare University Hospital, Garches, France; Université de Versailles-Saint Quentin, Boulogne-Billancourt, France.
AP-HP, Pitié-Salpêtrière Hospital, Genetics Department, Inserm UMR S975, CNRS UMR7225, ICM, Paris, France; Pierre et Marie Curie-Paris 6 University, Myology Institute, Pitié-Salpêtrière Hospital, Paris, France.
AP-HP, Pitié-Salpêtrière Hospital, Reference Center for Muscle Diseases Paris-Est, Myology Institute, Paris, France; AP-HP, Cochin Hospital, Cardiology Department, Paris Cedex, France; Université de Paris, Paris, France.
Sorbonne-Université, INSERM, Assistance Publique-Hôpitaux de Paris (AP-HP), Centre de Recherche en Myologie-UMR 974, Service de Neuro-Myologie, Institut de Myologie, Hôpital Universitaire Pitié-Salpêtrière, Paris, France.
Copenhagen Neuromuscular Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, United Kingdom.
Inherited Cardiac Conditions Unit, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom; Centre for Heart Muscle Disease, Institute for Cardiovascular Science, University College London, London, United Kingdom.
AP-HP, Cochin Hospital, Cardiology Department, Paris Cedex, France.
Cardiomyopathies Laboratory, 1st Aristotle University of Thessaloniki Cardiology Department, AHEPA University Hospital, Thessaloniki, Greece.
Equipe Mitolab, Unité Mixte de Recherche MITOVASC, CNRS 6015, INSERM U1083, Université d'Angers, Angers, France; Département de Biochimie et Génétique, Centre Hospitalier Universitaire, Angers, France.
Département de Biochimie et Génétique, Centre Hospitalier Universitaire, Angers, France; Neuromuscular Reference Center, Department of Neurology, CHU Angers, Angers, France.
Université de Lille, INSERMU1172, Lille, France; Centre de Référence des Maladies Neuromusculaires Nord Est Ile de France, CHU de Lille, Lille, France.
Service de Cardiologie, Pôle Cardio-vasculaire et Pulmonaire, CHRU de Lille, Lille, France; Inserm U1167, Institut Pasteur de Lille, Université de Lille 2, Lille, France.
Université de Lille, Inserm, CHU Lille, U1172-LilNCog-Lille Neuroscience and Cognition, Lille, France.
CHU de Lille, Département d'Endocrinologie et Métabolisme, Centre de Référence des Maladies Héréditaires du Métabolisme, Hôpital Huriez, Lille, France.
Department of Neurology, APHP, CHU de Bicêtre, Le Kremlin-Bicêtre, France; French National Reference Center for Rare Neuropathies (NNERF), Le Kremlin-Bicêtre, France; INSERM U1195, Paris-Saclay University, Le Kremlin-Bicêtre, France.
Inserm U1167, Institut Pasteur de Lille, Université de Lille 2, Lille, France; Nord/Est/Île-de-France Neuromuscular Reference Center, Neurology Department, Raymond-Poincaré Teaching Hospital, AP-HP, Garches, France; INSERM U1179, END-ICAP, Versailles-Saint-Quentin-en-Yvelines University, Université Paris Saclay, Montigny-le-Bretonneux, France.
AP-HP, Pitié-Salpêtrière Hospital, Reference Center for Muscle Diseases Paris-Est, Myology Institute, Paris, France; AP-HP, Cochin Hospital, Cardiology Department, Paris Cedex, France; Université de Paris, Paris, France; Paris Cardiovascular Research Center (PARCC), INSERM Unit 970, Paris, France.

Background

Patients with mitochondrial diseases are at risk of heart failure (HF) and arrhythmic major adverse cardiac events (MACE).

Objectives

We developed prediction models to estimate the risk of HF and arrhythmic MACE in this population.

Methods

We determined the incidence and searched for predictors of HF and arrhythmic MACE using Cox regression in 600 adult patients from a multicenter registry with genetically confirmed mitochondrial diseases.

Results

Over a median follow-up time of 6.67 years, 29 patients (4.9%) reached the HF endpoint, including 19 hospitalizations for nonterminal HF, 2 cardiac transplantations, and 8 deaths from HF. Thirty others (5.1%) reached the arrhythmic MACE, including 21 with third-degree or type II second-degree atrioventricular blocks, 4 with sinus node dysfunction, and 5 sudden cardiac deaths. Predictors of HF were the m.3243A>G variant (HR: 4.3; 95% CI: 1.8-10.1), conduction defects (HR: 3.0; 95% CI: 1.3-6.9), left ventricular (LV) hypertrophy (HR: 2.6; 95% CI: 1.1-5.8), LV ejection fraction <50% (HR: 10.2; 95% CI: 4.6-22.3), and premature ventricular beats (HR: 4.1; 95% CI: 1.7-9.9). Independent predictors for arrhythmia were single, large-scale mtDNA deletions (HR: 4.3; 95% CI: 1.7-10.4), conduction defects (HR: 6.8; 95% CI: 3.0-15.4), and LV ejection fraction <50% (HR: 2.7; 95% CI: 1.1-7.1). C-indexes of the Cox regression models were 0.91 (95% CI: 0.88-0.95) and 0.80 (95% CI: 0.70-0.90) for the HF and arrhythmic MACE, respectively.

Conclusions

We developed the first prediction models for HF and arrhythmic MACE in patients with mitochondrial diseases using genetic variant type and simple cardiac assessments.

中文翻译：

成人线粒体疾病的心脏结局

背景

线粒体疾病患者有发生心力衰竭 (HF) 和心律失常性主要不良心脏事件 (MACE) 的风险。

目标

我们开发了预测模型来估计该人群中 HF 和心律失常性 MACE 的风险。

方法

我们使用 Cox 回归确定了发生率，并在 600 名来自多中心登记处的经遗传证实的线粒体疾病成年患者中搜索了 HF 和心律失常性 MACE 的预测因子。

结果

在 6.67 年的中位随访时间内，29 名患者 (4.9%) 达到了 HF 终点，包括 19 名非晚期 HF 住院患者、2 名心脏移植患者和 8 名死于 HF 的患者。另有 30 例 (5.1%) 达到心律失常性 MACE，其中 21 例为三度或 II 型二度房室传导阻滞，4 例为窦房结功能障碍，5 例心源性猝死。HF 的预测因子是 m.3243A>G 变体（HR：4.3；95% CI：1.8-10.1）、传导缺陷（HR：3.0；95% CI：1.3-6.9）、左心室 (LV) 肥大（HR： 2.6；95% CI：1.1-5.8），左室射血分数 <50%（HR：10.2；95% CI：4.6-22.3）和室性早搏（HR：4.1；95% CI：1.7-9.9）。的独立预测因子心律失常是单个、大规模的 mtDNA 缺失（HR：4.3；95% CI：1.7-10.4）、传导缺陷（HR：6.8；95% CI：3.0-15.4）和 LV 射血分数 <50%（HR：2.7 ；95% CI：1.1-7.1）。对于 HF 和心律失常性 MACE，Cox 回归模型的 C 指数分别为 0.91（95% CI：0.88-0.95）和 0.80（95% CI：0.70-0.90）。