Department of Cardiology, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière Charles-Foix, Paris, France.
Department of Genetics and Cytogenetics, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière Charles-Foix, Paris, France3Institut du Cerveau et de la Moelle Epinière, Sorbonne Universités, Université Pierre et Marie Curie, Universi.
JAMA Neurol. 2015 Nov;72(11):1334-41. doi: 10.1001/jamaneurol.2015.1855.
Friedreich ataxia (FRDA) is the most common genetic sensory ataxia, and myocardial involvement is a major determinant of survival.
To assess FRDA survival and cardiac outcome to adapt future therapeutic trials.
DESIGN, SETTING, AND PARTICIPANTS: In a longitudinal follow-up study, all patients with genetically confirmed FRDA seen in the reference center and referred for cardiac evaluation (standard 12-lead electrocardiogram and transthoracic echocardiography) to the cardiology department were enrolled and followed up from April 27, 1990, to July 31, 2013. The setting was the French National Reference Center for Rare Diseases and the Department of Cardiology, Salpêtrière University Hospital, Paris, France. In total, 138 patients with FRDA were followed up. Among 133 patients homozygous for expanded GAA repeats, the mean (SD) age was 31 (10) years (age range, 11-62 years), with a mean (SD) age at disease onset of 16 (8) years (age range, 3-50 years) and a mean (SD) age at first wheelchair use of 26 (9) years (age range, 11-64 years). Cardiac hypertrophy was present in 57.9% (77 of 133), and electrocardiography was normal in 6.8% (9 of 133).
Long-term cardiac outcome and predictors of survival in FRDA.
After a mean (SD) follow-up of 10.5 (5.5) years (range, 0.6-23.0 years), the 10-year survival rate was 88.5%. In 80.0% of patients (12 of 15), death was due to cardiac causes. Predictors of survival were a shorter GAA repeat length on the smaller allele of the frataxin gene (hazard ratio [HR], 1.85; 95% CI, 1.28-2.69), left ventricular ejection fraction (HR, 0.42; 95% CI, 0.20-0.89), and left ventricular mass index (HR, 1.19; 95% CI, 1.04-1.36). Two cardiac evolutions were distinguished with a group-based trajectory model, including a low-risk cardiac group (78.6% [81 of 103] with normal ejection fraction at baseline that declined slightly over time but remained within the normal range) and a high-risk cardiac group (21.4% [22 of 103] in which the ejection fraction progressively declined during follow-up). The patients with the worse cardiac evolution had longer GAA repeats. Neurological impairment was not predictive of cardiac change over time.
Survival in FRDA is determined by cardiac complications, which are dependent on the mutation (ie, the size of the expanded GAA repeat). Patients with progressive decline of the left ventricular ejection fraction had a worse prognosis. This finding demonstrates that cardiac follow-up is important in FRDA to identify individuals at risk for further cardiac complications.
弗里德赖希共济失调（FRDA）是最常见的遗传性感觉共济失调，心肌受累是生存的主要决定因素。
评估 FRDA 的生存和心脏结局，以适应未来的治疗试验。
设计、设置和参与者：在一项纵向随访研究中，所有在参考中心就诊并因心脏评估（标准 12 导联心电图和经胸超声心动图）而转诊至心脏病科的遗传性 FRDA 患者均被纳入并随访，从 1990 年 4 月 27 日至 2013 年 7 月 31 日。该研究的地点是法国罕见病国家参考中心和巴黎 Salpêtrière 大学医院的心脏病科。共有 138 例 FRDA 患者接受了随访。在 133 例纯合扩展 GAA 重复的患者中，平均（SD）年龄为 31（10）岁（年龄范围为 11-62 岁），平均（SD）发病年龄为 16（8）岁（年龄范围为 3-50 岁），平均（SD）首次使用轮椅年龄为 26（9）岁（年龄范围为 11-64 岁）。57.9%（77/133）的患者存在心肌肥厚，6.8%（9/133）的患者心电图正常。
FRDA 的长期心脏结局和生存预测因素。
平均（SD）随访 10.5（5.5）年后（范围为 0.6-23.0 年），10 年生存率为 88.5%。80.0%（12/15）的患者死亡是由于心脏原因。生存的预测因素是较小等位基因 frataxin 基因上较短的 GAA 重复长度（危险比[HR]，1.85；95%CI，1.28-2.69）、左心室射血分数（HR，0.42；95%CI，0.20-0.89）和左心室质量指数（HR，1.19；95%CI，1.04-1.36）。通过基于群组的轨迹模型区分了两种心脏演变，包括低风险心脏组（78.6%[103 例中有 81 例]，基线时射血分数正常，随时间略有下降，但仍在正常范围内）和高风险心脏组（21.4%[103 例中有 22 例]，在此组中，左心室射血分数在随访期间逐渐下降）。心脏预后较差的患者 GAA 重复较长。神经功能损害不能预测心脏随时间的变化。
FRDA 的生存取决于心脏并发症，这取决于突变（即，扩展 GAA 重复的大小）。左心室射血分数进行性下降的患者预后较差。这一发现表明，在 FRDA 中进行心脏随访对于识别有进一步心脏并发症风险的个体非常重要。
