AP-HP, Hôpital Européen Georges Pompidou, Département de Génétique, Centre de Référence des Maladies Vasculaires Rares, Paris, France; INSERM, U 970, Paris Centre de Recherche Cardiovasculaire-PARCC, Paris, France.
AP-HP, Hôpital Européen Georges Pompidou, Département de Génétique, Centre de Référence des Maladies Vasculaires Rares, Paris, France; Université Paris Sorbonne Cité, Faculté de Médecine Paris Descartes, Paris, France.
J Am Coll Cardiol. 2019 Apr 23;73(15):1948-1957. doi: 10.1016/j.jacc.2019.01.058.
Vascular Ehlers-Danlos syndrome (vEDS) is a rare genetic connective tissue disorder secondary to pathogenic variants within the COL3A1 gene, resulting in exceptional arterial and organ fragility and premature death. The only published clinical trial to date demonstrated the benefit of celiprolol on arterial morbimortality.
The authors herein describe the outcomes of a large cohort of vEDS patients followed ≤17 years in a single national referral center.
All patients with molecularly confirmed vEDS were included in a retrospective cohort study. After an initial work-up, patients were treated or recommended for treatment with celiprolol (≤400 mg/day) in addition to usual care and scheduled for yearly follow-up. vEDS-related events and deaths were collected and recorded for each patient.
Between 2000 and 2017, 144 patients (median age at diagnosis 34.5 years, 91 probands) were included in this study. After a median follow-up of 5.3 years, overall patient survival was high (71.6%; 95% confidence interval: 50% to 90%) and dependent on the type of COL3A1 variant, age at diagnosis, and medical treatment. At the end of the study period, almost all patients (90.3%) were treated with celiprolol alone or in combination. More than two-thirds of patients remained clinically silent, despite a large number (51%) with previous arterial events or arterial lesions at molecular diagnosis. Patients treated with celiprolol had a better survival than others (p = 0.0004). The observed reduction in mortality was dose-dependent: the best protection was observed at the dose of 400 mg/day versus <400 mg/day (p = 0.003). During the period surveyed, the authors observed a statistically significant difference in the ratio of hospitalizations for acute arterial events/hospitalizations for regular follow-up before and after 2011.
In this long-term survey, vEDS patients exhibited a low annual occurrence of arterial complications and a high survival rate, on which the overall medical care seems to have a positive influence.
血管型埃勒斯-当洛斯综合征（vEDS）是一种罕见的遗传性结缔组织疾病，由 COL3A1 基因突变引起，导致动脉和器官异常脆弱，患者过早死亡。迄今为止，唯一发表的临床试验证明了塞利洛尔对动脉发病率和死亡率的有益作用。
作者在此描述了在单一国家转诊中心接受治疗的大量 vEDS 患者在≤17 年的随访结果。
所有经分子学证实的 vEDS 患者均纳入回顾性队列研究。在初始评估后，除常规治疗外，还建议患者使用塞利洛尔（≤400mg/天）进行治疗，并对每位患者进行每年一次的随访。收集并记录了 vEDS 相关事件和死亡情况。
在 2000 年至 2017 年间，共有 144 名患者（诊断时的中位年龄为 34.5 岁，91 名先证者）纳入本研究。中位随访 5.3 年后，患者的总体生存率较高（71.6%；95%置信区间：50%至 90%），且取决于 COL3A1 突变类型、诊断时的年龄和治疗方法。在研究结束时，几乎所有患者（90.3%）单独或联合使用塞利洛尔治疗。尽管大多数患者（51%）在分子诊断时存在动脉病变或之前有过动脉事件，但仍有超过三分之二的患者保持临床无症状。接受塞利洛尔治疗的患者生存率优于未接受者（p=0.0004）。观察到的死亡率降低与剂量有关：400mg/天剂量组的保护效果最好，优于<400mg/天剂量组（p=0.003）。在调查期间，作者观察到 2011 年前后，因急性动脉事件住院的比例与因常规随访住院的比例有显著统计学差异。
在这项长期调查中，vEDS 患者的动脉并发症年发生率较低，生存率较高，这似乎与整体医疗护理有积极影响。
