Author + information
- Received August 20, 2018
- Revision received January 9, 2019
- Accepted January 14, 2019
- Published online April 15, 2019.
- Michael Frank, MDa,b,
- Salma Adham, MDa,c,
- Stéphanie Seigle, MSca,
- Anne Legrand, PharmDa,b,c,
- Tristan Mirault, MD, PhDa,d,
- Pierrick Henneton, MDa,e,
- Juliette Albuisson, MD, PhDa,b,c,
- Nicolas Denarié, MDa,
- Jean-Michaël Mazzella, MSca,
- Elie Mousseaux, MD, PhDb,c,f,
- Emmanuel Messas, MD, PhDa,d,
- Pierre Boutouyrie, MD, PhDb,c,g and
- Xavier Jeunemaitre, MD, PhDa,b,c,∗ (, )@HopitalPompidou
- aAP-HP, Hôpital Européen Georges Pompidou, Département de Génétique, Centre de Référence des Maladies Vasculaires Rares, Paris, France
- bINSERM, U 970, Paris Centre de Recherche Cardiovasculaire–PARCC, Paris, France
- cUniversité Paris Sorbonne Cité, Faculté de Médecine Paris Descartes, Paris, France
- dAP-HP, Hôpital Européen Georges Pompidou, Service de Médecine Vasculaire, Paris, France
- eService de Médecine Vasculaire, CHU Montpellier, Montpellier, France
- fAP-HP, Hôpital Européen Georges Pompidou, Service de Radiologie Cardiovasculaire, Paris, France
- gAP-HP, Hôpital Européen Georges Pompidou, Département de Pharmacologie, Paris, France
- ↵∗Address for correspondence:
Dr. Xavier Jeunemaitre, National Referral Center for Rare Vascular Diseases, Hôpital Européen Georges Pompidou, AP-HP, 20-40, rue Leblanc, 75015 Paris, France.
Background 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.
Objectives The authors herein describe the outcomes of a large cohort of vEDS patients followed ≤17 years in a single national referral center.
Methods 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.
Results 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.
Conclusions 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.
The French Reference Centre for Rare Vascular Diseases is supported by the French Ministry of Health. The study was also supported by grants from Fondation pour la Recherche Médicale, the Association Française pour les Syndromes d’Ehlers-Danlos, and ANR Grant (NONAGES). This cohort is now part of a national French prospective cohort (RaDiCo SEDVasc), set up by the Rare Disease Cohorts (RaDiCo) INSERM programme funded by the Plan d’Investissements d’Avenir through the Agence Nationale pour la Recherche (ANR-lO-COHO-03-01). The statistical analysis was supported by an agreement between Acer Therapeutics and Assistance Publique-Hôpitaux de Paris. The grantor, however, had no access or influence on the original database, its analysis, or the presentation of findings. Dr. Boutouyrie has provided scientific advice for ACER therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received August 20, 2018.
- Revision received January 9, 2019.
- Accepted January 14, 2019.
- 2019 American College of Cardiology Foundation