title: Outcome of adults with Eisenmenger syndrome treated with drugs specific to pulmonary arterial hypertension: A French multicentre study.
abstract: BACKGROUND
  The relationship between pulmonary arterial hypertension-specific drug therapy (PAH-SDT) and mortality in Eisenmenger syndrome (ES) is controversial.
  
  
  OBJECTIVE
  To investigate outcomes in patients with ES, and their relationship with PAH-SDT.
  
  
  METHODS
  Retrospective, observational, nationwide, multicentre cohort study.
  
  
  RESULTS
  We included 340 patients with ES: genetic syndrome (n=119; 35.3%); pretricuspid defect (n=75; 22.1%). Overall, 276 (81.2%) patients received PAH-SDT: monotherapy (endothelin receptor antagonist [ERA] or phosphodiesterase 5 inhibitor [PDE5I]) 46.7%; dual therapy (ERA+PDE5I) 40.9%; triple therapy (ERA+PDE5I+prostanoid) 9.1%. Median PAH-SDT duration was 5.5 years [3.0-9.1 years]. Events (death, lung or heart-lung transplantation) occurred in 95 (27.9%) patients at a median age of 40.5 years [29.4-47.6]. The cumulative occurrence of events was 16.7% [95% confidence interval 12.8-21.6%] and 46.4% [95% confidence interval 38.2-55.4%] at age 40 and 60 years, respectively. With age at evaluation or time since PAH diagnosis as time scales, cumulative occurrence of events was lower in patients taking one or two PAH-SDTs (P=0.0001 and P=0.004, respectively), with the largest differences in the post-tricuspid defect subgroup (P<0.001 and P<0.02, respectively) versus patients without PAH-SDT. By multivariable Cox analysis, with time since PAH diagnosis as time scale, New York Heart Association/World Health Organization functional class III/IV, lower peripheral arterial oxygen saturation and pretricuspid defect were associated with a higher risk of events (P=0.002, P=0.01 and P=0.04, respectively), and one or two PAH-SDTs with a lower risk of events (P=0.009).
  
  
  CONCLUSIONS
  Outcomes are poor in ES, but seem better with PAH-SDT. ES with pretricuspid defects has worse outcomes despite the delayed disease onset.
authors.affiliation: Department of congenital heart diseases, centre de référence malformations cardiaques congénitales complexes M3C, hôpital Marie-Lannelongue, 133, avenue de la Résistance, 92350 Le Plessis-Robinson, France; Faculté de médecine Paris-Sud, université Paris-Sud, université Paris-Saclay, Paris, France. Electronic address: s.hascoet@ccml.fr.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Hascoet
authors.affiliation: Department of congenital heart diseases, centre de référence malformations cardiaques congénitales complexes M3C, hôpital Marie-Lannelongue, 133, avenue de la Résistance, 92350 Le Plessis-Robinson, France; Faculté de médecine Paris-Sud, université Paris-Sud, université Paris-Saclay, Paris, France; Department of congenital heart diseases, centre de compétence M3C, CHU de Bordeaux, Bordeaux, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Fournier
authors.affiliation: Service de pneumologie, centre de référence de l'hypertension pulmonaire sévère, DHU thorax innovation, hôpital Bicêtre, Le Kremlin-Bicêtre, France; UMR-S 999, Inserm, hôpital Marie-Lannelongue, université Paris-Sud, université Paris-Saclay, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Jaïs
authors.affiliation: Department of cardiology, centre de compétence M3C, CHU de Nantes, Nantes, France.
authors.forename: Lauriane
authors.initials: L
authors.lastname: Le Gloan
authors.affiliation: Department of cardiology, centre de compétence M3C, CHU de Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Dauphin
authors.affiliation: Department of paediatric cardiology, centre de compétence M3C, CHRU de Lille, Lille, France.
authors.forename: Ali
authors.initials: A
authors.lastname: Houeijeh
authors.affiliation: Department of paediatric cardiology, centre de compétence M3C, CHRU de Lille, Lille, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Godart
authors.affiliation: Department of congenital heart diseases, centre de compétence M3C, CHU de Bordeaux, Bordeaux, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Iriart
authors.affiliation: Paediatric and adult congenital heart diseases centre, cabinet Intercard Vendôme, Lille, France.
authors.forename: Adelaïde
authors.initials: A
authors.lastname: Richard
authors.affiliation: Fetal, paediatric and congenital cardiology, clinique de l'Orangerie, Strasbourg, France.
authors.forename: Jelena
authors.initials: J
authors.lastname: Radojevic
authors.affiliation: Paediatric and congenital cardiology department, M3C regional reference centre, university hospital, physiology and experimental biology of heart and muscles laboratory, PHYMEDEXP, UMR CNRS 9214-Inserm U1046, university of Montpellier, Montpellier, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Amedro
authors.affiliation: Department of congenital heart diseases and paediatric cardiology, centre de compétence M3C, CHRU de Nancy, Nancy, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Bosser
authors.affiliation: Department of cardiology, centre de compétence M3C, CHU de Toulouse, Toulouse, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Souletie
authors.affiliation: Department of cardiology, centre de compétence M3C, CHU de Besançon, Besançon, France.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Bernard
authors.affiliation: Department of cardiology, centre de compétence M3C, CHU de Nice, Nice, France.
authors.forename: Pamela
authors.initials: P
authors.lastname: Moceri
authors.affiliation: Department of cardiology, centre de compétence M3C, CHU de Grenoble, Grenoble, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Bouvaist
authors.affiliation: Department of paediatric and congenital cardiology, centre de compétence M3C, American memorial hospital, CHU de Reims, Reims, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Mauran
authors.affiliation: Department of paediatric and congenital cardiology, centre de compétence M3C, CHU de Rouen, Rouen, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Barre
authors.affiliation: Department of cardiology, centre de compétence M3C, CHU de Rennes, Rennes, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Basquin
authors.affiliation: Department of cardiology, centre de compétence M3C, CHU de Toulouse, Toulouse, France; Adult congenital heart diseases unit, department of cardiology, centre de référence M3C, hôpital européen Georges-Pompidou, Assistance publique-Hôpitaux de Paris, Paris, France; Paris cardiovascular research centre (PARCC), Inserm U970, Paris Descartes University, Paris, France.
authors.forename: Clement
authors.initials: C
authors.lastname: Karsenty
authors.affiliation: Centre de référence malformations cardiaques congénitales complexes M3C, hôpital universitaire Necker-Enfants-Malades, Assistance publique-Hôpitaux de Paris, université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Bonnet
authors.affiliation: Adult congenital heart diseases unit, department of cardiology, centre de référence M3C, hôpital européen Georges-Pompidou, Assistance publique-Hôpitaux de Paris, Paris, France; Paris cardiovascular research centre (PARCC), Inserm U970, Paris Descartes University, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Iserin
authors.affiliation: Service de pneumologie, centre de référence de l'hypertension pulmonaire sévère, DHU thorax innovation, hôpital Bicêtre, Le Kremlin-Bicêtre, France; UMR-S 999, Inserm, hôpital Marie-Lannelongue, université Paris-Sud, université Paris-Saclay, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Sitbon
authors.affiliation: Department of congenital heart diseases, centre de référence malformations cardiaques congénitales complexes M3C, hôpital Marie-Lannelongue, 133, avenue de la Résistance, 92350 Le Plessis-Robinson, France; Faculté de médecine Paris-Sud, université Paris-Sud, université Paris-Saclay, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Petit
authors.affiliation: UMR-S 999, Inserm, hôpital Marie-Lannelongue, université Paris-Sud, université Paris-Saclay, Paris, France; Department of thoracic surgery, hôpital Marie-Lannelongue, Plessis-Robinson, France; Faculté de médecine Paris-Sud, université Paris Sud, université Paris-Saclay, Paris, France.
authors.forename: Elie
authors.initials: E
authors.lastname: Fadel
authors.affiliation: Service de pneumologie, centre de référence de l'hypertension pulmonaire sévère, DHU thorax innovation, hôpital Bicêtre, Le Kremlin-Bicêtre, France; UMR-S 999, Inserm, hôpital Marie-Lannelongue, université Paris-Sud, université Paris-Saclay, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
authors.affiliation: Adult congenital heart diseases unit, department of cardiology, centre de référence M3C, hôpital européen Georges-Pompidou, Assistance publique-Hôpitaux de Paris, Paris, France; Paris cardiovascular research centre (PARCC), Inserm U970, Paris Descartes University, Paris, France; Centre de référence malformations cardiaques congénitales complexes M3C, hôpital universitaire Necker-Enfants-Malades, Assistance publique-Hôpitaux de Paris, université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Magalie
authors.initials: M
authors.lastname: Ladouceur
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D062186:Arterial Pressure / Q000187:drug effects*; D002423:Cause of Death; D016009:Chi-Square Distribution; D002648:Child; D018450:Disease Progression; D018572:Disease-Free Survival; D004541:Eisenmenger Complex / Q000150:complications* / Q000401:mortality / Q000503:physiopathology; D005260:Female; D005602:France; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality / Q000503:physiopathology; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011651:Pulmonary Artery / Q000187:drug effects* / Q000503:physiopathology; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents
keywords: Cardiopathies congénitales; Congenital heart diseases; Drug therapy; Eisenmenger syndrome; Hypertension artérielle pulmonaire; Médicament; Outcome; Pronostic; Pulmonary arterial hypertension; Syndrome d’Eisenmenger