title: Long-term outcomes of pulmonary arterial hypertension under specific drug therapy in Eisenmenger syndrome.
abstract: BACKGROUND
  The long-term effectiveness of pulmonary arterial hypertension-specific drug therapy (PAH-SDT) in Eisenmenger syndrome is controversial. We investigated short-term and long-term hemodynamic changes under PAH-SDT and their associations with outcomes in a bicentric cohort.
  
  
  METHODS
  Over 20 years, we included 69 patients with congenital heart disease, an indexed pulmonary vascular resistance (PVRi) >8 WU·m2, and 292 standardized catheterizations at baseline and after PAH-SDT initiation or intensification. Oxygen consumption was measured and the Fick principle applied to calculate indexed pulmonary output (Qpi) and PVRi.
  
  
  RESULTS
  After PAH-SDT initiation or intensification, median (interquartile range) PVRi decrease was 5.1 WU·m2(-1.4, -12.6) (p < 0.0001). Median Qpi and 6-minute walk test increases were +0.4 liter/min/m2(0.0, +0.9) (p < 0.0001) and +49 m (+15, +93) (p = 0.0003), respectively. Hemodynamic response combining increased Qpi with decreases in transpulmonary gradient and PVRi occurred in 68.0% of patients. After a median of 4.9 years, PVRi and Qpi changes were no longer significant. Over a median of 7.2 years, 23 (33.3%) patients met a composite criterion (death, n = 8; heart-lung transplantation or listing for transplantation, n = 15). The 15-year cumulative event rate was 49.2%. By multivariate analysis, independent predictors of events were superior vena cava oxygen saturation and hemodynamic response (p = 0.048 and p < 0.0001).
  
  
  CONCLUSIONS
  In Eisenmenger syndrome, PAH-SDT induces early hemodynamic improvements, which decline over time. Hemodynamic changes under PAH-SDT vary across patients. Hemodynamic parameters at baseline and under PAH-SDT are associated with events. PAH-SDT may need to be individualized based on hemodynamic changes.
authors.affiliation: Pôle de Cardiopathies Congénitales de l'Enfant et de l'Adulte, Centre de Référence Malformations Cardiaques Congénitales Complexes M3C, Hôpital Marie Lannelongue, le Plessis-Robinson, France. Electronic address: s.hascoet@ccml.fr.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Hascoët
authors.affiliation: Pôle de Cardiopathies Congénitales de l'Enfant et de l'Adulte, Centre de Référence Malformations Cardiaques Congénitales Complexes M3C, Hôpital Marie Lannelongue, le Plessis-Robinson, France.
authors.forename: Alban-Elouen
authors.initials: AE
authors.lastname: Baruteau
authors.affiliation: Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; Faculté de Médecine Paris-Sud, Université Paris-Sud, Université Paris-Saclay, le Kremlin-Bicêtre, France; Inserm UMR-S 999, Hôpital Marie Lannelongue, Université Paris-Sud, Université Paris-Saclay, le Kremlin-Bicêtre, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
authors.affiliation: Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; Faculté de Médecine Paris-Sud, Université Paris-Sud, Université Paris-Saclay, le Kremlin-Bicêtre, France; Inserm UMR-S 999, Hôpital Marie Lannelongue, Université Paris-Sud, Université Paris-Saclay, le Kremlin-Bicêtre, France.
authors.forename: Gérald
authors.initials: G
authors.lastname: Simonneau
authors.affiliation: Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; Faculté de Médecine Paris-Sud, Université Paris-Sud, Université Paris-Saclay, le Kremlin-Bicêtre, France; Inserm UMR-S 999, Hôpital Marie Lannelongue, Université Paris-Sud, Université Paris-Saclay, le Kremlin-Bicêtre, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Jais
authors.affiliation: Pôle de Cardiopathies Congénitales de l'Enfant et de l'Adulte, Centre de Référence Malformations Cardiaques Congénitales Complexes M3C, Hôpital Marie Lannelongue, le Plessis-Robinson, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Petit
authors.affiliation: Pôle de Cardiopathies Congénitales de l'Enfant et de l'Adulte, Centre de Référence Malformations Cardiaques Congénitales Complexes M3C, Hôpital Marie Lannelongue, le Plessis-Robinson, France.
authors.forename: Daniela
authors.initials: D
authors.lastname: Laux
authors.affiliation: Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; Faculté de Médecine Paris-Sud, Université Paris-Sud, Université Paris-Saclay, le Kremlin-Bicêtre, France; Inserm UMR-S 999, Hôpital Marie Lannelongue, Université Paris-Sud, Université Paris-Saclay, le Kremlin-Bicêtre, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Sitbon
authors.affiliation: Pôle de Cardiopathies Congénitales de l'Enfant et de l'Adulte, Centre de Référence Malformations Cardiaques Congénitales Complexes M3C, Hôpital Marie Lannelongue, le Plessis-Robinson, France; Inserm UMR-S 999, Hôpital Marie Lannelongue, Université Paris-Sud, Université Paris-Saclay, le Kremlin-Bicêtre, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Lambert
authors.affiliation: Faculté de Médecine Paris-Sud, Université Paris-Sud, Université Paris-Saclay, le Kremlin-Bicêtre, France; Inserm UMR-S 999, Hôpital Marie Lannelongue, Université Paris-Sud, Université Paris-Saclay, le Kremlin-Bicêtre, France; Laboratoire de Physiologie, Hôpital Marie-Lannelongue, Le Plessis-Robinson, France.
authors.forename: André
authors.initials: A
authors.lastname: Capderou
mesh_terms: D000293:Adolescent; D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D004334:Drug Administration Schedule; D004541:Eisenmenger Complex / Q000150:complications* / Q000503:physiopathology; D017079:Exercise Tolerance; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014655:Vascular Resistance; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents
keywords: Eisenmenger syndrome; catheterization; congenital heart diseases; drug therapy; outcome; pulmonary arterial hypertension