Sébastien Hascoët1, Alban-Elouen Baruteau2, Marc Humbert3, Gérald Simonneau3, Xavier Jais3, Jérôme Petit2, Daniela Laux2, Olivier Sitbon3, Virginie Lambert4, André Capderou5. 1. 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. 2. 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. 3. 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. 4. 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. 5. 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.
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.
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.