Sebastien Hascoet1, Emmanuelle Fournier2, Xavier Jaïs3, Lauriane Le Gloan4, Claire Dauphin5, Ali Houeijeh6, Francois Godart6, Xavier Iriart7, Adelaïde Richard8, Jelena Radojevic9, Pascal Amedro10, Gilles Bosser11, Nathalie Souletie12, Yvette Bernard13, Pamela Moceri14, Hélène Bouvaist15, Pierre Mauran16, Elise Barre17, Adeline Basquin18, Clement Karsenty19, Damien Bonnet20, Laurence Iserin21, Olivier Sitbon3, Jérôme Petit22, Elie Fadel23, Marc Humbert3, Magalie Ladouceur24. 1. 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. 2. 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. 3. 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. 4. Department of cardiology, centre de compétence M3C, CHU de Nantes, Nantes, France. 5. Department of cardiology, centre de compétence M3C, CHU de Clermont-Ferrand, Clermont-Ferrand, France. 6. Department of paediatric cardiology, centre de compétence M3C, CHRU de Lille, Lille, France. 7. Department of congenital heart diseases, centre de compétence M3C, CHU de Bordeaux, Bordeaux, France. 8. Paediatric and adult congenital heart diseases centre, cabinet Intercard Vendôme, Lille, France. 9. Fetal, paediatric and congenital cardiology, clinique de l'Orangerie, Strasbourg, France. 10. 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. 11. Department of congenital heart diseases and paediatric cardiology, centre de compétence M3C, CHRU de Nancy, Nancy, France. 12. Department of cardiology, centre de compétence M3C, CHU de Toulouse, Toulouse, France. 13. Department of cardiology, centre de compétence M3C, CHU de Besançon, Besançon, France. 14. Department of cardiology, centre de compétence M3C, CHU de Nice, Nice, France. 15. Department of cardiology, centre de compétence M3C, CHU de Grenoble, Grenoble, France. 16. Department of paediatric and congenital cardiology, centre de compétence M3C, American memorial hospital, CHU de Reims, Reims, France. 17. Department of paediatric and congenital cardiology, centre de compétence M3C, CHU de Rouen, Rouen, France. 18. Department of cardiology, centre de compétence M3C, CHU de Rennes, Rennes, France. 19. 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. 20. 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. 21. 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. 22. 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. 23. 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. 24. 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.
Abstract
BACKGROUND: The relationship between pulmonary arterial hypertension-specific drug therapy (PAH-SDT) and mortality in Eisenmenger syndrome (ES) is controversial. AIMS: 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.
BACKGROUND: The relationship between pulmonary arterial hypertension-specific drug therapy (PAH-SDT) and mortality in Eisenmenger syndrome (ES) is controversial. AIMS: 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: Brian B Graham; Rahul Kumar; Claudia Mickael; Biruk Kassa; Dan Koyanagi; Linda Sanders; Li Zhang; Mario Perez; Daniel Hernandez-Saavedra; Carolyn Valencia; Kandice Dixon; Julie Harral; Zoe Loomis; David Irwin; Travis Nemkov; Angelo D'Alessandro; Kurt R Stenmark; Rubin M Tuder Journal: Am J Respir Cell Mol Biol Date: 2018-10 Impact factor: 7.748
Authors: Nika Skoro-Sajer; Christian Gerges; Olga Hajnalka Balint; Dora Kohalmi; Monika Kaldararova; Iveta Simkova; Johannes Jakowitsch; Harald Gabriel; Helmut Baumgartner; Mario Gerges; Roela Sadushi-Kolici; David S Celermajer; Irene Marthe Lang Journal: Heart Date: 2018-02-07 Impact factor: 5.994
Authors: Harald Kaemmerer; Matthias Gorenflo; Dörte Huscher; David Pittrow; Christian Apitz; Helmut Baumgartner; Felix Berger; Leonhard Bruch; Eva Brunnemer; Werner Budts; Martin Claussen; Gerry Coghlan; Ingo Dähnert; Michele D'Alto; Marion Delcroix; Oliver Distler; Sven Dittrich; Daniel Dumitrescu; Ralf Ewert; Martin Faehling; Ingo Germund; Hossein Ardeschir Ghofrani; Christian Grohé; Karsten Grossekreymborg; Michael Halank; Georg Hansmann; Dominik Harzheim; Attila Nemes; Kalman Havasi; Matthias Held; Marius M Hoeper; Michael Hofbeck; Wolfgang Hohenfrost-Schmidt; Elena Jurevičienė; Lina Gumbienè; Hans-Joachim Kabitz; Hans Klose; Thomas Köhler; Stavros Konstantinides; Martin Köestenberger; Rainer Kozlik-Feldmann; Hans-Heiner Kramer; Cornelia Kropf-Sanchen; Astrid Lammers; Tobias Lange; Philipp Meyn; Oliver Miera; Katrin Milger-Kneidinger; Rhoia Neidenbach; Claus Neurohr; Christian Opitz; Christian Perings; Bjoern Andrew Remppis; Gabriele Riemekasten; Laura Scelsi; Werner Scholtz; Iveta Simkova; Dirk Skowasch; Andris Skride; Gerd Stähler; Brigitte Stiller; Iraklis Tsangaris; Carmine Dario Vizza; Anton Vonk Noordegraaf; Heinrike Wilkens; Hubert Wirtz; Gerhard-Paul Diller; Ekkehard Grünig; Stephan Rosenkranz Journal: J Clin Med Date: 2020-05-13 Impact factor: 4.241