User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

The effect of bosentan in patients with a failing Fontan circulation.

Primary tabs

Ovaert, Caroline [UCL] Thijs, Daisy Dewolf, Daniel Ottenkamp, Jaap Dessy, Hugues Mertens, Luc

OBJECTIVES: To investigate the effect of bosentan in patients with a failing Fontan circulation. DESIGN: A multicentric open label, non-controlled study. SETTING: 5 tertiary care centres for congenital cardiology.PatientsWe included 10 patients with a failing Fontan circulation. Their median age at inclusion was 12.12 years, with a range from 4.41 to 33,41 years. The median interval between the Fontan operation and inclusion was 7.84 years, with a range from 1.96 to 12,18 years. Participants received half the usual dose of bosentan for 4 weeks, and then the full dose for a further 12 weeks.Main measures of outcomesWe assessed saturations of oxygen at rest and during exercise, using a 6 minutes walk test, at baseline, and during and after 16 weeks of treatment. At each visit, we assessed blood chemistry and hepatic function, and asked the patients to complete a questionnaire concerning quality of life. All medical events and possible side effects were recorded. RESULTS: Of the cohort, 1 patient withdrew. The changes in saturations of oxygen, exercise performance, and scores for the questionnaire did not reach statistical significance for the whole group. We noted, nonetheless, that saturations of oxygen and/or exercise capacity improved in 5 of the patients. This was further confirmed when those patients deteriorated again when the drug was discontinued. CONCLUSIONS: Our study failed to show significant improvement after 3 months of treatment with bosentan in a small group of patients with failing Fontan circulations. Some individuals, nonetheless, did improve. When planning larger trials, it would be better to identify those patients who might potentially benefit from the treatment prior to commencing the trial.

  1. Gewillig M., THE FONTAN CIRCULATION, 10.1136/hrt.2004.051789
  2. d’Udekem, Circulation, 116, I157 (2007)
  3. Gentles Thomas L., Mayer, Jr John E., Gauvreau Kimberlee, Newburger Jane W., Lock James E., Kupferschmid John P., Burnett a Janice, Jonas Richard A., Castañeda Aldo R., Wernovsky Gil, Fontan operation in five hundred consecutive patients: Factors influencing early and late outcome, 10.1016/s0022-5223(97)70183-1
  4. Gentles Thomas L., Gauvreau Kimberlee, Mayer John E., Fishberger Steven B., Burnetta Janice, Colan Steven D., Newburger Jane W., Wernovsky Gil, Functional outcome after the Fontan operation: Factors influencing late morbidity, 10.1016/s0022-5223(97)70184-3
  5. Cetta Frank, Feldt Robert H., O'Leary Patrick W., Mair Douglas D., Warnes Carole A., Driscoll David J., Hagler Donald J., Porter Co-Burn J., Offord Kenneth P., Schaff Hartzell V., Puga Francisco J., Danielson Gordon K., Improved early morbidity and mortality after Fontan operation: The mayo clinic experience, 1987 to 1992, 10.1016/0735-1097(96)00135-0
  6. Earing Michael G., Cetta Frank, Driscoll David J., Mair Douglas D., Hodge David O., Dearani Joseph A., Puga Francisco J., Danielson Gordon K., O’Leary Patrick W., Long-Term Results of the Fontan Operation for Double-Inlet Left Ventricle, 10.1016/j.amjcard.2005.03.061
  7. Burkhart Harold M, Dearani Joseph A, Mair Douglas D, Warnes Carole A, Rowland Charles C, Schaff Hartzell V, Puga Francisco J, Danielson Gordon K, The modified fontan procedure: early and late results in 132 adult patients, 10.1016/s0022-5223(03)00117-x
  8. Mertens Luc, Hagler Donald J., Sauer Ursula, Somerville Jane, Gewillig Marc, Protein-losing enteropathy after the Fontan operation: An international multicenter study, 10.1016/s0022-5223(98)70406-4
  9. Khairy P., Fernandes S. M., Mayer J. E., Triedman J. K., Walsh E. P., Lock J. E., Landzberg M. J., Long-Term Survival, Modes of Death, and Predictors of Mortality in Patients With Fontan Surgery, 10.1161/circulationaha.107.738559
  10. Mitchell Max B., Campbell David N., Ivy Dunbar, Boucek Mark M., Sondheimer Henry M., Pietra Biagio, Das Bibhuti B., Coll Joseph R., Evidence of pulmonary vascular disease after heart transplantation for Fontan circulation failure, 10.1016/j.jtcvs.2004.07.013
  11. Khambadkone S., Basal Pulmonary Vascular Resistance and Nitric Oxide Responsiveness Late After Fontan-Type Operation, 10.1161/01.cir.0000074210.49434.40
  12. Schulze-Neick Ingram, Li Jia, Reader Jayne A., Shekerdemian Lara, Redington Andrew N., Penny Daniel J., The endothelin antagonist BQ123 reduces pulmonary vascular resistance after surgical intervention for congenital heart disease, 10.1067/mtc.2002.121492
  13. Yamagishi, J Cardiovasc Surg, 43, 793 (2002)
  14. Clozel Martine, Endothelin Receptor Antagonists: Current Status and Perspectives : , 10.1097/00005344-200000002-00015
  15. Barst R, Pharmacokinetics, safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension, 10.1016/s0009-9236(03)00005-5
  16. Rubin Lewis J., Badesch David B., Barst Robyn J., Galiè Nazzareno, Black Carol M., Keogh Anne, Pulido Tomas, Frost Adaani, Roux Sébastien, Leconte Isabelle, Landzberg Michael, Simonneau Gérald, Bosentan Therapy for Pulmonary Arterial Hypertension, 10.1056/nejmoa012212
  17. Varni James W., Seid Michael, Kurtin Paul S., PedsQL™ 4.0: Reliability and Validity of the Pediatric Quality of Life Inventory™ Version 4.0 Generic Core Scales in Healthy and Patient Populations : , 10.1097/00005650-200108000-00006
  18. Lammers A E, Hislop A A, Flynn Y, Haworth S G, The 6-minute walk test: normal values for children of 4-11 years of age, 10.1136/adc.2007.123653
  19. Sitbon O, Survival in patients with class III idiopathic pulmonary arterial hypertension treated with first line oral bosentan compared with an historical cohort of patients started on intravenous epoprostenol, 10.1136/thx.2005.040618
  20. Denton C P, Bosentan treatment for pulmonary arterial hypertension related to connective tissue disease: a subgroup analysis of the pivotal clinical trials and their open-label extensions, 10.1136/ard.2005.048967
  21. Denton C P, Pope J E, Peter H-H, Gabrielli A, Boonstra A, van den Hoogen F H J, Riemekasten G, De Vita S, Morganti A, Dolberg M, Berkani O, Guillevin L, , Long-term effects of bosentan on quality of life, survival, safety and tolerability in pulmonary arterial hypertension related to connective tissue diseases, 10.1136/ard.2007.079921
  22. Rosenzweig Erika Berman, Ivy D. Dunbar, Widlitz Allison, Doran Aimee, Claussen Lori R., Yung Delphine, Abman Steven H., Morganti Adele, Nguyen Ngoc, Barst Robyn J., Effects of Long-Term Bosentan in Children With Pulmonary Arterial Hypertension, 10.1016/j.jacc.2005.01.066
  23. Galie N., Bosentan Therapy in Patients With Eisenmenger Syndrome: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study, 10.1161/circulationaha.106.630715
  24. Barst Robyn J., Langleben David, Badesch David, Frost Adaani, Lawrence E. Clinton, Shapiro Shelley, Naeije Robert, Galie Nazzareno, Treatment of Pulmonary Arterial Hypertension With the Selective Endothelin-A Receptor Antagonist Sitaxsentan, 10.1016/j.jacc.2006.01.057
  25. Barst, Vasc Health Risk Manag, 3, 11 (2007)
  26. Benza Raymond L., Mehta Sanjay, Keogh Anne, Lawrence E. Clinton, Oudiz Ronald J., Barst Robyn J., Sitaxsentan Treatment for Patients With Pulmonary Arterial Hypertension Discontinuing Bosentan, 10.1016/j.healun.2006.10.019
  27. Humpl T., Beneficial Effect of Oral Sildenafil Therapy on Childhood Pulmonary Arterial Hypertension: Twelve-Month Clinical Trial of a Single-Drug, Open-Label, Pilot Study, 10.1161/circulationaha.104.473371
  28. Apostolopoulou Sotiria C., Papagiannis John, Rammos Spyridon, Bosentan Induces Clinical, Exercise and Hemodynamic Improvement in a Pre-Transplant Patient With Plastic Bronchitis After Fontan Operation, 10.1016/j.healun.2004.11.018
  29. Miyaji Kagami, Nagata Nobuhiro, Miyamoto Takashi, Kitahori Kazuo, Combined therapy with inhaled nitric oxide and intravenous epoprostenol (prostacyclin) for critical pulmonary perfusion after the Fontan procedure, 10.1067/mtc.2003.199
  30. Haseyama Keiji, Satomi Gengi, Yasukochi Satoshi, Matsui Hikoro, Harada Yorikazu, Uchita Shunji, Pulmonary vasodilation therapy with sildenafil citrate in a patient with plastic bronchitis after the Fontan procedure for hypoplastic left heart syndrome, 10.1016/j.jtcvs.2006.05.067
  31. Uzun Orhan, Wong Joon Kwang, Bhole Vinaj, Stumper Oliver, Resolution of Protein-Losing Enteropathy and Normalization of Mesenteric Doppler Flow With Sildenafil After Fontan, 10.1016/j.athoracsur.2006.08.043
  32. Giardini A., Balducci A., Specchia S., Gargiulo G., Bonvicini M., Picchio F. M., Effect of sildenafil on haemodynamic response to exercise and exercise capacity in Fontan patients, 10.1093/eurheartj/ehn215
Bibliographic reference Ovaert, Caroline ; Thijs, Daisy ; Dewolf, Daniel ; Ottenkamp, Jaap ; Dessy, Hugues ; et. al. The effect of bosentan in patients with a failing Fontan circulation.. In: Cardiology in the Young, Vol. 19, no. 4, p. 331-339 (2009)
Permanent URL http://hdl.handle.net/2078.1/22654