Abstract
Background. In patients with pulmonary hypertension, it is unknown whether the treatment effect of bosentan is dependent on the duration of pulmonary vessel changes. Therefore, we studied the response to bosentan in patients with life-long pulmonary vessel changes (pulmonary arterial hypertension (PAH) due to congenital heart disease (CHD)) and in patients with subacutely induced pulmonary vessel changes (chronic thromboembolic pulmonary hypertension (CTEPH)).
Methods. In this open-label study, 18 patients with PAH due to CHD and 16 patients with CTEPH were treated with bosentan for at least one year. All patients were evaluated at baseline and during follow-up by means of the six-minute walk distance (6-MWD) and laboratory tests.
Results. Improvement of 6-MWD was comparable in patients with PAH due to CHD (444±112 m to 471±100 m, p=0.02), and in CTEPH (376±152 m to 423±141 m, p=0.03) after three months of treatment. After this improvement, 6-MWD stabilised in both groups.
Conclusion. Although duration of pulmonary vessel changes is strikingly different in patients with PAH due to CHD and CTEPH, the effect of one year of bosentan treatment was comparable. The main treatment effect appears to be disease stabilisation and decreasing the rate of deterioration. (Neth Heart J 2009;17:334–8.)
Similar content being viewed by others
References
Simonneau G, Galie N, Rubin LJ, Langleben D, Seeger W, Domenighetti G, et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2004;43:5S–12S.
Engelfriet PM, Duffels MG, Moller T, Boersma E, Tijssen JG, Thaulow E, et al. Pulmonary arterial hypertension in adults born with a heart septal defect: the Euro Heart Survey on adult congenital heart disease. Heart. 2007;93:682–7.
Riedel M, Stanek V, Widimsky J, Prerovsky I. Longterm follow-up of patients with pulmonary thromboembolism. Late prognosis and evolution of hemodynamic and respiratory data. Chest. 1982;81: 151–8.
Duffels MG, Engelfriet PM, Berger RM, van Loon RL, Hoendermis E, Vriend JW, et al. Pulmonary arterial hypertension in congenital heart disease: an epidemiologic perspective from a Dutch registry. Int J Cardiol. 2007;120:198–204.
Oya H, Nagaya N, Uematsu M, Satoh T, Sakamaki F, Kyotani S, et al. Poor prognosis and related factors in adults with Eisenmenger syndrome. Am Heart J. 2002;143:739–44.
Fedullo PF, Auger WR, Kerr KM, Rubin LJ. Chronic thromboembolic pulmonary hypertension. N Engl J Med. 2001;345:1465–72.
Pengo V, Lensing AW, Prins M, Prins MH, Marchiori A, Marchiori A, et al. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med. 2004;350:2257–64.
Bresser P, Pepke-Zaba J, Jais X, Humbert M, Hoeper MM. Medical therapies for chronic thromboembolic pulmonary hypertension: an evolving treatment paradigm. Proc Am Thorac Soc. 2006;3:594–600.
Auger WR, Kerr KM, Kim NH, Ben-Yehuda O, Knowlton KU, Fedullo PF. Chronic thromboembolic pulmonary hypertension. Cardiol Clin. 2004;22:453–66, vii.
Bonderman D, Nowotny R, Skoro-Sajer N, Jakowitsch J, Adlbrecht C, Klepetko W, et al. Bosentan therapy for inoperable chronic thromboembolic pulmonary hypertension. Chest. 2005; 128:2599–603.
Apostolopoulou SC, Manginas A, Cokkinos DV, Rammos S. Long-term oral bosentan treatment in patients with pulmonary arterial hypertension related to congenital heart disease: a 2-year study. Heart. 2007;93:350–4.
D'Alto M, Vizza CD, Romeo E, Badagliacca R, Santoro G, Poscia R, et al. Long term effects of bosentan treatment in adult patients with pulmonary arterial hypertension related to congenital heart disease (Eisenmenger physiology): safety, tolerability, clinical, and haemodynamic effect. Heart. 2007;93:621–5.
Hoeper MM, Kramm T, Wilkens H, Schulze C, Schafers HJ, Welte T, et al. Bosentan therapy for inoperable chronic thromboembolic pulmonary hypertension. Chest. 2005;128:2363–7.
Gatzoulis MA, Beghetti M, Galie N, Granton J, Berger RM, Lauer A, et al. Longer-term bosentan therapy improves functional capacity in Eisenmenger syndrome: Results of the BREATHE-5 open-label extension study. Int J Cardiol. 2007;127:27–32.
Galie N, Beghetti M, Gatzoulis MA, Granton J, Berger RMF, Lauer A, et al. Bosentan therapy in patients with Eisenmenger syndrome: A multicenter, double-blind, randomized, placebocontrolled study. Circulation. 2006;114:48–54.
Rubin LJ, Badesch DB. Evaluation and management of the patient with pulmonary arterial hypertension. Ann Intern Med. 2005;143: 282–92.
ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002;166:111–7.
Apostolopoulou SC, Manginas A, Cokkinos DV, Rammos S. Effect of the oral endothelin antagonist bosentan on the clinical, exercise, and haemodynamic status of patients with pulmonary arterial hypertension related to congenital heart disease. Heart. 2005;91:1447–52.
Duffels MGJ, Berger RMF, Bresser P, de Bruin-Bon HACM, Hoendermis E, Bouma BJ, et al. Applicability of bosentan in Dutch patients with Eisenmenger syndrome: preliminary results on safety and exercise capacity. Neth Heart J. 2006;14:165–70.
Duffels M, van Loon L, Berger R, Boonstra A, Vonk-Noordergraaf A, Mulder B. Pulmonary arterial hypertension associated with a congenital heart defect: advanced medium-term medical treatment stabilizes clinical condition. Congenit Heart Dis. 2007;2:242–9.
Seyfarth HJ, Hammerschmidt S, Pankau H, Winkler J, Wirtz H. Long-term bosentan in chronic thromboembolic pulmonary hypertension. Respiration. 2007;74:287–92.
Diller GP, Dimopoulos K, Kaya MG, Harries C, Uebing A, Li W, et al. Long-term safety, tolerability and efficacy of bosentan in adults with pulmonary arterial hypertension associated with congenital heart disease. Heart. 2007;93:974–6.
van Loon RL, Hoendermis ES, Duffels MG, Vonk-Noordegraaf A, Mulder BJ, Hillege HL, et al. Long-term effect of bosentan in adults versus children with pulmonary arterial hypertension associated with systemic-to-pulmonary shunt: does the beneficial effect persist? Am Heart J. 2007;154:776–82.
Hughes RJ, Jais X, Bonderman D, Suntharalingam J, Humbert M, Lang I, et al. The efficacy of bosentan in inoperable chronic thromboembolic pulmonary hypertension: a 1-year follow-up study. Eur Respir J. 2006;28:138–43.
McLaughlin VV, Presberg KW, Doyle RL, Abman SH, McCrory DC, Fortin T, et al. Prognosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest. 2004; 126:78S–92S.
Hopkins WE, Waggoner AD. Severe pulmonary hypertension without right ventricular failure: the unique hearts of patients with Eisenmenger syndrome. Am J Cardiol.. 2002;89:34–8.
Enright PL, Sherrill DL. Reference equations for the six-minute walk in healthy adults. Am J Respir Crit Care Med. 1998;158: 1384–7.
Ulrich S, Fischler M, Speich R, Popov V, Maggiorini M. Chronic thromboembolic and pulmonary arterial hypertension share acute vasoreactivity properties. Chest. 2006;130:841–6.
Cenedese E, Speich R, Dorschner L, Ulrich S, Maggiorini M, Jenni R, et al. Measurement of quality of life in pulmonary hypertension and its significance. Eur Respir J. 2006;28:808–15.
Author information
Authors and Affiliations
Additional information
Department of Cardiology, Academic Medical Center, Amsterdam, the Netherlands
Department of Pulmonology, Academic Medical Center, Amsterdam, the Netherlands
Department of Cardiology, University Medical Center Nijmegen, the Netherlands
Department of Cardiology, University Medical Center Groningen, the Netherlands
Department of Paediatric Cardiology University Medical Center Groningen, the Netherlands
Departments of Cardiology, Academic Medical Center, Amsterdam and University Medical Center Utrecht, Utrecht, the Netherlands
B.J.M. Mulder Department of Cardiology, Rm B2–240, Academic Medical Center, PO Box 22660, 1100 DD Amsterdam, the Netherlands
Rights and permissions
About this article
Cite this article
Duffels, M.G.J., van der Plas, M.N., Surie, S. et al. Bosentan in pulmonary arterial hypertension: a comparison between congenital heart disease and chronic pulmonary embolism. NHJL 17, 334–338 (2009). https://doi.org/10.1007/BF03086279
Issue Date:
DOI: https://doi.org/10.1007/BF03086279