Bosentan as a bridge to pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension

Reesink, Herre J.; Surie, Sulaiman; Kloek, Jaap J.; Tan, Hanno L.; Tepaske, Robert; Fedullo, Peter F.; Bresser, Paul

doi:10.1016/j.jtcvs.2009.03.053

« Previous Next »The Journal of Thoracic and Cardiovascular Surgery
Volume 139, Issue 1 , Pages 85-91, January 2010

Bosentan as a bridge to pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension

Herre J. Reesink, MD, PhD
- Department of Pulmonology, University of Amsterdam, Amsterdam, The Netherlands
Sulaiman Surie, MD
- Department of Pulmonology, University of Amsterdam, Amsterdam, The Netherlands
Jaap J. Kloek, MD
- Department of Cardiothoracic Surgery, University of Amsterdam, Amsterdam, The Netherlands
Hanno L. Tan, MD, PhD
- Department of Cardiology, University of Amsterdam, Amsterdam, The Netherlands
Robert Tepaske, MD, PhD
- Department of Intensive Care Medicine of the Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Peter F. Fedullo, MD
- Division of Repiratory and Critical Care Medicine, University of California San Diego, San Diego, Calif
Paul Bresser, MD, PhD
- Department of Pulmonology, University of Amsterdam, Amsterdam, The Netherlands
- Address for reprints: P. Bresser, MD, PhD, Academic Medical Center, University of Amsterdam, Department of Pulmonology, F5-144, PO Box 22700, 1100 DE Amsterdam, The Netherlands.

Received 20 October 2008; received in revised form 23 March 2009; accepted 29 March 2009. published online 01 June 2009.

Objectives

In proximal chronic thromboembolic pulmonary hypertension, pulmonary endarterectomy is the treatment of first choice. In general, medical treatment before pulmonary endarterectomy is not indicated. However, selected “high-risk” patients might benefit by optimization of pulmonary hemodynamics. Moreover, in patients whose surgery is delayed owing to limited medical resources, pretreatment may prevent clinical deterioration. The primary objective of this study was to determine whether the dual endothelin-1 antagonist bosentan improves pulmonary hemodynamics and functional capacity in patients with proximal chronic thromboembolic pulmonary hypertension waiting for pulmonary endarterectomy.

Methods

We used an investigator-initiated, randomized, controlled single-blind study. Patients were randomized to receive bosentan (n = 13) or no bosentan (n = 12) for 16 weeks, next to “best standard of care.” The primary end point was change in total pulmonary resistance. Secondary end points included changes in 6-minute walk distance, mean pulmonary artery pressure, and cardiac index.

Results

After 16 weeks, the mean differences in change from baseline between the groups were as follows: total pulmonary resistance 299 dynes · s · cm⁻⁵ (P = .004), 6-minute walk distance 33 m (P = .014), mean pulmonary artery pressure 11 mm Hg (P = .005), and cardiac index 0.3 L · min⁻¹ · m⁻² (P = .08). Treatment with bosentan was safe. After pulmonary endarterectomy, 4 patients died (no-bosentan group: n = 3); the short-term in-hospital postoperative clinical course was similar in both groups of patients.

Conclusions

Patients with proximal chronic thromboembolic pulmonary hypertension may benefit hemodynamically and clinically from treatment with bosentan before pulmonary endarterectomy. Individual factors predictive of a beneficial response and whether this influences either morbidity or mortality associated with pulmonary endarterectomy remain to be established.

CTSNet classification: 11, 25, 26, 33

Abbreviations and Acronyms: 6-MWD, six-minute walk distance, BNP, brain natriuretic peptide, CI, cardiac index, CTEPH, chronic thromboembolic pulmonary hypertension, ET-1, endothelin-1, mPAP, mean pulmonary artery pressure, mRAP, mean right atrial pressure, PEA, pulmonary endarterectomy, TPR, total pulmonary resistance