Author + information
- Received August 11, 2002
- Revision received December 20, 2002
- Accepted January 2, 2003
- Published online April 16, 2003.
- Nazzareno Galiè, MD*,* (, )
- Alan L. Hinderliter, MD†,
- Adam Torbicki, MD‡,
- Thierry Fourme, MD§,
- Gerald Simonneau, MD§,
- Tomas Pulido, MD∥,
- Nilda Espinola-Zavaleta, MD∥,
- Guido Rocchi, MD*,
- Alessandra Manes, MD*,
- Robert Frantz, MD¶,
- Marcin Kurzyna, MD‡,
- Sherif F. Nagueh, MD#,
- Robyn Barst, MD**,
- Richard Channick, MD††,
- Karl Dujardin, MD‡‡,
- Andrew Kronenberg, MD†,
- Isabelle Leconte, PhD§§,
- Maurizio Rainisio, PhD§§ and
- Lewis Rubin, MD††
- ↵*Reprint requests and correspondence:
Dr. Nazzareno Galiè, Istituto di Cardiologia, Università di Bologna, via Massarenti, 9, 40138-Bologna, Italy.
Objectives The purpose of this study was to investigate the effects of bosentan (125 or 250 mg twice daily) on echocardiographic and Doppler variables in 85 patients with World Health Organization class III or IV pulmonary arterial hypertension (PAH).
Background Bosentan, an orally active dual endothelin-receptor antagonist, improves symptoms, exercise capacity, and hemodynamics in patients with PAH.
Methods Patients had primary pulmonary hypertension (84%) or PAH associated with connective tissue disease. Of these, 29 patients received placebo and 56 received bosentan (1:2 randomization). Six-minute walk tests and echocardiograms were performed at baseline and after 16 weeks of treatment.
Results Baseline characteristics were similar in the placebo and bosentan groups, and echocardiographic and Doppler findings were consistent with marked abnormalities of right ventricular (RV) and left ventricular (LV) structure and function that were due to PAH. The treatment effect on 6-min walking distance was 37 m in favor of bosentan (p = 0.036). Treatment effects of bosentan compared with placebo on other parameters were as follows: Doppler-derived cardiac index = +0.4 l/min/m2(p = 0.007), LV early diastolic filling velocity = +10.5 cm/s (p = 0.003), LV end-diastolic area = +4.2 cm2(p = 0.003), LV systolic eccentricity index = −0.12 (p = 0.047), RV end-systolic area = −2.3 cm2(p = 0.057), RV:LV diastolic areas ratio = −0.64 (p = 0.007), Doppler RV index = −0.06 (p = 0.03), and percentage of patients with an improvement in pericardial effusion score = 17% (p = 0.05).
Conclusions Bosentan improves RV systolic function and LV early diastolic filling and leads to a decrease in RV dilation and an increase in LV size in patients with PAH.
This study was supported by Actelion Pharmaceuticals Ltd., Allschwil, Switzerland.
- Received August 11, 2002.
- Revision received December 20, 2002.
- Accepted January 2, 2003.
- American College of Cardiology Foundation