Effects of the oral endothelin-receptor antagonist bosentan on echocardiographic and doppler measures in patients with pulmonary arterial hypertension.
OBJECTIVE
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/m(2) (p = 0.007), LV early diastolic filling velocity = +10.5 cm/s (p = 0.003), LV end-diastolic area = +4.2 cm(2) (p = 0.003), LV systolic eccentricity index = -0.12 (p = 0.047), RV end-systolic area = -2.3 cm(2) (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.
Galiè
Nazzareno
N
Institute of Cardiology, University of Bologna, Italy. n.galie@bo.nettuno.it
Hinderliter
Alan L
AL
Torbicki
Adam
A
Fourme
Thierry
T
Simonneau
Gerald
G
Pulido
Tomas
T
Espinola-Zavaleta
Nilda
N
Rocchi
Guido
G
Manes
Alessandra
A
Frantz
Robert
R
Kurzyna
Marcin
M
Nagueh
Sherif F
SF
Barst
Robyn
R
Channick
Richard
R
Dujardin
Karl
K
Kronenberg
Andrew
A
Leconte
Isabelle
I
Rainisio
Maurizio
M
Rubin
Lewis
L
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000077300:Bosentan; D015150:Echocardiography, Doppler; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000000981:diagnostic imaging; D017380:Hypertrophy, Right Ventricular / Q000000981:diagnostic imaging / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects*; D016278:Ventricular Function, Right / Q000187:drug effects*
D000959:Antihypertensive Agents; D013449:Sulfonamides; D000077300:Bosentan