Bosentan Treatment In Patients Research Articles

A comparison of echocardiographic variables of right ventricular function with exercise capacity after bosentan treatment in patients with pulmonary arterial hypertension: Results from a multicenter, prospective, cohort study.

Bosentan reduces pulmonary arterial pressure and improves exercise capacity in patients with pulmonary arterial hypertension (PAH). However, there are limited data regarding the extent to which the changes in echocardiographic variables reflect improvements in exercise capacity. We aimed to assess the improvement of echocardiographic variables and exercise capacity after 6 months of bosentan treatment for PAH. We performed a prospective study from June 2012 to June 2015 in seven participating medical centers. Echocardiography, including tissue Doppler imaging (TDI) and the 6-minute walk test distance (6MWD), was performed at baseline and after 6 months of bosentan treatment. We analyzed 19 patients with PAH: seven with congenital shunt, six with collagen vascular disease, and six with idiopathic PAH. After bosentan treatment, mean 6MWD increased by 50 meters. Right ventricle (RV) systolic pressure, tricuspid annular plane systolic excursion, myocardial performance index (MPI) derived from TDI (MPI-TDI) of RV and left ventricle (LV), RV fractional area change, and RV ejection fraction were significantly improved. In particular, the magnitude of RV and LV MPI-TDI showed good correlation with changes in the 6MWD. The magnitude of RV and LV MPI-TDI was strongly associated with improvements in exercise capacity. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:28-34, 2017.

Aspects étiologiques des hémoptysies à propos de 81 cas

Pulmonary arterial hypertension (PAH) in patients with congenital heart disease (CHD) usually has a homogeneous pressure distribution. More rarely, complex CHD patients have segmental PAH. This is often post-surgically. The characteristics of these patients and their responsiveness to specific pulmonary vasodilator therapy have not been described.Seven adults with segmental PAH complicating CHD were treated at 3 specialized adult CHD centers between January 2006 and December 2010. Clinical characteristics, six minute walking distances (6MWD), laboratory tests and images were obtained from medical records and the responses to Bosentan, an endothelin-1 receptor antagonist, were assessed.All patients (mean age 32 (23–42) years, five females) had a primary diagnosis pulmonary atresia (PA), four with major aortopulmonary collateral arteries (MAPCAs). Four segmental PAH patients had a right pulmonary artery stenosis, two a left pulmonary artery stenosis and one a unilateral MAPCA stenosis. All patients were symptomatic (functional class II or III) and bosentan was started empirically. Bosentan treatment led to a significant improvement in functional class compared to baseline (1.7 ± 0.5 versus 2.4 ± 0.5; p < 0.01). Mean 6MWD (available in 6 patients) increased by 62 m (22–150 m) from 386 ± 135 to 448 ± 133 m (p = 0.03) after 12 months treatment. Most improvement was seen in patients with low baseline 6MWD. Higher baseline exercise heart rate was significantly associated with lesser improvement in 6MWD (r = − 0.91 p = 0.01). Laboratory results did not change after initiation of bosentan treatment.This small retrospective case series suggested a significant improvement of functional class and exercise capacity after bosentan treatment in patients with segmental PAH. These findings warrant a prospective study of the potential benefit of selective pulmonary vasodilator therapy in these complex patients. Therefore, we call on treating physicians to share similar cases.

Treatment of segmental pulmonary artery hypertension in adults with congenital heart disease

IntroductionPulmonary arterial hypertension (PAH) in patients with congenital heart disease (CHD) usually has a homogeneous pressure distribution. More rarely, complex CHD patients have segmental PAH. This is often post-surgically. The characteristics of these patients and their responsiveness to specific pulmonary vasodilator therapy have not been described. MethodsSeven adults with segmental PAH complicating CHD were treated at 3 specialized adult CHD centers between January 2006 and December 2010. Clinical characteristics, six minute walking distances (6MWD), laboratory tests and images were obtained from medical records and the responses to Bosentan, an endothelin-1 receptor antagonist, were assessed. ResultsAll patients (mean age 32 (23–42) years, five females) had a primary diagnosis pulmonary atresia (PA), four with major aortopulmonary collateral arteries (MAPCAs). Four segmental PAH patients had a right pulmonary artery stenosis, two a left pulmonary artery stenosis and one a unilateral MAPCA stenosis. All patients were symptomatic (functional class II or III) and bosentan was started empirically. Bosentan treatment led to a significant improvement in functional class compared to baseline (1.7±0.5 versus 2.4±0.5; p<0.01). Mean 6MWD (available in 6 patients) increased by 62m (22–150m) from 386±135 to 448±133m (p=0.03) after 12months treatment. Most improvement was seen in patients with low baseline 6MWD. Higher baseline exercise heart rate was significantly associated with lesser improvement in 6MWD (r=−0.91 p=0.01). Laboratory results did not change after initiation of bosentan treatment. ConclusionThis small retrospective case series suggested a significant improvement of functional class and exercise capacity after bosentan treatment in patients with segmental PAH. These findings warrant a prospective study of the potential benefit of selective pulmonary vasodilator therapy in these complex patients. Therefore, we call on treating physicians to share similar cases.

Duration of right ventricular contraction predicts the efficacy of bosentan treatment in patients with pulmonary hypertension

In patients with pulmonary hypertension (PH), elevated endothelin-1 levels are associated with prolonged duration of right ventricular (RV) contraction, which induces leftward ventricular septal bowing with impaired left diastolic filling. We hypothesized that baseline RV contraction duration predicts efficacy of endothelin receptor antagonist, bosentan. Eighteen PH patients (age 57, range 35-79 years, 33% male) received bosentan. Six minute walk distance (6-MWD) and echocardiography were performed at baseline and after 1 year follow-up. After 1 year of treatment, 6-MWD increased (mean 60 +/- 41 m) in 67% of patients (responders). Baseline RV contraction duration was longer in responders, compared with non-responders (612 +/- 66 vs. 514 +/- 23 ms; P < 0.01). A baseline RV contraction duration >550 ms was associated with improved 6-MWD (sensitivity 83%, specificity 83%; P < 0.01). An improvement of 6-MWD during bosentan treatment was associated with a decrease in RV contraction duration and could be predicted by a baseline RV contraction duration >550 ms.

BUILD-1: A Randomized Placebo-controlled Trial of Bosentan in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease lacking effective treatment. To determine the effects of bosentan on exercise capacity and time to disease progression in patients with IPF. In a double-blind, multicenter trial, patients with IPF were randomized to receive oral bosentan 62.5 mg twice daily for 4 weeks, increased to 125 mg twice daily thereafter, or placebo, for 12 months or longer. The primary efficacy endpoint was change from baseline up to Month 12 in exercise capacity, as measured by a modified six-minute-walk test. Secondary endpoints were time to death or disease progression (worsening pulmonary function tests [PFTs] or acute decompensation), change in PFT scores, and quality of life (QOL) assessed using Short-Form 36 and St. George's Respiratory Questionnaire. A total of 158 patients randomly received bosentan (n = 74) or placebo (n = 84). Bosentan showed no superiority over placebo in six-minute-walk distance (6MWD) up to Month 12, the primary efficacy endpoint. A trend in favor of bosentan was observed in the secondary endpoint of time to death or disease progression (hazard ratio [HR], 0.613; 95% confidence interval [CI], 0.328-1.144; P = 0.119), which was more pronounced in a patient subgroup diagnosed using surgical lung biopsy (post hoc analysis; HR, 0.315; 95% CI, 0.126-0.789; P = 0.009). Changes from baseline up to Month 12 in assessments of dyspnea and QOL favored treatment with bosentan. No unexpected adverse events were reported. Bosentan treatment in patients with IPF did not show superiority over placebo on 6MWD. A trend in delayed time to death or disease progression, and improvement in QOL, was observed with bosentan. The more pronounced treatment effect in patients with biopsy-proven IPF warrants further investigation. Clinical trial registered with www.clinicaltrials.gov (NCT 00071461).

Effects of the Dual Endothelin Receptor Antagonist Bosentan in Patients With Pulmonary Arterial Hypertension: A 1-Year Follow-up Study

We report on the long-term safety and efficacy of bosentan treatment in patients with pulmonary arterial hypertension (PAH). In a preceding study, bosentan was well tolerated and significantly improved the exercise capacity and hemodynamics of patients with PAH after 12 weeks of treatment. The present study was an open-label extension to the preceding double-blind, placebo-controlled study of 32 patients with PAH (primary or associated with scleroderma) who received bosentan or placebo at 125 mg bid for 3 to 7 months. Twenty-nine of the original 32 patients received bosentan for an additional year (62.5 mg bid for 4 weeks and then 125 mg bid). Study end points included long-term safety, 6-min walk distance at week 4, modified New York Heart Association (NYHA) functional class of PAH at month 12, and the occurrence of withdrawal due to clinical worsening. Additional exploratory analyses included a walk test at month 6 for 19 patients and hemodynamic assessment at month 12 for 11 patients. At month 6, assessed patients continuing bosentan treatment maintained the improvement in walk distance observed at the end of the previous study (mean +/- SEM, 60 +/- 11 m), and patients starting bosentan treatment improved their walk distance by 45 +/- 13 m. Long-term treatment with bosentan for > 1 year was associated with an improvement in hemodynamic parameters and modified NYHA functional class. Overall, bosentan treatment was well tolerated. No patient underwent transplantation or died. Long-term treatment with bosentan is safe and has sustained benefits on exercise capacity and hemodynamics in patients with PAH.