Bosentan Treatment Is Associated With Improvement of Right Ventricular Function and Remodeling in Chronic Thromboembolic Pulmonary Hypertension

BACKGROUND: Medical pretreatment before pulmonary endarterectomy (PEA) can optimize right ventricular (RV) function and may improve postoperative outcome in high-risk patients. Using cardiac magnetic resonance imaging (cMRI), we determined whether the dual endothelin-1 antagonist bosentan improves RV function and remodeling in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who waited for PEA. HYPOTHESIS: We hypothesized that medical therapy prior to PEA will be associated with improvements in RV remodeling and function. METHODS: In this pilot study, 15 operable CTEPH patients were randomly assigned to either bosentan (n = 8) or no bosentan (n = 7, control) for 16 weeks, next to "best standard of care." Both before and after treatment, RV stroke volume index (RVSVI), RV ejection fraction (RVEF), RV mass, RV isovolumic relaxation time (rIVRT), leftward ventricular septal bowing (LVSB), and left ventricular ejection fraction (LVEF) were determined using cMRI. RESULTS: After 16 weeks, the change (Δ) from baseline (median [range]) in the studied cMRI parameters differed significantly between the bosentan group and the controls: Δ RVSVI: 6 [-4-11] vs 1 [-6-3] mL/m(-2) ; Δ RVEF: 8 [-10-15] vs -4 [-7-5]%; Δ RV mass: -3 [-6--2] vs 2 [-1-3] g/m(-2) ; Δ rIVRT: -30 [-130-20] vs 10 [-30-30] msec; Δ LVSB: 0.03 [-0.03-0.13] vs -0.03[-0.08-0.04] cm(-1) ; and Δ LVEF: 8 [-5-17] vs -2 [-14-2]% (all P < 0.05). The change from baseline in mean pulmonary artery pressure (-11 [-17-11] vs 5 [-6-21] mm Hg, P < 0.05) and 6-minute walk distance (20 [3-88] vs -4 [-40-40] m, P < 0.05) also differed significantly. CONCLUSIONS: In CTEPH, compared with control, treatment with bosentan for 16 weeks was associated with a significant improvement in cMRI parameters of RV function and remodelling.