Introduction:
We assessed the effects of upfront, combination therapy with a phosphodiesterase inhibitor (tadalafil) and endothelin receptor antagonist (ambrisentan) on changes in size and function of the right ventricle (RV), in a prospective open label trial for treatment naïve scleroderma-associated pulmonary arterial hypertension (SSc-PAH) patients.
Methods:
In this multicentric open-label trial, 24 treatment naïve SSc-PAH patients received tadalafil (40 mg daily) and ambrisentan (10 mg daily) daily for 36 weeks. Two-dimensional convenctional echocardiography (2D-E) with speckle tracking (ST) study and cardiac magnetic resonance imaging (cMRI) were performed at baseline and 36 weeks.
Results:
Treatment with upfront combination therapy resulted in RV reverse remodeling, defined as a relative decrease in RV end-systolic area of at least 15% at echocardiographic evaluation at 36 weeks. cMRI at follow up showed a reduction in RV end-systolic volume 82.1 (IQR 65.6-97.7) vs 55.8 (IQR 49.4-79.2), p= 0.001, RV mass index 17.2 (IQR 13.4-27.3) vs 15.4 (IQR 11.7-20.3), p= 0.02, and ventricular mass index (VMI= RV/LV mass index) 0.32 (IQR 0.29-0.45) vs 0.27 (IQR 0.23-0.33), p= 0.02. After 36 weeks of therapy, an improvement in RV function was observed by tricuspid annular plane systolic excursion (TAPSE; 1.7 ± 0.5 vs 2.2 ± 0.5, p=0.02) and RV fractional area (FAC; 31.5 ± 12.3 vs 42.8 ± 9.7, p=0.002) changes. Tricuspid annular S’, calculated using ST, was significantly improved (7 ± 2.3 vs 8.9 ± 2.4, p=0.01), while longitudinal strain (-16 ± 6.4 vs -19 ± 4.9, p=0.09) and systolic strain rate (-0.8 ± 0.2 vs -0.9 ± 0.2, p=0.08) showed a trend toward improvement.
Conclusion:
Upfront combination therapy in treatment naïve SSc-PAH patients induces both reverse remodeling of the RV, with reduction in systolic RV volume, RV mass index and VMI, and significant increase in RV systolic function as shown by the increase in TAPSE, FAC and S’.
Goal-Oriented Sequential Combination Therapy Evaluated Using Cardiopulmonary Exercise Parameters for the Treatment of Newly Diagnosed Pulmonary Arterial Hypertension ― Goal-Oriented Therapy Evaluated by Cardiopulmonary Exercise Testing for Pulmonary Arterial Hypertension (GOOD EYE) ―
