Effect of ambrisentan combined with sildenafil evaluated by echocardiograph on right ventricular pulmonary arterial coupling in patients with severe pulmonary hypertension

To explore the feasibility and clinical relevant factors of ambrisentan combined with sildenafil evaluated by echocardiograph in right ventricular pulmonary arterial coupling(RVPAC) patients with severe pulmonary hypertension (PAH).

A total of 33 patients with severe PAH were selected as research objects, ambesentan (5 to 10 mg/d) and sildenafil (50 mg/d) were given for at least 6 months. Plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) was detected by Enzyme linked immunosorbent assay (ELISA). Mean pulmonary artery pressure (mPAP), pulmonary arterial wedge pressure (PAWP), pulmonary vascular resistance (PVR) and cardiac index (CI) were measured by right heart catheterization. Conventional ultrasonic parameters were measured by echocardiography, and RVPAC related indexes including right ventricular fractional area change/pulmonary arterial systolic pressure (RVFAC/PASP), tricuspid annular plane systolic excursion(TAPSE)/PASP, tricuspid annular systolic velocity(S')/PASP and right ventricular stroke volume(RVSV)/right ventricular end systolic volume(RVESV)were calculated. The patients were followed up for 6 months, clinical prognosis was recorded, and end event was death. The correlations between RVPAC indexes and prognosis were analyzed by binary Logistic regression; receiver operating curve (ROC) was used to analyze the efficacy of RVPAC indexes for predicting clinical prognosis.

The level of NT-proBNP in 33 patients after 6 months treatment was significantly lower than before treatment[356.7(141.8, 1 126.2) pg/mL versus 1 748.4(696.8, 3 012.4) pg/mL, P < 0.001]. After treatment, S', TAPSE, right ventricular ejection fraction (RVEF) and RVFAC increased significantly, while PASP and RVESV decreased significantly, RVFAC/PASP, TAPSE/PASP, S'/PASP and RVSV/RVESV also increased significantly compared with before treatment (P < 0.05). Spearman test showed that RVFAC/PASP, TAPSE/PASP, S'/PASP and RVSV/RVESV were separately negatively correlated with NT-proBNP, mPAP, PAWP and PVR before treatment (P < 0.001), and were all positively correlated with end-systolic elastance-to-arterial elastance ratio (Ees/Ea) (P < 0.05). A total of 6 patients occurred endpoint events in 33 patients. Binary Logistic regression analysis showed that decreased RVFAC/PASP, TAPSE/PASP, S'/PASP and RVSV/RVESV before treatment were risk factors of the endpoint events (P < 0.05). ROC showed that area under the curve of RVFAC/PASP, TAPSE/PASP, S'/PASP and RVSV/RVESV before treatment in prediction of clinical prognosis were 0.839, 0.745, 0.768 and 0.856, respectively.

Ambrisentan combined with sildenafil in treatment of severe PAH could improve RVPAC. RVPAC indexes based on non-invasive echocardiographic detection has good correlations with NT-proBNP and right heart catheterization measurement index, and RVPAC index can also be used to evaluate the clinical prognosis of patients. RVPAC can also be used to evaluate clinical prognosis of patient.