Evaluating the efficacy and safety of oral triple sequential combination therapy for treating patients with pulmonary arterial hypertension: A multicenter retrospective study.

This study aimed to evaluate the effectiveness and safety of an oral sequential triple combination therapy with selexipag after dual combination therapy with endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5I)/riociguat in pulmonary arterial hypertension (PAH) patients. A total of 192 PAH patients from 10 centers had received oral sequential selexipag therapy after being on dual-combination therapy with ERA and PDE5i/riociguat for a minimum of 3 months. Clinical data were collected at baseline and after 6 months of treatment. The study analyzed the event-free survival at 6 months and all-cause death over 2 years. At baseline, the distribution of patients among the risk groups was as follows: 22 in the low-risk group, 35 in the intermediate-low-risk group, 91 in the intermediate-high-risk group, and 44 in the high-risk group. After 6 months of treatment, the oral sequential triple combination therapy resulted in reduced NT-proBNP levels (media from 1604 to 678 pg/mL), a decline in the percentage of WHO-FC III/IV (from 79.2% to 60.4%), an increased in the 6MWD (from 325 ± 147 to 378 ± 143 m) and a rise in the percentage of patients with three low-risk criteria (from 5.7% to 13.5%). Among the low-risk group, there was an improvement in the right heart remodeling, marked by a decrease in right atrium area and eccentricity index. The intermediate-low-risk group exhibited significant enhancements in WHO-FC and tricuspid annular plane systolic excursion. For those in the intermediate-high and high-risk groups, there were marked improvements in activity tolerance, as reflected by WHO-FC and 6MWD. The event-free survival rate at 6 months stood at 88%. Over the long-term follow-up, the survival rates at 1 and 2 years were 86.5% and 86.0%, respectively. In conclusion, the oral sequential triple combination therapy enhanced both exercise capacity and cardiac remodeling across PAH patients of different risk stratifications.

[Efficacy and safety of ambrisentan therapy in Chinese patients with pulmonary hypertension].

OBJECTIVE: To explore the efficacy, safety and tolerance of ambrisentan, a high-selective endothelin receptor antagonist, in Chinese patients with pulmonary hypertension (PH). METHODS: Twenty-eight PH patients (Group 1+Group 4) came from Shanghai East Hospital, Zhongshan Hospital of Fudan University and Fifth People's Hospital of Shanghai were recruited into this open-label, prospective multi-center trial between August 2012 and February 2013. They received 2.5-5.0 mg ambrisentan once daily for 12 weeks. The primary endpoint was the change in exercise capacity showed by six-minute walk distance (6MWD) from baseline to 12 weeks. Secondary endpoints included the changes in World Health Organization (WHO) function class, N-terminal brain natriuretic peptide (NT-proBNP) and liver function test results. RESULTS: There were 9 males and 19 females with an average age of (35 ± 17) years. The value of 6MWD increased from (372 ± 86) m at baseline to (443 ± 96) m (P = 0.000) after 12 weeks. WHO functional class improved after a 12-week therapy compared to the baseline level (P = 0.000). NT-proBNP decreased from a median of 732 ng/L at baseline to 329 ng/L after 12 weeks (P = 0.046). The baseline liver function test was normal. And liver function test didn't significantly change after a 12-week therapy. CONCLUSION: Ambrisentan therapy is well-tolerated and it improves the exercise capacity and WHO function class in Chinese PH patients.

A Study of the Efficacy and Safety of Aerobic Exercise Training in Pulmonary Arterial Hypertension (the Saturday Study): Protocol for a Prospective, Randomized, and Controlled Trial.

Background: Patients with pulmonary arterial hypertension (PAH) have reduced exercise capacity and poor quality of life. Exercise-based rehabilitation in PAH results in clinically relevant improvements in exercise capacity and hemodynamics. To clarify the mechanism, we will evaluate the effect of aerobic exercise training rehabilitation on right ventricular (RV) remodeling and function as determined measured by cardiac magnetic resonance imaging (CMR). Methods: We will conduct a 26-week multicenter randomized controlled trial. Patients on stable and unchanged PAH-targeted medication are randomly assigned (1:1) to the control and training groups. The primary endpoint is the RV stroke volume (RVSV) change from baseline to Week 26, determined by CMR. Comprehensive RV function is also performed using CMR. Other characteristics of the RV and left ventricle, World Health Organization functional class, 6-min walk distance, and N-terminal pro-B-type natriuretic peptide are included in secondary endpoints. We also investigate the proteomic, metabolomic, and transcriptomic changes after exercise training as exploratory endpoints. Ethics and Dissemination: The study and protocol were approved by the Ethics Committee of Shanghai Pulmonary Hospital (Approved No. of ethics committee: L20-17). The results will be disseminated at medical conferences and in journal publications. All participants will sign written informed consent. Trial Registration Number: ChiCTR2000031650.

[Clinical characteristics and survival of patients with pulmonary veno-occlusive disease].

OBJECTIVE: To investigate the clinical presentation, diagnosis, treatment and outcome of patients with pulmonary veno-occlusive disease (PVOD). METHODS: Data from patients diagnosed as PVOD from May 2008 to May 2011 in Shanghai Pulmonary Hospital, Tongji University were retrospectively reviewed. RESULTS: During this period, 5 patients [4 female, aged from 12 to 42 (22 ± 12) years old] were diagnosed as PVOD. The durations from symptoms onset to PVOD diagnosis was 2 to 50 (16 ± 20) months and four of them were previously diagnosed as idiopathic pulmonary arterial hypertension. All patients at the time of PVOD diagnosis had a severely impaired WHO pulmonary hypertension functional class (3 in class III and 2 in class IV). Furthermore, all patients characterized by a typical sign of centrilobular ground-glass opacities in high-resolution computed tomography, a markedly reduction of diffusing capacity of the lung for carbon monoxide [(38 ± 12)% of predicted value] in pulmonary functional test and severely compromised cardio-pulmonary hemodynamics identified by right heart catheterization. All patients received conventional and pulmonary arterial hypertension specific therapies, and then followed-up regularly. Up to now, 4 out of 5 patients died due to refractory right heart failure. The durations from symptoms onset to death and from PVOD establish to death were 5 - 65 (27 ± 26) months and 1 - 16 (9 ± 9) months, respectively. CONCLUSIONS: PVOD is a rare and malignant cardio-pulmonary disorder that often be misdiagnosed as idiopathic pulmonary arterial hypertension. Given the poor responses to modern pulmonary arterial hypertension specific therapies, lung transplantation remains the treatment of choice.

Serum high-density lipoprotein cholesterol levels as a prognostic indicator in patients with idiopathic pulmonary arterial hypertension.

High-density lipoprotein (HDL) cholesterol levels are a strong, independent inverse predictor of cardiovascular disease. The present study aimed to determine whether serum HDL cholesterol levels correlated with disease severity and clinical outcomes in patients with idiopathic pulmonary arterial hypertension (IPAH). The serum HDL cholesterol levels were measured in 76 Chinese patients with IPAH and 45 healthy controls, together with other clinical variables. Univariate and multivariate Cox proportional hazards analysis was performed to assess the prognostic value of HDL cholesterol and event-free survival. Event-free survival was estimated using the Kaplan-Meier method. Serum HDL cholesterol levels were significantly decreased in patients with IPAH compared with controls (1.0 ± 0.3 vs 1.5 ± 0.3 mmol/L; p <0.001). The serum HDL cholesterol levels decreased in proportion to the severity of World Health Organization functional class. Compared to the high HDL cholesterol group, the low HDL cholesterol group demonstrated a significantly lower 6-minute walking distance, cardiac index, mixed venous saturation, and arterial carbon dioxide pressure but significantly greater pulmonary vascular resistance and serum uric acid levels. The serum HDL cholesterol levels correlated positively with the cardiac index (r = 0.42; p = 0.002) and negatively with the pulmonary vascular resistance (r = -0.25; p = 0.04). Serum HDL cholesterol was independently related to event-free survival on multivariate Cox proportional hazards analysis. Kaplan-Meier survival curves according to the median HDL cholesterol value showed that lower HDL cholesterol levels were associated with lower event-free survival. In conclusion, serum HDL cholesterol levels might serve as an indicator of disease severity and prognosis in patients with IPAH.