Targeted Drug Treatment And Prognosis Of Pulmonary Hypertension

Part I:Inhaled Low-dose Iloprost for Pulmonary Hypertension:A Prospective, Multicenter, and Open-label StudyObjective:Inhaled iloprost (average>30μg/d) has been considered an effective treatment for severe pulmonary hypertension. Further evidence also showed that low-dose iloprost given intravenously was equal effective as high-dose iloprost in the therapy of systemic sclerosis. Patients with pulmonary hypertension will benefit from inhalation of low-dose iloprost.Method:Sixty-two patients with pulmonary hypertension (24patients with idiopathic pulmonary arterial hypertension,31patients with associated pulmonary arterial hypertension and7patients with chronic thromboembolic pulmonary hypertension) were enrolled and initiated with neubulized low-dose iloprost (2.5μg per inhalation,6times daily) for24-week in13medical centers in China. Efficacy endpoints included changes of6-minute walking distance (6MWD), World Health Organization functional class (WHO-FC) and hemodynamic parameters.Result:Fourteen patients (22.6%) prematurely discontinued the study:8patients due to clinical worsening (six patients in WHO-FC III or IV at baseline),4patients because of protocol changed and2patients lost during follow-up. In remaining48patients,6MWD was increased from356±98m to414±99m (P<0.001) and WHO-FC improved significantly (P=0.006) after24-week inhalation therapy. Cardiac output, cardiac index and mixed venous oxygen saturation improved significantly compared with baseline (n=34, P<0.05). Most of hemodynamic parameters improved significantly in patients with WHO-FC II (P<0.05) but not in patients with WHO-FC III/IV.Conclusion:Low-dose iloprost inhalation significantly improved exercise capacity and functional status in patients with pulmonary hypertension. It was well tolerated. The improvement of hemodynamics was confirmed in patients with WHO-FC I/II but not in patients with WHO-FC Ⅲ/Ⅳ, suggesting the importance of early treatment in patients with advanced disease stages. Part Ⅱ:Impact of Sildenafil on Survival of Patients with Eisenmenger SyndromeObjective:The favorable effects of short-term use of sidenafil on patients with Eisenmenger syndrome have been reported. Furthermore, pulmonary arterial hypertension targeted therapy on the long-term survival benefit in patients with Eisenmenger syndrome has been demonstrated in an observational cohort study. However, it remains unknown that wether the long-term sildenafil treatment would benefit the survival of patients with Eisenmenger syndrome. We further studied the impact of sildenafil on survival of these patients.Method:Baseline data on all Eisenmenger patients who newly diagnosed in our hospital between January2005and December2009were retrospectively collected. Patients were followed-up either by telephone contact or during visit in out-patient clinic. Survival rates between patients treated with sildenafil and with conventional therapy were compared using a log-rank test. Multivariate Cox model was used to analyze the variables independently associated with survival.Result:A total of121patients (mean aged30±10years;71.9%female) were included finally. The majority of patients (n=75,62.0%) had a simple post-tricuspid shunt, followed by patients with simple pre-tricuspid shunts (n=34,28.1%), and with combined shunts (n=10,8.3%) as well as complex abnormality (n=2,1.7%). There were4(3.3%),72(59.5%),42(36.4%), and1(0.8%) patients had been classified as WHO functional class Ⅰ,Ⅱ,Ⅲ and Ⅳ, respectively. The mean6MWD was379±71m and mean resting arterial oxygen saturation was86.1±7.3%. According to wether or not they received sildenafil treatment, patients were divided into the two groups:"conventional group"(n=53) and "sildenafil group"(n=68).29patients in sildenafil group were re-evaluated after sildenafil therapy for3-4months. Compared with the baseline,6-minute walk distance, World Health Organization functional class, plasma hemoglobin level and hemodynamics were improved significantly after sildenafil treatment. During a median follow-up period of35.8months,15patients died, including11patients in conventional group and4patients in sildenafil group (P=0.024). The1-and3-year survival rates in sildenafil group were97.0%and95.2%, significant higher than90.6%and82.9%in conventional group (P=0.025). Multivariate analysis showed that sildenafil therapy, functional class and mean pulmonary arterial pressure were independently associated with survival.Conclusion:The long-term sildenafil therapy improved survival in patients with Eisenmenger syndrome Part III:Impact of sildenafil on survival of patients with idiopathic pulmonary arterial hypertensionObjective:It has been reported that short-term sildenafil therapy is safe and effective for patients with pulmonary arterial hypertension. However, data regarding the impact of sildenafil on survival of patients with idiopathic pulmonary arterial hypertension remains limited. The aim of the current study was to investigate the survival benifit of chronic sildenafil treatment in patients with idiopathic pulmonary arterial hypertension.Method:The study was conducted on77patients with newly diagnosed idiopathic pulmonary arterial hypertension at Fu Wai Hospital between September2005and September2009. Patients were divided into2groups:the "sildenafil group"(n=51) and the "conventional group"(n=26). Nine patients treated with sildenafil were re-evaluated by right heart catheterization after3months.6-minute walk distance, World Health Organization (WHO) functional class and hemodynamic parameters were used to evaluate the short-term effect of sildenafil therapy. Survival curves were calculated by the Kaplan-Meier method and compared using a log-rank test. Multivariate Cox analyses were performed to identify variables related to survival.Result:Of the77patients enrolled,47patients (61%) were female. The mean age was32±11years. Ninety-two percent of patients were in WHO functional class Ⅱ/Ⅲ. Our data demonstrated that the6-minute walk distance significantly increased from314±55m to366±61m after sildenafil therapy for three months. WHO functional class, mixed venous oxygen saturation and hemodynamics significantly improved after3months of sildenafil therapy (P<0.05) at the same time. The baseline characteristics of the sildenafil group were similar to those of the conventional group. The1,2and3years survival rates in the sildenafil group were88%,72%, and68%, compared with61%,36%, and27%in the conventional group (P<0.001). The absence of sildenafil therapy (HR4.86, P<0.001), lower body mass index (HR0.41, P=0.001) and lower mixed venous oxygen saturation (HR0.68, P=0.003) were found to be independent predictors of mortality.Conclusion:Sildenafil therapy was found to be associated with improved survival in patients with idiopathic pulmonary arterial hypertension.