Oral sildenafil treatment for Eisenmenger syndrome: a prospective, open-label, multicentre study.

BACKGROUND: Although sildenafil has been shown to be safe and effective in idiopathic pulmonary arterial hypertension (PAH) and PAH related to connective tissue disease, its effects in Eisenmenger syndrome are less clear. OBJECTIVE: To investigate whether long-term treatment (12 months) with the phosphodiesterase type 5 inhibitor sildenafil improves clinical and haemodynamic parameters in patients with Eisenmenger syndrome. DESIGN: Prospective, open-label, multicentre study. SETTING: Four pulmonary hypertension centres in China. PATIENTS: 84 Eisenmenger syndrome functional class II-IV patients. INTERVENTIONS: Oral sildenafil 20 mg orally three times a day. OUTCOME MEASURES: 6-min walk distance (6MWD) test, resting systemic arterial blood oxygen saturation (SaO(2)) in room air, haemodynamic parameters assessed by right heart catheterisation, safety and tolerability. RESULTS: The overall treatment effects at 12 months versus baseline (mean changes with 95% CIs) were 56 m increase (42 to 69, p<0.0001) in 6MWD, and 2.4% increase (1.8% to 2.9%, p<0.0001) in resting room air SaO(2). Improvements were also seen in mean pulmonary arterial pressure and pulmonary vascular resistance index (-4.7 mm Hg (-7.5 to -1.9), p=0.001; and -474 dyn×s×cm(-5)×m(2) (-634 to -314), p<0.0001, respectively). Sildenafil was well tolerated. Most adverse events were mild and transient, and occurred in the first 2 weeks of treatment. CONCLUSIONS: Twelve months of oral sildenafil treatment was well tolerated and appeared to improve exercise capacity, systemic arterial oxygen saturation and haemodynamic parameters in patients with Eisenmenger syndrome.

[The efficacy and safety of bosentan therapy for Chinese patients with idiopathic pulmonary arterial hypertension: an open-label, prospective multicenter study].

OBJECTIVE: To investigate the efficacy, safety and tolerance of bosentan, a dual endothelin receptor antagonist, in Chinese patients with idiopathic pulmonary arterial hypertension (IPAH). METHODS: Totally 79 IPAH patients (hemodynamic criteria confirmed by right heart catheterization) were included in this open-label, prospective multicenter study. Patients received 62.5 mg of bosentan twice daily for the first 4 weeks, and then up-titrated to 125 mg twice daily for another 12 weeks. The primary end point was the change in exercise capacity showed by six-minute walk distance (6MWD) from baseline to 16 weeks. Secondary end points included the change in World Health Organization (WHO) functional class, Borg dyspnoea scale and systolic pulmonary artery pressure measured by echocardiography. RESULTS: The 6MWD increased from (343.7 ± 93.7) meters at baseline to (397.5 ± 104.4) meters after 16 weeks (P < 0.01), WHO functional class and Borg dyspnoea scale were also significantly improved after 16 weeks therapy compared to baseline levels (all P < 0.01). Furthermore, the systolic pulmonary artery pressure was significantly decreased from (97.8 ± 25.2) mm Hg (1 mm Hg = 0.133 kPa) to (92.8 ± 29.5) mm Hg (P < 0.05) after 16 weeks bosentan treatment. There was no patient withdrawal from this study for safety consideration. CONCLUSION: Bosentan therapy is well tolerated and can improve the exercise capacity and WHO functional class in Chinese IPAH patients.

Survival of Chinese patients with pulmonary arterial hypertension in the modern treatment era.

BACKGROUND: In a previous study of Chinese patients with idiopathic pulmonary arterial hypertension (IPAH) in the nontargeted therapy era (defined as the time before 2006 when new pulmonary arterial hypertension-specific drugs were not available in China), we reported 1- and 3-year survival estimates of only 68% and 39%, respectively. However, it is not yet known whether the survival of patients with pulmonary arterial hypertension is improved in the modern treatment era (defined in China as after 2006). METHODS: A retrospective cohort study was undertaken in 276 consecutive patients with newly diagnosed incident IPAH and connective tissue disease-related pulmonary arterial hypertension (CTDPAH) who were referred between 2007 and 2009. Baseline characteristics and survival rates in the two groups were compared. RESULTS: The 1- and 3-year survival estimates were 92.1% and 75.1%, respectively, in patients with IPAH, and 85.4% and 53.6%, respectively, in patients with CTDPAH. Patients with CTDPAH had a significantly lower mean pulmonary artery pressure, more pericardial effusion, and more severe impairment of the diffusion capacity of the lung for carbon monoxide than patients with IPAH. A diagnosis of CTDPAH, World Health Organization functional class III or IV, single-breath diffusion capacity of the lung for carbon monoxide < 80% predicted, and the presence of pericardial effusion were independent predictors of mortality. The 1- and 3-year survival rates of male patients were 93.5% and 77.5%, respectively, in those with IPAH, and 71.1% and 47.4%, respectively, in those with CTDPAH. CONCLUSIONS: The survival rates of patients with pulmonary arterial hypertension have improved in China in the modern treatment era, despite the high costs of treatment and financial constraints. However, the survival rates of patients with CTDPAH are inferior to those of patients with IPAH. Our study also indicates poorer survival rates in male patients with CTDPAH.

[Diagnosis value of electrocardiogram in patients with pulmonary artery hypertension].

OBJECTIVES: To analyze the diagnostic value of electrocardiogram (ECG) in patients with pulmonary artery hypertension (PAH) confirmed by right-heart catheterization (RHC). METHODS: A total of 64 patients with suspected PAH [sPAP > or = 36 mm Hg (1 mm Hg = 0.133 kPa) estimated by echocardiography] were enrolled in this study. All patients were examined by 12-lead ECG within half an hour before RHC. RESULTS: PAH was excluded in 26 patients and confirmed in 38 patients. ECG analysis showed that S amplitude > 0.21 mV in lead I, QRS axis > 87 degrees , R(V1) + S(V5) > 0.76 mV were good parameters for diagnosing PAH with sensibility and specificity of 89%, 81%; 86%, 92%; 84%, 83%, respectively. QRS axis was positively correlated with mean pulmonary artery pressure (mPAP) (r = 0.75, P < 0.001), R(V1) + S(V5) was positively correlated with pulmonary vascular resistance (PVR) (r = 0.74, P < 0.001), R(V1) + S(V5) and S amplitude in lead I was negatively correlated with cardiac index (CI) (r = -0.62, P < 0.001). CONCLUSION: ECG combined with echocardiography are adequate screening tools to rule out the presence of PAH. QRS axis, R(V1) + S(V5) and S amplitude in lead I were significantly correlated with hemodynamic parameters derived from RHC in PAH patients.

[Clinical efficacy of intravenous L-carnitine in patients with right-sided heart failure induced by pulmonary arterial hypertension].

OBJECTIVE: To investigate the efficacy of L-carnitine in patients with right-sided heart failure induced by pulmonary arterial hypertension (PAH). METHODS: A total of 66 pulmonary arterial hypertension patients (14 idiopathic, 36 congenital heart disease associated and 16 connective-tissue disease associated PAH, WHO heart functional class III, n = 38 or IV, n = 28) were enrolled in this study and divided into control group (26 cases) and L-carnitine group (40 cases). All patients received conventional treatment according to guideline for treatment of right-sided heart failure. The patients in L-carnitine group received 5 g/d L-carnitine intravenously for seven days. Six-minute walking distance, WHO heart functional class, physical examination, and serum markers were evaluated at baseline and 7 days after enrollment. RESULTS: Compared to the baseline, six-minute walking distance was significantly increased (75 m vs. 45 m, P < 0.05), WHO heart functional class significantly improved (improved 2 classes in 16 patients, improved 1 class in 13, no improved in 6, worsen in 5 vs. 3, 8, 9, 6 respectively in the control, P = 0.04), BNP level significant decreased (58.16 ng/L vs. 33.29 ng/L, P = 0.01) and systolic blood pressure significantly increased [8.1 mm Hg vs. 2.4 mm Hg (1 mm Hg = 0.133 kPa), P = 0.03] in L-carnitine group compared with those in control group. No patient was withdrawn from this study for safety reasons. CONCLUSIONS: L-carnitine could improve short-term exercise capacity and WHO heart functional class in right-sided heart failure patients induced by PAH.