Zhi-Hui Zhao

Long-term effects of continuous positive airway pressure on blood pressure and prognosis in hypertensive patients with coronary heart disease and obstructive sleep apnea: a randomized controlled trial.

BACKGROUND Obstructive sleep apnea (OSA) can result in hypertension and significantly increase cardiovascular morbidity and mortality. There are few reports on the long-term effects of continuous positive airway pressure (CPAP) on blood pressure in patients with uncontrolled hypertension with coronary heart disease (CHD) and OSA. METHODS We conducted a prospective, long-term follow-up study in 83 patients with uncontrolled hypertension, CHD, and OSA randomized to control or CPAP groups. Daytime systolic blood pressure (SBP), diastolic blood pressure (DBP), and severe cardiovascular and cerebrovascular events (SCCEs) were recorded at baseline and follow-up. RESULTS Seventy-three patients completed the study with a median follow-up of 36 (interquartile range = 24-54) months. The 2 groups had similar characteristics at baseline. CPAP was used for 4.5±1.1 hour/night. SBP in the CPAP group was significantly reduced at follow-up (143±7 mm Hg vs. 139±7 mm Hg, P = 0.04), and SBP decreased by 8mm Hg (95% confidence interval = 1.4-9.9; P = 0.01). Hypertension control was improved (CPAP, 69.4% for CPAP users vs. 43.2% for control subjects; P = 0.02); however, DBP did not reach statistical difference between the groups (81±10 mm Hg vs. 79±8 mm Hg; P = 0.49). In the CPAP group, the Epworth Sleepiness Scale was markedly reduced (7.0±3.4 vs. 3.7±2.3; P < 0.001). There was 1 SCCE in the CPAP group (heart failure), and 5 SCCEs in the control group (acute myocardial infarction: 2 (with 1 death); stroke: 3), but there was no significant difference identified. CONCLUSIONS Long-term CPAP application in uncontrolled hypertension with CHD and OSA significantly reduced daytime SBP, improved hypertension control and daytime sleepiness, and decreased the trend in SCCEs compared with control subjects. CLINICAL TRIAL REGISTRATION NUMBER ClinicalTrials.gov NCT02059993.

Impact of untreated sleep apnea on prognosis of patients with congestive heart failure

128 congestive heart failure (CHF) patients with a median age of 55 years and median left ventricular ejection fraction of 35.4% were followed up for a median period of 35 months. 23 (18%) had no sleep apnea (CHF-N), 55 (43%) had obstructive sleep apnea (CHF-OSA), and 50 (39%) had central sleep apnea (CHF-CSA). At the end of follow-up, mortality was greater in the CHF-CSA group than in the CHF-N group (18.2 vs 6.7/100 person-years, p=0.017). However, after adjusting age and the New York Heart Association functional class central sleep apnea, obstructive sleep apnea, or the severity of sleep apnea are not predictors for survival in CHF. In addition, the percentages of combined events were not significantly different among three groups. Untreated sleep apnea has no independent impact on the prognosis of patients with CHF.

Plasma Soluble ST2 Levels Correlate With Disease Severity and Predict Clinical Worsening in Patients With Pulmonary Arterial Hypertension

Soluble suppression of tumorigenicity (sST2) has been proposed to be a marker for biomechanical strain and a possible predictor of mortality in patients with chronic heart failure. The use of sST2 in pulmonary arterial hypertension (PAH) has not been well defined.

The efficacy and safety of sildenafil in patients with pulmonary arterial hypertension associated with the different types of congenital heart disease.

The difference in underlying pathophysiology in different congenital heart disease (CHD) may have an influence on clinical outcome. It remains unclear whether the effect of sildenafil on pulmonary arterial hypertension (PAH) varies in different types of CHD.

The Ratio of 18F-FDG Activity Uptake Between the Right and Left Ventricle in Patients With Pulmonary Hypertension Correlates With the Right Ventricular Function

Purpose It is known that patients with pulmonary hypertension (PH) can have elevated 18F-FDG uptake in the right ventricle (RV) on PET imaging. This study was designed to assess possible relationship between FDG uptake of ventricles and the function/hemodynamics of the RV in patients with PH. Patients and Methods Thirty-eight patients with PH underwent FDG PET imaging in both fasting and glucose-loading conditions. The standard uptake value (SUVs) corrected for partial volume effect in both RV and left ventricle (LV) were measured. The ratio of FDG uptake between RV to LV (SUVR/L) was calculated. Right heart catheterization and cardiac magnetic resonance (CMR) were performed in all patients within 1 week. The FDG uptake levels by the ventricles were compared with the result form the right heart catheterization and CMR. Results The SUV of RV (SUVR) and SUV of LV were significantly higher in glucose-loading condition than in fasting condition. In both fasting and glucose-loading conditions, SUVR and SUVR/L showed reverse correlation with right ventricular ejection fraction derived from CMR. In addition, in both fasting and glucose-loading conditions, SUVR and SUVR/L showed positive correlations with pulmonary vascular resistance. However, only SUVR/L in glucose-loading condition could independently predict right ventricular ejection fraction after adjusted for age, body mass index, sex, mean right atrial pressure, mean pulmonary arterial pressure, and pulmonary vascular resistance (P = 0.048). Conclusions The FDG uptake of RV increases with decreased right ventricular function in patients with PH. Increased FDG uptake ratio between RV and LV might be useful to assess the right ventricular function.

Impact of sildenafil on survival of patients with Eisenmenger syndrome.

The favorable effects of short‐term use of sildenafil on patients with Eisenmenger syndrome have been reported. We further studied the impact of long‐term use of sildenafil on survival of these patients. In this study, the baseline data of patients newly diagnosed as Eisenmenger syndrome in our hospital between January 2005 and December 2009 were retrospectively collected. Patients were followed‐up either by telephone contacts or during visits in our out‐patient clinic. A total of 121 patients (68 patients in conventional group and 53 patients in sildenafil group) were finally included and 29 patients were re‐evaluated after sildenafil therapy for 3–4 months. Compared with the baseline, a 6‐minute walk distance, functional classes, plasma hemoglobin level, and hemodynamics were significantly improved after sildenafil treatment. During a median follow‐up period of 35.8 months, 15 patients died (11 patients in conventional group). The 1‐ and 3‐year survival rates in sildenafil group were 97.0% and 95.2%, significantly higher than 90.6% and 82.9% in conventional group P = .025). Multivariate analysis showed that sildenafil therapy, functional class and mean pulmonary arterial pressure were independently associated with survival. Therefore, long‐term sildenafil therapy improved survival in patients with Eisenmenger syndrome.

Increased levels of plasma CXC-Chemokine Ligand 10, 12 and 16 are associated with right ventricular function in patients with idiopathic pulmonary arterial hypertension.

OBJECTIVE To investigate plasma levels of CXC-Chemokine Ligand 10 (CXCL10), CXC-Chemokine Ligand 12 (CXCL12) and CXC-Chemokine Ligand 16 (CXCL16) in patients with idiopathic pulmonary arterial hypertension (IPAH). METHODS Plasma levels of biomarkers were measured by enzyme-linked immunosorbent assay in 61 patients with IPAH and 20 healthy volunteers. RESULTS Plasma CXCL10, CXCL12 and CXCL16 concentrations were increased significantly in IPAH patients compared with controls, and significantly correlated with N-terminal pro-brain natriuretic peptide, tricuspid annulus plane systolic excursion and right ventricular ejection fraction. CONCLUSIONS Increased levels of CXCL10, CXCL12 and CXCL16 are associated with right ventricular dysfunction in patients with IPAH.

Red cell distribution width predicts chronic thromboembolic pulmonary hypertension in patients with acute pulmonary embolism in a long-term follow-up.

Chronic thromboembolic pulmonary hypertension (CTEPH) is defined as mean pulmonary arterial pressure > 25 mm Hg that persists 6 months after pulmonary embolism (PE) is diagnosed [1]. It occurs in 1%–4% of patients after acute PE [2, 3] and in up to 10% of those with a history of recurrent PE [4]. CTEPH represents a serious predicament that leads to progressive right ventricular dysfunction and death. However, previous studies have demonstrated that the likelihood of developing CTEPH diminishes with more intense treatment of acute PE [5]. Hence, a rapid and reliable predictor of CTEPH might help physicians in the early detection of patients requiring closer monitoring and possibly benefiting from more effective treatment. Red blood cell distribution width (RDW), an index of heterogeneity of erythrocytes, is routinely reported as part of the complete blood count. It has been reported in studies that elevated RDW on admission is an independent predictor of short-term mortality in acute PE [6]. However, the prognostic role of RDW for long-term outcomes in patients with acute PE has not been investigated. We, therefore, explored in this study whether RDW is useful to predict CTEPH in a Chinese cohort with acute PE. A total of 214 consecutive adult patients with symptomatic acute PE that were admitted to the Center for Pulmonary Vascular Disease of Fuwai Hospital, a tertiary teaching hospital in Beijing, China from January 2009 through December 2012 were analyzed in this study. The symptomatic acute PE confirmed by objective examination was included, and the exclusion criteria were any of the following: 1) a prior documented episode of PE or deep venous thrombosis (DVT); 2) a life expectancy of < 6 months; 3) recent blood transfusion history (within 3 months before admission); 4) patients receiving hemodialysis. Data collection included demographic information, medical history, baseline clinical characteristics, laboratory data, treatment received, and clinical outcomes. The study was approved by the Institutional Review Board of Fuwai Hospital and written informed consent was obtained from all patients. The diagnosis was made using a standard protocol as we reported previously [7]. The provoked PE patients were defined as those with trigger factors including active cancer, prolonged immobilization, chronic heart or respiratory failure, recent trauma, surgical intervention, pregnancy, and the use of oral contraceptives or hormone replacement therapy. All other patients were classified as unprovoked PE. Anticoagulation with unfractioned heparin or low molecular weight heparin was initiated without delay aQunying Xi and Yong Wang contributed equally to this work. *Corresponding author: Prof. Zhihong Liu, Center for Pulmonary Vascular Diseases, Fuwai Hospital and Cardiovascular Institute, 167 Beilishi Road, Beijing 100037, P.R. China, Phone: +86 010 88396589, Fax: +86 010 88396589, E-mail: fuwaipumc@163.com Qunying Xi: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China; and Center for Pulmonary Vascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China Yong Wang, Zhihui Zhao and Qin Luo: Center for Pulmonary Vascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China

Platelet Distribution Width and Mean Platelet Volume in Idiopathic Pulmonary Arterial Hypertension

BACKGROUND Previous studies have demonstrated that platelet activation occurs in patients with pulmonary arterial hypertension (PAH). Mean platelet volume (MPV) and platelet distribution width (PDW) are two markers of platelet activation, and have recently been recognised as risk predictors of cardiovascular diseases. This study aimed to investigate whether MPV and PDW would be useful to reflect disease severity and predict prognosis in idiopathic PAH (IPAH). METHODS MPV and PDW levels were measured in 82 IPAH patients without antiplatelet or anticoagulant treatment on admission and 82 healthy controls. Concurrent collected data included clinical, haemodynamic and biochemical variables. All patients were followed-up from the date of blood testing. The endpoint was all-cause mortality. RESULTS MPV and PDW were significantly higher in patients with IPAH than in age and sex-matched control subjects (11.4±0.9fl vs. 10.3±0.9fL and 14.3±2.9% vs. 11.9±1.9%, respectively; p=0.000). Pearsons correlation analysis revealed that MPV and PDW correlated positively with right ventricular systolic pressure, mean pulmonary arterial pressure and pulmonary vascular resistance. After a mean follow-up of 14±8 months, 12 patients died of right heart failure. Receiver operating characteristic analysis showed that MPV and PDW could not predict all-cause mortality. Multivariate Cox regression analysis suggested that right/left ventricular end-diastolic diameter ratio and NT-proBNP were independent predictive parameters of all-cause mortality. CONCLUSIONS Our results suggest that MPV and PDW were elevated in patients with IPAH. They could partly reflect disease severity, but did not predict prognosis.

Oral Sildenafil Therapy for Chinese Patients With Pulmonary Arterial Hypertension: A Multicenter Study

The impact of sildenafil on pulmonary arterial hypertension (PAH) in Chinese patients has been less investigated. A prospective, open‐label, uncontrolled and multicenter study, therefore, was carried out to address this issue. Ninety patients with multicause‐induced PAH received oral sildenafil (75 mg/day) for 12 weeks. The 6‐minute walk test (SMWT) and cardiac catheterization were performed at the beginning and the end of the 12 weeks. The primary endpoint was the changes in exercise capacity assessed by the SMWT; the secondary endpoint included assessment of functional class, evaluation of cardiopulmonary hemodynamics, and clinical worsening. Drug safety and tolerability were also examined. The results showed that there was a significant improvement in SMWT distances (342 ± 93 m vs 403 ± 88 m, P < .0001), Borg dyspnea score (2.9 ± 2.6 vs 2.4 ± 2.0, P = .0046), World Health Organization functional class, and cardiopulmonary hemodynamics (mean pulmonary artery pressure, P < .0001; cardiac index, P < .0001; pulmonary vascular resistance, P < .0001) after 12 weeks of oral sidenafil therapy. Almost all enrolled patients did not experience significant clinical worsening. This study confirms and extends the findings of previous studies relating to effects of sildenafil on PAH, suggesting that oral sildenafil is safe and effective for the treatment of adult patients with PAH in the Chinese population.