The clinical characteristics and long-term prognosis of pulmonary arterial hypertension associated with hereditary hemorrhagic telangiectasia.

Pulmonary arterial hypertension (PAH) is a severe complication of hereditary hemorrhagic telangiectasia (HHT); however, little is known about its clinical characteristics and prognosis. Nine newly diagnosed HHT-PAH patients were prospectively recruited between October 2007 and January 2016 and were followed up every half-year. Eighteen idiopathic pulmonary arterial hypertension (IPAH) patients, matched with HHT-PAH patients on mean pulmonary arterial pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, cardiac index, and World Health Organization (WHO) functional class (FC), were recruited. The clinical characteristics of HHT-PAH patients were described and the prognosis of these two cohorts were compared. Of HHT-PAH patients, 55.56% were WHO FC III. Kaplan-Meier survival analysis showed one- and three-year survival rates of HHT-PAH patients were 77.8% and 53.3% respectively, which were worse than matched IPAH patients (log rank: P = 0.047). HHT-PAH patients had higher red cell distribution width (14.88 ± 2.93% versus 13.19 ± 0.83%, P = 0.031), larger right ventricular anteroposterior diameter (34.67 ± 6.67 mm versus 28.56 ± 6.35 mm, P = 0.029), and lower mean corpuscular hemoglobin concentration (317.38 ± 17.71 g/L versus 335.72 ± 14.68 g/L, P = 0.011) than matched IPAH patients. Multivariate Cox proportional hazards regression analyses showed baseline total bilirubin independently predicted the mortality of HHT-PAH after adjusting by age, cardiac index, mixed venous oxygen saturation, or serum uric acid. HHT-PAH patients may have a worse prognosis than matched IPAH patients. Baseline total bilirubin may be a promising predictor for the long-term prognosis in HHT-PAH patients.

Prognostic Value of Pulmonary Artery Compliance in Patients with Pulmonary Arterial Hypertension Associated with Adult Congenital Heart Disease.

In congenital heart disease (CHD), the presence of pulmonary arterial hypertension (PAH) is associated with a poor prognosis. In this study, we aim to investigate the role of pulmonary artery compliance (Cp) in predicting the mortality of PAH associated with adult congenital heart disease (APAH-CHD). One-hundred and seventy-five patients of APAH-CHD who underwent a comprehensive clinical evaluation were included in this study. All patients were followed up in a 6-month interval and the primary end point was all cause of death. The duration of mean follow-up was 67±26 months, of which there were twenty-three death. Cp had an inverse correlation with pulmonary artery resistance (PVR), regardless of the clinical phenotype (Eisenmenger syndrome, PAH with small defect and PAH after defect correction). Patients in the lowest Cp group (Cp ≤ 0.84 mL/mmHg) had advanced WHO function class, worse exercise tolerance, liver function, and status of oxygen saturation. In univariate cox regression analysis, Cp (HR = 1.359, P < 0.001), PVR (HR = 0.972, P = 0.001), pulmonary blood flow (HR = 1.092, P = 0.001), heart rate (HR = 1.038, P = 0.028) and 6-minute walking distance (HR = 1.003, P = 0.037) were predictors of survival. After adjustment by bivariate analysis, Cp was the independent predictor. Kaplan-Meier survival curves showed that patients with Cp < 1.04 mL/mmHg had worse prognosis. In conclusion, Cp possibly reflects disease severity and decreased Cp was associated with poor prognosis in patients with APAH-CHD.

The Value of the Electrocardiogram for Evaluating Prognosis in Patients with Idiopathic Pulmonary Arterial Hypertension.

BACKGROUND: Association between electrocardiography (ECG) features and right ventricular anatomy and physiology has been established. This study is aimed to identify the value of 12-lead ECG in evaluating prognosis of patients with idiopathic pulmonary arterial hypertension (IPAH). METHOD: 194 patients with newly diagnosed IPAH were included in this study. Correlations between electrocardiography variables and hemodynamics were assessed. Univariate and multivariable cox regression analysis were performed to identify ECG variables for predicting all-cause mortality in IPAH. RESULTS: Partial correlation analysis showed that P wave amplitude in lead II correlated with the mean pulmonary arterial pressure (mPAP, r = 0.349, p ≤ 0.001) and cardiac index (CI, r = -0.224, p = 0.002); R wave amplitude in V1 correlated with mPAP (r = 0.359, p ≤ 0.001); S wave amplitude in V6 correlated with mPAP (r = 0.259, p = 0.030) and CI (r = -0.220, p = 0.003). P wave amplitude in lead II (HR 1.555, p = 0.033) and R wave amplitude in lead aVR (HR 5.058, p < 0.001) were the independent predictors of all-cause mortality. Kaplan-Meier survival curves showed patients with a p ≥ 0.25 mv in lead II, and R ≥ 0.4 mv in lead aVR had lower 3-year survival (55 vs. 91%, p < 0.001). CONCLUSION: Specific lead-12 ECG features could reflect right ventricular overload hemodynamics, and are useful to evaluate prognosis of patients with IPAH.

Prognostic value of right ventricular ejection/filling parameters in IPAH using cardiac magnetic resonance: A prospective pilot study.

BACKGROUND AND OBJECTIVE: The potential prognostic value of cardiovascular magnetic resonance (CMR)-derived right ventricular (RV) ejection/filling parameters in the assessment of RV function remains to be fully established. The goal of this study was to explore the prognostic value of these parameters in idiopathic pulmonary arterial hypertension (IPAH) patients. METHODS: In this prospective investigation, newly diagnosed IPAH patients without targeted therapy were recruited. Patients underwent right heart catheterization (RHC), 6-min walk test and CMR imaging within 1 week. Cardiopulmonary haemodynamics derived from RHC, and RV ejection/filling parameters derived from CMR were collected. RESULTS: A total of 41 IPAH patients were recruited with the median follow-up time of 824 days. During this period, 13 patients significantly deteriorated and among them, 7 patients died. CMR-derived RV peak ejection rate (PER) correlated significantly with CMR-derived RV stroke volume index (r = 0.574, P < 0.001) and RV cardiac index (r = 0.611, P < 0.001), but had no significant correlation with RV end diastolic volume index (EDVI, r = 0.201, P = 0.208) and pulmonary vascular resistance (r = -0.134, P = 0.403). Multivariate Cox regression analysis showed that RV time to PER (TPER, hazard ratio (HR) = 1.010, 95% CI: 1.003-1.017, P = 0.005) and RV TPER/time of a cardiac cycle (TPER/TCC, HR = 1.085, 95% CI: 1.031-1.141, P = 0.002) were predictors of clinical deterioration after adjusting for N-terminal pro-brain natriuretic peptide (NT-proBNP) and RV EDVI. Kaplan-Meier survival analyses showed that patients with RV TPER ≥ 199.01 ms (log rank: P = 0.036) or RV TPER/TCC ≥ 20.02% (log rank: P = 0.007) had worse prognosis. CONCLUSION: CMR-derived RV TPER and TPER/TCC can reflect RV early systolic function, and may be promising predictors for long-term prognosis in IPAH patients.

Pulmonary Vascular Capacitance is Associated with Vasoreactivity and Long-Term Response to Calcium Channel Blockers in Idiopathic Pulmonary Arterial Hypertension.

PURPOSE: This study aimed to identify the relationship between pulmonary vascular capacitance (PVC) and vasoreactivity in patients with idiopathic pulmonary arterial hypertension (IPAH), and the value of PVC in predicting long-term response to CCB treatment. METHODS: Pulmonary vasodilator testing with inhaling iloprost was performed in 308 newly diagnosed IPAH patients. Acute vasodilator-responsive patients accepted CCBs treatment. Patients who benefit from long-term CCB were defined as those being in World Health Organization (WHO) functional class II or I after at least 1 year on CCB monotherapy. RESULTS: PVC had significant correlations with WHO function class, 6-min walk distance, mean pulmonary arterial pressure, and pulmonary vascular resistance (r = -0.363, p < 0.001; r = 0.333, p < 0.001; r = -0.514, p < 0.001; r = -0.739, p < 0.001). Thirty-five acute vasodilator-responsive IPAH patients (11.4 %) displayed less severe disease and a higher baseline PVC (1.5 ± 0.6 vs. 1.1 ± 0.7 ml/mmHg, p = 0.003). During acute vasodilator testing, PVC increased significantly by mean of 79 ± 48 % and reached to a higher absolute value of 2.6 ± 1.5 ml/mmHg compared with non-responsive patients (1.4 ± 1.5 ml/mmHg, p < 0.001). Furthermore, PVC increased more during acute vasodilator testing in the 24 patients who benefit from long-term CCB treatment (1.4 ± 1.3 vs. 0.5 ± 0.4 ml/mmHg, p = 0.004). The OR of increased PVC during vasodilator testing for predicting patients with long-term response to CCB was 1.24 (95 % CI 1.02-1.50, p = 0.031) as assessed by multivariable logistic regression analysis. CONCLUSIONS: PVC was higher in acute vasodilator-responsive IPAH patients and may be a predictor of long-term response to CCBs therapy.

The Prognostic Value of 18F-FDG Uptake Ratio Between the Right and Left Ventricles in Idiopathic Pulmonary Arterial Hypertension.

PURPOSE: Metabolic changes occur in the right ventricle (RV) under increased afterload in pulmonary arterial hypertension. FDG PET imaging has potential to assess RV function. In this study, we aimed to determine the prognostic value of metabolic changes of RV using FDG PET imaging in idiopathic pulmonary arterial hypertension (IPAH). PATIENTS AND METHODS: In this prospective investigation, patients newly diagnosed with IPAH were recruited. Patients underwent right heart catheterization, FDG PET imaging, and cardiac MR (CMR) within 1 week. Right ventricle hemodynamics, glucose metabolism derived from the FDG uptake levels, and functional parameters were obtained. The FDG uptake ratio between the RV and the left ventricle (LV) and its relation with the patients' survival were analyzed. RESULTS: A total of 45 IPAH patients were enrolled in this study, which included 13 male (28.9%) and 32 female (71.1%). The median follow-up time of this study was 1043 days. At the end of the follow-up, 36 patients survived, whereas 9 patients were deceased because of right heart failure. Multivariate Cox proportional hazard analysis showed that the ratio between the corrected RV and LV FDG uptake (cRV/LV) in both glucose-loading (cRV/LVg) and fasting (cRV/LVf) conditions independently predicted the mortality after adjusting for pulmonary vascular resistance index, mean right atrial pressure, and World Health Organization functional class. Kaplan-Meier survival analysis showed that patients with cRV/LVf greater than 143.65% in fasting condition (log rank, P = 0.030) or cRV/LVg greater than 120.55% in glucose-loading condition (log rank, P = 0.014) had worse prognosis. CONCLUSIONS: The FDG uptake ratio between the RV and LV can be an independent predictor for long-term prognosis of IPAH patients.

High levels of serum lactate dehydrogenase correlate with the severity and mortality of idiopathic pulmonary arterial hypertension.

Liver dysfunction reflects the status of heart failure, and previous studies have demonstrated that serum lactate dehydrogenase (S-LDH) levels are increased in patients exhibiting heart failure and liver dysfunction. Right heart failure is a main characteristic of idiopathic pulmonary arterial hypertension (IPAH). The aim of the present study was to assess the prognostic significance of S-LDH levels in patients with IPAH. S-LDH levels were determined in 173 patients with IPAH, and these patients were subclassified into two groups according to a defined upper reference limit of S-LDH (250 IU/l). Right heart catheterization was performed in all patients. A total of 53 patients were found to have elevated S-LDH to ≥250 IU/l. In a mean follow-up period of 31.2±17.9 months, 57 patients succumbed. In the group with lower S-LDH levels (S-LDH <250 IU/l), 16.7% of the patients succumbed, compared with 69.8% of patients in the group with higher S-LDH levels (S-LDH ≥250 IU/l). The Kaplan-Meier survival curves demonstrated that patients with higher S-LDH levels had a significantly lower survival rate than did those with lower S-LDH levels (log-rank test, P<0.001). Cox proportional hazard analyses identified reduced body mass index, reduced cardiac index, elevated World Health Organization functional class, higher S-LDH and an absence of PAH-targeted therapy as significant predictors of adverse outcomes. In conclusion, elevated S-LDH is a risk factor for mortality in patients with IPAH.

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). Pearson's 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.

Plasma soluble ST2 levels correlate with disease severity and predict clinical worsening in patients with pulmonary arterial hypertension.

BACKGROUND: 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. HYPOTHESIS: Plasma sST2 levels may correlate with the disease severity and predict clinical worsening in PAH. METHODS: We performed a cohort study of 40 idiopathic PAH patients with data on demographics, exercise capacity, echocardiographic parameters, laboratory tests, hemodynamics, and medications. Plasma sST2 was assessed with the high-sensitivity ST2 ELISA kit at diagnostic catheterization. All patients were followed up from the date of blood sampling. The endpoint was clinical worsening. RESULTS: sST2 was significantly elevated in patients with idiopathic PAH compared with control subjects (28.9 ± 13.9 vs 20.7 ± 7.5 ng/mL, P = 0.003). Pearson correlation analysis revealed that sST2 levels correlated with cardiac index (r = -0.534, P = 0.000) and pulmonary vascular resistance (r = 0.350, P = 0.027), and could reflect disease severity of PAH. After a mean follow-up of 14 ± 5 months, 12 patients showed clinical worsening. Receiver operating characteristic analysis suggested that sST2 levels >31.4 ng/mL discriminated clinical worsening with a sensitivity and specificity of 83.3% and 78.6%, respectively. Kaplan-Meier analysis showed that higher sST2 levels (>31.4 ng/mL) were associated with poor clinical outcomes (P = 0.008). Multivariate Cox regression analysis showed that sST2 was an independent predictor of clinical worsening (hazard ratio: 6.067, 95% confidence interval: 1.317-27.948, P = 0.021). CONCLUSIONS: sST2 correlates with disease severity and is a significant predictor of clinical worsening in patients with PAH.

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.

Elevated plasma YKL-40 as a prognostic indicator in patients with idiopathic pulmonary arterial hypertension.

BACKGROUND AND OBJECTIVE: Pulmonary vascular remodelling and inflammation have been implicated in pulmonary arterial hypertension (PAH). YKL-40, a marker of tissue remodelling and inflammation, has recently been recognized as a risk predictor of cardiovascular and inflammatory diseases. The study aimed to investigate a potential role of YKL-40 in predicting prognosis in idiopathic PAH (IPAH). METHODS: Plasma YKL-40 levels were measured in 82 IPAH patients without current or previous PAH-specific treatment during right heart catheterization and in 54 healthy volunteers. Concurrent data included clinical, haemodynamic and biochemical variables. RESULTS: Plasma YKL-40 levels were increased in IPAH patients compared with control subjects (median, interquartile range: IPAH: 24.90, 17.68-39.78 ng/mL; controls: 16.58, 14.20-19.64 ng/mL; P < 0.001). YKL-40 levels correlated with cardiac index (r = -0.244, P = 0.027) and N-terminal pro-brain natriuretic peptide (NT-proBNP, r = 0.263, P = 0.017). After a median follow-up of 578 days, YKL-40 outperformed NT-proBNP, uric acid, and 6-min walk distance in receiver operating characteristic (ROC) analyses in predicting both clinical worsening (area under the curve (AUC) 0.681) and death (AUC 0.717). Compared with patients with YKL-40 below the ROC-derived cut-off point (24.5 ng/mL), the high YKL-40 group showed higher pulmonary vascular resistance and serum uric acid levels, and showed more clinical worsening events and deaths in Kaplan-Meier analyses. Plasma YKL-40 was independently associated with clinical worsening in univariate and multivariate Cox analyses (all P < 0.05). CONCLUSIONS: Plasma YKL-40 might serve as a promising indicator of disease severity and prognosis in patients with IPAH.

The ratio of (18)F-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 F-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.

Red blood cell distribution width predicts survival in patients with Eisenmenger syndrome.

BACKGROUND: Previous studies identified an independent relationship between red blood cell distribution width (RDW) and prognosis in patients with pulmonary hypertension of mixed etiologies and idiopathic pulmonary arterial hypertension. This study aimed to investigate the significance of RDW for predicting survival in patients with Eisenmenger syndrome (ES). METHODS: We retrospectively reviewed the clinical records and collected baseline data for patients newly diagnosed with ES in our hospital between January 2005 and October 2009. Follow-up data were collected periodically using a specifically designed network database until December 31, 2012. The end point was all-cause death. RESULTS: A total of 109 patients with ES were included in the study. Twenty-one patients (19.3%) died during a median follow-up period of 4.2 years (interquartile range 3.7-5.0 years). Baseline RDW was significantly correlated with mixed venous oxygen saturation (r=-0.286, p=0.003), arterial oxygen saturation (r=-0.423, p<0.001), mean pulmonary arterial pressure (r=0.271, p=0.004) and total pulmonary resistance (r=0.465, p<0.001). The 1-, 3- and 5-year survival rates for all 109 patients were 94%, 87% and 78%, respectively. Kaplan-Meier analysis showed that patients with RDW ≥13.9% had a lower survival rate than patients with RDW <13.9% (p=0.001). Multivariate Cox regression analysis showed that RDW was an independent prognostic marker in ES, with a hazard ratio of 1.162 (95% CI 1.036-1.302; p=0.010). CONCLUSIONS: Baseline RDW correlates with hemodynamics and is an independent prognostic marker in ES.

Survival advantages of excess body mass index in patients with idiopathic pulmonary arterial hypertension.

OBJECTIVE: An obesity paradox, a "paradoxical" decrease in morbidity and mortality with increasing body mass index (BMI), has been shown in patients with heart failure. However, the impact of BMI in patients with idiopathic pulmonary arterial hypertension (IPAH) has not been studied. This study aims to find out whether BMI is a prognostic factor in IPAH. METHODS AND RESULTS: We analysed 173 patients with IPAH. The patients were subclassified into categories of BMI defined as: under-weight (< 18.5 kg/m2), normal weight (18.5 to 24.9 kg/m2), overweight and obese (25 to 34.9 kg/m2). The three BMI groups had similar profiles in terms of haemodynamic parameters assessed by right heart catheterization and level of NT-proBNP. The overweight and obese group had higher age, and lower WHO functional class, larger left ventricular end-diastolic dimensions (LVEDDs) than the other two groups.The Kaplan-Meier survival curves for the three BMI categories demonstrated that the overweight and obese group had a significantly higher survival rate than the normal weight and underweight groups (log-rank test, P = 0.027, P = 0.000, respectively). In a stepwise forward regression, lower BMI, higher WHO functional class, lower cardiac index, smaller LVEDDs and absence of targeted medication remained independent predictors of mortality. CONCLUSIONS: Excess body mass is a protective factor for death in patients with IPAH.

[Clinical observation of cardiopulmonary exercise test in patients with idiopathic pulmonary arterial hypertension].

OBJECTIVE: To explore the exercise characteristics of patients with idiopathic pulmonary arterial hypertension (IPAH). METHODS: From November 2010 to September 2012 , 76 consecutive IPAH patients and 24 healthy controls from Fuwai Cardiovascular Hospital were enrolled to undergo cardiopulmonary exercise testing. The exercise parameters were compared. Correlations among peak oxygen consumption, anaerobic threshold, peak oxygen pulse, New York Heart Association (NYHA) class, N-terminal pro-brain natriuretic peptide (NT-proBNP), 6-minute walking distance (6 MWD) and cardiac index are analyzed in IPAH. RESULTS: There were 21 males and 55 females in IPAH and 8 males and 16 females in controls. Their mean ages were (31.5 ± 10.6) and (35.5 ± 6.4) years respectively. Significant differences (P = 0.000) existed between two groups in peak oxygen consumption ((12.7 ± 3.3) vs (25.6 ± 5.8) ml·min(-1)·kg(-1)), anaerobic threshold ((9.8 ± 2.5) vs (16.7 ± 3.9) ml·min(-1)·kg(-1)), peak oxygen pulse ((5.3 ± 1.6) vs (9.9 ± 2.5) ml/bpm) and ventilator efficiency (slope of minute ventilation in relation to CO2 produced) ((42.6 ± 2.0) vs (25.5 ± 3.5)). In IPAH, peak oxygen consumption was significantly correlated with NYHA class (r = -0.509, P = 0.000), 6 MWD (r = 0.443, P = 0.002) and NT-proBNP levels (r = -0.423, P = 0.011). And anaerobic threshold was significantly correlated with NYHA class (r = -0.362, P = 0.002), 6MWD (r = 0.343, P = 0.004) and NT-proBNP levels (r = -0.275, P = 0.017). Peak oxygen pulse and ventilator efficiency were both correlated well with total pulmonary vascular resistance. Partial correlation analysis demonstrated that there were significant correlations among peak oxygen consumption, anaerobic threshold, NYHA class, NT-proBNP levels and 6MWD after adjusting for age, gender and weight. CONCLUSIONS: Peak oxygen consumption and anaerobic threshold decrease ventilator efficiency in IPAH patients. Cardiopulmonary exercise testing is an invasive tool of assessing safely the function of IPAH patients.

[Application of cardiopulmonary exercise testing in patients with chronic thromboembolic pulmonary hypertension].

OBJECTIVE: To evaluate the application value of cardiopulmonary exercise testing in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: A total of 116 consecutive patients admitted into the Cardiology Department of Fuwai Hospital.They were divided into 3 groups of CTEPH (n = 44), CPE (without pulmonary hypertension in chronic pulmonary embolism) (n = 24) and control (without pulmonary embolism or pulmonary hypertension) (n = 48) respectively. Their levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured. Incremental cardiopulmonary exercise testing was performed to compare its differential results among 3 groups and evaluate the correlation between NT-proBNP and its parameters. RESULTS: The body mass index (BMI) in the CTEPH group was lower than those in the CPE and control groups ((23.8 ± 3.9) vs (26.1 ± 3.6) and (26.7 ± 3.2) kg/m(2) ), both P < 0.05); the medical history in the CTEPH group was longer than those in the CPE and control groups ((58 ± 48) vs (12 ± 10) and (29 ± 25) months, both P < 0.05). The plasma concentrations of NT-proBNP in the CTEPH group were higher than those in the CPE and control groups ((1678 ± 1255) vs (577 ± 167) and (608 ± 247) pmol/L, both P < 0.05). All of them completed the test and there were no severe complications such as syncope or exacerbation of disease. Maximum oxygen consumption (VO2max), percentage of predicted maximum oxygen consumption (VO2 %), oxygen consumption in relation to body weight (VO2/kg), anaerobic threshold and O2 pulse in the CTEPH group were significantly lower than those in the CPE and control groups (P < 0.05). The ratios of dead space volume (VD) to tidal volume (VT) in the CTEPH and CPE groups were higher than those in the control group (P < 0.05). The plasma concentrations of NT-proBNP were inversely correlated with right ventricular internal diameter (r = -0.690, P = 0.000) and VO2/kg (r = -0.496, P = 0.000). The right ventricular internal diameter (ß = 0.583, P = 0.000) and VO2/kg (ß = 0.233, P = 0.032) were strong independent determinants of NT-proBNP. CONCLUSION: As a reliable pathophysiological indictor of CTEPH, cardiopulmonary exercise testing may be used objectively and safely to evaluate the cardiopulmonary function of CTEPH patients.

[Clinical features of adult patients with Eisenmenger syndrome associated with different types of congenital heart disease].

OBJECTIVE: To explore the clinical features and hemodynamics of adult patients with Eisenmenger syndrome in different types of congenital heart diseases (CHD). METHODS: Patients with Eisenmenger syndrome with different types of CHD diagnosed by right heart catheterization were enrolled from 31 clinical centers in China during the period from May 2007 to October 2010. Age, gender, body mass index (BMI), symptoms and signs, World Health Organization functional class (WHO-FC) of pulmonary hypertension, six-minute walk distance (6MWD) and hemodynamics were recorded. All the above indices were analyzed and compared. RESULTS: A total of 224 patients with Eisenmenger syndrome with 3 kinds of CHD were enrolled, including atrial septal defect (n = 67), ventricular septal defect (n = 104) and patent ductus arteriosus (n = 53). Among them, there were 67 males (29.9%) and 157 females (70.1%) with a mean age of (29.6 ± 9.9) years (range: 15-63). Mean BMI was (19.9 ± 4.0) kg/m(2) and mean 6MWD (371 ± 75) m. The majority of patients were in WHO-FC II (n = 158, 70.5%) and III (n = 64, 28.6%). Electrocardiogram of 77.2% of them indicated hypertrophic right ventricle. Mean right atrial pressure was (8.9 ± 5.7) mm Hg (1 mm Hg = 0.133 kPa), mean pulmonary arterial pressure (mPAP) (77.2 ± 19.1) mm Hg, cardiac index (3.03 ± 1.35) L·min(-1) · m(-2) and pulmonary vascular resistance (PVR) (1621 ± 887) dyn · s · cm(-5). CONCLUSIONS: The majority of patients with Eisenmenger syndrome with different types of CHD are young females and ventricular septal defect is the most frequent underlying cause. The deterioration of heart function in patients with Eisenmenger syndrome is non-parallel to mPAP and PVR in CHD.

Echocardiographic parameters in patients with pulmonary arterial hypertension: correlations with right ventricular ejection fraction derived from cardiac magnetic resonance and hemodynamics.

BACKGROUND: Echocardiography is the most convenient method used to evaluate right ventricular function, and several echocardiographic parameters were studied in previous studies. But the value of these parameters to assess the right ventricular function in patients with pulmonary arterial hypertension (PAH) has not been well defined. METHODS: Patients with PAH were observed prospectively. Right heart catheterization, echocardiography and cardiac magnetic resonance (CMR) were performed within 1 week interval. The correlations between echocardiographic parameters and right ventricular ejection fraction (RVEF) derived from CMR as well as hemodynamics were analyzed. RESULTS: Thirty patients were enrolled including 24 with idiopathic PAH, 5 with PAH associated with connective tissue diseases and 1 with hereditary PAH. All echocardiographic parameters except right ventricular myocardial performance index (RVMPI) correlated significantly with RVEF (tricuspid annual plane systolic excursion [TAPSE], r = 0.440, P = 0.015; tricuspid annular systolic excursion velocity [S'], r = 0.444, P = 0.016; isovolumic acceleration [IVA], r = 0.600, P = 0.001; right ventricular fraction area change [RVFAC], r = 0.416, P = 0.022; ratio of right ventricular transverse diameter to left ventricular transverse diameter [RVETD/LVETD], r = -0.649, P<0.001; RVMPI, r = -0.027, P = 0.888). After adjusted for mean right atrial pressure, mean pulmonary arterial pressure and pulmonary vascular resistance (PVR), only IVA and RVETD/LVETD could independently predict RVEF. Four echocardiographic parameters displayed significant correlations with PVR (TAPSE, r = -0.615, P<0.001; S', r = -0.557, P = 0.002; RVFAC, r = -0.454, P = 0.012; RVETD/LVETD, r = 0.543, P = 0.002). CONCLUSIONS: The echocardiographic parameters IVA and RVETD/LVETD can reflect RVEF independently regardless of hemodynamics in patients with PAH. In addition, TAPSE, S', RVFAC and RVETD/LVETD can also reflect PVR in PAH patients.

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.