Chang-Ming Xiong

Diagnosis of chronic thromboembolic pulmonary hypertension: comparison of ventilation/perfusion scanning and multidetector computed tomography pulmonary angiography with pulmonary angiography.

ObjectiveThe correct and prompt diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) plays a pivotal role in determining appropriate therapy. This study aimed to compare the diagnostic efficacy of pulmonary ventilation/perfusion (V/Q) scanning and computed tomography pulmonary angiography (CTPA) using pulmonary angiography as the golden standard. MethodsA total of 114 consecutive patients (49 men and 65 women, age 43.3±15.3 years) suspected of having CTEPH were prospectively enrolled. All patients underwent V/Q scanning, CTPA, and pulmonary angiography within an interval of 7 days from one another. Interpretation of V/Q images was based on the refined Pulmonary Embolism Diagnosis criteria. For threshold 1, high-probability and intermediate-probability V/Q scan findings were considered to be positive, and low-probability/normal V/Q scan findings were negative. For threshold 2, only a high-probability V/Q scan finding was considered to be positive, and intermediate-probability and low-probability/normal V/Q scan findings were considered to be negative. ResultsFifty-one patients (44.7%) had a final diagnosis of CTEPH. V/Q scan showed high probability, intermediate probability, and low probability/normal scan in 52, three, and 59 patients, respectively. CTPA revealed 50 patients with CTEPH and 64 patients without CTEPH. The sensitivity, specificity, and accuracy of the V/Q scan were 100, 93.7, and 96.5%, respectively, with threshold 1, and 96.1, 95.2, and 95.6%, respectively, with threshold 2; similarly, the sensitivity, specificity, and accuracy of CTPA were 92.2, 95.2, and 93.9%, respectively. ConclusionIn conclusion, both V/Q scanning and CTPA are accurate methods for the detection of CTEPH with excellent diagnostic efficacy.

Comparison of 18F-FDG uptake by right ventricular myocardium in idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with congenital heart disease.

This study measured glucose uptake in the right ventricle (RV) of patients with pulmonary hypertension and investigated the relationship to hemodynamics and survival. Myocardial 18F-fluorodeoxy-glucose (FDG) uptake was measured using single-photon positron emission tomography (SPECT) in 24 patients with idiopathic pulmonary arterial hypertension (IPAH) and 43 patients with congenital heart disease (CHD). In both IPAH and CHD-PAH, RV FDG uptake (RV/LV ratio) was associated with pulmonary vascular resistance (PVR). A second SPECT scan was performed in nine patients after 6 months treatment with sildenafil. PVR decreased from 1683±426 to 1207±383 dyn s−1 cm−5 (P < 0.05) and cardiac index improved from 2.2±0.2 to 2.8±0.5 L/min/m2 (P < 0.01). RV/LV FDG uptake decreased from 1.28±0.32 before treatment to 0.99±0.23 (P < 0.05). Survival in the IPAH group with a baseline RV/LV FDG uptake greater than the median value of 1.20 was significantly lower than that of the group with RV/LV FDG uptake below 1.20 (log-rank test, P < 0.05). In contrast, baseline RV/LV FDG was of little informative value in CHD. FDG uptake by the RV reflects the severity of PVR in PAH. Increased RV FDG uptake is a marker of poor prognosis in IPAH and is reduced in patients receiving effective therapy. It could prove useful in the early clinical assessment of novel therapies for PAH.

Atorvastatin Decreases C-Reactive Protein-Induced Inflammatory Response in Pulmonary Artery Smooth Muscle Cells by Inhibiting Nuclear Factor-κB Pathway

C-reactive protein (CRP) is well-known inflammatory marker, and recognized as a risk predictor of pulmonary arterial diseases. Although statins have a beneficial effect in animal models and patients with pulmonary arterial hypertension (PAH), the underlying mechanisms of their actions have less been investigated. The aims of this study was to examined the effects of CRP on expressions of interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1), and the possible mechanisms of atorvastatin on CRP-induced IL-6 and MCP-1 production in cultured human pulmonary artery smooth muscle cells (PASMCs). In a preliminary study, the human PASMCs were stimulated by a variety of concentrations of CRP (5-200 microg/mL) at different time points (0, 3, 6, 9, 12, 18 and 24 h) for the purpose of determining the dose- and time-dependent effects of CRP on inflammatory response of the cells. Then, the cells were pre-incubated for 2 h with atorvastatin (0.1-10 micromol/L) in the presence of CRP. The supernatant levels of both IL-6 and MCP-1 secretion were examined by ELISA. The cellular mRNA expressions of IL-6 and MCP-1 and nuclear factor-kappaB (NF-kappaB) activity were determined by real-time reverse transcription and polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assay (EMSA), respectively. CRP resulted in elevated IL-6 and MCP-1 secretion and mRNA expression in a dose- and time-dependent manner. In addition, CRP also significantly activated the NF-kappaB pathway. Preincubation with 0.1-10 micromol/L of atorvastatin significantly decreased the secretions of IL-6 and MCP-1 induced by CRP. Moreover, 10 micromol/L of atorvastatin completely abrogated CRP-induced increase in IL-6 and MCP-1 by attenuating the activation of NF-kappaB. The present study demonstrated that inhibiting effect of atorvastatin on CRP-induced inflammatory response in cultured PASMCs was associated with NF-kappaB pathway. This pathway might represent a promising target for controlling CRP-induced inflammatory response in pulmonary arterial diseases.

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.

Potential diagnostic biomarkers in serum of idiopathic pulmonary arterial hypertension

BACKGROUND The pathogenesis of idiopathic pulmonary arterial hypertension (IPAH) is unknown, and the syndrome of IPAH remains a diagnostic and therapeutic challenge. The present study investigated the disease-specific proteins that aid in the diagnosis of IPAH and thus to study their role in the disease process. METHODS A comparative proteomic analysis was used for clinical screening of serum proteins in 10 patients with IPAH and compared with 10 normal subjects. Furthermore, enzyme linked immunosorbent assay (ELISA) was performed for comparison with serum proteins between individual IPAH patients and controls. RESULTS Nine proteins and their isoforms, including leucine-rich alpha-2-glycoprotein (LRG), haptoglobin precursor, albumin isoform 2, transferrin variant, C3 complement, hydroxypyruvate reductase isoform 1, RAF1, fibrinogen isoformgamma-A and fibrinogen isoformgamma-B showed significant changes in serum of IPAH patients compared with controls by proteomic analysis. And significant higher serum levels of LRG in IPAH patients compared with controls were found by ELISA. Correlation analysis disclosed a significant association between serum LRG concentrations and New York Heart Association (NYHA) functional class (r=0.71, P<0.01) and cardiac output (CO) (r=-0.65, P<0.01). CONCLUSIONS These results indicate that there are significant differences in the expression of proteins in the serum of patients with IPAH and normal subjects. And the measurement of LRG, RAF1 and C3 complement levels in the serum may be helpful for the diagnosis of IPAH. In particular, LRG may be a specific prognostical biomarker of IPAH.

Comparison of lung scintigraphy with multi-slice spiral computed tomography in the diagnosis of pulmonary embolism.

Purpose: To compare the diagnostic efficacy of lung perfusion scan combined with ventilation (V/Q) scan and/or chest radiography (CR) with contrast-enhanced multislice spiral CT pulmonary angiography (CTPA) in diagnosing pulmonary embolism (PE). Materials and Methods: Eighty-two consecutive patients with suspected PE underwent CTPA, lung perfusion scan, and CR. Of them, 28 patients underwent V/Q scans. The final diagnosis was made using a composite reference test. Results: The overall sensitivity and specificity were 89.2% and 92.1% for V/Q scan or perfusion scan combined with CR, and 97.3% and 97.4% for CTPA. For the 28 patients with V/Q scan, the sensitivity and specificity were 91.7% and 92.9% for V/Q scan, and 91.7% and 100.0% for CTPA. The segmental agreement rate between perfusion scan and CTPA was 69.5% (kappa = 0.30, P < 0.05). The perfusion scan revealed significantly more subsegmental abnormalities than CTPA (59 vs. 10, &khgr;2 test, P < 0.05). Conclusions: V/Q scan, perfusion scan combined with CR and CTPA all show high efficacy in diagnosing PE. V/Q scan or perfusion scan combined with CR is as accurate as CTPA.

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.

Chinese multi-center study of lung scintigraphy and CT pulmonary angiography for the diagnosis of pulmonary embolism

To evaluate diagnostic value of the PISA-PED and PIOPED II criteria for lung scintigraphy and compare it with CT pulmonary angiography (CTPA) for the detection of pulmonary embolism (PE). Five hundred and forty-four consecutive patients with suspected PE were enrolled. All patients underwent lung ventilation/perfusion (V/P) scan, chest radiography, and CTPA. Two readers used the PIOPED II criteria, and 2 used the PISA-PED criteria for the interpretation of lung scintigraphy. CTPA scans were interpreted by two experienced radiologists. Lung scintigraphy and CTPA were categorized as PE present, absent or non-diagnostic. PE was present in 321 of 544 patients. Using PIOPED II criteria, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 85.1, 82.5, 88.1, and 78.4% respectively for V/P scan. Using PISA-PED criteria, sensitivity, specificity, PPV, and NPV were 86.0, 81.2, 86.8, and 80.1% respectively, and none was non-diagnostic. Sensitivity, specificity, PPV, and NPV were 81.7, 93.4, 94.9, and 77.3%, respectively for CTPA. PISA-PED interpretation has similar diagnostic accuracy to PIOPED II interpretation, does not have non-diagnostic scan, with lower cost and radiation, thus should be considered as a choice for patients with suspected PE.

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.