Evaluating the efficacy of balloon pulmonary angioplasty using quantitative analysis of SPECT pulmonary ventilation/perfusion scintigraphy in patients with chronic thromboembolic pulmonary hypertension.

Background: Single-photon emission computed tomography (SPECT) ventilation perfusion imaging is the main imaging method for the diagnosis of pulmonary embolism, and its application in the diagnosis and efficacy evaluation of chronic thromboembolic pulmonary hypertension (CTEPH) has been paid more and more attention. In recent years, with the development of computer software technology, ventilation/perfusion (V/Q) imaging quantitative analysis technology has become more and more mature. The objective of this study was to investigate the utility of quantitative analysis of pulmonary V/Q scintigraphy in evaluating the efficacy of balloon pulmonary angioplasty (BPA) in patients with CTEPH. Methods: In this retrospective analysis, we collected data of patients diagnosed with CTEPH who underwent BPA at the China-Japan Friendship Hospital from April 2018 to September 2020. The sample consisted of 23 males and 28 females, with an average age of 55.1±12.7 years. All patients underwent V/Q scintigraphy within one week before surgery, and we reviewed the pulmonary angiography within 1-3 months following the last BPA procedure. We repeated V/Q scintigraphy within 1 week before or after the pulmonary angiography, at the time of collecting clinical and hemodynamic parameters of these patients. We divided the patients into two groups based on the presence of residual pulmonary hypertension post-surgery and compared the pre- and post-operative quantitative pulmonary perfusion defect percentage scores (PPDs%) using the t-test. Results: In all, 102 V/Q scintigraphy scans were performed in 51 patients. The quantitative PPDs% were positively correlated with the hemodynamic indexes mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and mean right ventricular pressure (RVP) (r=0.605, 0.391, and 0.464, respectively, all P<0.001) and negatively correlated with the 6-minute walking distance (6MWD) (r=-0.254, P=0.010). The average preoperative quantitative PPDs% were (49.0±15.6)% which significantly decreased to (33.5±13.9)% after surgery (t=11.249, P<0.001). The preoperative quantitative PPDs% were (54.7±15.7)% and (44.0±13.8)% in the residual pulmonary hypertension group and the non-residual pulmonary hypertension group, respectively (t=2.599, P=0.012). The postoperative quantitative PPDs% were (41.5±12.5)% and (26.3±11.0)%, in the residual pulmonary hypertension group and the non-residual pulmonary hypertension group, respectively (t=4.647, P<0.001). Conclusions: In this study, we found that quantitative analysis of SPECT pulmonary V/Q scintigraphy adequately reflected the pulmonary artery pressure and clinical status in patients with CTEPH. Our results demonstrate its definite utility in predicting residual pulmonary hypertension and in evaluating the postoperative efficacy of BPA in patients with CTEPH.

Publishing clinical prActice GuidelinEs (PAGE): Recommendations from editors and reviewers.

Transparency Ecosystem for Research and Journals in Medicine (TERM) working group summarized the essential recommendations that should be considered to review and publish a high-quality guideline. These recommendations from editors and reviewers included 10 components of essential requirements: systematic review of existing relevant guidelines, guideline registration, guideline protocol, stakeholders, conflicts of interest, clinical questions, systematic reviews, recommendation consensus, guideline reporting and external review. TERM working group abbreviates them as PAGE (essential requirements for Publishing clinical prActice GuidelinEs), and recommends guideline authors, editors, and peer reviewers to use them for high-quality guidelines.

A simpler noninvasive method of predicting markedly elevated pulmonary vascular resistance in patients with chronic thromboembolic pulmonary hypertension.

Several echocardiographic methods to estimate pulmonary vascular resistance (PVR) have been proposed. So far, most studies have focused on relatively low PVR in patients with a nonspecific type of pulmonary hypertension. We aimed to clarify the clinical usefulness of a new echocardiographic index for evaluating markedly elevated PVR in chronic thromboembolic pulmonary hypertension (CTEPH). We studied 127 CTEPH patients. We estimated the systolic and mean pulmonary artery pressure using echocardiography (sPAPEcho, mPAPEcho) and measured the left ventricular internal diameter at end diastole (LVIDd). sPAPEcho/LVIDd and mPAPEcho/LVIDd were then correlated with invasive PVR. Using receiver operating characteristic curve analysis, a cutoff value for the index was generated to identify patients with PVR > 1000 dyn·s·cm-5. We analyzed pre- and postoperative hemodynamics and echocardiographic data in 49 patients who underwent pulmonary endarterectomy (PEA). In this study, mPAPEcho/LVIDd moderately correlated with PVR (r = 0.51, p < 0.0001). There was a better correlation between PVR and sPAPEcho/LVIDd (r = 0.61, p < 0.0001). sPAPEcho/LVIDd ≥ 1.94 had an 77.1% sensitivity and 75.4% specificity to determine PVR > 1000 dyn·s·cm-5 (area under curve = 0.804, p < 0.0001, 95% confidence interval [CI], 0.66-0.90). DeLong's method showed there was a statistically significant difference between sPAPEcho/LVIDd with tricuspid regurgitation velocity2/velocity-time integral of the right ventricular outflow tract (difference between areas 0.14, 95% CI, 0.00-0.27). The sPAPEcho/LVIDd and mPAPEcho/LVIDd significantly decreased after PEA (both p < 0.0001). The sPAPEcho/LVIDd and mPAPEcho/LVIDd reduction rate (ΔsPAPEcho/LVIDd and ΔmPAPEcho/LVIDd) was significantly correlated with PVR reduction rate (ΔPVR), respectively (r = 0.58, p < 0.01; r = 0.69, p < 0.05). In conclusion, the index of sPAPEcho/LVIDd could be a simpler and reliable method in estimating CTEPH with markedly elevated PVR and also be a convenient method of estimating PVR both before and after PEA.

The accuracy and influencing factors of Doppler echocardiography in estimating pulmonary artery systolic pressure: comparison with right heart catheterization: a retrospective cross-sectional study.

BACKGROUND: Noninvasive assessment of pulmonary artery systolic pressure by Doppler echocardiography (sPAPECHO) has been widely adopted to screen for pulmonary hypertension (PH), but there is still a high proportion of overestimation or underestimation of sPAPECHO. We therefore aimed to explore the accuracy and influencing factors of sPAPECHO with right heart catheterization (RHC) as a reference. METHODS: A total of 218 highly suspected PH patients who underwent RHC and echocardiography within 7 days were included. The correlation and consistency between tricuspid regurgitation (TR)-related methods and RHC results were tested by Pearson and Bland-Altman methods. TR-related methods included peak velocity of TR (TR Vmax), TR pressure gradient (TR-PG), TR mean pressure gradient (TR-mPG), estimated mean pulmonary artery pressure (mPAPECHO), and sPAPECHO. With mPAP ≥ 25 mm Hg measured by RHC as the standard diagnostic criterion of PH, the ROC curve was used to compare the diagnostic efficacy of sPAPECHO with other TR-derived parameters. The ratio (sPAPECHO-sPAPRHC)/sPAPRHC was calculated and divided into three groups as follows: patients with an estimation error between - 10% and + 10% were defined as the accurate group; patients with an estimated difference greater than + 10% were classified as the overestimated group; and patients with an estimation error greater than - 10% were classified as the underestimated group. The influencing factors of sPAPECHO were analyzed by ordinal regression analysis. RESULTS: sPAPECHO had the highest correlation coefficient (r = 0.781, P < 0.001), best diagnostic efficiency (AUC = 0.98), and lowest bias (mean bias = 0.07 mm Hg; 95% limits of agreement, - 32.08 to + 32.22 mm Hg) compared with other TR-related methods. Ordinal regression analysis showed that TR signal quality, sPAPRHC level, and pulmonary artery wedge pressure (PAWP) affected the accuracy of sPAPECHO (P < 0.05). Relative to the good signal quality, the OR values of medium and poor signal quality were 0.26 (95% CI: 0.14, 0.48) and 0.23 (95% CI: 0.07, 0.73), respectively. Compared with high sPAPRHC level, the OR values of low and medium sPAPRHC levels were 21.56 (95% CI: 9.57, 48.55) and 5.13 (95% CI: 2.55, 10.32), respectively. The OR value of PAWP was 0.94 (95% CI: 0.89, 0.99). TR severity and right ventricular systolic function had no significant effect on the accuracy of sPAPECHO. CONCLUSIONS: In this study, we found that all TR-related methods, including sPAPECHO, had comparable and good efficiency in PH screening. To make the assessment of sPAPECHO more accurate, attention should be paid to TR signal quality, sPAPRHC level, and PAWP.

A Feasibility Study on Using Single-Photon Emission Computed Tomography Pulmonary Perfusion/Ventilation Imaging for the Diagnosis of Chronic Thromboembolic Pulmonary Hypertension and Patient Risk Assessment.

OBJECTIVE: The study is designed to evaluate the diagnostic ability of single-photon emission computed tomography (SPECT) pulmonary ventilation/perfusion (V/Q) imaging in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and investigate its feasibility in assessing patient risk. METHODS: A total of 83 patients suspected of having CTEPH who received V/Q tomography were retrospectively analyzed. The consistency between SPECT V/Q imaging and pulmonary angiography was compared to investigate the correlation between the percentage of pulmonary perfusion defect score (PPDs%) and the hemodynamic indices. Patients were grouped according to the pulmonary arterial hypertension risk stratification, and the V/Q imaging results were compared between different groups. RESULTS: For the 1494 pulmonary segments of the 83 patients, the sensitivity, specificity, and accuracy of identifying pulmonary segments with defects using V/Q imaging was 87.05%, 82.78% (668/807), and 84.74% (1266/1494), respectively. The average PPDs% (58.8 ± 12.6%) was positively correlated with the mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and right ventricular pressure (RVP; r =0.316, 0.318, and 0.432, respectively; P < 0.05) and negatively correlated with the six-minute walk distance (6MWD; r = -0.309; P < 0.05). There were 37 patients in the low-risk group and 46 in the medium-high-risk group. The number of pulmonary segments with perfusion defects (NPSPDs) and PPDs% were higher in the medium-high risk than in the low-risk group (t = -6.721, -5.032; P < 0.05). In the low- and medium-high-risk groups, the cut-off values for the NPSPDs (7.2 ± 2.1 and 10.2 ± 2.0) and PPDs% (51.9 ± 11.1% and 64.3 ± 11.1%,) were 8.5 and 61.25%, respectively. CONCLUSION: SPECT V/Q imaging achieved an accurate diagnosis of CTEPH. The semi-quantitative analysis index (PPDs%) was correlated with the hemodynamic indices and 6MWD. SPECT V/Q could be used for the preoperative risk assessment of patients with CTEPH.

Global reporting of pulmonary embolism-related deaths in the World Health Organization mortality database: Vital registration data from 123 countries.

INTRODUCTION: Pulmonary embolism (PE) has not been accounted for as a cause of death contributing to cause-specific mortality in global reports. METHODS: We analyzed global PE-related mortality by focusing on the latest year available for each member state in the World Health Organization (WHO) mortality database, which provides age-sex-specific aggregated mortality data transmitted by national authorities for each underlying cause of death. PE-related deaths were defined by International Classification of Diseases, Tenth Revision codes for acute PE or nonfatal manifestations of venous thromboembolism (VTE). The 2001 WHO standard population served for standardization. RESULTS: We obtained data from 123 countries covering a total population of 2 602 561 422. Overall, 50 (40.6%) were European, 39 (31.7%) American, 13 (10.6%) Eastern Mediterranean, 13 (10.6%) Western Pacific, 3 (2.4%) Southeast Asian, and 2 (1.6%) African. Of 116 countries classifiable according to population income, 57 (49.1%) were high income, 42 (36.2%) upper-middle income, 14 (12.1%) lower-middle income, and 3 (2.6%) low income. A total of 18 726 382 deaths were recorded, of which 86 930 (0.46%) were attributed to PE. PE-related mortality rate increased with age in most countries. The reporting of PE-related deaths was heterogeneous, with an age-standardized mortality rate ranging from 0 to 24 deaths per 100 000 population-years. Income status only partially explained this heterogeneity. CONCLUSIONS: Reporting of PE-related mortality in official national vital registration was characterized by extreme heterogeneity across countries. These findings mandate enhanced efforts toward systematic and uniform coverage of PE-related mortality and provides a case for full recognition of PE and VTE as a primary cause of death.

Regional right ventricular longitudinal systolic strain for detection of severely impaired right ventricular performance in pulmonary hypertension.

OBJECTIVES: Right ventricular (RV) function is identified as a key determinant of the outcome in patients with pulmonary hypertension (PH). Several studies have assessed the role of peak global longitudinal RV strain in PH patients; however, less emphasis was given to the RV regional longitudinal strain. The aim of this study was to evaluate the regional RV systolic strain in PH patients and investigate the relationship of these parameters with the severity of PH. METHODS: RV regional longitudinal peak systolic strain (LPSS) and strain rate (LPSSR) were measured using speckle tracking echocardiography on 100 patients with PH who underwent right heart catheterization, and 29 control subjects. Severe PH was identified by a decreased cardiac index (CI) (<2.0 L/min/m2 ). RESULTS: LPSS and LPSSR of the RV free wall were significantly lower in PH patients than control subjects, especially when comparing the basal and mid regions (P < .001). When comparing severe PH and nonsevere PH, basal and mid LPSS and LPSSR were significantly lower (P < .001). RV free wall mid LPSSR correlated with CI (r = -.703, P < .001). In the multiple logistic regression analysis, mid LPSSR was identified as an independent predictor of severe PH (odds ratio 1.82; 95% confidential interval 1.39-2.40; P < .001). In the receiver operating characteristics curve analysis, a cutoff value of mid LPSSR of -0.92 s-1 predicted severe PH, with a sensitivity and specificity of 75.0% and 93.7%, respectively (AUC = 0.889, P < .001). CONCLUSIONS: RV free wall mid longitudinal peak systolic strain rate may be useful for the detection of severely impaired RV performance in PH.

Awareness and management of pulmonary embolism among physicians in China: a nationwide cross-sectional study.

Pulmonary embolism (PE) is a leading cause of cardiovascular mortality. We intended to evaluate the awareness and management status of PE among Chinese physicians and provide the basis for establishing Chinese clinical guidelines on PE. We designed a nationwide survey to collect data on physicians' awareness of diagnosis, treatment and follow-up on PE. The questionnaires were distributed to physicians during offline academic meetings and by the online platforms from August 2016 to October 2016. Also, results were sub-grouped by age, hospital grades, departments and trained or not. A total of 2954 valid questionnaires were collected. We observed that there were several defects in the management of PE among Chinese physicians. First, a considerable proportion of physicians chose the incorrect clinical prediction rules for acute PE. Second, a considerable percentage of hospitals could not carry out computed tomographic pulmonary angiography (22.4%) or ventilation-perfusion scintigraphy (65.2%). Third, only a few physicians knew the use of new oral anticoagulants clearly (33.4%). Fourth, only 49% of physicians achieved follow-up management in over half of their patients. Additionally, physicians in the tertiary hospitals, aged > 35 years, trained and from respiratory department have a better knowledge of the management of PE. In conclusion, our survey demonstrates the enhancement of PE-related trainings, especially for physicians in lower-level hospitals, aged ≤ 35 years and from non-respiratory department, can help to improve the management of PE in Chinese physicians. And our study also highlights the need for the establishment of national guidelines for the management of PE in China.

The value of speckle-tracking echocardiography in identifying right heart dysfunction in patients with chronic thromboembolic pulmonary hypertension.

Right ventricular (RV) function is a significantly important factor in the determination of the prognosis of chronic thromboembolic pulmonary hypertension (CTEPH) patients. Speckle-tracking echocardiography (STE) is an angle-independent new technique for quantifying myocardial deformation that is capable of providing data on multiple parameters including longitudinal and transverse information of the myocardium. In the present study, we aimed to study the advantages of STE-derived parameters in identifying RV dysfunction in CTEPH patients. Sixty CTEPH patients (mean age: 55 years ± 13 years; 25 males) and 30 normal controls (mean age: 54 years ± 14 years; 14 males) were enrolled in this study. RV free wall (RVFW) systolic peak longitudinal strain (LS) including the basal, mid-, and apical-segments and the basal longitudinal and transverse displacement (basal-DL and basal-DT) were measured by STE. Global LS (GLS) of the RV was calculated by averaging the LS value of the 3 segments of RVFW. Clinical data of CTEPH patients were collected. CTEPH patients were divided into 2 subgroups according to the World Health Organization function classification. Clinical right heart failure (RHF) was defined as the presence of symptoms of heart failure and signs of systemic circulation congestion during hospitalization. The apical segment LS of the RVFW was lower than that in the basal and mid-segments in the control group (P < 0.001), but no significant difference was found among the 3 segments of LS in the CTEPH group (P = 0.263). When we used the cutoff value recommended by the American Society of Echocardiography guidelines to identify abnormal RV function, 30 CTEPH patients (50%) by tricuspid annular plane systolic excursion (TAPSE), 42 patients (70%) by fractional area change (FAC), 20 patients (33.33%) by RV index of myocardial performance (RVIMP), and 46 patients (77%) patients by GLS were determined to have abnormal RV function, respectively. Among multiple RV function indicators, TAPSE, FAC, GLS, basal-DL, and N-terminal pronatriuretic B-type natriuretic peptide showed significant differences between CTEPH patients with mild (WHO II) and severe symptoms (WHO III/IV) (all P < 0.001), while RVIMP and basal-DT showed no significant difference (P = 0.188 and P = 0.394, respectively). Pearson correlation analysis showed that GLS has no correlation with sPAP as evaluated by echocardiography in CTEPH patients (r = - 0.079, P = 0.574), and a weak to moderate correlation with RA area (r = 0.488, P = 0.000), the RV diameter (r = 0.429, P = 0.001), and the RVFW thickness (r = 0.344, P = 0.009). On receiver operating characteristic analysis, GLS has the largest area under the curve to identify RHF when the cutoff value was - 13.45%, the sensitivity was 78.2%, and the specificity was 84.6%, separately. Our study demonstrated that the depression of regional LS of RVFW is more pronounced in the basal and middle segments in CTEPH patients. Also, the longitudinal movement is much more important than the transverse movement when evaluating RV systolic function. As compared with conventional parameters, RVFW GLS showed more sensitivity to identify abnormal RV function and had the largest AUC for identifying RHF. Additionally, GLS showed no correlation with sPAP and a weak correlation with right heart morphological parameters in our CTEPH cohort.

Identification of haptoglobin as a potential diagnostic biomarker of acute pulmonary embolism.

: Acute pulmonary embolism is a common disease, which is associated with high mortality and morbidity. There is significant relationship between haptoglobin and pulmonary embolism, however, the usefulness of haptoglobin as a biomarker for the diagnosis of pulmonary embolism remains poorly defined. The aim of the present study was to investigate the change and clinical diagnostic value of haptoglobin in pulmonary embolism. A comparative proteomic analysis was used for clinical screening of serum proteins in 18 patients (9 patients with pulmonary embolism and 9 controls). ELISA was used to validate the dysregulated proteins in 48 patients (24 patients with pulmonary embolism and 24 controls). Immunohistochemical staining was performed to detect the expression of haptoglobin in pulmonary artery of both groups. The diagnostic value of the differential protein and its association with the severity of pulmonary embolism were evaluated. Eight proteins showed significant changes in serum of pulmonary embolism patients. Haptoglobin, as one of the eight differential proteins, was significantly overexpressed in the serum of pulmonary embolism patients. In accordance, the expression of haptoglobin was increased in pulmonary artery of pulmonary embolism patients. The ROC curve showed that serum haptoglobin was a specific parameter in the diagnosis of pulmonary embolism with an area under the curve of 0.764 (95% confidence interval, 0.622-0.906; P < 0.01); in particular, the haptoglobin level at least 256.74 mg/l was the most useful cut-off value, with the sensitivity of 62% and specificity of 83%. Increased haptoglobin level may be an acceptable diagnostic parameter for pulmonary embolism.

Differential Diagnosis of Pulmonary Artery Sarcoma and Central Chronic Pulmonary Thromboembolism Using CT and MR Images.

BACKGROUND: Clinical and imaging manifestations are similar in pulmonary artery sarcomas (PAS) and thromboembolic diseases, especially central chronic pulmonary thromboembolism (CPTE). The feasibility of utilising clinical imaging tools such as computed tomography (CT) and magnetic resonance imaging (MRI) for differential diagnosis of PAS and CPTE has not been fully explored, especially MRI. METHODS: Patients with PAS (n=18) and central CPTE (n=20) treated at our hospital between January 2013 and September 2016 were identified retrospectively. Computed tomography and MRI findings of pulmonary artery (PA) filling defects including the location, the involvement of pulmonary artery, morphology, signal intensities and enhancement in MRI, calcification, sizes of right atrium and ventricle, inner diameters of the pulmonary artery trunk and branches, and mediastinal collateral circulation in both groups were examined, and differences were analysed by Fisher exact test and independent sample t-test. RESULTS: Compared to those of central CPTE, PAS lesions were in full shape or expansive growth (p<0.001), and the proximal end of the tumours was often bulging or lobulated (p<0.001). These lesions were aneurysm- or grape-like distally (p<0.01) with inhomogeneous enhancement (p<0.001). The MRI contrast enhancement pattern of PAS lesions were cloudy with inhomogeneous delayed enhancement and the time-density curves for some of the lesions increased gradually. CONCLUSION: Computed tomographic and MR imaging manifestations may resemble PAS and central CPTE; however, some manifestations still have great value for the differential diagnosis of these two conditions, specifically the morphology and MRI enhancement patterns.

Renin-angiotensin system regulates pulmonary arterial smooth muscle cell migration in chronic thromboembolic pulmonary hypertension.

Pulmonary arterial smooth muscle cell (PASMC) migration plays a key role in vascular remodeling, which occurs during development of chronic thromboembolic pulmonary hypertension (CTEPH). Activation of the renin-angiotensin system (RAS) contributes to vascular remodeling observed in many diseases, including idiopathic pulmonary arterial hypertension. However, the role of RAS imbalance in CTEPH has not been characterized. Here, we hypothesize that RAS imbalance regulates vascular remodeling by promoting PASMC migration in CTEPH. Serum renin and angiotensin II levels in patients with CTEPH were quantified by ELISA. The pulmonary endarterectomy tissues were stained and analyzed by immunohistochemistry. PASMCs were isolated and verified by immunofluorescence staining. PASMC migration was determined by Transwell assay. Phosphorylation and protein level were detected by Western blotting. Serum levels of renin and angiotensin II were increased in patients with CTEPH {renin [median (25th percentile, 75th percentile) in pg/ml], 1,199.94 [690.85, 1,656.90] vs. 595.43 [351.48, 936.43], P < 0.001; angiotensin II [in pg/ml], 63.97 [45.97, 345.24] vs. 56.85 [11.20, 90.37], P < 0.05}. The migration of PASMCs isolated from patients with CTEPH was enhanced compared with control. Angiotensin II promoted the migration of PASMCs via activation of angiotensin II receptor 1 and phosphorylation of ERK1/2, whereas angiotensin-(1-7) counteracted this effect through activation of the Mas receptor and ERK1/2. These results demonstrate that the renin-angiotensin system regulates migration of PASMCs from patients with CTEPH via the ERK1/2 pathway. Our findings suggest that angiotensin-(1-7) or reagents targeting the renin-angiotensin system will be beneficial in the development of novel therapies for CTEPH.

A Case of Pulmonary Hypertension Due to Fistulas Between Multiple Systemic Arteries and the Right Pulmonary Artery in an Adult Discovered for Occulted Dyspnoea.

BACKGROUND: Pulmonary hypertension (PH) can be caused by a fistula between the systemic and pulmonary arteries. Here, we report a case of PH due to multiple fistulas between systemic arteries and the right pulmonary artery where the ventilation/perfusion scan showed no perfusion in the right lung. METHODS: A 32-year-old male patient was hospitalised for community-acquired pneumonia. After treatment with antibiotics, the pneumonia was alleviated but dyspnoea persisted. Pulmonary hypertension was diagnosed using right heart catheterisation, which detected the mean pulmonary artery pressure as 37mmHg. The anomalies were confirmed by contrast-enhanced CT scan (CT pulmonary angiography), systemic arterial angiography and pulmonary angiography. RESULTS: Following embolisation of the largest fistula, the haemodynamics and oxygen dynamics did not improve, and even worsened to some extent. After supportive therapy including diuretics and oxygen, the patient's dyspnoea, WHO function class and right heart function by transthoracic echocardiography all improved during follow-up. CONCLUSIONS: Pulmonary hypertension can be present even when the right lung perfusion is lost. Closure of fistulas by embolisation, when those fistulas act as the proliferating vessels, may be harmful.

Clinical Study of Acute Vasoreactivity Testing in Patients with Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: The clinical significance of acute vasoreactivity testing (AVT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We analyzed changes in hemodynamics and oxygenation dynamics indices after AVT in patients with CTEPH using patients with pulmonary arterial hypertension (PAH) as controls. METHODS: We analyzed retrospectively the results of AVT in 80 patients with PAH and 175 patients with CTEPH registered in the research database of Beijing Chao-Yang Hospital between October 2005 and August 2014. Demographic variables, cardiopulmonary indicators, and laboratory findings were compared in these two subgroups. A long-term follow-up was conducted in patients with CTEPH. Between-group comparisons were performed using the independent-sample t-test or the rank sum test, within-group comparisons were conducted using the paired t-test or the Wilcoxon signed-rank test, and count data were analyzed using the Chi-squared test. Survival was estimated using the Kaplan-Meier method and log-rank test. RESULTS: The rates of positive response to AVT were similar in the CTEPH (25/175, 14.3%) and PAH (9/80, 11.3%) groups (P > 0.05). Factors significantly associated a positive response to AVT in the CTEPH group were level of N-terminal pro-brain natriuretic peptide (≤1131.000 ng/L), mean pulmonary arterial pressure (mPAP, ≤44.500 mmHg), pulmonary vascular resistance (PVR, ≤846.500 dyn·s-1·m-5), cardiac output (CO, ≥3.475 L/min), and mixed venous oxygen partial pressure (PvO2, ≥35.150 mmHg). Inhalation of iloprost resulted in similar changes in mean blood pressure, mPAP, PVR, systemic vascular resistance, CO, arterial oxygen saturation (SaO2), mixed venous oxygen saturation, partial pressure of oxygen in arterial blood (PaO2), PvO2, and intrapulmonary shunt (Qs/Qt) in the PAH and CTEPH groups (all P > 0.05). The survival time in patients with CTEPH with a negative response to AVT was somewhat shorter than that in AVT-responders although the difference was not statistically significant (χ2 =3.613, P = 0.057). The survival time of patients with CTEPH who received calcium channel blockers (CCBs) was longer than that in the group with only basic treatment and not shorter than that of patients who receiving targeted drugs or underwent pulmonary endarterectomy (PEA) although there was no significant difference between the four different treatment regimens (χ2 =3.069, P = 0.381). CONCLUSIONS: The rates of positive response to AVT were similar in the CTEPH and PAH groups, and iloprost inhalation induced similar changes in hemodynamics and oxygenation dynamics indices. A positive response to AVT in the CTEPH group was significantly correlated with milder disease and better survival. Patients with CTEPH who cannot undergo PEA or receive targeted therapy but have a positive response to AVT might benefit from CCB treatment.

Red cell distribution width is increased in chronic thromboembolic pulmonary hypertension.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition characterized by single or recurrent pulmonary embolisms, which promotes pulmonary vascular remodeling. There is significant relationship between red cell distribution width (RDW) and pulmonary hypertension; however, the usefulness of RDW as biomarker for the diagnosis of CTEPH remains poorly defined. OBJECTIVE: This study sought to assess the change and the diagnostic value of RDW in CTEPH. METHODS: This retrospective study included 56 CTEPH patients and 56 sex- and age-matched healthy controls treated at Beijing Chao-Yang Hospital. Correlations between RDW and hematological and hemodynamic parameters were assessed. A logistic regression model was applied to test independent parameters in relation to the diagnosis of CTEPH, and receiver operating characteristic curve was plotted to determine the diagnostic value of RDW in CTEPH. RESULTS: RDW values were significantly higher in CTEPH patients (13.82% ± 1.14%) compared with healthy controls (12.75% ± 0.49%) and in World Health Organization (WHO), functional class III-IV cases (14.39% ± 1.24%) compared with class I-II cases (13.32% ± 0.78%) (both P = 0.000). RDW levels in CTEPH patients showed negative correlations with hemoglobin (r = -0.357, P = 0.007) and cardiac index (r = -0.288, P = 0.031), and positive correlations with pulmonary vascular resistance (r = 0.292, P = 0.029) and WHO functional class (r = 0.450, P = 0.001). Moreover, RDW was an independent parameter in the diagnosis of CTEPH (95% confidence interval: 2.866-13.698, P = 0.000); in particular, an RDW level ≥ 13.05% was the most useful cut-off value, with a sensitivity of 82.1% and a specificity of 71.4%. CONCLUSION: Increased RDW level may be an acceptable diagnostic parameter for CTEPH.

Serum Bilirubin and 6-min Walk Distance as Prognostic Predictors for Inoperable Chronic Thromboembolic Pulmonary Hypertension: A Prospective Cohort Study.

BACKGROUND: Inoperable chronic thromboembolic pulmonary hypertension (CTEPH) is a severe clinical syndrome characterized by right cardiac failure and possibly subsequent liver dysfunction. However, whether serum markers of liver dysfunction can predict prognosis in inoperable CTEPH patients has not been determined. Our study aimed to evaluate the potential role of liver function markers (such as serum levels of transaminase, bilirubin, and gamma-glutamyl transpeptidase [GGT]) combined with 6-min walk test in the prediction of prognosis in patients with inoperable CTEPH. METHODS: From June 2005 to May 2013, 77 consecutive patients with inoperable CTEPH without confounding co-morbidities were recruited for this prospective cohort study. Baseline clinical characteristics and 6-min walk distance (6MWD) results were collected. Serum biomarkers of liver function, including levels of aspartate aminotransferase, alanine aminotransferase, GGT, uric acid, and serum bilirubin, were also determined at enrollment. All-cause mortality was recorded during the follow-up period. RESULTS: During the follow-up, 22 patients (29%) died. Cox regression analyses demonstrated that increased serum concentration of total bilirubin (hazard ratio [HR] = 7.755, P < 0.001), elevated N-terminal of the prohormone brain natriuretic peptide (HR = 1.001, P = 0.001), decreased 6MWD (HR = 0.990, P < 0.001), increased central venous pressure (HR = 1.074, P = 0.040), and higher pulmonary vascular resistance (HR = 1.001, P = 0.018) were associated with an increased risk of mortality. Serum concentrations of total bilirubin (HR = 4.755, P = 0.007) and 6MWD (HR = 0.994, P = 0.017) were independent prognostic predictors for CTEPH patients. Patients with hyperbilirubinemia (≥23.7 µmol/L) had markedly worse survival than those with normobilirubinemia. CONCLUSION: Elevated serum bilirubin and decreased 6MWD are potential predictors for poor prognosis in inoperable CTEPH.