non-PAH Group Research Articles

Intra-individual structural covariance network in schizophrenia patients with persistent auditory hallucinations

Neuroimaging studies have revealed that the mechanisms of auditory hallucinations are related to morphological changes in multiple cortical regions, but studies on brain network properties are lacking. This study aims to construct intra-individual structural covariance networks and reveal network changes related to auditory hallucinations. T1-weighted MRI images were acquired from 90 schizophrenia patients with persistent auditory hallucinations (pAH group), 55 schizophrenia patients without auditory hallucinations (non-pAH group), and 83 healthy controls (HC group). Networks were constructed using the voxel-based gray matter volume and the intra-individual structural covariance was based on the similarity between the morphological variations of any two regions. One-way ANCOVA was employed to compare global and local network metrics among the three groups, and edge analysis was conducted via network-based statistics. In the pAH group, Pearson correlation analysis between network metrics and clinical symptoms was conducted. Compared with the HC group, both the pAH group (p = 0.01) and the non-pAH group (p = 3.56 × 10−4) had lower nodal efficiency of the left medial superior frontal gyrus. Compared to the non-pAH group and HC group, the pAH group presented lower nodal efficiency of the temporal pole of the left superior temporal gyrus (p = 1.09 × 10−3; p = 7.67 × 10−4) and right insula (p = 0.02; p = 8.99 × 10−6), and lower degree centrality of the right insula (p = 0.04; p = 1.65 × 10−5). The pAH group had a subnetwork with reduced structural covariance centered by the left temporal pole of the superior temporal gyrus. In the pAH group, the normalized clustering coefficient (r = −0.36, p = 8.45 × 10−3) and small-worldness (r = −0.35, p = 9.89 × 10−3) were negatively correlated with the PANSS positive scale score. This study revealed network changes in schizophrenia patients with persistent auditory hallucinations, and provided new insights into the structural architecture related to auditory hallucinations at the network level.

Diagnostic values of serum BNP, PTX3, and VEGF in acute pulmonary embolism complicated by pulmonary artery hypertension and their correlations with severity of pulmonary artery hypertension.

This paper aimed to unveil the diagnostic values of serum brain natriuretic peptide (BNP), pentraxin 3 (PTX3), and vascular endothelial growth factor (VEGF) in acute pulmonary embolism complicated by pulmonary artery hypertension (APE-PAH) and their correlations with severity of PAH. A total of 153 patients with APE were selected for our study and divided into the PAH and Non-PAH groups according to the measurement of pulmonary artery pressure by echocardiography. Serum BNP levels were measured by chemiluminescence immunoassay, and serum PTX3 and VEGF levels were appraised by ELISA. The predictive values of BNP, PTX3, and VEGF for APE-PAH were evaluated by applying the receiver operating characteristic (ROC) curve. Spearman test was implemented to correlate BNP, PTX3, and VEGF with the severity of PAH. Higher serum levels of BNP, PTX3, and VEGF were observed in the PAH group versus the Non-PAH group (p < .05). ROC curve analysis indicated that BNP, PTX3, and VEGF had acceptable diagnostic value for predicting APE-PAH. Higher serum levels of BNP, PTX3, and VEGF were witnessed in the moderate and severe PAH groups in contrast to the mild PAH group (p < .05), and the levels of these parameters were elevated in the severe PAH group versus the moderate PAH group (p < .05). Spearman correlation analysis signified that serum BNP (r = 0.377), PTX3 (r = 0.488), and VEGF (r = 0.575) levels were positively correlated with the severity of PAH in APE-PAH patients. Serum BNP, PTX3, and VEGF levels are significantly elevated in APE-PAH patients. Serum BNP, PTX3, and VEGF levels are of clinical value in the diagnosis of APE-PAH patients, and serum BNP, PTX3, and VEGF levels are positively correlated with the severity of PAH and can be used as predictors of the severity of PAH.

Clinical characteristics of pulmonary hypertension patients who underwent right heart catheterization in Thailand: 5-year retrospective single-centre study.

Pulmonary arterial hypertension (PAH) is an uncommon and difficult-to-recognize condition. There is still limited evidence on Asian populations. This study aimed to clarify the clinical characteristics of pulmonary hypertension (PH) patients who underwent right heart catheterization (RHC). A single-centre retrospective observational analysis. An observational analysis of adult patients diagnosed with PH by RHC from 2015 to 2019; clinical characteristics and investigations were recorded and compared between PAH and non-PAH. The correlations between maximal tricuspid regurgitation velocity (TRVmax) and mean pulmonary arterial pressure (mPAP) were also estimated. From a total of 243 RHC patients, 79 PH patients were enrolled. The mean (SD) age was 56 (19) years. Dyspnea on exertion (DOE) was the most common clinical manifestation; 70 (89%). Most of them were in functional class II; 58 (73%). PAH was the most prevalent PH group; 46 (58%), followed by PH due to left heart disease; 26 (33%). In the PAH group, congenital heart disease-associated PAH was the most common aetiology; 25 (54%). Compared with the non-PAH group, PAH patients were younger and had fewer comorbidities, particularly atrial fibrillation. There were strong correlations between TRVmax and mPAP (r = 0.62, P < 0.01). PAH was the most prevalent among PH who underwent RHC. The most common presentation of PH patients was DOE. There were strong correlations between parameters from echocardiography and RHC (TRVmax and mPAP).

Decreased low-density lipoprotein and the presence of pulmonary arterial hypertension among newly diagnosed drug-naïve patients with systemic lupus erythematosus: D-dimer as a mediator.

Pulmonary arterial hypertension (PAH) is commonly associated with systemic lupus erythematosus (SLE). The present study investigated the relationship between coagulation and changes in lipid parameters in newly-diagnosed patients with SLE in the presence of PAH and whether the coagulation parameters were mediators between lipids and PAH presence. A total of 301 subjects scheduled for new-onset drug-naïve SLE were consecutively enrolled. Baseline data for patients without PAH and with PAH were gathered and compared. Coagulation and lipid parameters were compared across patients without lipid regulating and anticoagulation medications. Multivariable logistic regression model was applied to examine potential predictors of PAH in SLE. The relationships between them were examined using Spearman's correlation analysis. The relationship between coagulation index and lipids with SLE-PAH was evaluated using mediation analysis. Female patients accounted for 88.0% of the 301 subjects, and the average age was 32 years (range, 25-45 years). A total of 40 patients (13.3%) had PAH, and the average pulmonary artery systolic pressure (sPAP) was 55.825±26.67 mmHg. Patients with PAH were older and had higher levels of fibrin/fibrinogen degradation products (FDP), D-dimer, C-reactive protein, lower levels of complement 3, complement 4 and 25-hydroxy vitamin D3 compared with the non-PAH group. Multivariable logistic regression analysis showed that age and D-dimer were independent predictor factors for PAH. Among patients without lipid regulating and anticoagulation medications, patients in the PAH group had higher levels of D-dimer and FDP, and lower low-density lipoprotein (LDL) levels compared with patients without PAH. There was also a positive relationship between sPAP and D-dimer and FDP, and a negative relationship between sPAP and total cholesterol and LDL. Mediation analysis indicated that 25.61% of the effect of low LDL on PAH presence in systemic lupus erythematosus was mediated by D-dimer. Overall, the effect of low LDL on SLE-PAH appeared to be mediated by D-dimer, which mediated 25.61% of this effect.

Role of Highly Sensitive Cardiac Troponin I in the Prediction of Pediatric Pulmonary Hypertension due to Congenital Heart Disease

Background: CHD is a major health problem in pediatric population. It is associated with abnormal hemodynamic load and neurohormonal activation. Which leads to pulmonary hypertension causing myocardial injury. So, it needs timely intervention. Cardiac troponins are specific for myocardial injury. HscT I enhances accuracy for diagnosis of myocardial injury even in early stage of Pulmonary Hypertension. In recent years role of HscT I suggested to be useful in evaluation of PAH due to CHD in children. Objectives: To analyze the role of HscT I as a diagnostic tool for PAH due to CHD in Children. Methods: This prospective cross-sectional study was conducted in Pediatric cardiology department, BSMMU over a period of 1 year. The study included total 54 patients with moderate to large VSD/PDA. Patients were selected according to inclusion and exclusion criteria. Results: Total 54 cases was divided into two group PAH group (n=27) and non-PAH (n=27) group. Among PAH group 20 patient (74.1%) had VSD and 7 patient (25.9%) had PDA. In non PAH group 15 had VSD (55.6%) and 12 had PDA (44.4%). The mean troponin I level was significantly higher in PAH group than non-PAH group (0.03052±0.0511 vs. 0.0087±0.0075, p=0.03). Conclusion: In this study, there was significant difference between HscT I level of PAH group and non-PAH group and significant positive correlation between HscT I level and mean PAP. As a marker of myocardial injury, HscT I can be a predictor of raised pulmonary arterial pressure in children with post tricuspid left to right shunt.

Clinical characteristics and therapeutic outcomes of pulmonary arterial hypertension secondary to congenital portosystemic shunts.

The aim of this retrospective study was to investigate the clinical characteristics and therapeutic outcomes of pulmonary arterial hypertension (PAH) secondary to congenital portosystemic shunts (CPSS). Thirty-three pediatric patients diagnosed in our institution with CPSS between 2012 and 2019 were enrolled in this study. The patients were divided into PAH and non-PAH groups. The PAH group included 15 patients who presented with unexplained PAH when CPSS was diagnosed. Two patients with microangiopathic hemolytic anemia died of right heart failure shortly after diagnosis. One patient received a liver transplant at the age of 4.3 years and showed a mild decrease in pulmonary artery pressure (PAP) 4 years after the operation. Seven patients underwent one-stage shunt closure at a median age of 2.8 years (1.4-13 years). Follow-up examinations, from 1.6 to 4.1 years after intervention, showed marked reduction of PAP in one patient and stabilization of PAH in six others. However, in one patient who underwent two-stage shunt closure, a marked increase in PAP was noted after partial ligation of the shunt. The remaining four patients received only pulmonary vasodilator therapy, and one of them died of right heart failure 12 years after the PAH diagnosis. The non-PAH group included 18 patients without evidence of PAH upon CPSS diagnosis. Shunt closure was carried out in eight of these patients, but one patient subsequently developed PAH after the resolution of hepatopulmonary syndrome.Conclusion: CPSS may be a more likely cause of unexplained PAH in pediatric patients than previously thought. Shunt closure or liver transplantation may prevent the progression of PAH, or even improve it for the majority of CPSS patients.

P925Cardiac autonomic dysfuntion in adult patient with uncorrected atrial septal defect : a role of pulmonary arterial hypertension

Abstract Background Atrial Septal Defect (ASD) is a congenital heart disease that often under-diagnosed in youth. Atrial septal defect has a poor clinical manifestation at Pulmonary Arterial Hypertension (PAH) condition. Cardiac autonomic dysfunction may occur in PAH due to over sympathetic activation. This condition in general population is associated with increase risk of sudden cardiac death. Despite the case, there are only limited studies which associated cardiac autonomic dysfunction and PAH in adult patient with uncorrected ASD. Purpose This study aims to compare cardiac autonomic dysfunction, using heart rate variability, in adult patient with uncorrected ASD between PAH and non-PAH group. Methods Adult (18+) patient with uncorrected ASD who listed in ASD registry in Indonesia, were selected in this analytical observational study. Patients in whom no other congenital defect and atrial fibrillation in electrocardiogram were eligible for inclusion. Diagnose of PAH was established when mean pulmonary arterial pressure value from right heart catheterization is ≥ 25 mmHg. Arrhythmias and heart rate variability, using Standard Deviation of Normal-Normal (SDNN), High Frequency (HF) and Low Frequency (LF) parameters, were collected from holter monitoring. These procedures were performed on the same day. Results We enrolled 55 adult patients with uncorrected ASD (mean age: 33.3 ± 10.3 years, 89.1% women), consist of 51 secundum ASD, 3 sinus venosus ASD and 1 primum and secundum ASD patient. They were divided into PAH group (28 patients) and non-PAH group (27 patients). Patients in PAH group had a higher incidence of paroxysmal atrial fibrillation and ventricular extrasystole compare to those in non-PAH group (28.5% vs. 14.8% and 75% vs. 70%). All parameters of heart rate variability was significantly reduced in PAH group compare to non-PAH group (SDNN : mean difference 14.5 ± 2.98 ms, CI 95%, P &amp;lt; 0.001; HF : median difference 99.5 ms2, P &amp;lt; 0.001; LF : median difference 129.6 ms2, P &amp;lt; 0.001). Conclusion A marked reduction in cardiac autonomic function occur in adult uncorrected ASD patient with PAH compare to patient with non-PAH, that might be the result of decreasing baroreceptor and increasing chemoreceptor function in PAH.

Normalization of the right heart and the preoperative factors that influence the emergence PAH after surgical closure of atrial septal defect

BackgroundSurgical closure of atrial septal defect (ASD) is contraindicated in the condition with severe pulmonary arterial hypertension (PAH), whereas ASD closure in an effective intervention to normalize the structure and function of the right heart after previously experiencing volume overload due to shunting from the defect. This study aimed to evaluate normalization of the right heart and emergence of PAH after surgical closure of ASD.MethodsThis retrospective study was carried out in 45 patients over 18 years who had undergone surgical closure of ASD. The study has the aim to evaluate the morphological and functional parameters before and after the surgical approach and the preoperative factors that influenced the development of pulmonary arterial hypertension (PAP) after the ASD closure.ResultsThe majority of subjects were female (73.3%) although there were no significant differences between males and females from the various parameters. The average of mPAP in the group that experienced PAH was higher than non-PAH group after ASD closure (p = 0.019, 31.23 ± 12.70 mmHg vs 24.07 ± 13.08 mmHg). Significant differences were found in the Right Atrium (RA) dimension, Right Ventricle (RV) dimension, Tricuspid Regurgitation Velocity (TRV) and Tricuspid Annular Plane Systolic Excursion (TAPSE) between before and at 6 months after ASD closure (p = 0.000, p = 0.000, p = 0.000, p = 000, respectively). The sensitivity of the predictive model to estimate PAH at 6 months after surgical closure of ASD was 58%, with a specificity of 62.5%.ConclusionStructural and functional normalization of the right heart occurs at 6 months after surgical closure of ASD with the decrease of RA and RV dimensions and improvement from tricuspid regurgitation. Emergence of PAH after ASD closure was influenced by higher mPAP before surgical approach.

MIF associated with pulmonary hypertension susceptibility and severity in non-dialysis Chronic kidney disease patients

Pulmonary hypertension (PAH) is one of the more serious complications of Chronic kidney disease (CKD), and its exact pathogenesis has not been clarified. As an upstream proinflammatory factor, macrophage migration inhibitor (MIF) is involved in the occurrence and development of many diseases. This study aimed to detect the relationship between serum MIF and PAH in non-dialysis CKD patients. A total of 382 non-dialysis CKD patients were enrolled in this study. Bio-Plex cytokine assay was used to detect MIF. CKD patients were divided into the PAH group and non-PAH group according to echocardiographic results. Relative risk was determined by logistic regression analysis. The pulmonary artery pressure in the CKD group was higher than that in the control group ( p &lt; 0.01). Pulmonary arterial pressure was higher in stage 4 to 5 CKD patients than in Stage 1 to 3 CKD patients ( p &lt; 0. 01), and the incidence of PAH was also increased ( p &lt; 0. 01). MIF in the CKD group were higher than in the control group ( p &lt; 0.05). MIF in CKD patients with PAH were higher than those without PAH ( p &lt; 0.05). Multivariate logistic regression analysis showed that MIF is correlated with PAH (OR = 10.745; 95% CI 2.288–89.447, p &lt; 0.05). PAH is common in non-dialysis CKD patients, and with the deterioration of kidney disease, the incidence of PAH is gradually increased, indicating that MIF plays an important role in the development of PAH in CKD patients.

The relationship between endothelial progenitor cells and pulmonary arterial hypertension in children with congenital heart disease

BackgroundPulmonary arterial hypertension (PAH) caused by congenital heart disease (CHD) is very common in clinics. Some studies have shown that PAH is related to the number of endothelial progenitor cells (EPCs), but there is no report on the relationship between PAH and the number of EPCs in children with CHD.MethodsIn this study, a total of 173 cases with CHD (from 0 to 6 years old) were collected. According to the mean pulmonary arterial pressure (mPAP) measured by right heart catheterization, these cases were divided into PAH groups (including high PAH group, mPAP> 25 mmHg, n = 32, and the middle PAH group, 20 mmHg ≤ mPAP≤25 mmHg, n = 30) and non-PAH group (mPAP< 20 mmHg, n = 111). Peripheral blood was taken for flow cytometry, and the number of EPCs (CD133+/KDR+ cells) was counted. The number of EPCs /μL of peripheral blood was calculated using the following formula: EPCs /μL = WBC /L × lymphocytes % × EPCs % × 10− 6.ResultsThe median EPCs of the non-PAH group, middle PAH group and high PAH group is 1.86/μL, 1.30 /μL and 0.98/μL, respectively. The mPAP decreases steadily as the level of EPCs increases (P < 0.05). After adjustment of gender, age and BMI, the number of EPCs was significantly associated with a decreased risk of high PAH (OR = 0.37, 95% CI: 0.16–0.87, P < 0.05). However, EPCs was not significantly associated with middle PAH (P > 0.05).ConclusionThe findings revealed that the EPCs and high PAH in patients with CHD correlate significantly and EPCs may become an effective treatment for PAH in patients with CHD. EPCs may be a protective factor of high PAH for children with CHD.

LENGTH OF HOSPITAL STAY AND DISCHARGE OUTCOMES AMONG PATIENTS WITH HIV-ASSOCIATED PULMONARY ARTERIAL HYPERTENSION (HIV-PAH) IN THE UNITED STATES

SESSION TITLE: Monday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM PURPOSE: Studies have shown that PAH is the leading cause of hospitalization and death in patients with HIV associated PAH (HIV-PAH). However, not much is known about the length of hospital stay (LOS), an indicator of healthcare resource utilization and the different discharge outcomes in hospitalized patients with HIV-PAH compared to patients with HIV without PAH (HIV non-PAH) METHODS: We conducted a retrospective analysis of the National Hospital Discharge Survey data for the time period 2001–2010. Cases of HIV infection or AIDS were identified using ICD-9 codes 042, 043, 044, 079.53, and V08 in any of the discharge diagnoses. PAH was identified using ICD-9 code 416.0. We determined the prevalence of HIV-PAH in the cohort stratified by age, sex, and race. LOS in patients with HIV-PAH was compared with patients that are HIV non-PAH. We also evaluated and compared the discharge status between the two groups. In-hospital mortality in both groups was calculated based on patients whose discharge status was listed as death and logistic regression was used to determine the odds of mortality. Data analysis was conducted using STATA 13 for MAC RESULTS: Seven hundred ninety-seven of 1,944,388 discharged patients with HIV infection were identified as having HIV-PAH (prevalence of 0.04%). The mean age (±SD) of the cohort was 44 years (±7.5) and African Americans (AA) had a higher prevalence of HIV-PAH than whites (0.05% vs. 0.009%). HIV-PAH prevalence was also higher in females than males (0.061% vs. 0.037%). LOS was longer in patients with HIV-PAH than HIV non-PAH (9.8 days vs. 5.3 days, P < 0.05). The most common discharge status for patients with HIV-PAH was discharge to home (81.7%) followed by leaving against medical advice (LAMA) (8.1%), death (8%), and long-term acute facilities (LTAC) (1.8%). While in patients with HIV non-PAH, 74% were discharged home, 2% left against medical advice (LAMA), 4.2% were listed as dead, and 7.7% transferred to LTAC. The differences between the percentage of patients in both groups were statistically significant for all categories of discharge status reviewed (P < 0.05). Patients with HIV-PAH were more likely to have a mortality outcome at discharge compared to HIV non-PAH patients independent of race or sex (OR 2.98. 95% CI: 1.67 – 3.2). CONCLUSIONS: Our study shows a significantly higher LOS and increased risk of mortality in patients with HIV-PAH compared to HIV non-PAH. Though the HIV-PAH group had a higher percentage of patients discharged home, the significantly higher proportion of patients LAMA compared to the HIV non-PAH group may lead to poorer outcomes overall. CLINICAL IMPLICATIONS: PAH is associated with increased healthcare resource utilization and poorer clinical outcomes in patients with HIV compared to HIV patients without PAH. Future studies should evaluate the predictors of in-patient mortality and different discharge outcomes in patients with HIV-PAH. DISCLOSURES: No relevant relationships by Abimbola Chris-Olaiya, source=Web Response No relevant relationships by Valery Effoe, source=Web Response No relevant relationships by Mesfin Fransua, source=Web Response No relevant relationships by Titilope Olanipekun, source=Web Response No relevant relationships by Gloria Westney, source=Web Response

Characteristics and risk factors for pulmonary arterial hypertension associated with primary Sjögren's syndrome: 15 new cases from a single center.

This study aimed to retrospectively describe 15 new primary Sjögren's syndrome-pulmonary arterial hypertension (pSS-PAH) cases confirmed by right heart catheterization (RHC). Demographic and clinical characteristics were analyzed and risk factors for PAH in pSS were explored. We retrospectively described 15 new pSS-PAH cases confirmed by RHC referred to our institution between January 2013 and March 2018. We present PAH and pSS characteristics, hemodynamic evaluations, medical management, and outcomes. A matched case control study was carried out to determine the risk factors of PAH in pSS compared with pSS-non-PAH patients. All patients were female with a mean age at PAH diagnosis of 52.9±14.6years. The delay between the first symptom and PAH diagnosis was 18.7±19.7months. The most common primary manifestation at PAH onset was exertional dyspnea (13/15). At diagnosis of PAH, PAH was severe with a mean pulmonary artery pressure of 48.8±13.7mmHg (range, 27-72mmHg) and a mean cardiac index of 2.3±0.6L/min/m2 (range, 1.47-3.41L/min/m2 ). Compared with the pSS-PAH without pericardial effusion, pSS-PAH with pericardial effusion had larger right arterial (53 [45-56.75] vs 38 [35.5-46.5], P=.018) and right ventricular sizes (47 [42.75-51.25] vs 36 [32.5-41], P=.007). Compared with the pSS non-PAH group, we identified 2 risk factors for PAH in pSS: pericardial effusion (odds ratio [OR] [95% CI], 14.29 [1.14-166.67], P=.039) and liver involvement (OR [95% CI], 14.71 [1.14-166.67], P=.035). For pSS patients, PAH can be the first manifestation. We believe that systemic evaluation, especially in patients with pericardial effusion and liver involvement, is important to identify high-risk patients for PAH, improving their prognosis.

Unique wreath-like smooth muscle proliferation of the pulmonary vasculature in pulmonary veno-occlusive disease versus pulmonary arterial hypertension

Pulmonary veno-occlusive disease (PVOD) is a rare but fatal cause of pulmonary hypertension reported to be linked to mutations of eukaryotic initiation factor 2 alpha kinase 4 (EIF2AK4), also known as general control nonderepressible 2 kinase (GCN2). PVOD is difficult to diagnose and often initially misdiagnosed as other types of idiopathic pulmonary arterial hypertension (IPAH). To rapidly and correctly identify PVOD patients and explore the possible pathogenesis, we thoroughly investigated histopathological features and GCN2 protein levels in non-PAH, PVOD and PAH patients. Lung specimens were examined for histopathological changes, including those of pulmonary arteries and veins, by Masson's trichrome, modified Verhoeff's and α-SMA staining in the PVOD, IPAH, and non-PAH groups. GCN2 and α-SMA expression in lung tissue was examined by immunohistochemistry and western blotting. PVOD and IPAH patients showed significant intimal and medial thickening of muscular pulmonary arteries compared with non-PAH patients. PVOD patients had more prominent intimal and medial thickening of muscular pulmonary veins than the other two groups. Interestingly, specialized muscle bundles surrounding the tunica adventitia of the pulmonary artery and vein were observed in PVOD patients. A significant decrease in GCN2 expression in the PVOD group was confirmed by immunohistochemistry and western blotting. Our study is the first to show remarkable histological structures, including the wreath-like arrangement of a hyperplastic muscle bundle in the adventitia of pulmonary arteries, in PVOD patients as a diagnostic clue and to disclose the biological difference between PAH and PVOD in a Taiwanese population.

Whole blood viscosity in systemic sclerosis: a potential biomarker of pulmonary hypertension?

Our goal was to determine if whole blood viscosity (WBV) can be used to predict the risk of pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc). Patients with SSc were analyzed. Out of 107 patients, 26 patients, found to have confirmed diagnosis of PAH, were classified as those with (n= 26, PAH group) and without PAH (n= 81, non-PAH group). We calculated estimated WBV at both high (HSR) and low shear rates (LSR) from hematocrit and total serum protein levels. Total protein levels were significantly higher and the anti-centromere antibody (ACA) was more frequent in the PAH group. Furthermore, anti-topoisomerase antibody (anti-scl-70) was significantly less frequent in the PAH group. The WBV values were significantly higher at HSR (16.68 ± 0.38 vs. 16.24 ± 0.58; p< 0.001) and at LSR (51.81 ± 7.21 vs. 42.97 ± 11.76; p< 0.001) in PAH group. The multivariate analysis revealed that the WBV at both shear rates independently designated the presence of PAH in SSc patients. The ROC curve showed that the sensitivity and specificity of LSR and HSR were 92.3% and 61.7% (AUC 0.759, p< 0.001), and 88.5% and 65.4% (AUC 0.770, p< 0.001) with a cutoff value of 43.56 and 16.32 for WBV, respectively. Higher WBV levels in SSc patients were an independent indicator for PAH development in this cohort. WBV-LSR and WBV-HSR values might help exclude the PAH possibility in patients diagnosed with SSc and remain as an independently associated biomarker for follow-up of these patients for future risk of PAH development. Findings remain to be confirmed by other cohorts.Key Points• The most important cause of morbidity and mortality in systemic sclerosis patients is considered to be pulmonary arterial hypertension.• When the symptoms of PAH are not recognized earlier in the course of the SSc, the prognosis might be worse.• Higher whole blood viscosity levels in scleroderma patients with PAH was an independent indicator for PAH development.

Validation of claims‐based algorithms for pulmonary arterial hypertension

Administrative claims studies do not adequately distinguish pulmonary arterial hypertension (PAH) from other forms of pulmonary hypertension (PH). Our aim is to develop and validate a set of algorithms using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes and electronic medical records (EMR), to identify patients with PAH. From January 2012 to August 2015, the EMRs of patients with ICD-9-CM codes for PH with an outpatient visit at the University of Texas Medical Branch were reviewed. Patients were divided into PAH or non-PAH groups according to EMR encounter diagnosis. Patient demographics, echocardiography, right heart catheterization (RHC) results, and PAH-specific therapies were assessed. RHC measurements were reviewed to categorize cases as hemodynamically determined PAH or not PAH. Weighted sensitivity, specificity, and positive and negative predictive values were calculated for the developed algorithms. A logistic regression analysis was conducted to determine how well the algorithms performed. External validation was performed at the University of Virginia Health System. The cohort for the development algorithms consisted of 683 patients with PH, PAH group (n = 191) and non-PAH group (n = 492). A hemodynamic diagnosis of PAH determined by RHC was recorded in the PAH (26%) and non-PAH (3%) groups. The positive predictive value for the algorithm that included ICD-9-CM and PAH-specific medications was 66.9% and sensitivity was 28.2% with a c-statistic of 0.66. The positive predictive value for the EMR-based algorithm that included ICD-9-CM, EMR encounter diagnosis, echocardiography, RHC, and PAH-specific medication was 69.4% and a c-statistic of 0.87. A validation cohort of 177 patients with PH examined from August 2015 to August 2016 using EMR-based algorithms yielded a similar positive predictive value of 62.5%. In conclusion, claims-based algorithms that included ICD-9-CM codes, EMR encounter diagnosis, echocardiography, RHC, and PAH-specific medications better-identified patients with PAH than ICD-9-CM codes alone.

Effective shunt closure for pulmonary hypertension and liver dysfunction in congenital portosystemic venous shunt.

Congenital portosystemic venous shunt (CPSVS) is a rare vascular malformation with a high risk of mortality from pulmonary arterial hypertension (PAH), but the treatment outcome of CPSVS closure remains elusive. Our aim was to investigate the clinical features and establish the optimal management of CPSVS with or without PAH. Twenty-four patients with CPSVS treated in Kyushu University Hospital between 1990 and 2015 were enrolled in this study. The patients were divided into a PAH group (n = 9) and a non-PAH group (n = 15). Clinical characteristics and outcomes were evaluated. The first manifestation of CPSVS at diagnosis (28.5 [1-216] months) was hypergalactosemia in 13 (54%) or PAH in six (25%) patients. PAH was the cause of all three deaths. The PAH group had higher levels of serum total bile acid, manganese, and total bilirubin, along with higher pulmonary vascular resistance index (PVRI) than the non-PAH group (7.2 [5.1-38.1] vs 1.2 [0.5-3.3] unit/m2 , P < 0.001). Five of nine PAH patients underwent CPSVS closure at a median of 38 months (range 21-118) after PAH diagnosis. Pulmonary artery pressure improved after CPSVS closure with PAH-specific therapy, but normal range was not achieved. CPSVS closure improved the hepatic synthetic function of four PAH patients. Eigh-t of 15 non-PAH patients who received CPSVS closure did not develop PAH for a median of 34.5 months (range 6-164) after the procedure. CPSVS closure with PAH-specific therapy successfully controlled PAH. Early CPSVS closure may prevent the occurrence and progression of PAH with CPSVS.

Pulmonary Arterial Hypertension after Ibuprofen Treatment for Patent Ductus Arteriosus in Very Low Birth Weight Infants

To describe the clinical course and risk factors for pulmonary arterial hypertension (PAH) after ibuprofen treatment to close patent ductus arteriosus. All neonates weighing < 1500 g at birth who received ibuprofen to close patent ductus arteriosus and were admitted to Seoul National University Children's Hospital's neonatal intensive care unit in 2010-2014 were eligible for this study. The study population was divided into the PAH and non-PAH groups, and medical records were retrospectively reviewed. Of the 144 eligible infants, 10 developed PAH (6.9%). Relative to the non-PAH group, the PAH group exhibited greater respiratory severity and more frequent severe bronchopulmonary dysplasia or death before 36 weeks postmenstrual age. Multivariable analysis demonstrated that lower gestational age, birth weight in less than the third percentile for age, maternal hypertension of pregnancy, and oligohydramnios were risk factors for developing PAH after ibuprofen treatment. A high incidence of PAH after ibuprofen treatment was observed in the study population. Furthermore, younger gestational age and several prenatal conditions were identified as risk factors for developing PAH after ibuprofen treatment. Additional large cohort studies are necessary to confirm our results.

Prevalence and risk factors for pulmonary arterial hypertension in end-stage renal disease patients undergoing continuous ambulatory peritoneal dialysis

Background: Pulmonary arterial hypertension (PAH) is a major complication in renal failure patients, but very little information is available on the cardiovascular parameters in these patients. The prevalence and risk factors for PAH were systematically evaluated in patients with end-stage renal diseases (ESRD) undergoing continuous ambulatory peritoneal dialysis (CAPD). Methods: Between January 2010 and January 2014, 177 ESRD patients (85 males and 92 females) undergoing CAPD therapy were recruited. General data, biochemical parameters and echocardiographic findings were collected and PAH risk factors studied. Results: Study participants consisted of 65 patients (36.52%) with PAH (PAH group) and 112 patients without PAH (non-PAH group). The interdialytic weight gain, systolic blood pressure and diastolic blood pressure (DBP), mean arterial pressure and hypertensive nephropathy incidence in the PAH group were significantly higher than the non-PAH group (all p < 0.05). There were significant differences between PAH group and non-PAH group in C-reactive protein-positive rate, N-terminal pro-brain natriuretic peptide (NT-proBNP), hemoglobin, prealbumin and serum albumin levels (all p < 0.05). Compared with non-PAH group, PAH group showed significant increases in right ventricular internal diameter (RVID), right ventricular outflow tract diameter (RVOTD), main pulmonary artery diameter, left atrial diameter (LAD), left ventricular end-diastolic diameter, interventricular septal thickness, left ventricular mass index, early diastolic mitral annulus velocity and valve calcification incidence (all p < 0.05), and decreased left ventricular ejection fraction (LVEF), tricuspid annulus plane systolic excursion (TAPSE) and early diastolic blood flow peak and mitral annulus velocity (E/E’) (all p < 0.05). Logistic regression analysis revealed that DBP, NT-proBNP, LAD, RVID, RVOTD, LVEF, TAPSE and E/E’ are major risk factors for PAH. Conclusion: We observed a high incidence of PAH in ESRD patients undergoing CAPD. Logistic regression analysis revealed that DBP, NT-proBNP, LAD, RVID, RVOTD, LVEF, TAPSE and E/E’ are high-risk factors for PAH in ESRD patients undergoing CAPD.

Value of intravascular ultrasound in the assessment of pulmonary vascular properties and mortality in patients with pulmonary artery hypertension associated with connective tissue diseases

To investigate the value of intravascular ultrasound (IVUS) on assessing pulmonary vascular properties (PVPs) and its relationship with hemodynamics, and mortality rate in patients with pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD). Patients (n=51) with highly suspected PAH-CTD were prospectively enrolled in our department between July 2011 and March 2014. All patients underwent right heart catheterization (RHC) and IVUS, and were divided into 3 groups: PAH-CTD (n=25), PAH due to other reasons (n=15), and non-PAH control group (n=11). Based on IVUS, PAH patients were divided into distal (n=22) and proximal (n=18) remodeling subtypes.A total of 408 pulmonary segments were detected by IVUS, and all patients were followed up to (19 ± 10) months. IVUS evidenced higher mean wall thickness (MWT) ((0.30 ± 0.02) mm and (0.33 ± 0.02) mm vs. (0.21 ± 0.02) mm) and percentage of MWT (WTP) ((13.62 ± 0.59)% and (14.39 ± 0.77)% vs. (9.57 ± 0.97)%) values in PAH patients compared to control patients (all P<0.01). Pulmonary vascular mechanical properties (PVMPs) including compliance ((8.85 ± 0.82) × 10(-2)mm(2)/mmHg(1 mmHg=0.133 kPa) and (6.28 ± 0.65) × 10(-2)mm(2)/mmHg vs. (41.59 ± 5.02) × 10(-2) mm(2)/mmHg, all P<0.01), distensibility ((0.83 ± 0.09)%/mmHg and (0.55 ± 0.06)%/mmHg vs. (3.16 ± 0.38) %/mmHg, all P<0.01), elastic modulus ((169.25 ± 15.10) mmHg and (253.00 ± 22.11) mmHg vs.(43.78 ± 4.27) mmHg, all P<0.01) and stiffness index β (4.19 ± 0.41 and 5.18 ± 0.34 vs. 2.39 ± 0.27, P<0.05 or 0.01) in PAH groups were all significantly worse than in control group (all P<0.01). An inverse exponential association was found between PVMPs and hemodynamics with R(2) ranging from 0.544 to 0.777 (P<0.001). PVMPs tended to be better in group PAH-CTD than in PAH group due to other reasons.Mortality rate was similar between the two PAH groups, while PAH with distal remodeling subtype was linked with significantly higher mortality rate than PAH with the proximal remodeling subtype (23 % vs. 0, HR=10.14, P<0.05). IVUS plays an important role in the assessment of PAH-CTD patients in terms of evaluating PVPs and predicting mortality rate. PAH patients have deteriorated PVPs, but PVMPs tended to be better in PAH-CTD than in PAH patients due to other reasons. The mortality rate was similar between PAH groups, while PAH patients with the distal remodeling subtype is linked with a higher mortality rate than PAH patients with the proximal remodeling subtype.

Low WSS and High OSI Measured by 3D Cine PC MRI Reflect High Pulmonary Artery Pressures in Suspected Secondary Pulmonary Arterial Hypertension.

Purpose:Institutional Review Board (IRB)-approved prospective study was conducted to test whether objective and quantitative hemodynamic markers wall shear stress (WSS) and oscillatory shear index (OSI) measured by three-dimensional (3D) cine phase-contrast (PC) can reflect pulmonary arterial hypertension (PAH).Patients and Methods:Seventeen consecutive patients of suspected secondary PAH were examined for pulmonary artery pressures (PAPs) with right heart catheterization (RHC) and three-dimensional (3D) cine PC MR. Based on the RHC data, patients were subdivided into two groups of 12 non-PAH (median age of 74.5 years) and 5 PAH (median age of 77 years) patients. Based on 3D cine PC magnetic resonance (MR), hemodynamic parameters including spatially averaged systolic WSS (sWSS), diastolic WSS (dWSS), mean WSS (mWSS), OSI and blood vessel section area (BVSA) at the pulmonary arterial trunk were calculated. Streamline images in the pulmonary arteries were also assessed. All the parameters were compared between non-PAH and PAH groups.Results:sWSS (N/m2) and mWSS (N/m2) of PAH group was lower than that of non-PAH group (0.594 ± 0.067 vs. 0.961 ± 0.590, P = 0.001), (0.365 ± 0.035 vs. 0.489 ± 0.132, P = 0.027). OSI of PAH group was higher than that of non-PAH (0.214 ± 0.026 vs. 0.130 ± 0.046, P = 0.001). sWSS, mWSS, and dWSS were inversely correlated and OSI was positively correlated to mean PAP or systolic PAP with r values of –0.638 (P = 0.005), –0.643 (P = 0.005), –0.485 (P = 0.049), and 0.625 (P = 0.007); or –0.622 (P = 0.008), –0.629 (P = 0.007), –0.484 (P = 0.049), and 0.594 (P = 0.012), respectively. sWSS was also inversely correlated to BVSA with r value of –0.488 (P = 0.049), and OSI was correlated to BVSA with r value of 0.574 (P = 0.016). Vortex or helical flows were observed more frequently in PAH patients.Conclusions:The low sWSS and mWSS as well as high OSI measured with 3D cine PC MR could be potential hemodynamic markers for the increased PAP in suspected secondary PAH patients.