Risk Of Pulmonary Hypertension Research Articles

Racial differences in venous thromboembolism: A surveillance program in Durham County, North Carolina

BackgroundVenous thromboembolism (VTE) affects approximately 1–2 individuals per 1000 annually and is associated with an increased risk for pulmonary hypertension, postthrombotic syndrome, and recurrent VTE. ObjectiveTo determine risk factors, incidence, treatments, and outcomes of VTE through a 2‐year surveillance program initiated in Durham County, North Carolina (population approximately 280,000 at time of study). Patients/MethodsWe performed a retrospective analysis of data actively collected from three hospitals in Durham County during the surveillance period. ResultsA total of 987 patients were diagnosed with VTE, for an annual rate of 1.76 per 1000 individuals. Hospital‐associated VTE occurred in 167 hospitalized patients (16.9%) and 271 outpatients who were hospitalized within 90 days of diagnosis (27.5%). Annual incidence was 1.98 per 1000 Black individuals compared to 1.25 per 1000 White individuals (p < 0.0001), and Black individuals with VTE were younger than White individuals (p < 0.0001). Common risk factors included active cancer, prolonged immobility, and obesity, and approximately half were still taking anticoagulant therapy 1 year later. A total of 224 patients died by 1 year (28.5% of patients for whom outcomes could be confirmed), and Black patients were more likely to have recurrent VTE than White patients during the first 6 months following initial presentation (9.4% vs. 4.1%, p = 0.01). ConclusionsOngoing surveillance provides an effective strategy to identify patients with VTE and monitor treatment and outcomes. We demonstrated that hospital‐associated VTE continues to be a major contributor to the burden of VTE and confirmed the higher incidence of VTE in Black compared to White individuals.

Systemic Sclerosis-Specific Antibodies: Novel and Classical Biomarkers

Disease-specific autoantibodies are considered the most important biomarkers for systemic sclerosis (SSc), due to their ability to stratify patients with different severity and prognosis. Anti-nuclear antibodies (ANA), occurring in subjects with isolated Raynuad’s phenomenon, are considered the strongest independent predictors of definite SSc and digital microvascular damage, as observed by nailfold videocapillaroscopy. ANA are present in more than 90% of SSc, but ANA negativity does not exclude SSc diagnosis: a little rate of SSc ANA negative exists and shows a distinct subtype of disease, with less vasculopathy, but more frequent lower gastrointestinal involvement and severe disease course. Anti-centromere, anti-Th/To, and anti-Topoisomerase I antibodies could be considered as classical biomarkers, covering about 60% of SSc and defining patients with well-described cardio-pulmonary complications. In particular, anti-Topoisomerase I represent a risk factor for development of diffuse cutaneous involvement and digital ulcers in the first 3 years of disease, as well as severe interstitial lung disease (ILD). Anti-RNA polymerase III is a biomarker with new clinical implications: very rapid skin thickness progression, gastric antral vascular ectasia, the occurrence of synchronous cancers, and possible association with silicone breast implants rupture. Moreover, novel SSc specific autoantibodies have been globally described in about 10% of “seronegative” SSc patients: anti-elF2B, anti-RuvBL1/2 complex, anti-U11/U12 RNP, and anti-BICD2 depict specific SSc subtypes with severe organ complications. Many autoantibodies could be considered markers of overlap syndromes, including SSc. Anti-Ku are found in 2–7% of SSc, strictly defining the PM/SSc overlap. They are associated with synovitis, joint contractures, myositis, and negatively associated with vascular manifestation of disease. Anti-U3RNP are associated with a well-defined clinical phenotype: Afro-Caribbean male patients, younger at diagnosis, and higher risk of pulmonary hypertension and gastrointestinal involvement. Anti-PM/Scl define SSc patients with high frequency of ILD, calcinosis, dermatomyositis skin changes, and severe myositis. The accurate detection of autoantibodies SSc specific and associated with overlap syndromes is crucial for patients’ stratification. ANA should be correctly identified using indirect immunofluorescent assay and a standardized way of patterns’ interpretation. The gold-standard technique for autoantibodies’ identification in SSc is still considered immunoprecipitation, for its high sensitivity and specificity, but other assays have been widely used in routine practice. The identification of SSc autoantibodies with high diagnostic specificity and high predictive value is mandatory for early diagnosis, a specific follow-up and the possible definition of the best therapy for every SSc subsets. In addition, the validation of novel autoantibodies is mandatory in wider cohorts in order to restrict the gap of so-called seronegative SSc patients.

Risk Stratification and Outcomes in Patients With Pulmonary Hypertension: Insights into Right Ventricular Strain by MRI Feature tracking.

Despite a recommended multidimensional approach for pulmonary hypertension (PH) risk stratification and guidance of treatment decisions, this may not always be achievable in patients with advanced disease. One issue is the lack of an imaging modality to assess right ventricular (RV) structure and function abnormalities. To explore the risk stratification and prognostic value of cardiac MR feature tracking (MR-FT)-derived RV strain. Retrospective. A total of 80 patients with idiopathic pulmonary artery hypertension (N=52) or chronic thromboembolic PH (N=28). A 1.5 T or 3.0 T, balanced steady-state free precession sequence. All patients underwent laboratory testing, right heart catheterization, and MR imaging (and in 37 cases, a cardiopulmonary exercise test was also performed) within a 1-month period. Cardiac functional parameters and both global longitudinal strain (GLS) and global circumferential strain (GCS) were analyzed. Patients were stratified into low, intermediate, and high-risk groups by guideline suggested stratified values of risk factors. The combined endpoint was death or hospitalization for congestive heart failure assessed during follow-up since the date of MR examination. Kolmogorov-Smirnov's test, independent-sample t-tests, Wilcoxon's rank-sum tests, one-way analysis of variance, χ2 tests or Fisher's exact test, receiver operating characteristic analysis, Kaplan-Meier survival analysis, and Cox regression analysis. A P value < 0.05 was considered statistically significant. The median follow-up duration was 3.4 years. Thirty-five patients presented with combined endpoint including 10 cardiac deaths. RV structural and deformation impairments were significantly associated with combined endpoint (ejection fraction: 31.3% ± 13.2% vs. 38.0% ± 14.8%, hazard ratio [HR: 0.974; GLS: -14.5 [-18.6, -10.9] % vs. -20.4 [-26.0, -13.2] %, HR: 1.071; GCS: -9.8 [-14.5, -7.3] % vs. -12.3 [-19.9, -8.4] %, HR: 1.059). There were significant differences in RVGLS among low, intermediate, and high-risk groups (-19.3% ± 7.2% vs. -17.3% ± 9.4% vs. -11.5% ± 4.4% by cardiac functional class, -21.8% ± 7.3% vs. -19.4% ± 8.2% vs. -12.7 ± 5.3% by NT-proBNP, -19.7% ± 7.7 vs. -15.8% ± 6.5% vs. -12.6% ± 8.2% by cardiac index). RV deformation may aid risk stratification in patients with PH, providing crucial information for RV remodeling, pulmonary hemodynamic condition and exercise capacity. 3 TECHNICAL EFFICACY: Stage 2.

Neonatal morbidity after fetal exposure to antipsychotics: a national register-based study

ObjectiveTo investigate the admission rate to neonatal care and neonatal morbidity after maternal use of antipsychotics during pregnancy.DesignA population-based register study.SettingInformation on all singleton births between July 2006 and December...

Novel biomarkers in systemic sclerosis

Introduction. Due to the heterogeneous nature of systemic sclerosis, it is difficult to predict disease progression and complications. Despite the discovery of novel autoantibodies associated with systemic sclerosis (SSc), there is an unmet need for biomarkers for diagnosis, disease progression, and response to treatment. Materials and methods. An analytical, qualitative study was performed with a narrative review of literature in the form of a synthesis article. Relevant primary sources published in 2020-2022 were identified and selected, using data extraction and analysis. Results. Anti-citrullinated protein/peptide antibody could be useful in identifying patients with a more prominent joint disease. Of most interest, the anti-carbamylated protein antibodies (anti-CarP) could be a relevant biomarker related to fibrotic skin and lung disease. Positive anti-RNA (Ribonucleic acid) polymerase III antibody and antinuclear antibodies (ANA) negativity were significantly associated with GAVE (gastral antral vascular ectasia). Autoantibodies against telomeres may help identify systemic sclerosis with lung disease. Osteopontin links myeloid activation and disease progression in systemic sclerosis. CTRP (C1q tumor necrosis factor-related proteins) 9 protein levels may be biomarker of lung disease severity. CD (cluster differentiation) 21-low B cells are linked to vascular damage. L-tyrosine, L-tryptophan, and 1-methyl-adenosine distinguished healthy controls from SSc patients. L-leucine, L-isoleucine, xanthosine, and adenosine monophosphate differentiated between progressing and stable SSc-ILD. CECs (circulating endothelial cells) are a direct indicator of systemic vascular damage. Levels of the protein, galectin-3, are associated with heart involvement in people with systemic sclerosis. Low levels of the galectin-10 protein (Gal-10) in scleroderma patients associate with inflammation and vascular changes in the lungs, leading to pulmonary arterial hypertension (PAH). High levels of the CD146 protein may be a potential biomarker in identifying people with systemic sclerosis. Blood levels of the protein endocan increased in scleroderma patients who are at risk for pulmonary arterial hypertension. FLCs (free light chain) could be employed as useful potential biomarker of early diagnosis and to follow disease activity. Conclusions. Novel discovered biomarkers could predict disease development, activity, and severity of diverse organ involvement, predict risk of complications of systemic sclerosis.

PROGNOSTIC STRATIFICATION ROLE OF STROKE VOLUME INDEX IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION AT INTERMEDIATE RISK

TYPE: Abstract TOPIC: Pulmonary Vascular Disease PURPOSE: Current guidelines stratify the risk of pulmonary arterial hypertension (PAH) patients with a multiparametric approach. This risk assessment and a simplified risk table have been recently proposed and validated. However, most patients are classified in the intermediate risk category. We evaluate the prognostic value of stroke volume index (SVI) to further stratify intermediate-risk patients. METHODS: 621 treatment naïve patients with PAH referred to a single Centre were assessed were assessed at baseline and at the first 3-4 months follow-up after starting PAH-specific therapy with right heart catheterization, brain natriuretic peptide plasma levels, 6-min walking distance and WHO functional class. We applied the simplified risk assessment strategy recently validated in the Bologna cohort of patients. We assessed the prognostic value of SVI using Cox regression analysis and we considered the value of SVI that best discriminate prognosis to discriminate intermediate risk patients at follow-up into intermediate-low and intermediate-high risk. RESULTS: SVI is an independent predictor of prognosis in intermediate-risk PAH patients at first follow-up. The value of SVI that best discriminate prognosis is 35 ml/m2 (AUC 0.63; sensitivity 58%; specificity 68%). This value is able to discriminate intermediate risk patients at follow-up into intermediate-low and intermediate-high risk patients that have a significantly different prognosis (p-value= 0.010). CONCLUSIONS: SVI assessed at first follow-up is predictive of prognosis and the cut-point value of 35 ml/m2 is able to further stratify the survival of intermediate risk PAH patients. CLINICAL IMPLICATIONS: SVI should be used to further stratify intermediate-risk PAH patients after first-line treatment to tailor the potency of triple sequential combination therapy needed. DISCLOSURE: Nothing to declare. KEYWORD: stroke volume index

Vascular Disorders of Pregnancy Increase Susceptibility to Neonatal Pulmonary Hypertension in High-Altitude Populations.

Preeclampsia and fetal growth restriction increase cardiopulmonary disease risk for affected offspring and occur more frequently at high-altitude (≥2500 m). Retrospective studies indicate that birth to a preeclampsia woman at high altitude increases the risk of pulmonary hypertension (PH) in later life. This prospective study asked whether preeclampsia with or without fetal growth restriction exaggerated fetal hypoxia and impaired angiogenesis in the fetal lung, leading to neonatal cardiopulmonary circulation abnormalities and neonatal or infantile PH. We studied 79 maternal-infant pairs (39 preeclampsia, 40 controls) in Bolivia (3600-4100 m). Cord blood erythropoietin, hemoglobin, and umbilical artery and venous blood gases were measured as indices of fetal hypoxia. Maternal and cord plasma levels of angiogenic (VEGF [vascular endothelial growth factor]) and antiangiogenic (sFlt1 [soluble fms-like tyrosine kinase]) factors were determined. Postnatal echocardiography (1 week and 6-9 months) assessed pulmonary hemodynamics and PH. Preeclampsia augmented fetal hypoxia and increased the risk of PH in the neonate but not later in infancy. Pulmonary abnormalities were confined to preeclampsia cases with fetal growth restriction. Maternal and fetal plasma sFlt1 levels were higher in preeclampsia than controls and positively associated with PH. The effect of preeclampsia with fetal growth restriction to increase fetal hypoxia and sFlt1 levels may impede normal development of the pulmonary circulation at high altitude, leading to adverse neonatal pulmonary vascular outcomes. Our observations highlight important temporal windows for the prevention of pulmonary vascular disease among babies born to highland residents or those with exaggerated hypoxia in utero or newborn life.

A Nomogram for Predicting the Risk of Pulmonary Hypertension for Patients with Chronic Obstructive Pulmonary Disease.

BackgroundPulmonary hypertension (PH) is a life-threatening complication of chronic obstructive pulmonary disease (COPD). Timely diagnosis of PH in COPD patients is vital to achieve proper treatment; however, there is no algorithm to identify those at high risk. We aimed to develop a predictive model for PH in patients with COPD that provides individualized risk estimates.MethodsA total of 527 patients with COPD who were admitted to our hospital between May 2019 and December 2020 were retrospectively enrolled in this study. Using echocardiographic results as a standard, patients were stratified into a moderate- or high-PH probability group and a low-PH probability group. They were randomly grouped into either the training set (n = 368 patients) or validation set (n = 159 patients) in a ratio of 7:3. We utilized the least absolute shrinkage and selection operator (LASSO) regression model to select the feature variables. The characteristic variables selected in the LASSO regression were analyzed using multivariable logistic regression to construct the predictive model. The predictive model was displayed using a nomogram. We used the receiver operating characteristic curve, calibration curve, and clinical decision curve analysis (DCA) to evaluate model performance, and internal validation was assessed.ResultsThe predictive factors included in the prediction model were Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage, emphysema, PaCO2, NT-pro-BNP, red blood cell (RBC) distribution width-standard deviation (RDW-SD), and neutrophil/lymphocyte ratio (NLR). The predictive model yielded an area under the curve (AUC) of 0.770 (95% confidence interval [CI], 0.719–0.820); in the internal validation, the AUC was 0.741 (95% CI, 0.659–0.823). The predictive model was well calibrated, and the DCA showed that the proposed nomogram had strong clinical applicability.ConclusionThis study showed that a simple nomogram could be used to calculate the risk of PH in patients with COPD which can be useful for the individualized clinical management of COPD patients who may be occur with PH. Further studies need to be confirmed by larger sample sizes and validated in the stable COPD population.

Multi‐Omics Integration and the Development of Gestational High Altitude Induced Pulmonary Arterial Hypertension

High altitude (&gt; 2500 meters) during pregnancy reduces oxygen delivery to the fetus (i.e., gestational hypoxia), causing abnormal fetal lung development. The pulmonary arteries become thicker and less functional, increasing the risk of pulmonary hypertension, which is a multiorgan disease that promotes right heart failure and under five‐years mortality rate. Our previous work showed endoplasmic reticulum stress and metabolomic alterations in fetal sheep pulmonary arteries indicative of an unregulated inflammatory response after gestational hypoxia. To understand the relationships between inflammation, vascular remodeling, and pulmonary arterial hypertension development, we examined the omic links between the pulmonary arteries and plasma exosomes in fetal sheep exposed to high altitude (3801 meters) for the majority of the pregnancy (110+ days out of 138‐141 days of pregnancy). Specifically, metabolomics and proteomic analyses from the pulmonary arteries and transcriptomic analysis of plasma exosomes were integrated from fetal sheep to understand the mechanisms driving this multiorgan disease. Sixteen miRNAs and 75 proteins were differentially expressed between normoxic and hypoxic samples. Gestational hypoxia resulted in significant changes in 90 metabolites in fetal pulmonary arteries. These results show exosomal microRNA are linked with pulmonary artery proteins and metabolites important to cell membrane composition which might explain their role in the facilitation of changes in vascular remodeling, inflammation, and cell signaling. Top canonical pathways noted in omics data integration were acute phase response signaling, atherosclerosis signaling, FXR/RXR activation, intrinsic prothrombin activation pathway, and LXR/RXR activation. This multi‐omics study illustrates the intricacy of complex adaptations that occur in the fetal sheep lung in response to gestational hypoxia.

Screening Echocardiography Identifies Risk Factors for Pulmonary Hypertension at Discharge in Premature Infants with Bronchopulmonary Dysplasia.

Premature infants with bronchopulmonary dysplasia (BPD) are at increased risk of secondary pulmonary hypertension (BPD-PH). Prior studies yielded mixed results on the utility of echocardiographic screening at 36weeks post-menstrual age (PMA). We present our experience using echocardiographic screening at the time of BPD diagnosis to identify infants at highest risk of BPD-PH at discharge. Retrospective cohort analysis of clinical/ demographic data and screening echocardiograms in patients with BPD.Discharge echocardiograms identified infants with or without BPD-PH at discharge. 36weeks PMA screening echocardiograms and clinical data were then reviewed to identify which factors were associated with increased odds of BPD-PH at discharge. Associations between echocardiographic findings were evaluated with 2- and 3-variable models to predict increased risk of BPD-PH at discharge. In our cohort of 64 infants with severe BPD, BPD-PH was present in 22/64 (34%) infants at discharge. There were no clinical differences at time of 36weeks PMA screening evaluation (mean PMA 36.6 ± 2.9weeks). PH at screening was poorly predictive of PH at discharge as PH at screening resolved in 49% of patients. However, having an ASD, RV dilation, hypertrophy, or reduced function on screening, especially in combination, were associated with BPD-PH at discharge. In our cohort of premature infants with BPD, 36weeks PMA screening echocardiogram identified patients at increased risk for BPD-PH at discharge when ASD, RVH, or impaired RV function were present. Larger prospective studies are indicated to validate these findings.

Understanding the Pathobiology of Pulmonary Hypertension Due to Left Heart Disease.

The development of pulmonary hypertension (PH) is common and has adverse prognostic implications in patients with heart failure due to left heart disease (LHD), and thus far, there are no known treatments specifically for PH-LHD, also known as group 2 PH. Diagnostic thresholds for PH-LHD, and clinical classification of PH-LHD phenotypes, continue to evolve and, therefore, present a challenge for basic and translational scientists actively investigating PH-LHD in the preclinical setting. Furthermore, the pathobiology of PH-LHD is not well understood, although pulmonary vascular remodeling is thought to result from (1) increased wall stress due to increased left atrial pressures; (2) hemodynamic congestion-induced decreased shear stress in the pulmonary vascular bed; (3) comorbidity-induced endothelial dysfunction with direct injury to the pulmonary microvasculature; and (4) superimposed pulmonary arterial hypertension risk factors. To ultimately be able to modify disease, either by prevention or treatment, a better understanding of the various drivers of PH-LHD, including endothelial dysfunction, abnormalities in vascular tone, platelet aggregation, inflammation, adipocytokines, and systemic complications (including splanchnic congestion and lymphatic dysfunction) must be further investigated. Here, we review the diagnostic criteria and various hemodynamic phenotypes of PH-LHD, the potential biological mechanisms underlying this disorder, and pressing questions yet to be answered about the pathobiology of PH-LHD.

Changes in Lung Perfusion in Patients Treated with Percutaneous Mechanical Thrombectomy for Intermediate-Risk Pulmonary Embolism

BackgroundCurrent pulmonary embolism treatment options rely heavily on anatomical clot location. However, anatomical location does not necessarily determine adverse outcomes; rather, clinical severity is secondary to the degree of perfusion impairment. Dual-energy computed tomography pulmonary angiogram (DE-CTPA) can map perfusion at the time of pulmonary embolism diagnosis. Single-photon emission computed tomography ventilation-perfusion scans allow for perfusion tracking similar to DE-CTPA. MethodsWe present 3 patients with intermediate-risk pulmonary embolism treated with mechanical thrombectomy using the Inari FlowTriever System (Inari Medical, Irvine, Calif). Lung perfusion scoring was applied to pre-procedure and post-procedure imaging. We graded perfusion of each lobe in 3 planes. If the entire lobe was perfused, a score of 3 was assigned. If lung perfusion is normal, total perfusion score is 15. All patients had pre-procedure and follow-up transthoracic echocardiograms. ResultsAll 3 patients were diagnosed with pulmonary embolism via DE-CTPA that showed right ventricle strain and had deep venous thrombosis. Following mechanical thrombectomy, patients immediately experienced improvement in perfusion score; scores continued to improve at follow-up. All patients also had improvement in right ventricle size or function on follow-up echocardiogram. DiscussionIntermediate-risk pulmonary embolism often has large initial clot burden that predicts residual pulmonary vascular obstruction. Residual pulmonary vascular obstruction is associated with increased risk of death, recurrent thrombus, and chronic thromboembolic pulmonary hypertension. Clot removal via thrombectomy may decrease the prevalence of residual pulmonary vascular obstruction by improving lung perfusion. We found that mechanical thrombectomy increased lung perfusion immediately and at follow-up assessments.

Health Supervision for Children and Adolescents With Down Syndrome.

Health Supervision for Children and Adolescents With Down Syndrome.

Phosphodiesterase‐5 inhibitors in pregnancy: Systematic review and meta‐analysis of maternal and perinatal safety and clinical outcomes

The efficacy and safety profile of phosphodiesterase-5 inhibitors (PDE-5i) in pregnancy are unclear from the few relatively small diverse studies that have used them. To assess the safety profile and clinical outcomes of PDE-5i use in pregnancy. We searched Embase, PubMed, CENTRAL, Prospero and Google Scholar to identify randomised controlled trials (RCTs) reporting the use of any PDE-5i in pregnancy up to September 2021. RCTs reporting obstetric or perinatal outcomes or maternal adverse outcomes in women taking PDE5i in pregnancy. Risk ratios (RR), 95% confidence intervals (95% CI) and 95% prediction intervals were calculated and pooled for analysis. We identified 1324 citations, of which 10 studies including 1090 participants met the inclusion criteria. Only tadalafil and sildenafil were reported as used in pregnancy. Two studies using tadalafil and eight sildenafil. Nine of ten studies were assessed at having of low risk of bias. PDE-5i use was associated with an increased risk of headaches (RR 1.41, 95% CI 0.97-2.05), flushing (RR 2.59, 95% CI 0.69-9.90) and nasal bleeding (RR 10.53, 95% CI 1.36-81.3); an increase in vaginal birth when used for non-fetal growth restriction (FGR) indications (RR 1.24, 95% CI 1.00-1.55) and a reduction in risk of operative birth for intrapartum fetal compromise (RR 0.58, 95% CI 0.38-0.88). There was no evidence of any increase in risk of perinatal death (RR 0.89, 95% CI 0.56-1.43). However, use for the treatment of FGR increased the risk of persistent pulmonary hypertension of the newborn (PPHN) (RR 2.52, 95% CI 1.00-6.32). This meta-analysis suggests PDE-5i use in pregnancy is associated with mild maternal side effects and lower risk of operative birth for intrapartum fetal distress. Prolonged use for the treatment of FGR may increase the risk of PPHN. PDE-5i use in pregnancy is associated with mild maternal side effects, lower operative birth for intrapartum fetal distress and a possible increase in persistent pulmonary hypertension of the newborn when used for the treatment of fetal growth restriction.

Polychlorinated Biphenyls and Pulmonary Hypertension.

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that were banned because of their potential carcinogenicity. Population studies have shown that PCBs are associated with lung toxicity and hypertension. The objective of this study was to evaluate whether higher exposure to PCB congeners is associated with the risk of pulmonary hypertension. Serum levels of PCBs in 284 subjects with combined risk factors for pulmonary arterial hypertension (PAH) were compared to 4210 subjects with no risk for PAH using the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. The major findings from this study include significantly higher PCB levels in PAH subjects compared to non-PAH subjects; for example, the geometric mean (GM) of PCB74 was 15.91 (ng/g) (14.45–17.53) vs. 11.48 (ng/g) (10.84–12.16), respectively. Serum levels of PCB congeners showed an increasing trend in the age group 20–59 years as PCB180 GM was 19.45 (ng/g) in PAH vs. 12.75 (ng/g) in the control. A higher body burden of PCB153 followed by PCB138, PCB180, and PCB118 was observed. Estimated age, race, BMI, and gender-adjusted ORs for PCB congener levels in subjects with the combined risk factors for PAH compared to controls was significant; for example, PCB99 (OR: 1.5 (CI: 1.49–1.50). In summary, these findings indicate that exposure, as well as body burden estimated based on lipid adjustment of PCBs, were higher in people with risk factors for PAH, and PCB congeners accumulated with age. These findings should be interpreted with caution because of the use of cross-sectional self-reported data and a small sample size of subjects with combined risk factors for pulmonary arterial hypertension. Nonetheless, our finding emphasizes a need for a comprehensive environmental molecular epidemiologic study to determine the potential role of environmental exposures to PCBs in the development of pulmonary arterial hypertension.

Validation of the New Pediatric Pulmonary Hypertension Risk Score by Cardiac Magnetic Resonance Imaging and Speckle Tracking Echocardiography. The European Pediatric Pulmonary Vascular Disease Network (EPPVDN)

<h3>Purpose</h3> The European Pediatric Pulmonary Vascular Disease Network (EPPVDN) developed in 2019 a pediatric pulmonary hypertension (PH) risk score to assess the risk and severity of PH in children and young adults. This prospective observational study seeks to validate the EPPVDN pediatric PH risk score by correlations with suitable and independent variables from cardiac magnetic resonance imaging (CMR) and speckle tracking echocardiography. <h3>Methods</h3> Twenty children with PAH were enrolled into the study (age: 10.8±1.0, range 4.0- 17.6 years). During the same inpatient stay the invasive and non-invasive EPPVDN pediatric PH risk scores were determined and a protocol-driven CMR study was performed. Subsequently, we correlated the risk scores with conventional and strain CMR variables and advanced echocardiographic variables, including strain analysis (speckle-tracking). In addition, we applied the risk score to 9 children with PAH who received add-on selexipag therapy. Before and approximately 6 months after selexipag start the risk score and echocardiographic RV strain were determined and delta-changes of both were correlated. <h3>Results</h3> We observed significant (p<0.001) and strong correlations of conventional CMR (r=0.69-0.88), CMR strain (r=0.71-0.88), advanced echocardiographic (r=0.65-0.88) and echocardiographic strain variables (r=0.67-0.86), with the EPPVDN PHrisk score. The EPPVDN higher risk scores correlated stronger with the CMR-, ECHO-, and CMR-strain variables, when compared to the lower risk scores. In the add-on selexipag cohort, the change in ECHO-derived RV strain correlated most strongly and significantly with the change in the invasive higher risk score (r= -0.72, p<0.004). <h3>Conclusion</h3> We found strong correlations of conventional, outcome-relevant CMR and strain variables (CMR, ECHO) with the EPPVDN pediatric PH risk scores, and thus validated the score via independent methods. The novel EPPVDN pediatric PH risk score will be very useful in routine clinical care, and can now be applied in larger prospective, pharma-interventional PAH studies in children and young adults. According open access online tools for rapid, comprehensive risk assement are in preparation.

Extremely premature infants born at 23–25 weeks gestation are at substantial risk for pulmonary hypertension

ObjectiveExtremely low gestational age newborns (ELGANs) represent an especially vulnerable population. Herein, we aimed to determine incidence and severity of pulmonary hypertension associated with bronchopulmonary dysplasia (BPD-PH) in extremely immature ELGANs (gestational age: 230/6–256/7 weeks).MethodsIn this prospective observational cohort study, we assessed BPD-PH by means of several echocardiography markers and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at 3 and 12 months of chronological age. In addition, we analyzed incidence and efficacy of pharmacologic treatment for BPD-PH.ResultsAt 3 months 15/34 ELGANs had echocardiographic evidence of BPD-PH, while at 12 months of age 6/34 still had PH. PH-targeted therapy consisted of sildenafil monotherapy in 11 and dual oral combination therapy (sildenafil and macitentan) in four ELGANs at 3 and 12 months.Conclusion44% (15/34) of ELGANs developed BPD-PH. All received PH-targeted pharmacotherapy at 3 months, leading to hemodynamic improvements at 12 months in most infants.

A comparative analysis on risk of pulmonary hypertension in children with Atrio-ventricular (AV) canal defect: a multi-centre study.

This study is aimed at determining the risk of pulmonary hypertension in children with AV canal defect when compared with children with other congenital heart disease. A descriptive study carried out in three institutions over a six-year period among children who presented with AV canal defect and their controls who presented with other congenital heart defects. A large proportion of the children with AV canal (77.5%) had pulmonary hypertension. Among the patients with pulmonary hypertension, 45.2% were males compared 54.8% females (χ2 = 3.2, p = 0.2). There was a positive correlation between pulmonary hypertension and size of VSD and ASD, although the correlation was not significant (Pearson correlation coefficient = 0.01 and 0.4, p = 0.9 and 0.1 respectively). Children with AV canal defect had higher odds of developing most clinical symptoms and pulmonary hypertension than children with other congenital heart disease and this is statistically significant. Majority of children with AV canal defect presented with pulmonary hypertension. These children present with higher odds of having pulmonary hypertension and clinical symptoms than children with other types of congenital heart disease.

Cytokine signatures differentiate systemic sclerosis patients at high versus low risk for pulmonary arterial hypertension

BackgroundPulmonary arterial hypertension (PAH) affects approximately 10% of patients with systemic sclerosis (SSc) and is a leading cause of death. We sought to identify serum cytokine signatures that risk stratify SSc patients for this potentially fatal complication.MethodsSubjects at high risk for PAH and with incident PAH based on right heart catheterization (RHC) were enrolled in the multi-center prospective registry, Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS). Low-risk SSc patients were enrolled at Stanford and had normal pulmonary function test and echocardiogram parameters. Serum was available from 71 high-risk patients, 81 incident PAH patients, 10 low-risk patients, and 20 healthy controls (HC). Custom 14- and 65-plex arrays were used for cytokine analysis. Cytokine expression was compared between patient groups by principal component analysis and Tukey’s test result. A multiple hypotheses corrected p value <0.05 was considered significant.ResultsExploratory analysis using principal components showed unique clustering for each patient group. There was a significant difference in cytokine expression in at least one group comparison for every cytokine. Overall, there was very little difference in cytokine expression comparing high-risk and PAH patient groups; however, these groups had substantially different cytokine profiles compared to low-risk patients and HC.ConclusionThese data suggest that cytokine profiles can distinguish SSc patients who are at high-risk for or have PAH from SSc patients who may be at lower risk for PAH and HC. However, high-risk and PAH patients had very similar cytokine profiles, suggesting that these patients are on a disease continuum.

Low serum 25-hydroxyvitamin D (vitamin D) level among children with ventricular septal defect: how big is the risk for pulmonary hypertension?

Ventricular septal defect is the most common CHD, leading to pulmonary hypertension. Significantly lower 25-hydroxyvitamin D level was reported in children with CHD compared with healthy controls. The current study aimed to investigate the correlation between 25-hydroxyvitamin D level and pulmonary hypertension in children with ventricular septal defect. A cross-sectional study was conducted on ventricular septal defect paediatric patients from January to June, 2019. Serum 25-hydroxyvitamin D was measured using electrochemiluminescence. Pulmonary hypertension was defined as mean pulmonary artery systolic pressure > 20 mmHg for children >3 months of age at sea level, measured by Doppler echocardiography. From forty-four subjects, the majority of the subjects were female (56.8%) with normal nutritional status and perimembranous ventricular septal defect. Bivariate analysis showed that 25-hydroxyvitamin D level was associated with pulmonary hypertension (p < 0.01), type and size of ventricular septal defect (p = 0.02), and heart failure (p < 0.01). Higher 25-hydroxyvitamin D level was correlated with better nutritional status (p = 0.04, r = 0.26), and lower 25-hydroxyvitamin D level was correlated with the occurence of perimembranous ventricular septal defect (p = 0.01, r = -0.39), larger defect size (p < 0.01, r = -0.70), history of pneumonia (p = 0.02, r = -0.31), and heart failure (p < 0.01, r = -0.64). Subjects with 25-hydroxyvitamin D deficiency had prevalence ratio of 24.0 times for pulmonary hypertension. Higher pulmonary artery pressure was correlated to the occurence perimembranous ventricular septal defect (p = 0.01, r = 0.47), larger defect size (p < 0.01, r = 0.78), history of pneumonia (p = 0.01, r = 0.38), and heart failure (p < 0.01, r = 0.75). Children with ventricular septal defect who had low 25-hydroxyvitamin D level posed a higher risk of having pulmonary hypertension.