Pulmonary Hypertension Research Articles

Clinical course and prognosis of patients with idiopathic pulmonary arterial hypertension after COVID-19

The coronavirus disease of 2019 (COVID-19) is an infectious disease caused by severe acute respiratory coronavirus (SARS-CoV-2). This virus has many factors in its pathogenesis that affect the function of the right ventricle and pulmonary hemodynamics, which can negatively influence the clinical course of IPAH. According to the results of our study, the fact of getting over COVID-19 in patients with IPAH leads to some changes in laboratory and instrumental parameters. But no significant effect of COVID-19 on risk modification during the year was detected. This result can be explained by a combination of pathophysiological features of the pulmonary hypertension and the protective effect of constantly taken PAH-specific and anticoagulant therapy.

Awake thoracic surgery for severe pulmonary hypertension: A case report

Not available

Assessing personalized molecular portraits underlying endothelial-to-mesenchymal transition within pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a progressive and rapidly fatal disease with an intricate etiology. Identifying biomarkers for early PAH lesions based on the exploration of subtle biological processes is significant for timely diagnosis and treatment. In the present study, nine distinct cell populations identified based on gene expression profiles revealed high heterogeneity in cell composition ratio, biological function, distribution preference, and communication patterns in PAH. Notably, compared to other cells, endothelial cells (ECs) showed prominent variation in multiple perspectives. Further analysis demonstrated the endothelial-to-mesenchymal transition (EndMT) in ECs and identified a subgroup exhibiting a contrasting phenotype. Based on these findings, a machine-learning integrated program consisting of nine learners was developed to create a PAH Endothelial-to-mesenchymal transition Signature (PETS). This study identified cell populations underlying EndMT and furnished a potential tool that might be valuable for PAH diagnosis and new precise therapies.

Identification of metabolic biomarkers in idiopathic pulmonary arterial hypertension using targeted metabolomics and bioinformatics analysis

Pulmonary arterial hypertension (PAH) is a life-threatening disease with a poor prognosis, and metabolic abnormalities play a critical role in its development. This study used metabolomics, machine learning algorithms and bioinformatics to screen for potential metabolic biomarkers associated with the diagnosis of PAH. In this study, plasma samples were collected from 17 patients diagnosed with idiopathic pulmonary arterial hypertension (IPAH) and 20 healthy controls. Plasma metabolomic profiling was performed by high-performance liquid chromatography-mass spectrometry. Gene profiles of PAH patients were obtained from the GEO database. Key differentially expressed metabolites (DEMs) and metabolism-related genes were subsequently identified using machine learning algorithms. Twenty differential plasma metabolites associated with IPAH were identified (VIP score > 1 and p < 0 0.05), and enrichment analysis revealed the arginine biosynthesis pathway as the most altered pathway. Using machine learning models, including least absolute shrinkage and selection operator (LASSO), random forest (RF) and support vector machine (SVM), we extracted key metabolites that correlated with clinical phenotypes. Our results suggested that five metabolites, kynurenine, homoserine, tryptophan, AMP, and spermine, are potential biomarkers for IPAH. Bioinformatics analysis also identified 3 metabolism-related genes, MAPK6, SLC7A11 and CDC42BPA, that are strongly correlated with pulmonary hypertension, demonstrating strong predictive power and clinical relevance. Our findings revealed some key genes associated with metabolism in PH, and provided crucial information about complex metabolic reprogramming signals and may lead to the identification of useful metabolic biomarkers for the diagnosis of PAH.

Pulmonary arterial hypertension in human immunodeficiency virus infections

Pulmonary arterial hypertension (PAH) is an important health issue in the twenty-first century. The introduction of highly active retroviral therapy has prolonged survival in patients infected with the human immunodeficiency virus (HIV), and this has led to the emergence of new health issues, including PAH, in those patients. This review considers the advances in understanding the pathophysiology of PAH in HIV infections and the approaches to the treatment of these patients. Keywords: Pulmonary arterial hypertension, HIV, pathophysiology, treatment

Autonomic control of the pulmonary circulation: Implications for pulmonary hypertension.

The autonomic regulation of the pulmonary vasculature has been under-appreciated despite the presence of sympathetic and parasympathetic neural innervation and adrenergic and cholinergic receptors on pulmonary vessels. Recent clinical trials targeting this innervation have demonstrated promising effects in pulmonary hypertension, and in this context of reignited interest, we review autonomic pulmonary vascular regulation, its integration with other pulmonary vascular regulatory mechanisms, systemic homeostatic reflexes and their clinical relevance in pulmonary hypertension. The sympathetic and parasympathetic nervous systems can affect pulmonary vascular tone and pulmonary vascular stiffness. Local afferents in the pulmonary vasculature are activated by elevations in pressure and distension and lead to distinct pulmonary baroreflex responses, including pulmonary vasoconstriction, increased sympathetic outflow, systemic vasoconstriction and increased respiratory drive. Autonomic pulmonary vascular control interacts with, and potentially makes a functional contribution to, systemic homeostatic reflexes, such as the arterial baroreflex. New experimental therapeutic applications, including pulmonary artery denervation, pharmacological cholinergic potentiation, vagal nerve stimulation and carotid baroreflex stimulation, have shown some promise in the treatment of pulmonary hypertension.

Expression and Diagnostic Value of miR-3591-5p in Patients with Congenital Heart Disease-Associated Pulmonary Arterial Hypertension.

This study explored the expression and diagnostic value of differentially expressed miR-3591-5p in congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH). A total of 110 CHD patients were divided into four groups based on their mean pulmonary artery pressure (PAPm). The plasma miR-3591-5p expression was determined by reverse transcription polymerase chain reaction. The correlation between the miR-3591-5p expression and various clinical indices, as well as its diagnostic value for CHD-PAH patients, were analyzed. The plasma levels of miR-3591-5p were significantly higher in the patients in the no PAH group, mild PAH group, and moderate to severe PAH group than in the control group, and they were significantly higher in the moderate to severe PAH group than in the no PAH group. Correlation analysis revealed that the miR-3591-5p expression level was significantly positively correlated with various clinical indicators, including the PAPm, pulmonary artery systolic pressure, brain natriuretic peptide, pulmonary vascular resistance, red blood cell distribution width, uric acid, Na + , systolic blood pressure, left atrial internal dimension, left ventricular end-diastolic dimension, and left ventricular end-systolic dimension. Univariate and multivariate regression analyses identified the plasma miR-3591-5p level as an independent risk factor for CHD-PAH. Receiver operating characteristic curve analysis demonstrated that the plasma miR-3591-5p level had a moderate diagnostic value for CHD-PAH, which was further improved when combined with a B-type natriuretic peptide. This study identified the expression profiles of differentially expressed plasma miRNAs in patients with CHD-PAH, focusing on the upregulation of miR-3591-5p. Bioinformatics analysis suggested that miR-3591-5p is involved in the pathogenesis of CHD-PAH and may serve as a circulating biomarker that may have diagnostic and prognostic value in CHD-PAH.

Transcatheter closure of the Gerbode type ventricular septal defect after redo mitral valve replacement

Gerbode defect is an uncommon ventricular septal defect (VSD) resulting in a left ventricle to right atrium shunt. Although typically congenital, acquired defects have been reported following infective endocarditis, cardiac surgery, trauma, or acute myocardial infarction. This condition causes left-to-right intracardiac shunt and potential hemodynamic instability. This complex anatomy poses therapeutic challenges, and optimal management is often unclear. We present a case of acquired Gerbode defect following a redo mitral valve replacement surgery in a 71-year-old man who developed severe dyspnea and pulmonary hypertension. Treatment was successfully performed with percutaneous transcatheter VSD closure using an Amplatzer device. This case highlights the importance of considering Gerbode defects in postoperative patients and demonstrates the efficacy of transcatheter closure in reducing symptoms and avoiding high-risk redo cardiac surgery. Transcatheter repair offers shorter recovery times, reduces pain, and avoids repeat sternotomy, making it a valuable and minimally invasive alternative for patients with acquired Gerbode defects. Keywords: Gerbode defect, left ventricle to right atrium shunt, redo mitral valve replacement, transcatheter closure

Global research landscape on the genetics of congenital heart disease: A bibliometric and visualized analysis via VOSviewer and CiteSpace.

Genetic factors play a significant role in the development of congenital heart disease (CHD). Many studies on the genetics of CHD have been published worldwide; however, no research has assessed and mapped the global research landscape of these studies. This bibliometric and visualized study aimed to delineate research hotspots and trends in the field of CHD genetics. Scientific papers on the genetics of CHD from January 1, 1950, to December 31, 2023, were obtained by searching the Web of Science Core Collection. The bibliometric metadata of each chosen research paper were extracted, analyzed, and visualized using tools such as Microsoft Excel 2021, VOSviewer, and CiteSpace. The final analysis included 5317 papers discussing the genetics of CHD. The countries and journals that published the highest number of papers were the United States (n = 2118), and American Journal of Medical Genetics Part A (n = 332), respectively. In addition to CHD and genetics, keywords such as tetralogy of Fallot, ventricular septal defect, and atrial septal defect appeared most frequently among 8365 keywords. Eight clusters were formed to categorize the keywords. Keywords such as case-control study, whole genome sequencing, and whole exome sequencing in clusters 6, 7, and 8, respectively, had the latest average publication year among all clusters. To the best of our knowledge, this is the first bibliometric analysis of CHD genetics studies. Tetralogy of Fallot, ventricular septal defect, and atrial septal defect are global research topics. The interactions between environmental and genetic factors in the pathogenesis of CHD, genetic etiology of CHD-associated pulmonary arterial hypertension, and molecular genetics of CHD via high-throughput genomic technology are possible areas of future research on the genetics of CHD.

Capillaroscopic Insights: Exploring the Connection Between Microvascular Changes and Pulmonary Manifestations in Systemic Sclerosis.

Systemic sclerosis (SSc) is a complex connective tissue disease characterized by microangiopathy, immune dysregulation, and fibrosis. Early detection of microvascular abnormalities using nailfold videocapillaroscopy (NVC) is crucial in assessing disease progression and associated disease's involvement such as interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). This study aims to explore the relationships correlation between NVC patterns, clinical manifestations, and systemic complications in SSc. We analyzed the data of 63 patients, predominantly female (95%), with a mean age of 49 years and an average disease duration of 42 months. Patients were categorized into early, active, and late patterns based on NVC findings. Clinical features, including digital ulcers (DU), ILD, and PAH, were assessed. Pearson correlation analyses were performed to evaluate the relationships between capillary loss, neoangiogenesis, ILD, and PAH. The early pattern group (mean mRSS 2.36) exhibited minimal microvascular damage and systemic involvement, with no DUs. In the active pattern group (mean mRSS 10.40), 34.38% had diffuse cutaneous SSc (dcSSc), with 15.63% presenting DUs, 65.63% ILD, and 37.5% PAH. The late pattern group (mean mRSS 18.00) showed the most severe disease, with 80% having DUs, 70% dcSSc, 90% ILD, and 70% PAH. Pearson correlation analyses revealed strong correlations between capillary loss and ILD (r = 0.7255) and PAH (r = 0.6369). A moderate correlation was found between neoangiogenesis and PAH (r = 0.5592). The study demonstrates that progressive microvascular damage in SSc, as visualized by NVC, correlates strongly with the severity of systemic complications. Early detection of capillary loss and neoangiogenesis using NVC is critical for timely interventions, which could improve patient outcomes by mitigating the progression of ILD and PAH.

The management of high flow arteriovenous fistula and possible solutions.

The development of a high flow rate arteriovenous fistula (AVF) can expose the patient to development of heart failure due to increased cardiac preload and pulmonary hypertension. AVF flow measurement (Qa) is considered a screening tool for AVF surveillance, aiming to evaluate the access dysfunction and prevent complications, like a non-maturation, suspected stenosis, high-flow AVF, and distal ischemia. In the upper arm AVF, a high Qa may develops, which can expose the patient to the risk of high-output heart failure and ischemia. Although, the exact threshold to define high-flow access is not universally accepted, AVF with a Qa of 1-1.5 L/min or cardio-pulmonary recirculation (Qa/CO) >20% are considered at risk. In our work we describe the treatment performed in three patients with high flow AVF treated with DRIL technique with interposition of a Prosthetic Patch, revascularization procedures such as distal inflow revision or RUDI and with innovative technique a "tench snout," removal the previous anastomosis and reconstruction of the integrity of the radial artery at the terminal in pre and post anastomosis. A PTFE prosthetic segment measuring 5 cm in length and 5 mm in diameter was interposed, terminally anastomosed with the efferent cephalic vein and terminally lateral with the radial artery, reducing the anastomosis to approximately 4 mm. All treated patients showed a clear improvement in the clinical picture in particularly heart failure. The calculation of the post-intervention flow rate approximately 1500 mL/min. The patient on hemodialysis with arteriovenous fistula must be constantly monitored with clinical examination, monitoring during the hemodialysis session and color Doppler ultrasound of the AVF with calculation of the flow rate. The surgical technique used for flow reduction is chosen on the surgical experience of each operator with the main objective of preserving the autologous AVF.

A scoping review of the epidemiology of systemic sclerosis and its organ manifestations: 2018-2024.

Updates from large, observational cohorts and new statistical techniques have resulted in new data on the epidemiology of systemic sclerosis (SSc). This scoping review uses data from 2018 to 2024 to describe the current understanding of the epidemiology of SSc and several of its organ- manifestations. Our review identified new estimates for the global incidence and prevalence of SSc (1.4-8.6 per 100 000 person-years and 17.6-18.9 per 100 000 individuals, respectively). Mortality rates remain high, though mortality at younger ages has decreased. interstitial lung disease and pulmonary arterial hypertension remain the most common causes of death for patients with SSc. Literature on gastrointestinal (GI) manifestations of SSc was scarce, and we identified significant heterogeneity in results. Furthermore, data on the epidemiology of racial, ethnic and sex-based disparities was lacking. New techniques for the evaluation of the epidemiology of SSc highlight the high morbidity and mortality of SSc, and a growing prevalence rate compared with prior eras. Further research is needed to address notable heterogeneity in the reporting of epidemiological data and understudied disease manifestations, including GI disease and health disparities in disease outcomes.

High-Flow Oscillatory Ventilation: A Possible Therapeutic Option for Pediatric Patients with Cardiovascular Diseases

High-flow oscillatory ventilation (HFOV) is a common rescue treatment in infants and children with respiratory failure. This type of ventilation is an effective technique in numerous diseases that affect a child in the postnatal period, such as ARDS, meconium aspiration syndrome (MIS), postnatal pulmonary bleeding and idiopathic pulmonary hypertension (IPH). Although this ventilation technique is commonly recognized as a valuable therapeutic option in the general pediatric population, this is not the same for children with congenital cardiovascular diseases. The key mechanism of oscillatory ventilation is continuous positive pressure administered within the airways via a small tidal volume at high frequency. Tidal volumes are between 1 and 3 mL/kg delivered at 5–15 Hz, equivalent to 300–900 breaths per minute. A few older studies conducted on humans and animals highlight that HFOV may be dangerous for congenital heart patients. According to these evidences, hemodynamic parameters such as blood pressure, wedge pressure, central venous pressure, heart rate and inotrope level can be dangerously changed for patients with congenital heart disease; therefore, oscillatory ventilation should be avoided. Numerous retrospective studies have pointed out how oscillatory ventilation constitutes a valid therapeutic option in children with congenital heart disease. Recently, new evidences have highlighted how hemodynamic parameters are modified in a non-significant way by this type of ventilation, remaining beneficial as in the normal pediatric population. This narrative review aims to describe the mechanisms of oscillatory ventilation and collect all the available evidences to support its use in pediatric patients with congenital heart problems.

Prognosis of different hemodynamic classifications in patients with pulmonary hypertension due to left heart disease

Objective: To compare the prognostic values of different classification by using transpulmonary pressure gradient (TPG), diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) in patients with pulmonary hypertension due to left heart disease (PH-LHD), and investigated hemodynamic and clinical factors associated with mortality in patients with PH-LHD. Methods: This was a single-center prospective cohort study. In-hospital patients diagnosed with PH-LHD via right heart catheterization at the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, from September 2013 to December 2019 were enrolled. Patients were divided according to TPG (cutoff value 12 mmHg; 1 mmHg=0.133 kPa), DPG (cutoff value 7 mmHg), PVR (cutoff value 3 Wood Units), and the combination of TPG and PVR. Baseline characteristic was recorded. All patients were followed up until the occurrence of endpoint event, defined as all-cause death that occurred during the follow-up period, or until April 18, 2022. Receiver operating characteristic curves were used to compare the predictive value of 3 classification methods for all-cause death in PH-LHD patients. The optimal cutoff values were calculated using Jorden index. Survival analysis was performed using Kaplan-Meier analysis, and log-rank test was used to compare the predictive efficacy of classification methods based on optimal cutoff values or guidance-recommended thresholds for the survival of PH-LHD patients. Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality. Results: A total of 243 patients were enrolled, aged (54.9±12.7) years old, including 169 (69.5%) males. During a median follow-up of 57 months, there were 101 (41.6%) deaths occurred. Grouping results were as follows: (1) TPG: TPG≤12 mmHg group 115 patients, TPG>12 mmHg group 128 patients; (2) DPG: DPG<7 mmHg group 193 patients, DPG≥7 mmHg group 50 patients; (3) PVR: PVR≤3 Wood Units group 108 patients, PVR>3 Wood Units group 135 patients; (4) TPG and PVR: TPG≤12 mmHg and PVR≤3 Wood Units group 89 patients, TPG>12 mmHg and PVR>3 Wood Units group 109 patients. PVR (AUC=0. 698,95%CI:0.631-0.766) had better predictive value for all-cause mortality than TPG (AUC=0.596, 95%CI: 0.523-0.669) and DPG (AUC=0.526, 95%CI: 0.452-0.601) (all P<0.05). The optimal cutoff values for TPG, DPG, and PVR were13.9 mmHg, 2.8 mmHg, and 3.8 Wood Units, respectively. Kaplan-Meier analysis based on the optimal cutoff values or guidance-recommended thresholds showed that PVR and TPG were the predictors of survival (P<0.05), while DPG did not showed significance (P>0.05). Multivariate Cox regression analysis showed that age, PVR and log2N-terminal pro-B-type natriuretic peptide were independent risk factors for all-cause mortality in PH-LHD patients (all P<0.05). Conclusion: Classification according to PVR was most valuable in predicting all-cause death in PH-LHD patients, while TPG showed moderate predictive ability and DPG had no predictive value.

Pulmonary arterial hypertension: updates and perspective with newer therapies.

Pulmonary arterial hypertension (PAH) is a rare condition for which a remarkable change has been witnessed in the epidemiology, assessment and treatment landscape over the last three decades. Well-established registries from the Western world have not only highlighted the shift in the epidemiology to an older, more comorbid cohort but have also identified markers of prognosis that have been validated as part of risk stratification scores in multiple cohorts. The emphasis on early identification through a systematic assessment pathway and the option of upfront combination therapy with serial risk stratification assessment has laid the foundation for the standard of care and improved prognosis. This review provides an update on the assessment and newer therapies for PAH.

Time Interval Between Right Ventricular Early Diastolic Velocity by Tissue and Pulse Wave Doppler: An Index of Right Atrial Pressure in Pulmonary Hypertension Patients

Background: A reversal of time difference between the onset of early diastolic velocity (e’) during tissue Doppler imaging and the onset of mitral inflow (E) has been observed in cases of elevated left atrial pressure. Whether this interval (Te’-E) may be useful to assess right atrial pressure has never been investigated, neither in healthy subjects nor in pulmonary hypertension patients. Methods: Right ventricular Te’-E was assessed in patients with pre-capillary pulmonary hypertension and compared with healthy volunteers who underwent comprehensive echocardiography examination. Te’-E is the difference between the interval from R wave at the superimposed electrocardiogram to the e’ wave during right ventricular tissue Doppler imaging and the interval from the R wave to transtricuspid E wave during pulsed wave Doppler imaging. Right atrial pressure was invasively measured in pulmonary hypertension patients. Results: Fifty-six patients were enrolled. Te’-E was prolonged in pulmonary hypertension subjects compared with healthy subjects (p &lt; 0.001). Amongst the pulmonary hypertension patients, strong correlations were found between Te’-E and right atrial pressure (r = −0.885, p &lt; 0.001), systolic pulmonary pressure (r = −0.85, p &lt; 0.001) and the duration of tricuspid regurgitation (r = 0.72, p &lt; 0.001). The area under the receiver operating characteristic curve of Te’-E in identifying right atrial pressure higher than 15 mm of mercury was 0.992 (sensitivity 100%, specificity 83%). Conclusions: In contrast to the left ventricle, there is a delay in the proto-diastolic filling in pulmonary hypertension patients, which correlates with the increase in systolic pulmonary arterial pressure, right atrial pressure, tricuspid regurgitation duration and restrictive diastolic pattern.

Transforming respiratory diseases management: a CMO-based hospital pharmaceutical care model

IntroductionRespiratory diseases encompass a diverse range of conditions that significantly impact global morbidity and mortality. While common diseases like asthma and COPD exhibit moderate symptoms, less prevalent conditions such as pulmonary hypertension and cystic fibrosis profoundly affect quality of life and mortality. The prevalence of these diseases has surged by approximately 40% over the past 3 decades. Despite advancements in pharmacotherapy, challenges in drug administration, adherence, and adverse effects persist. This study aimed to develop and perform an interim validation of a Capacity-Motivation-Opportunity (CMO) model tailored for respiratory outpatients to enhance pharmaceutical care, which is the direct, responsible provision of medication-related care for the purpose of achieving definite outcomes that improve a patient’s quality of life, and overall wellbeing.MethodologyThis cross-sectional, multicenter study was conducted from March 2022 to March 2023. It comprised four phases: 1) forming an expert panel of 15 hospital pharmacists, 2) selecting respiratory pathologies based on prevalence and severity, 3) developing the CMO model’s pillars, and 4) integrating and conducting an interim validation of the model. The Capacity pillar focused on patient stratification and personalized care; the Motivation pillar aligned therapeutic goals through motivational interviewing; and the Opportunity pillar promoted the use of information and communication technologies (ICTs) for telemedicine.ResultsThe model included eight respiratory diseases based on expert assessment. For the Capacity pillar, 22 variables were defined for patient stratification, leading to three priority levels for personalized pharmaceutical care. In a preliminary test involving 201 patients across six hospitals, the stratification tool effectively classified patients according to their needs. The Motivation pillar adapted motivational interviewing techniques to support patient adherence and behavior change. The Opportunity pillar established teleconsultation protocols and ICT tools to enhance patient monitoring and care coordination.ConclusionThe CMO model, tailored for respiratory patients, provides a comprehensive framework for improving pharmaceutical care. By focusing on patient-centered care, aligning therapeutic goals, and leveraging technology, this model addresses the multifaceted needs of individuals with respiratory conditions. Future studies are necessary to validate this model in other healthcare systems and ensure its broad applicability.

Neurodevelopmental outcome in children between one and five years after persistent pulmonary hypertension of term and near-term newborns

BackgroundPersistent pulmonary hypertension of the newborn (PPHN) is a serious condition that affects 1–2 per 1,000 newborns. Scientific data report the existence of neurological developmental abnormalities between 10 and 30%, but the description of these disorders linked with this situation of cerebral hypoxia and haemodynamic failure remains poorly documented.ObjectiveThe main goal of this study was to describe the prevalence of neuro-psychomotor developmental disorders in children aged between one and five years old who have been hospitalised at birth in a neonatal intensive care unit for the management of PPHN.MethodsAll of the newborns ≥34 weeks of gestational age (WGA) with PPHN, treated with inhaled nitric oxide in our neonatal intensive care unit between January 2015 and December 2019 were retrospectively enrolled. An ASQ-3 standardised questionnaire, adapted to the appropriate age (12, 24, 36, 48 and 60 months) was performed by the parents.ResultsFifty-five children (81% of answers) with a median age of 36 months (11–68), whose real age was close to the one of the questionnaire (12, 24, 36, 48 and 60 months), have been included in this study. There was 47% of pathological score [borderline: less than 1 standard deviation (SD) or suspect: less than 2SD] in at least one of the five studied domains, mainly in communication (25%) and individual and social skills (22%), despite a high overall score of 250 [220; 285] out of 300 that improved with age.ConclusionThis study showed a significant prevalence of neuro-psychomotor developmental disorders which justifies making more accessible a prolonged and adapted follow-up for early and multidisciplinary screening and management of these children with PPHN history. Larger cohorts are needed to better explore long term outcome of these vulnerable term neonates.

63 Utilization of vasopressin and norepinephrine in neonates with cardiorespiratory compromise: A multicenter retrospective cohort study in Canada

Abstract Background Data regarding neonatal clinical experience with Vasopressin (VA) and Norepinephrine (NE) are limited to small studies. The lack of large-scale studies with safety and efficacy data is preventing the widespread adoption of these agents. Objectives To describe epidemiological data on utilization of NE and VA in neonates including their indications, effectiveness and overall outcomes across 3 tertiary Neonatal Intensive Care Units (NICU) in Canada. Design/Methods This retrospective cohort study involved neonates who received NE or VA between January 1, 2015-December 31, 2020 at 3 tertiary NICUs. Data regarding demographic information, indications of use, dosing details, and clinical outcomes were described using mean, standard deviations (SD), frequencies and percentages. When appropriate, a comparative analysis was performed using Mann-Whitney U tests or the chi-square test as appropriate. Post-initiation changes in physiological variables and laboratory parameters over time were analyzed using repeated measure ANOVA. Results 133 neonates (VA:70, NE:63) were included in this study. Baseline demographic features, clinical characteristics at initiation, indication of use, dosing details and clinical response in neonates exposed to both agents are summarized in Table 1. VA was commonly used for oxygenation failure due to persistent pulmonary hypertension of the newborn (PPHN), while NE was commonly used for hypotension due to septic shock. NE was frequently used as a 1st line inotropic agent, whereas VA was used more as an additive agent [30 (47.6%) vs 12 (18.6%); p=&amp;lt;0.001]. During treatment, lower sodium levels were recorded in the VA group vs the NE group [126.5 (8.6) vs 132 (7); p=.035], but other safety parameters were similar. The time to reach predefined stability parameters were similar in both groups. Significant improvement in physiological parameters were seen over time with both agents (Figure 1). Mortality within 7 days of use was high in the cohort, but comparable between VA and NE groups [18 (25.7%) vs 22 (34.9%), p=0.206]. Other neonatal morbidities were comparable between groups (Table 1). Conclusion This multicenter study provides pragmatic insights into the current use of NE and VA in neonates. Our study reports the effective use of each agent in distinct patient subgroups. This cohort represented neonates with high illness severity; however, exposure to either agent did not independently increase the risk of mortality or adverse outcomes. Further prospective studies exploring its optimal use and cardiopulmonary effects would be interesting.

Proteomic Signatures of Right Ventricular Outcomes in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a disease of progressive right ventricular (RV) failure with high morbidity and mortality. Our goal is to investigate proteomic features and pathways associated with RV-focused outcomes including mortality, RV dilation, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) in PAH. Participants in a single-institution cohort with 3 years of follow-up underwent proteomic profiling of their plasma using 7288 aptamers (targeting 6467 unique human proteins). Partial least squares discriminant analysis was performed to assess global protein variation associated with mortality, RV dilation, and NT-proBNP levels. Differentially abundant proteins and enriched pathways associated with outcomes were identified following baseline adjustments. RV vulnerability models estimated associations for individuals with similar afterload following adjustment for pulmonary vascular resistance. A total of 117 participants with PAH were included. Partial least squares discriminant analysis of the proteome showed clear separation between survivors and nonsurvivors, participants with dilated versus nondilated RVs, and across NT-proBNP levels. Proteins and pathways involving the ECM (extracellular matrix) were upregulated in participants who died during follow-up, those with severe RV dilation, and those with higher levels of NT-proBNP. Pulmonary vascular resistance adjustment reinforced the importance of ECM proteins in the association with RV vulnerability, independent of afterload. These findings were confirmed in independent PAH cohorts with available plasma proteomics and RV tissue gene and protein expression. Distinct plasma proteomic profiles are associated with mortality, RV dilation, and NT-proBNP in PAH. Proteins and pathways governing tissue remodeling are strongly associated with poor outcomes, may mediate RV vulnerability to right heart failure, and represent promising candidates as biomarkers and potential therapeutic targets.