Severe Pulmonary Arterial Hypertension Research Articles

Abstract 11703: Proteomic Analysis for the Formation of the Plexiform Lesions of a Rat Pulmonary Arterial Hypertension Model

Introduction: Although plexiform lesions (PLs) are the hallmark of the severe pulmonary arterial hypertension, the mechanism of this lesion formation has not been fully elucidated. In this study, to explore the pathways associated PLs formation, we examined the proteome analysis using vascular tissue before and after the formation of PLs obtained by laser capture microdissection (LCM). Methods: 7 weeks old rats were injected Sugen 5416 subcutaneously, followed by exposed to hypoxia for 3 weeks. In addition, the rats were kept in room air for 5 weeks (8-week model) or 10 weeks (13-week model) thereafter. We obtained the tissue of vessels with medial hypertrophy from 8-week models (n=5) and PLs from 13-week models (n=5) by LCM. Those micro-dissected samples were then subject to a qualitative and then quantitative proteomics approach. Differentially expressed proteins (DEPs) were defined by abundance in mass spectrometry (MS) (P-value < 0.05 and |log2 (fold change)| > 0.5 or proteins deteced only in lesions extracted from one model). In addition, we investigated enhanced pathway by gene ontology (GO) analysis of the identified DEPs in each of the 8-week and 13-week models. Results: We identified 718 uniquely expressed proteins including 57 DEPs (31 in 8-week model versus 26 in 13-week model) by using LCM-MS. GO analysis revealed that the actin cytoskeleton organization, actin filament-based process, and actomyosin structure organization processes were enhanced in 8-week model. On the other hand, the innate immune system, G2/M check points, and cellular response to reactive oxygen species were enhanced in 13-week model. Conclusion: Pulmonary vascular lesions of 8-week and PLs of 13-week Sugen hypoxia model evaluated by proteomics using samples obtained by LCM methods showed differential protein expression. Analysis of these DEPs may contribute to elucidate the mechanisms of PLs formation.

Abstract 17450: Sex Influences the Gut-Lung Microbiome Composition in Schistosomiasis-Associated Pulmonary Arterial Hypertension

Introduction: Pulmonary arterial hypertension (PAH) is an uncurable cardiopulmonary disease highly incident in women. Infection by the intravascular parasite Schistosoma mansoni recapitulates several aspects of widespread inflammation that leads to PAH (Sch-PAH). Our data indicate that after infection, the S. mansoni eggs translocate within the cardiopulmonary system, disturbing gut-lung microbiome and leading to severe PAH. Hypotheses: S. mansoni eggs disturb the lung microbiome, contributing to vascular inflammation and PAH in a sex-dependent manner. Methods: To test this hypothesis, we induced Sch-PAH in end-Scl.creERT2;Rosamt/mg mice by intraperitoneal sensibilization with 240 eggs/gram body weight (bw; 2 weeks) followed by intravenous injection of 175 eggs/gram bw. After 7 days, we analyzed the Right Ventricular Systolic Pressure and hypertrophy (RVSP; RVH). Lung sections were used for TUNEL stain and for microbiome analysis by shotgun metagenomics. Results: Metagenomic analysis revealed that S. mansoni egg infection disrupted the lung microbiome reducing α-diversity compared to controls. Infection also reduced the Phylum Ascomycota in the lungs, whereas the ratio Firmicutes:Bacteroidetes (F/B) remained similar between groups. No difference was observed in the Simpson and Chao index. In the guts, the infection did not alter the α-diversity or the relative abundance of Deferribacteres and Proteobacteria, but it significantly increased the ratio F/B, indicative of gut dysbiosis. In terms of sex, our preliminary data indicated female mice exhibit a lower lung α-diversity compared to male mice, characterized by a significant reduction in the Firmicutes Phylum (Mean reads: 0.013 and 0.119, respectively; reads normalized by Readcount with Children). Principal coordinate analysis identified a distance in the clustering pattern between sexes, which may account for microbiome differences in Sch-PAH. Finally, our data revealed increased RVH and presence of microvascular apoptosis in female compared to male group. Conclusion: Understanding whether the disrupted gut and lung microbiome composition contributes to the onset and progression of Sch-PAH in a sex-dependent manner opens a novel therapeutic direction.

Abstract 18413: Therapeutic Genome Editing of Endothelial FABP4 by Endothelium-Targeted Nanoparticle Delivery of the CRISPR/Cas9 System Inhibits Pulmonary Arterial Hypertension in Mice and Rats

Introduction: Pulmonary arterial hypertension (PAH) is a devastating disease characterized by progressive vasoconstriction and obliterative vascular remodeling. The molecular mechanisms of obliterative pulmonary vascular remodeling remain elusive. Hypothesis: Therapeutic genome editing of endothelial Fabp4 will knockout FABP4 expression selectively in endothelial cells and inhibit PAH in mice and rats. Methods: Employing the newly developed endothelial cell (EC)-targeted nanoparticle delivery technology, plasmid DNA expressing CRISPR/Cas9 controlled by Cdh5 promoter and Fabp4 -specific guide RNAs driven by U6 promoter was administered i.v. to adult SD rats and Egln1 Tie2Cre mice which exhibit severe PAH and obliterative pulmonary vascular remodeling. One week after nanoparticle administration, the rats were injected with a single dose of monocrotaline (MCT) to induce PAH. At 4 weeks post-MCT, right ventricular systolic pressure (RVSP), ratio of right ventricular versus left ventricular plus septum (RV/LV+S) and pulmonary vascular remodeling were determined. Pharmacological FABP4 inhibitor was also employed to treat MCT rats as a comparison. Similarly, the pulmonary hypertensive phenotype in genome-edited Egln1 Tie2Cre mice was also characterized. Results: Nanoparticle delivery of the all-in-one CRISPR rCdh5 plasmid DNA knockout Fabp4 selectively in endothelial cells in adult rats and Egln1 Tie2Cre mice leading to reduced RVSP, RV hypertrophy and pulmonary vascular remodeling in MCT rats and also in Egln1 Tie2Cre mice. Obliterative pulmonary vascular remodeling seen in Egln1 Tie2Cre mice was inhibited and the mortality rate in endothelial Fabp4-deficient Egln1 Tie2Cre mice was reduced. Treatment of FABP4 inhibitor also inhibits PAH in MCT rats. We also observed a marked increase of FABP4 expression in endothelial cells of lung samples of IPAH patients. Overexpression of FABP4 in primary cultures of human lung microvascular endothelial cells resulted in a 70% increase of cell proliferation. Conclusions: These findings demonstrate endothelial FABP4 is a promising target for PAH therapy. EC-targeted nanoparticle delivery of the genome editing system may represent an effective and safer gene therapy approach for PAH treatment.

Abstract 15932: Lactobacillus Suppresses Glycoprotein-130-Mediated Microtubule Remodeling to Support Right Ventricular Function in Pulmonary Arterial Hypertension

Introduction: Microtubules (MTs) are crucial for cardiomyocyte function as they regulate t-tubule structure, nuclear morphology, and gap junction protein localization. Glycoprotein-130 (GP130) signaling promotes pathological MT remodeling and right ventricular (RV) dysfunction in pulmonary arterial hypertension (PAH), but the trigger for the inflammation-MT connection is unknown. Microbiome dysbiosis activates systemic inflammation, and levels of the anti-inflammatory bacteria Lactobacillus are associated with RV function in rodents. However, the direct effects of Lactobacillus on GP130 signaling, MT remodeling, and RV function in PAH are unknown. Methods: Rats were randomly allocated into 3 groups: control, MCT-water, and MCT rats given Lactobacillus (MCT- Lactobacillus ). Echocardiography and pressure-volume loops defined RV function. Next-generation sequencing evaluated the composition of the bacterial components of the fecal microbiome. SomaScan proteomics quantified the serum proteome. RV and jejunal morphology were assessed with light and super resolution confocal microscopy. The relationship between Lactobacillus abundance and RV response to afterload was assessed in 65 PAH patients. Results: Lactobacillus augmented RV function (A) and reduced RV hypertrophy and fibrosis without altering PAH severity. Lactobacillus shifted the serum proteomic signature towards control (B) and reduced circulating GP130 ligands, normalized RV t-tubule architecture (C), MT density (D), and nucleus size (E), and prevented connexin-43 lateralization in RV cardiomyocytes (F). Lactobacillus restructured the microbiome, and concomitantly improved jejunal epithelial cell morphology with increased villus/microvillus length and glycocalyx thickness. PAH patients with fecal Lactobacillus had superior RV adaptation as afterload increased (G). Conclusion: Lactobacillus combats GP130-mediated MT remodeling to support RV function.

Perioperative Management of Parturient Women With Severe Pulmonary Arterial Hypertension Secondary to Atrial Septal Defect

Perioperative Management of Parturient Women With Severe Pulmonary Arterial Hypertension Secondary to Atrial Septal Defect

Effects of maternal pulmonary arterial hypertension on fetal hemodynamics and maternal-fetal outcome in late pregnancy.

The aim of this study was to investigate the effects of maternal pulmonary arterial hypertension (PAH) on fetal hemodynamics in the third trimester and to identify hemodynamic indicators associated with adverse maternal and fetal outcomes. We recruited 48 pregnant women with PAH in the third trimester and 32 women with normal pregnancies as controls matched for age and gestational week. Fetal growth and hemodynamic parameters were assessed by two-dimensional and color Doppler. All cases were followed up until delivery and maternal and fetal outcomes were collected. High throughput sequencing method was used to determine differential miRNA patterns in plasma exposed to pulmonary arterial hypertension (PAH) in pregnant women. We then performed the validated of key differentially expressed miRNAs by real-time PCR. Compared with the normal and mild PAH groups, resistance index (RI), pulsatility index (PI) of the fetal umbilical artery (UA) and quantitative ductus venosus (QDV) blood flow were increased in subjects with moderate to severe PAH, while PI and the ratio of peak systolic velocity (PSV) to end-diastolic velocity (EDV) (S/D) of the middle cerebral artery (MCA) were decreased. Compared with the normal group, subjects in the mild and moderate PAH groups had lower neonatal weight, shorter neonatal height, and higher preterm birth rates. In addition, miRNA sequencing data showed that PAH affected the levels of 23 miRNAs in plasma. At the same time, we showed that PAH significantly decreased the level of miR-1255a and increased the level of miR-548ar-3p by real-time PCR. In the group of pregnant women with moderate to severe pulmonary hypertension, there was a higher proportion of preterm births and low birth weight babies. Hemodynamic changes in the fetal UA, MCA, and ductus venosus (DV) during late pregnancy were associated with adverse fetal outcomes. At the same time, miRNA sequencing results showed that miR-1255a and miR-548ar-3p may play an important role in the development of PAH.

Olverembatinib(HQP1351)-Based Therapy in Adults with Relapsed or Refractory Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Advanced Chronic Myeloid Leukemia: Results of the Real-Life Study

Background Relapsed or refractory (R/R) Philadelphia chromosome positive acute lymphoid leukemia (ALL) and advanced chronic myeloid leukemia (CML) including accelerated phase (AP) and blast phase (BP) usually result in treatment failure due to therapeutic resistance, intolerance, T315I mutations, or compound mutations, with a poor prognosis. Olverembatinib (HQP1351) is a novel third generation BCR-ABL tyrosine kinase inhibitor (3G-TKI), exhibiting a high potency of inhibition on wild and almost all mutated BCR-ABL1 kinases, including the T315I mutation and exhibiting preliminary favorable efficacy and safety profile in clinical trials. Methods In this open label, single-arm, single-center study, patients with advanced Ph+ leukemia (including CML-BP, CML-AP and R/R Ph+ ALL) were enrolled. Patients with severe cardiovascular diseases, arterial occlusion, hypertension, and pulmonary arterial hypertension were excluded . Eligible patient received olverembatinib monotherapy, combined chemotherapy, or combined immunotherapy. The primary endpoints was overall response rate (ORR) at 28 days, including complete remission (CR) and complete remission with incomplete hematological recovery (CRi), in patients with advanced Ph+ leukemia. Results Between Dec 8, 2021, to Jun 1, 2023, a total of 56 patients (Ph+ALL (n=40), CML-BP (n=13) and CML-AP(n=3)) assessed were included and received olverembatinib-based therapy. 34(60.7%) patients were men and 22 (39.3%) were women. The median age was 38 years old (IQR 29-48) and the median duration of follow-up was 8.3 months (IQR 4.6-11.9). BCR::ABL1 transcript was of p210 type in 29 (51.8%), p190 in 27 (48.2%). 13 (23.2%) and 11 (19.6%) patients had received 2 and ≥ 3 prior TKIs, respectively. 17 (30.4%) patients were pretreated with third-generation TKI (ponatinib). Genetic testing revealed mutations in 48 (85.7%) patients including compound mutation in 11 (19.6%%) patients, of whom 8 (72.3%) patients had the T315I mutation. 11 (19.6%) patients had central nervous system leukemia (CNSL) and 1 (1.8%) had extramedullary disease. Of 56 evaluable patients, 48 (85.7%) patients reached CR/CRi. After achieving CR/CRi, 13/48 (27.1%) patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), 3/48 (6.3%) patients received donor lymphocyte infusion (DLI), and 3/48 (6.3%) patients received chimeric antigen receptor T-cell immunotherapy (CAR-T therapy). During further follow-up, 24 (42.9%) patients achieved BCR::ABL1< 0.1% and 29 (49.2%) achieved BCR::ABL1 < 1%. In additional, probabilities of DFS, EFS and OS at 12 months were 80.3% (95%CI 61.0%-90.7%), 80.2% (95%CI 61.0%-90.7%), 93.3% (95%CI 75.8%-98.3%) in R/R Ph+ALL and 55.4% (95%CI 18.4%-81.4%), 38.6% (95%CI 9.8%-67.6%), 80.0% (95%CI 37.4%-95.1%) in advanced CML, respectively (Fig. 1). Common treatment-related adverse events (TRAEs) included skin hyperpigmentation, proteinuria, Elevated liver enzyme and hypertriglyceridemia (Table 1). Most nonhematologic TRAEs were grade 1/2. Only one patient died from pulmonary embolism. As of the data cutoff date, 37 (66.1%) patients continued on treatment and 19(33.9%) discontinued because of disease progression, intolerance, loss to follow-up or death. Conclusion Olverembatinib-based therapy showed strong efficacy and tolerable toxicity in advanced Ph+ leukemia.

Postpartum diagnosis and management of pulmonary arterial hypertension

A 38-year-old female who was found to have severe pulmonary arterial hypertension (PAH) secondary to HIV in the postpartum period. This case illustrates the treatment and challenges of postpartum PAH. It also demonstrates the need for expert guidance and additional research on the optimal management of PAH in pregnancy and postpartum.

NAMPT mediates PDGF-induced pulmonary arterial smooth muscle cell proliferation by TLR4/NF-κB/PLK4 signaling pathway

Nicotinamide phosphoribosyltransferase (NAMPT), a pleiotropic protein, promotes the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs), which is associated with the genesis and progression of pulmonary arterial hypertension (PAH). NAMPT is highly increased in PAH patient's plasma and highly relevant to PAH severity. The mRNA and protein levels of NAMPT are elevated in PAH animal models. However, the underlying molecular mechanisms how NAMPT mediated platelet-derived growth factor (PDGF)-induced PASMCs proliferation are still unclear. The present study aimed to address these issues. Primary cultured PASMCs were attained from male Sprague-Dawley (SD) rats. Western blotting, RT-PCR, ELISA, cell transfection, Cell Counting Kit-8 (CCK-8) and EdU incorporation assays were used in the experiments. We showed that PDGF upregulated NAMPT expression through the activation of signal transducers and activators of transcription 5 (STAT5), and elevated extracellular NAMPT further promoted the activation of NF-κB through Toll-like receptor 4 (TLR4), which ultimately upregulated polo-like kinase 4 (PLK4) expression leading to PASMCs proliferation. Knockdown of STAT5, NAMPT or PLK4, and inhibition of TLR4 or NF-κB suppressed PDGF-induced PASMCs proliferation. Our study suggests that NAMPT plays an essential role in PDGF-induced PASMCs proliferation via TLR4/NF-κB/PLK4 pathway, suggesting that targeting NAMPT might be valuable in ameliorating pulmonary arterial hypertension.

A Multidisciplinary Approach as a Goal for the Management of Complications in Systemic Scleroderma: A Literature Review and Case Scenario.

Systemic sclerosis (also known as scleroderma) is a chronic fibrosing autoimmune disease with both skin and multisystem organ involvement. Scleroderma has the highest mortality among all rheumatic diseases. The pathophysiology mechanism of systemic sclerosis is a progressive self-amplifying process, which involves widespread microvascular damage, followed by a dysregulation of innate and adaptive immunity and inflammation and diffuse fibrosis of the skin and visceral organs. Fibrosis of internal organs is a hint for systemic sclerosis, moreover associated with interstitial lung disease (SSc-ILD) is a complex process. In order to correlate scientific data from the literature with clinical experience, we present the case of a 56-year-old woman who was diagnosed with systemic sclerosis 16 years ago. The association of numerous comorbidities characterized by a considerable level of seriousness characterizes this case: the highly extensive systemic damage, the cardiovascular impact of the illness, and the existence of severe pulmonary arterial hypertension. The systemic and clinical manifestations, respiratory functional tests, radiological features, and specific therapy are discussed.

Home-inhaled nitric oxide in a child with pulmonary arterial hypertension associated with post-operative pulmonary venous obstruction.

Home-inhaled nitric oxide therapy was effective and feasible in the patients with intractable pulmonary arterial hypertension. We present the case of a child with severe pulmonary arterial hypertension associated with post-operative pulmonary venous obstruction who was treated with home-inhaled nitric oxide therapy.

Prevalence of pulmonary arterial hypertension in post-tuberculosis lung fibrosis patients: A cross-sectional observational study

Introduction: Post-tuberculosis (TB) lung fibrosis is an infrequently reported cause of Pulmonary arterial hypertension (PAH). Pulmonary TB still being an important global health problem, especially in developing countries, PAH developing after pulmonary TB deserves attention. This study was undertaken to know the prevalence of PAH among patients with post-TB lung fibrosis. Methods: A cross-sectional observational study was carried out in two tertiary care hospitals in Kolkata over a period of 1 year. Sixty adult post-TB lung fibrosis patients without any cardiovascular or other pulmonary comorbidities were included in this study. Results: Out of the 60 patients with varying degrees of lung fibrosis confirmed radiologically, eight patients were found to have PAH (13.33% of the study population). Among the eight cases, six were males and two were females. Five of the males were smokers with a mean of 17.6 pack years of smoking. Out of the eight diagnosed PAH cases, three were mild PAH, four were moderate, and one case had severe PAH (grading based on 2D echocardiography findings). Pulmonary function test (PFT) revealed obstructive pattern in three cases, restrictive pattern in three cases, and mixed in two cases. On PFT, smokers with PAH exhibited obstructive pattern and mixed pattern, whereas the nonsmoker PAH cases exhibited restrictive pattern. Conclusion: All post-TB lung fibrosis cases must be followed up at regular intervals and screened to rule out PAH. Early diagnosis and prompt treatment of the cases will help to reduce morbidity and mortality of the disease which otherwise has a poor prognosis.

TCT-149 Severe Pulmonary Artery Hypertension and Rheumatic Disease: Long-Term Follow-Up After Percutaneous Mitral Balloon Commissurotomy

TCT-149 Severe Pulmonary Artery Hypertension and Rheumatic Disease: Long-Term Follow-Up After Percutaneous Mitral Balloon Commissurotomy

Surgical outcomes and long-term follow-up of patients with large ventricular septal defects with severe pulmonary arterial hypertension: single-center experience

Purpose: In this retrospective study, pediatric patients who underwent surgery for large ventricular septal defect (VSD) with severe pulmonary arterial hypertension (PAH) were evaluated in detail in terms of clinical characteristics, and long-term results, and reinterpreted with the current surgical criteria.
 Materials and Methods: Twenty-four patients who underwent surgery for large VSD due to PAH between 1994 and 2005 were included in the study. The patients were divided into two groups according to their pulmonary vascular resistance index (PVRI) and compared (group 1 with PVRI

Congenital Hepatic Arteriovenous Malformation: Often Missed Cause for Neonatal Pulmonary Arterial Hypertension

Congenital hepatic arteriovenous malformations (AVM) are extremely rare, with an incidence of less than 1 in 1 hundred thousand, and the literature is limited to only a few case reports. They are characterised by an abnormal arterial connection to a fistulous venous connection within the liver. This results in high flow, low resistance circulation that causes high output cardiac failure. We report a late-preterm male newborn who presented with respiratory distress and signs of cardiac failure on day 1 of life. The newborn is diagnosed with hepatic AVM as the cause of severe pulmonary arterial hypertension (PAH) and cardiac failure. This case report, along with the literature review, emphasises the need for a high index of suspicion to look for hepatic AVM in a newborn presenting with unexplained PAH and cardiac failure and also discusses different management strategies for hepatic AVM.

Prediction of Operability by Pulmonary Artery Acceleration Time and Right Ventricular Ejection Time in Large Ventricular Septal Defects with Severe Pulmonary Arterial Hypertension

Background: Diagnosing and treating cardiopulmonary illnesses in children depend heavily on evaluating pulmonary hemodynamics. Severe pulmonary artery hypertension (PAH) and Eisenmenger’s syndrome are most frequently seen in post-tricuspid shunts. Right heart catheterization is the gold standard test for calculating pulmonary vascular resistance and pulmonary artery pressures, but it has many flaws, especially regarding shunt abnormalities. Right ventricular ejection and pulmonary artery acceleration times can be useful alternatives for determining pulmonary vascular resistance. Aims and Objectives: This study aimed to correlate pulmonary artery acceleration time (PAAT) and right ventricular ejection time (RVET) with PAH. Materials and Methods: We included 52 patients with large ventricular septal defects (VSD) and severe pulmonary artery hypertension. All children with large VSD and severe PAH admitted for diagnostic catheterization after satisfying the inclusion criteria were included in the study following approval from the institutional ethics committee. All pre-catheterization echocardiographic data were collected with a Philips iE33 ultrasound machine. All of them underwent diagnostic catheterizations. Results: We observed that the chance of operability was high earlier in the age of presentation. PAAT: RVET had a positive correlation with Qp:Qs (pulmonary flow: systemic flow) and were negatively correlated with pulmonary vascular resistance index (PVRI), pulmonary vascular resistance: systemic vascular resistance (PVR:SVR), and mean pulmonary artery pressure (mPAP). In our study, we found that both PAAT and PAAT: RVET were moderately negatively correlated with PVRI and PVR: SVR (r: -0.72, P < 0.001, r: -0.71, P < 0.001 and r: -0.67, P < 0.001, r: -0.71, P < 0.001 respectively). PAAT and PAAT: RVET were moderately negatively correlated with mPAP (r: -0.7. P < 0.001; r: -0.71, P < 0.001 respectively) and positively with Qp:Qs (r: +0.63, P < 0.001; r: 0.67, P < 0.001 respectively). Conclusion: PAAT and PAAT: RVET index are important parameters in assessing pulmonary arterial pressure in large VSD with severe PAH.

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.

Epidemiological and clinical characteristics of pulmonary arterial hypertension in Indian patients: A hospital-based observational study

Context: Pulmonary hypertension (PH) is a condition characterized by an increase in pulmonary artery pressure, leading to morbidity and poor survival. In India, the high prevalence of certain diseases contributes to the burden of PH. To address this, this study provides epidemiological data and clinical characteristics of pulmonary artery hypertension. Materials and Methods: A cross-sectional study was conducted at a tertiary cardiac care hospital, recruiting 964 patients with severe pulmonary arterial hypertension (PAH). Patient data were obtained through a detailed history and physical examination, including 12-lead electrocardiogram, two-dimensional echocardiography, coronary angiography, right heart catheterization, and hematological and serological investigations. Results: The majority of patients (28.94%) were in the age group of 31–40 years, with a female preponderance in PAH disease. Idiopathic PAH (IPAH) was the most common type, accounting for 69.78% of all cases. The most common comorbid conditions were hypertension (48.55%) and Type-2 diabetes mellitus (44.81%). Dyspnea on exertion (98.34%) and edema of extremities (91.18%) were the most common symptoms. The mean survival rate was 50.98 months, with Type 1 PAH having the worst survival rate of 47.56 months. The statistical analysis showed a significant association between smoking and PAH. Conclusion: This study provides epidemiological data and clinical characteristics of PAH patients in India, emphasizing the need for early diagnosis, prompt management, and smoking cessation programs. The high prevalence of IPAH and female preponderance was also observed in this study. These findings can help in the development of targeted interventions and management strategies for PH patients in India.

Long-Term Safety, Outcome, and Clinical Effects of Subcutaneous and Intravenous Treprostinil Treatment in Patients with Severe Chronic Pulmonary Arterial Hypertension

Background: Current guidelines recommend treatment with parenteral prostacyclin analogs in patients with severe pulmonary arterial hypertension (PAH), who have insufficient response to treatment. Real-life data are sought to help physicians in treatment decisions and clinical care of patients. Objective: This study analyzed safety, clinical effects, and long-term outcomes of subcutaneous (sc) and/or intravenous (iv) treprostinil via different pump systems in consecutive patients with PAH. Methods: Thirty-seven patients with severe progressive PAH despite dual combination therapy (20 female, mean age: 52.3 ± 15 years, mean pulmonary vascular resistance: 12.1 ± 5.1 WU) were initiated with add-on treprostinil sc and were routinely clinically assessed. Changes in clinical parameters, adverse events, and outcome were analyzed retrospectively. Results: In 24 of 37 patients, treprostinil administration was continued iv via implantation of LENUS Pro® pump after 3 ± 1.3 months, 6 patients continued with sc therapy, and 7 discontinued treatment. After 3, 6, 9, and 12 months of treprostinil treatment, patients showed a significant improvement in mean 6-min walk distance and tricuspid annular plane systolic excursion compared to baseline. In 8 of the 24 patients, iv pumps required surgical revision. During a mean follow-up of 2.82 ± 1.95 years, 12 patients died, four received lung transplantation. Transplant-free survival after 1, 2, and 3 years was 85.7%, 69.2%, and 65.3%, respectively. Conclusion: sc treprostinil as add-on to double combination treatment significantly improved exercise capacity and right heart function. In most patients, treprostinil could be continued via more tolerable iv administration approach (LENUS Pro® pump), showing reasonable overall survival with respect to the severity of PAH.

Initial Triple Combination Therapy Including Intravenous Prostaglandin I2 for the Treatment of Patients with Severe Pulmonary Arterial Hypertension.

Upfront combination therapy including intravenous prostaglandin I2 (PGI2-IV) is recognized as the most appropriate treatment for patients with severe pulmonary arterial hypertension (PAH). This retrospective study aimed to determine reasons why this therapy is not used for some patients with severe PAH and describe the hemodynamic and clinical prognoses of patients receiving initial combination treatment with (PGI2-IV+) or without (PGI2-IV-) PGI2-IV.Data for patients with severe PAH (World Health Organization Functional Class III/IV and mean pulmonary arterial pressure [mPAP] ≥ 40 mmHg) were extracted from the Japan Pulmonary Hypertension Registry. Overall, 73 patients were included (PGI2-IV + n = 17; PGI2-IV- n = 56). The PGI2-IV+ cohort was younger than the PGI2-IV- cohort (33.8 ± 10.6 versus 52.6 ± 18.2 years) and had higher mPAP (58.1 ± 12.9 versus 51.8 ± 9.0 mmHg), greater prevalence of idiopathic PAH (88% versus 32%), and less prevalence of connective tissue disease-associated PAH (0% versus 29%). Hemodynamic measures, including mPAP, showed improvement in both cohorts (post-treatment median [interquartile range] 38.5 [17.0-40.0] for the PGI2-IV + cohort and 33.0 [25.0-43.0] mmHg for the PGI2-IV - cohort). Deaths (8/56) and lung transplantation (1/56) occurred only in the PGI2-IV - cohort.These Japanese registry data indicate that older age, lower mPAP, and non-idiopathic PAH may influence clinicians against using upfront combination therapy including PGI2-IV for patients with severe PAH. Early combination therapy including PGI2-IV was associated with improved hemodynamics from baseline, but interpretation is limited by the small sample size.