Pulmonary Hypertension Research Articles

Infants With a Congenital Diaphragmatic Hernia Had Favourable Pulmonary Hypertension Outcomes at 1 Year of Age.

Pulmonary hypertension is frequent in neonates with a congenital diaphragmatic hernia, but long-term data have been scarce. Our aim was to examine its prevalence, evolution and management and identify factors associated with its persistence. This French retrospective cohort study compared the characteristics of neonates who had persistent pulmonary hypertension, or died with it, and those with normalised pulmonary pressures at 1 month and 1 year of age. Most (92%) of the 88 neonates we studied underwent surgery. Two-thirds (67%) had preoperative pulmonary hypertension and they included 10 of the 11 who died after surgery. Pulmonary hypertension resolved after a median of 31 days in the 70 who were discharged alive and 27% required prolonged sildenafil treatment. At 1 year, 6 (9%) of the 65 children with echocardiographic data available still had elevated pulmonary pressures. Preoperative pulmonary hypertension, associated malformations and longer invasive ventilation were independently associated with persistent pulmonary hypertension at 1 month. Only prolonged invasive ventilation remained significant at 1 year. Despite its high initial prevalence and impact on mortality, pulmonary hypertension resolved within weeks of surgery in the surviving neonates. The duration of invasive ventilation may have been a key factor in its persistence.

Rare but relevant: The injection of tablet preparations and pulmonary hypertension.

Intravascular injection of dissolved medicinal preparations such as crushed tablets is associated with a risk of injecting particulate material into the vasculature. This particulate material will naturally pass to the lungs where it will be largely filtered out in the pulmonary vascular bed, and in turn, it can result in a range of pathological processes in the lungs including pulmonary arterial hypertension, granulomatous lung disease, and pulmonary fibrosis. On rare occasions, a rapid increase in pulmonary vascular resistance can result in sudden death of the injecting drug user.

Comprehensive insights and In silico analysis into the emerging role of LincRNAs in lung diseases pathogenesis; a step toward ncRNA precision.

Long non-coding RNAs (lncRNAs) have emerged as essential regulators of gene expression, significantly influencing various biological processes. Approximately half of all lncRNAs are classified as long intergenic non-coding RNAs (lincRNAs), which are situated among coding genes. Recent studies have documented the role of lincRNAs in the pathogenesis of lung diseases, including lung cancer, pulmonary fibrosis, and pulmonary arterial hypertension. These lincRNAs can modulate gene expression through various mechanisms, including epigenetic modifications, transcriptional regulation, and post-transcriptional regulation. By functioning as competing endogenous RNAs (ceRNAs), lincRNAs can affect the activity of microRNAs (miRNAs) and their corresponding target genes. This review delves into the intricate mechanisms by which lincRNAs contribute to the development and progression of various lung diseases. Furthermore, it discusses the potential of lincRNAs as therapeutic targets.

Liposomal amphotericin-B-induced atrial fibrillation with hypomagnesaemia in acute invasive mucormycosis of the right maxillary sinus

Liposomal amphotericin B (LAmB) is the preferred drug for treating mucormycosis, a dangerous opportunistic infection caused by fungal pathogens. This case report details the medical history and treatment of a female patient who had type 2 diabetes, pulmonary artery hypertension and congenital heart disease. She was diagnosed with acute invasive mucormycosis in her right maxillary sinuses and underwent right endoscopic debridement. Throughout her treatment, she received 50 mg of injection LAmB. However, her magnesium levels decreased, and on the 10th day of treatment, she developed abnormal heart rhythms, specifically atrial flutter. This condition was successfully managed with an injection of digoxin (0.25 mg). Thus, continuous monitoring of magnesium and potassium levels, as well as electrocardiogram monitoring, is crucial in these cases. Failure to correct low potassium and magnesium levels in patients with congenital heart disease may result in heart rhythm disturbances or artery spasms. In our case, they treated it with syrup potassium chloride, and an injection of magnesium was given as a stat doses. Careful management and close monitoring are required to treat some cardiac-related effects of drugs and to achieve optimal outcomes in complex cases of mucormycosis treated with LAmB in our case continuous monitoring helped us with the achievement of treatment.

Detection of pulmonary hypertension in preterm infants with bronchopulmonary dysplasia using oxygen saturation data

Detection of pulmonary hypertension in preterm infants with bronchopulmonary dysplasia using oxygen saturation data

Super-Enhancer Target Gene CBP/p300-Interacting Transactivator With Glu/Asp-Rich C-Terminal Domain, 2 Cooperates With Transcription Factor Forkhead Box J3to Inhibit Pulmonary Vascular Remodeling.

The function of super-enhancers (SEs) in pulmonary hypertension (PH), especially in the proliferation of pulmonary artery smooth muscle cells (PASMCs), is currently unknown. We identified SEs-targeted genes in PASMCs with chromatin immunoprecipitation (ChIP)-sequence by H3K27ac antibody and proved that CBP/p300-interacting transactivator with Glu/Asp-rich C-terminal domain, 2 (CITED2) is an SEs-targeted gene through bioinformatics prediction, ChIP-PCR, dual-luciferase reporter gene assays and other experimental methods. We also found that the expression of CITED2 and the transcription factor Forkhead Box J3 (FOXJ3) was reduced in hypoxic mouse PASMCs. In addition, the expression of CITED2 and FOXJ3 also decreased in both the patients with idiopathic pulmonary arterial hypertension (iPAH) and the human PASMCs exposed to hypoxia. The decreased expression of CITED2 was reversed by co-transfection of FOXJ3 and SEs plasmids. Overexpressing of CITED2 attenuated the PASMCs proliferation induced by hypoxia. Lentiviral overexpression of CITED2 also reversed hypoxia-induced pulmonary hypertension mice model. Mechanically, the expression of CITED2 by affecting by FOXJ3, which binding with three SEs located in the about 2000 bp of TSS. In conclusion, we first identified that CITED2 is a kind of SEs-targeted gene, modulated by FOXJ3. The FOXJ3/SEs/CITED2 axis may become a new therapeutic target of PH.

Role of the calcium-sensing receptor in regulating vascular function.

Functional expression of the calcium-sensing receptor (CaSR) in calcitropic tissues, for example, parathyroid glands and kidneys, is important for maintaining Ca2+ homeostasis. It is also established that the CaSR is present in tissues previously thought to be noncalcitropic and this review discusses the role of the CaSR in vascular function, focusing mainly on contractility but also outlining its role in cell proliferation and calcification. Stimulation of the CaSR by extracellular Ca2+ concentration ([Ca2+]o) on perivascular sensory nerves and vascular endothelial cells is associated with vasodilatation through the release of vasoactive substances and stimulation of IKCa channels and nitric oxide synthesis, respectively, which mediate endothelium-derived hyperpolarizations and activation of BKCa channels and KATP channels in vascular smooth muscle cells (VSMCs). CaSR-induced vasoconstrictions are mediated by the CaSR expressed in VSMCs, which are coupled to the Gq/11 protein-coupled pathway. In addition, the CaSR expressed on VSMCs also regulates proliferation and calcification. Consequently, the CaSR has been implicated in regulating systemic and pulmonary blood pressure and calcimimetics and calcilytics are potential therapeutic targets for cardiovascular diseases, such as hypertension, pulmonary artery hypertension, and atherosclerosis.

Problems of the state of the oral cavity and anesthetic care in users of various forms of cocaine (scientific and literary review)

The prevalence of cocaine among the narcotic substances used by the population of Europe and America is second only to cannabinoids. Cocaine and crack use can cause various types of damage to the oral cavity, ranging from bad breath (halitosis) and gingivitis to cancer. These lesions are due to the anesthetic, vasoconstrictor, local prothrombotic properties of cocaine and its components in combination with cytotoxic effects and tissue damage associated with the method of use. Dentists quite often and treat cocaine users unknowingly, and they should be aware of the significant risks of possible problems and complications and be prepared to deal with them. Consuming this narcotic immediately before or after tooth extraction can cause excessive bleeding. Active cocaine users had significantly more complications related to anesthesia. Anesthesiologists should know the specifics of managing such patients, regardless of whether they are acutely intoxicated or suffering from the effects of chronic drug use. Monoamine oxidase inhibitors, class I antiarrhythmic drugs, and methadone in combination with cocaine lead to arrhythmias. The prescription of β-blockers should be avoided. The use of atropine and adrenaline can cause dangerous tachycardia in cocaine addicts. With general anesthesia during intubation, uncontrolled hypertension, arrhythmia and myocardial infarction, difficulty in mask ventilation and tracheal intubation due to inflammation, mucosal edema, defects of the palate, nasal membrane, pulmonary hypertension, which can complicate oxygenation or ventilation, may occur. Sympathomimetics are contraindicated if cocaine has been used within the last 24 hours. This must be explained to the patient (who must ensure that the drug was not used during this period), if local anesthesia with vasoconstrictors is indicated to reduce periodontal bleeding, since the use of a local anesthetic alone may not provide the necessary duration of anesthesia or the degree of hemostasis. Planned intervention using general anesthesia is possible at least 48 hours after the last use of cocaine (with certain risks), and optimally — after a week.

Depression in Pulmonary Hypertension: A Systematic Review of Clinical Outcomes, Treatment Interactions, and Emerging Technologies

Background: Pulmonary hypertension (PH) is characterized by elevated pulmonary artery pressure, often leading to right heart failure and poor prognosis. Depression, a common comorbidity in PH, significantly affects the quality of life. However, mechanistic insights into the bidirectional relationship between PH and depression and specific treatment interactions remain scarce. Objective: The object was to examine the clinical and therapeutic implications of depression in PH, focusing on its impact on patient outcomes and cost efficiency. Methods: A systematic review of Medline and Google Scholar was conducted to identify studies on depression in PH, emphasizing evidence-based interventions, clinical outcomes, and cost efficiency. Special consideration was given to potential drug interactions between PH medications and depression treatments and to the role of emerging technologies in managing PH-related depression. Results: While depression reduces the quality of life and exacerbates disease severity in PH, depression treatment improves outcomes, particularly when tailored to PH-targeted therapies, considering potential drug–drug interactions. Emerging technologies, including telemedicine, offer innovative approaches to manage depression in PH, enhancing access to care and improving adherence to treatment regimens. Conclusions: Depression in PH must no longer be neglected and should be acknowledged as both a critical comorbidity and a significant driver of disease progression. Interdisciplinary treatment approaches are necessary, considering potential pharmacological interactions and incorporating emerging technologies like telemedicine to improve patient care. Further research is needed to assess the long-term outcomes of depression treatment in different groups of PH.

Pulmonary vascular remodeling in Fra-2 transgenic mice is driven by type 2 inflammation and accompanied by pulmonary vascular hyperresponsiveness.

Lung vessel remodeling leads to increased pulmonary vascular resistance, causing pulmonary arterial hypertension (PAH), and consequently right ventricular hypertrophy and failure. In patients suffering from systemic sclerosis (SSc), PAH can occur and is a life-threatening complication. Dysregulation of immune processes plays a crucial role in pulmonary vascular remodeling, as has previously been shown in Fos-related antigen-2 (Fra-2) transgenic (TG) mice, a model of SSc-PAH. Here, we investigate whether vascular remodeling in the Fra-2 TG model is driven by type 2 inflammation and is associated with vascular hyperresponsiveness, an important feature of PAH pathobiology. Basal pulmonary arterial pressure and pulmonary vascular responsiveness to hypoxic ventilation and serotonin were increased in isolated, perfused and ventilated lungs of Fra-2 TG mice compared to wild-type (WT) littermates. Similarly, contractile responses of isolated intrapulmonary arteries were elevated in Fra-2 TG mice. We also observed increased expression of contractile genes in Fra-2 overexpressing human pulmonary artery smooth muscle cells (PASMCs) with elevated intracellular calcium levels after IL-13 stimulation. These findings were corroborated by transcriptomic data highlighting dysregulation of vascular smooth muscle cell contraction and type 2 inflammation in Fra-2 TG mice. In vivo, type 2-specific anti-inflammatory treatment with IL-13 neutralizing antibodies improved vascular remodeling in Fra-2 TG mice, similar to corticosteroid treatment with budesonide. Our results underscore the importance of type 2 inflammation and its potential therapeutic value in PAH-associated pulmonary vascular remodeling and hyperresponsiveness in SSc-PAH.

Integrated Transcriptomic and Metabolomic Analysis of Rat PASMCs Reveals the Underlying Mechanism for Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a kind of pulmonary vascular lesion characterized by vasoconstriction and reshaping of small pulmonary arteries, ultimately resulting in increased pulmonary artery pressure and pulmonary vascular resistance, and eventually leading to right ventricular failure and death. This study was aimed to construct a platelet-derived growth factor BB (PDGF-BB)-induced rat pulmonary artery smooth muscle cells (PASMCs) model and conduct a combined transcriptomic and metabolomic analysis to identify proliferation-related targets, thereby enhancing understanding of the pathogenesis underlying PAH. Rat PASMCs were isolated and cultured in the presence or absence of PDGF-BB for 24 hours. Cells were collected for transcriptomics and metabolomics investigations. A total of 1288 differentially expressed genes (572 up-regulated and 716 down-regulated) were identified in PDGF-BB-treated rat PASMCs compared to control cells. Subsequently, Gene ontology (GO) enrichment analysis revealed that 791 enriched GO terms were significantly enriched in PDGF-BB treated cells. Similarly, 294 differential metabolic pathways were enriched in PDGF-BB treated cells according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene Set Enrichment Analysis (GSEA) were performed on the differentially expressed genes (DEGs). It turned out that 7219 gene sets were more enriched in PDGF-BB treated cells. In addition, a total of 28 secondary differential metabolites were identified in PDGF-BB-treated rat PASMCs compared to control cells (p-value < 0.05 and VIP > 1). We speculate that Mylk, Pla2g4a, Gucy1b1, Adcy8, Adcy4, Gucy1a2, Col3a1, and Plcb4 are potential targets for the treatment of PAH.

Pulmonary Arterial Compliance and the FREEDOM-EV study

This video explains pulmonary arterial compliance, its relevance in pulmonary arterial hypertension, and how oral treprostinil improves PAC in PAH.

Point-of-Care Ultrasound Diagnosis of Restrictive Cardiomyopathy in a 3-Year-Old Patient.

Restrictive cardiomyopathy is a rare form of cardiomyopathy in children, representing only 2.5%-3% of all pediatric cardiomyopathies, and is typically diagnosed between the ages of 6 and 10. The underlying etiology varies depending on age and region; however, idiopathic, genetic, and endomyocardial fibrosis are among the most common. Cohort studies have demonstrated mortality as high as 50% within 2 years of diagnosis, as well as high rates of adverse events including thromboembolism, pulmonary hypertension, and sudden cardiac death. There is a paucity of literature on point-of-care ultrasound (POCUS) for the diagnosis of pediatric restrictive cardiomyopathy. We present a case of a 3-year-old female whose diagnosis of heart failure was rapidly identified via POCUS which subsequently expedited life-saving treatment.

Unusual presentation of anomalous origin of the right pulmonary artery from the ascending aorta: case report.

Anomalous origin of the right pulmonary artery (AORPA) from the ascending aorta is a rare congenital anomaly, representing approximately 0.12% of all congenital heart defects. Early diagnosis and timely intervention are essential to prevent severe complications such as heart failure and pulmonary vascular disease. We report a case of a full term neonate presented with respiratory distress and cyanosis. Echocardiography revealed an anomalous right pulmonary artery (RPA) origin from the ascending aorta, a large patent ductus arteriosus (PDA) with right-to-left shunt, and moderate tricuspid regurgitation. Despite initial management with prostaglandin E1 (PGE1) infusion, discontinuation of the drug led to clinical deterioration characterized by severe metabolic acidosis and low cardiac output syndrome. Resuming PGE1 infusion stabilized the patient's hemodynamics and improved systemic blood flow, allowing for successful surgical repair. In cases of AORPA associated with aortic arch flow reversal, pulmonary hypertension, and inadequate interatrial communication, maintaining PDA patency with PGE1 infusion until surgical repair is critical for survival. The right-to-left flow across the PDA counteracts the steal from the aorta and decompresses the right ventricle, preventing right ventricular failureand maintaining systemic blood flow.

Analysis of clinical features and risk factors of pulmonary hypertension associated with interstitial lung disease

Analysis of clinical features and risk factors of pulmonary hypertension associated with interstitial lung disease

PLACE: Multicenter Study for Right Ventricular Failure on Mechanical Cardiocirculatory Supports.

Isolated acute right ventricular failure (aRVF) is associated with poor prognosis in different scenarios. In severe conditions, temporary mechanical cardiocirculatory support (tMCS) is required. PLACE is an international, retrospective, multicenter registry including 17 centers that investigated patients affected by isolated aRVF and treated with various types of tMCS from January 2000 to December 2020. The registry included 644 (69.6% males, mean age: 55 years) patients. The most frequent etiologies were post-left ventricular assist device implantation (LVAD) and postcardiotomy shock. These patients received mostly mechanical circulatory support (MCS) and veno-arterial extracorporeal membrane oxygenation. Mean tMCS duration was 9 days, weaning was achieved in 70.5% of the patients, and the major cause of death on support was multiorgan failure (50.5%). The mortality rate was 45 and 48.4% in-hospital and at 3 month follow-up, respectively. Multivariable logistic regression analysis identified age, aRVF due to acute pulmonary hypertension, bilirubin level, and oliguria or anuria at tMCS implantation as risk factors for in-hospital mortality. Conversely, aRVF after LVAD was found to be associated with a lower risk of early mortality. In-hospital and 3 months mortality occurred in less than half of the aRVF-supported subjects. Furthermore, several preimplant aspects such as age, organ function, and type of tMCS are independently associated with in-hospital and 3 month mortality.

Inhalation of the Novel Tryptophan Hydroxylase 1 Inhibitor TPT-004 Alleviates Pulmonary Arterial Hypertension.

Inhaled pharmacotherapies are promising treatment options for patients with pulmonary arterial hypertension (PAH) as they minimize extrapulmonary adverse effects. Recently, we developed a highly specific inhibitor (TPHi) of the serotonin synthesizing enzyme tryptophan hydroxylase 1, TPT-004. We hypothesized that repetitive nose-only inhalation of TPT-004 alleviates PAH and pulmonary vascular remodeling in the Sugen-hypoxia (SuHx) rat model. Male Sprague-Dawley rats were divided into 3 groups: (i) ConNx, control animals kept in room air during the study; (ii) SuHx [rats subcutaneously injected with the VEGFR2-inhibitor SU5416, then exposed to chronic hypoxia (3 weeks), followed by 5.5 weeks of room air]; (iii) SuHx + TPHi [SuHx animals treated with TPHi by inhalation for 4 weeks]. Closed-chest right-left heart catheterization and cardiac MRI were performed in spontaneously breathing rats. Lungs underwent histological and mRNA-seq analysis. SuHx-exposed rats had severe PAH, RV hypertrophy, and RV dilation. In comparison with SuHx-exposed rats, TPHi-treated SuHx rats had significantly lower RV systolic pressure (67.25 vs.51.47mmHg; p<0.0001), normalized RV end-systolic volume (182.6 vs. 105.1µL; p<0.0001) and improved RV ejection fraction by cardiac MRI (47.9 vs. 66.8%; p<0.0001). Inhaled TPT-004 did not affect LV end-diastolic or systemic blood pressure. TPT-004 therapy reversed pulmonary vascular remodeling and alveolar macrophage infiltration. RNA-sequencing unraveled TPHi-induced changes in pulmonary gene expression: 1) increased cell adhesion and reduced cell motility/migration; 2) suppressed extracellular matrix remodeling; 3) modulated immune response; 4) suppressed pulmonary vascular remodeling via modulating proliferation, apoptosis, and homeostasis. Taken together, TPT-004 is an effective therapeutic PAH agent, does not cause any hemodynamic adverse effects in rodents, and thus, should be tested further towards a clinical phase 1b/phase 2 study in PAH patients.

Prognostic and Diagnostic Value of Platelet Distribution Width in COPD Patients with Pulmonary Hypertension: A Retrospective Study.

The objective of the study was to investigate the value of platelet distribution width (PDW) as a prognostic biomarker by comparing PDW between COPD patients with pulmonary hypertension (PH) (PASP 50mmHg) and those without PH (PASP < 50mmHg) and to explore its diagnostic and predictive value in this population. A retrospective study of 270 COPD patients in Liaocheng People's Hospital (July 2018 to July 2019) was done by dividing them into two groups according to pulmonary artery systolic pressure (PASP): COPD-only (PASP <50mmHg) and COPD with PH (PASP ≥50mmHg). Routine blood tests, C-reactive protein, pulmonary function tests, echocardiography, Chronic Obstructive Pulmonary Disease Assessment Questionnaire (CAT), Clinical COPD Questionnaire were performed. PDW was higher in COPD with PH group than COPD-only group. After adjusting for confounders including age, smoking history, CAT scores, white blood cell count, PDW, and NT-proBNP in COPD with PH, PDW was positively correlated with various parameters. PDW can diagnose COPD with PH, also prognostic value and cardiovascular distinction in these patients. The study concluded that PDW is a prognostic marker, reflecting pulmonary and cardiovascular physiology in COPD patients with PH. It can be used for early diagnosis, risk stratification, and individualized management for this high-risk population.

Severity, complications and outcome of meconium aspiration syndrome in neonates.

Objective: To determine the severity, complications, and outcomes of meconium aspiration syndrome (MAS) in neonates. Study Design: Cross-sectional study. Setting: Neonatal Intensive Care Unit (NICU) of the National Institute of Child Health, Karachi, Pakistan. Period: January 2024 to June 2024. Methods: Neonates aged 1-28 days of either gender, and having MAS were analyzed. Vital signs were noted and necessary laboratory investigations were done. Presenting clinical features and associated complications of MAS were noted. Outcome was noted in the form of discharged, admitted to pediatric unit, or mortality. Results: In a total of 92 neonates, 66 (71.7%) were male. The mean age was 12.47±6.55 days. Evaluation of MAS severity revealed mild, moderate, and severe cases among 2 (2.2%), 16 (17.4%), and 74 (80.4%) neonates, respectively. The most frequently noted complications were sepsis 65 (70.7%), hyperinflated lungs 55 (59.8%), respiratory distress 34 (37.0%), and pulmonary hypertension 31 (33.7%), were the most commonly associated complications of MAS. Two neonates left against medical advice so those were excluded from the final outcome analysis. In the remaining 90 neonates, mortality was reported in 6 (6.7%). Mortality had significant association with bluish skin at presentation (p=0.044), severe MAS (p=0.001), and pulmonary hypertension (p=0.001). Conclusion: Vast majority of the neonates (80.4%) presented with severe MAS which should raise alarm about the time identification of these high risk neonates. The most frequently noted MAS associated complications were sepsis, hyperinflated lungs, respiratory distress, and pulmonary hypertension. At presentation, bluish skin, pulmonary hypertension, and severe MAS were significantly associated with mortality.

Relationships that perceived barriers to physical activity have with functional capacity and quality of life in patients with pulmonary hypertension

Objective: Barriers to physical activity can affect the functional capacity and quality of life of patients with pulmonary hypertension (PH). This study aimed to identify the main barriers to physical activity in patients with PH and to examine whether those barriers are related to functional capacity, echocardiographic variables, or quality of life. Methods: This was a cross-sectional observational study involving 70 patients. Participants scored seven potential barriers to their activities, with a score = 5 indicating a significant barrier. Participants completed the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) and Manchester Respiratory Activity of Daily Living questionnaire, as well as the six-minute walk test. Correlation analysis, univariate analysis and multiple logistic regression were performed. Results: As a perceived barrier to physical activity, 'lack of will' or 'lack of energy' was cited by 67% of the patients. The 'lack of will' barrier was found to correlate with all SF-36 domains except bodily pain. We also identified a correlation between the SF-36 vitality domain and the barriers 'lack of energy', 'lack of will' and 'lack of structure'. The logistic regression analysis indicated that the vitality domain correlated significantly with the barriers 'social influence', 'lack of energy', 'lack of will', and 'lack of structure'. For each unit decrease in the vitality score, there was a 10% increase in the probability of citing the barrier 'lack of will'. No significant correlations were identified between any of the perceived barriers and echocardiographic parameters. Conclusions: The perceived barrier most commonly reported was 'lack of will/energy', which correlated with almost all SF-36 domains, especially vitality. The 'lack of will' barrier also correlated with functional capacity.