Pulmonary Artery Research Articles

12199 Uncontrolled Graves Disease Leading To The Development Of Pulmonary Hypertension

Abstract Disclosure: A. Agrawal: None. N. Shaykh: None. C. Marsalisi: None. L. Lam: None. C. Harrison: None. G.Y. Gandhi: None. Introduction: Graves’ disease can cause cardiorespiratory complications by increasing cardiac output, inducing endothelial dysfunction, and increasing the metabolism of intrinsic pulmonary vasodilating substances. Case: A 26-year-old female with a one-year history of Graves’ disease presented with chest pressure, shortness of breath, worsening orthopnea, a 40-pound weight loss, and subjective fevers. Her home methimazole dose was 10 mg daily, which she had missed for four days before admission. Her BP was 153/90 mmHg, heart rate 117 bpm, and temperature 100.7° F. She had mild bilateral proptosis and an enlarged but non-tender thyroid, which caused her difficulty swallowing. TSH was undetectable less than 0.005 mIU/L (0.27-4.2 mIU/L), and thyroid hormone levels were significantly elevated free T4 greater than 7.77 ng/dL (0.8-1.7 ng/dL) and free T3 29.1 pg/mL (2-4.4 pg/mL). TSI was high at 5.66 IU/L (0-0.55 IU/L) as was BNP at 1,642 pg/mL (0-125 pg/mL). Cardiac troponin was 105 ng/dL (less than 14 ng/dL) with a peak of 106 ng/dL. A Burch-Warsofsky score of 50 was highly suggestive of thyroid storm. She initially received 1 mg of IV propranolol, 1,000 mg of PTU, and 4 mg of dexamethasone followed by hydrocortisone 100 mg, methimazole 20, propanol 20 mg, and two doses of SSKI. A transthoracic echocardiogram was remarkable for severe right atrial and ventricular enlargement, and pulmonary artery pressure measured 55 mmHg (normal 20-30 mmHg). Autoimmune testing, including ANA, c-ANCA, p-ANCA, rheumatoid factor, anti-CCP, anti-SS-A, anti-SS-B antibodies, ultrasound for deep vein thrombosis, and ventilation-perfusion scan were negative. There was no history of congenital heart defects or valvulopathy. The patient reached a euthyroid state and was discharged home on methimazole 20 mg daily. Discussion: Although frequently underappreciated, pulmonary hypertension is present in 30 to 65% of Graves’ disease patients when systematically ascertained. Elevated thyroid hormones can increase heart rate, contractility, venous return, and cardiac output. An imbalance between vasoconstriction and vasodilation, along with endothelial dysfunction, can cause pulmonary vascular effects of hyperreactivity, remodeling, and thrombosis. An autoimmune mechanism is plausible due to an association between antithyroid antibodies and pulmonary hypertension. Right heart catheterization remains the gold standard for diagnosis, though in this case, it was not pursued in the acute setting. This case reinforces the importance of screening for pulmonary hypertension in patients with Graves’ disease and possibly normalizing pulmonary hypertension, thereby avoiding irreversible complications. Clinicians should consider reassessing for pulmonary hypertension even after long-term control of the thyrotoxic state, as about 30% of these patients have persistent pulmonary hypertension. Presentation: 6/3/2024

Quercetin regulates pulmonary vascular remodeling in pulmonary hypertension by downregulating TGF-β1-Smad2/3 pathway

BackgroundPulmonary arterial hypertension (PAH) is a worldwide challenging disease characterized by progressive elevation of pulmonary artery pressure. The proliferation, migration and phenotypic transformation of pulmonary smooth muscle cells are the key steps of pulmonary vascular remodeling. Quercetin (3,3', 4', 5, 6-pentahydroxyflavone, Que) is a natural flavonol compound that has antioxidant, anti-inflammatory, anti-tumor and other biological activities. Studies have shown that Que has therapeutic effects on PAH. However, the effect of quercetin on pulmonary vascular remodeling in PAH and its mechanism remain unclear.Methods and resultsIn vivo, PAH rats were constructed by intraperitoneal injection of monocrotaline (MCT) at 60 mg/kg. Human pulmonary artery smooth muscle cells (HPASMCs) were treated with platelet-derived growth factor BB (PDGF-BB) 20 ng/mL to construct PAH cell model in vitro. The results showed that in vivo studies, MCT could induce right ventricular wall hyperplasia, narrow the small and medium pulmonary artery cavity, up-regulate the expression of proliferating and migration-related proteins proliferating cell nuclear antigen (PCNA) and osteopontin (OPN), and down-regulate the expression of alpha-smooth muscle actin (α-SMA). Que reversed the MCT-induced results. This process works by down-regulating the transforming growth factor-β1 (TGF-β1)/ Smad2/3 signaling pathway. In vitro studies, Que had the same effect on PDGF-BB-induced proliferation and migration cell models.ConclusionsQue inhibits the proliferation, migration and phenotypic transformation of HPASMCs by down-regulating TGF-β1/Smad2/Smad3 pathway, thereby reducing right ventricular hyperplasia (RVH) and pulmonary vascular remodeling, providing potential pharmacological and molecular explanations for the treatment of PAH.

Quercetin as a therapeutic agent activate the Nrf2/Keap1 pathway to alleviate lung ischemia-reperfusion injury

Lung ischemia-reperfusion injury (LIRI) causes oxidative stress, inflammation, and immune system activation. The Nrf2/Keap1/HO-1 pathway is important in cellular defense against these effects. Quercetin, a flavonoid with antioxidant, anti-inflammatory, and anti-cancer properties, has been investigated. Our aim in this study was to investigate the effect of quercetin on preventing lung ischemia-reperfusion injury and the role of the Nrf2/Keap1/HO-1 pathway. Sixty-four male Wistar rats were divided into four distinct groups(n = 16). Sham, lung ischemia-reperfusion (LIR), Saline + LIR, Quercetin + LIR (30 mg/kg i.p for a week before LIR). LIR groups were subjected to 60 min of ischemia (left pulmonary artery, vein, and bronchus) and 120 min of reperfusion. Our assessment encompassed a comprehensive analysis of various factors, including the evaluation of expression Nrf2, Keap1, and Heme Oxygenase-1 (HO-1) levels and NF-κB protein. Furthermore, we examined markers related to inflammation (interleukin-1β and tumor necrosis factor alpha), oxidative stress (malondialdehyde, total oxidant status, superoxide dismutase, glutathione peroxidase, total antioxidant capacity), lung edema (Wet/dry lung weight ratio and total protein concentration), apoptosis (Bax and Bcl2 protein), and histopathological alterations (intra-alveolar edema, alveolar hemorrhage, and neutrophil infiltration). Our results show that ischemia-reperfusion results in heightened inflammation, oxidative stress, apoptosis, lung edema, and histopathological damage. Quercetin showed preventive effects by reducing these markers, acting through modulation of the Nrf2/Keap1 pathway and inhibiting the NF-κB pathway. This anti-inflammatory effect, complementary to the antioxidant effects of quercetin, provides a multifaceted approach to cell protection that is important for developing therapeutic strategies against ischemia-reperfusion injury and could be helpful in preventive strategies against ischemia-reperfusion.

Agenesis of the Left Pulmonary Artery Associated With Hypoplasia of the Homolateral Lung: An Unusual Cause of Recurrent Respiratory Infection

Agenesis of the Left Pulmonary Artery Associated With Hypoplasia of the Homolateral Lung: An Unusual Cause of Recurrent Respiratory Infection

Clinical and echocardiographic parameters associated with outcomes in patients with moderate secondary mitral regurgitation

BackgroundSignificant secondary mitral regurgitation (SMR) is known to be associated with worse prognosis. However, data focusing specifically on moderate SMR and associated risk factors are lacking. In the present study,...

Cardiac power output associated with hospitalization and mortality in coronary artery disease patients at stage B heart failure

BackgroundCardiac power output (CPO) predicts outcomes in advanced heart failure (HF) and cardiogenic shock, but its role in early HF stages is unclear. This study assessed the prognostic value of CPO in coronary artery disease patients with asymptomatic left ventricular systolic dysfunction (ALVSD) at stage B HF. MethodsWe conducted a retrospective analysis of coronary artery disease patients who underwent coronary and pulmonary artery catheterization between 2006 and 2016. Stage B HF with ALVSD was defined as left ventricular ejection fraction < 50 %, without HF symptoms, signs, or prior HF hospitalization. CPO was derived from invasive hemodynamic parameters. Endpoints included HF hospitalization, cardiovascular mortality, and all-cause mortality over a 5-year follow-up. ResultsA total of 783 coronary artery disease patients with ALVSD at stage B HF were enrolled. Incidence rates (per 1000 person-years) were 13.9 for HF hospitalization, 14.5 for cardiovascular mortality, and 23.7 for all-cause mortality.Multivariate analysis adjusting for covariates demonstrated that CPO was independent associated with all endpoints. Patients with a low CPO (<0.97 Watts) were at significantly higher risk for HF hospitalization (adjusted hazard ratio [HR]: 4.04; 95 % CI: 1.53 – 10.6; p = 0.005), cardiovascular mortality (adjusted HR: 2.73; 95 % CI: 1.19 – 6.27; p = 0.018), and all-cause mortality (adjusted HR: 1.86; 95 % CI: 1.05 – 3.30; p = 0.035) compared to those with higher CPO, regardless of subgroup classification. ConclusionResting CPO in patients with ALVSD is significantly associated with adverse events, including HF hospitalization and mortality, highlighting its value in early-stage HF management.

Comparison of pulmonary artery growth between ductus stent and systemic-to-pulmonary shunt as single-ventricle palliation

ObjectiveWe aimed to compare the pulmonary artery (PA) growth between infants with univentricular hearts who underwent a ductus stenting (DS) and those who received a systemic to pulmonary shunt (SPS) as an initial palliation. MethodsAll infants with ductal-dependent pulmonary blood flow who underwent initial palliation with either a DS or SPS between 2009 and 2022 in our institution were reviewed. PA development was compared between the groups using the PA index and the symmetry index. ResultsA total of 130 patients were evaluated including 49 patients after DS and 81 after SPS. The most frequent primary diagnosis was tricuspid atresia in 27, followed by pulmonary atresia with intact ventricular septum in 19. At stage II palliation, PA index (p=0.926), right PA index (p=0.692), left PA index (p=0.297) and the symmetry index (p=0.650) were similar between the groups. At stage III Fontan completion, PA index (p=0.115), right PA index (p=0.868), and the symmetry index (p=0.144) were similar between the groups. However, left PA index (60 vs. 74mm2/m2, p=0.015) was lower, and the incidence of veno-venous collaterals (24.2 vs. 7.8%, p=0.036) was higher in DS group compared to SPS group. Freedom from PA interventions between stage II and III palliation was lower in DS group compared to SPS group (p=0.009). ConclusionsIn patients after DS in infants with univentricular heart, freedom from PA interventions after stage II was lower and the left PA index was smaller, compared to those after SPS. Long-term outcomes after the Fontan procedure should be addressed in patients after DS.

LncRNA VELRP Modulates Pulmonary Arterial Smooth Muscle Cell Proliferation and Promotes Vascular Remodeling in Pulmonary Hypertension.

Pulmonary hypertension is a devastating vascular disorder characterized by extensive pulmonary vascular remodeling, ultimately leading to right ventricular failure and death. Activation of PDGF (platelet-derived growth factor) signaling promotes the hyperproliferation of pulmonary arterial smooth muscle cells (PASMCs), thus contributing to the pulmonary vascular remodeling. However, the molecular mechanisms that govern hyperproliferation of PASMCs induced by PDGF remain largely unknown, including the contribution of long noncoding RNAs (lncRNAs). In this study, we aimed to identify a novel lncRNA regulated by PDGF implicated in PASMC proliferation in pulmonary vascular remodeling. RNA-sequencing analysis was conducted to identify a novel lncRNA named vessel-enriched lncRNA regulated by PDGF-BB (VELRP). Functional investigations of VELRP were performed using knockdown and overexpression strategies along with RNA sequencing. Validation of the function and potential mechanisms of VELRP were performed through Western blot, RNA immunoprecipitation, and chromatin immunoprecipitation assays. We identified a novel vessel-enriched lncRNA with an increased response to PDGF-BB stimulus. VELRP was identified as an evolutionarily conserved RNA molecules. Modulation of VELRP in PASMCs significantly altered cell proliferation. Mechanistically, VELRP enhances trimethylation of H3K4 by interacting with WDR5 (WD repeat-containing protein 5), leading to increased expression of CDK (cyclin-dependent kinase) 1, CDK2, and CDK4 and consequent hyperproliferation of PASMCs. The pathological relevance of VELRP upregulation in pulmonary artery was confirmed using rat pulmonary hypertension models in vivo, as well as in PASMCs from patients with idiopathic pulmonary arterial hypertension patients. Specific knockdown of VELRP in smooth muscle cells using adeno-associated virus type 9 SM22α (smooth muscle protein 22α) promoter-shRNA-mediated silencing of VELRP resulted in a significant decrease in right ventricular systolic pressure and vascular remodeling in rat pulmonary hypertension model. VELRP, as an lncRNA upregulated by PDGF-BB, mediates PASMC proliferation via WDR5/CDK signaling. In vivo studies demonstrate that targeted intervention of VELRP in smooth muscle cells can prevent the development of pulmonary hypertension.

Incidence, pathophysiology, and treatment of failing Fontan after the total cavopulmonary connection.

Failing Fontan poses a significant clinical challenge. This study aims to improve patients' outcomes by comprehensively understanding the incidence, pathophysiology, risk factors, and treatment of failing Fontan after total cavopulmonary connection. We performed a retrospective analysis of patients who underwent total cavopulmonary connection at the German Heart Center Munich between 1994 and 2022. The onset of failing Fontan was defined as: protein-losing enteropathy, plastic bronchitis, NYHA class IV, NYHA class III for > one year, unscheduled hospital admissions for heart failure symptoms, and evaluation for heart transplantation. Among 634 patients, 76 patients presented with failing Fontan, and the incidence was 1.48 per 100 patient-years. Manifestations included protein-losing enteropathy (n = 34), hospital readmission (n = 28), NYHA III (n = 18), plastic bronchitis (n = 16), evaluation for heart transplantation (n = 14), and NYHA IV (n = 4). Risk factors for the onset of failing Fontan were dominant right ventricle (p = 0.010) and higher pulmonary artery pressure before total cavopulmonary connection (p = 0.004). A total of 72 interventions were performed in 59 patients, including balloon dilatation/stent implantation in the total cavopulmonary connection pathway (n = 49) and embolization of collaterals (n = 24). Heart transplantation was performed in four patients. The survival after the onset of Fontan failure was 77% at 10 years. Patients with failing Fontan revealed significantly higher zlog-NT-proBNP levels after onset compared to those without (p = 0.021). The incidence of Fontan failure was 1.5 per 100 patient years. Dominant right ventricle and higher pulmonary artery pressure before total cavopulmonary connection were significant risks for the onset of failing Fontan. Zlog-NT-proBNP is only a late marker of Fontan failure.

NUPR1 modulates pulmonary embolism progression via smooth muscle cells phenotypic transformation

ObjectiveThis study aimed to investigate the role of Nuclear Protein 1 (NUPR1) in pulmonary embolism (PE) and its impact on the phenotypic transformation of pulmonary artery smooth muscle cells (PASMCs). MethodsA PE model was established via autologous pulmonary emboli infusion into the jugular vein. Partial Pressure of Oxygen (PaO2), Oxygenation Index (OI), Brain Natriuretic Peptide (BNP), and Troponin I (TnI) were measured, and lung tissue was subjected to hematoxylin-eosin (HE) staining. NUPR1 expression was assessed through Immunofluorescence and Western blot analyses. To investigate role of NUPR1, PE rats were treated with lentiviral vectors for NUPR1 knockdown (si-NUPR1) or overexpression (ov-NUPR1), and the effects on lung pathology were examined. NUPR1 expression was evaluated in human PASMCs. Additionally, PASMCs from SD rats were cultured under normoxic and hypoxic conditions to evaluate NUPR1 expression. Transfection of NUPR1 expression vectors into PASMCs allowed monitoring of phenotypic transformation-associated protein changes and PASMCs activity. ResultsIncreased NURP1 was observed in human-derived PASMCs. In PE rats, histological examination revealed ruptured pulmonary alveoli, exudate accumulation, interstitial edema, and infiltration of inflammatory cells, concomitant with elevated NUPR1 expression levels. Knockdown of NUPR1 in PE rats significantly improved lung tissue structure, reducing alveolar rupture and interstitial edema. Conversely, NUPR1 overexpression exacerbated lung damage, leading to increased inflammatory infiltration. NUPR1 expression in rat PASMCs remained stable under normoxic conditions; however, under hypoxic conditions, NUPR1 protein expression increased progressively over time. Subsequent upregulation of NUPR1 expression led to a decrease in the levels of contractile phenotype markers α-SMA and SM22α in PASMCs, accompanied by increased expression of synthetic phenotype markers Vimentin and OPN. This phenotypic shift was associated with enhanced cellular proliferation, invasion, and migration. ConclusionsElevated NUPR1 expression in PE exacerbates abnormal PASMCs proliferation by promoting their phenotypic transformation, thereby fostering the pathological progression of PE.

Coronary artery compression by dilated pulmonary artery in an early infantile case of tetralogy of Fallot with absent pulmonary valve: ventricular fibrillation as the initial symptom of myocardial ischaemia.

Coronary artery compression by a dilated pulmonary artery is a rare complication in patients with tetralogy of Fallot with absent pulmonary valve. We present a case in which this condition manifested at two months of age, with ventricular fibrillation as the initial symptom of myocardial ischaemia. It is important to recognise that this potentially fatal complication can occur in early infancy.

Estimating pulmonary arterial remodeling via an animal-specific computational model of pulmonary artery stenosis.

Pulmonary artery stenosis (PAS) often presents in children with congenital heart disease, altering blood flow and pressure during critical periods of growth and development. Variability in stenosis onset, duration, and severity result in variable growth and remodeling of the pulmonary vasculature. Computational fluid dynamics (CFD) models enable investigation into the hemodynamic impact and altered mechanics associated with PAS. In this study, a one-dimensional (1D) fluid dynamics model was used to simulate hemodynamics throughout the pulmonary arteries of individual animals. The geometry of the large pulmonary arteries was prescribed by animal-specific imaging, whereas the distal vasculature was simulated by a three-element Windkessel model at each terminal vessel outlet. Remodeling of the pulmonary vasculature, which cannot be measured in vivo, was estimated via model-fitted parameters. The large artery stiffness was significantly higher on the left side of the vasculature in the left pulmonary artery (LPA) stenosis group, but neither side differed from the sham group. The sham group exhibited a balanced distribution of total distal vascular resistance, whereas the left side was generally larger in the LPA stenosis group, with no significant differences between groups. In contrast, the peripheral compliance on the right side of the LPA stenosis group was significantly greater than the corresponding side of the sham group. Further analysis indicated the underperfused distal vasculature likely moderately decreased in radius with little change in stiffness given the increase in thickness observed with histology. Ultimately, our model enables greater understanding of pulmonary arterial adaptation due to LPA stenosis and has potential for use as a tool to noninvasively estimate remodeling of the pulmonary vasculature.

Discriminating bronchiolar adenoma from peripheral lung cancer by thin-section computed tomography (CT): a 2-center study.

Bronchiolar adenoma (BA) is frequently misdiagnosed as peripheral lung cancer (PLC) because it resembles PLC. Computed tomography (CT) examination is an effective tool for detecting and diagnosing lung diseases. To date, there has been no comprehensive study on the differential diagnosis of BAs and PLCs using thin-section computed tomography (TSCT) based on a large sample, and the efficiency of CT in diagnosing BAs has not been verified. The goal of this study was to distinguish BA from PLC by summarizing their clinical and TSCT characteristics. A retrospective cross-sectional study on 71 cases with BAs and 218 matched controls with PLCs (from March 2020 to May 2023) within 2 centers (The First Affiliated Hospital of Chongqing Medical University and the Second Affiliated Hospital of Army Medical University) was conducted to investigate their clinical and radiological differences. The clinical characteristics and TSCT features of BAs and PLCs were summarized and compared. A multivariate logistic regression analysis was performed to reveal the key predictors of BAs. The BAs and PLCs exhibited significant differences in TSCT features. Multivariate analysis revealed that the lesion being located in basal segments [odds ratio (OR), 17.835; 95% confidence interval (CI): 6.977-45.588; P<0.001], irregular shape (OR, 4.765; 95% CI: 1.877-12.099; P=0.001), negative of spiculation sign (OR, 7.436; 95% CI: 2.063-26.809; P=0.002), central vessel sign with pulmonary artery (OR, 3.576; 95% CI: 1.557-8.211; P=0.003), peripheral vessel sign with pulmonary vein (OR, 12.444; 95% CI: 4.934-31.383; P<0.001), and distance from lesion edge to pleura (D-ETP) ≤5 mm (OR, 5.535; 95% CI: 2.346-13.057; P<0.001) were independent predictors of BAs, and the area under the curve (AUC) of this model was 0.935; 95% CI: 0.901-0.960 (sensitivity: 88.0%, specificity: 86.03%, P<0.001). Peripheral pulmonary nodules locating in the basal segment of lower lobe with irregular shape, central vessel sign with pulmonary artery, peripheral vessel sign with pulmonary vein and D-ETP ≤5 mm, but without spiculation sign, should be highly suspected of BAs.

Ginsenoside Rg1 improves hypoxia-induced pulmonary vascular endothelial dysfunction through TXNIP/NLRP3 pathway-modulated mitophagy

BackgroundVascular endothelial dysfunction (VED) is one of the main pathogenic events in pulmonary arterial hypertension (PAH). Previous studies have demonstrated that the ginsenoside Rg1 (Rg1) can ameliorate PAH, but the mechanism by which Rg1 affects pulmonary VED in hypoxia-induced PAH remains unclear. MethodsNetwork pharmacology, molecular docking and other experiments were used to explore the mechanisms by which Rg1 affects PAH. A PAH mouse model was established via hypoxia combined with the vascular endothelial growth factor (VEGFR) inhibitor su5416 (SuHx), and a cell model was established via hypoxia. The functions of Rg1 in VED, oxidative stress, inflammation, mitophagy, and TXNIP and NLRP3 expression were examined. ResultsIn hypoxia-induced VED, progressive exacerbation of oxidative stress, inflammation, and mitophagy were observed, and were associated with elevated TXNIP and NLRP3 expression in vivo and in vitro. Rg1 improved hypoxia-induced impaired endothelium-dependent vasodilation and increased nitric oxide (NO) and endothelial NO synthase (eNOS) expression. Rg1, SRI37330 (a TXNIP inhibitor), MCC950 (an NLRP3 inhibitor), and Liensinine (a mitophagy inhibitor) attenuated oxidative stress, inflammation, and mitophagy by reducing the expression of TXNIP and NLRP3 in mice and cells. Furthermore, the combination of SB203580 (a mitophagy agonist) with Rg1 disrupted the protective effect of Rg1 on hypoxia-induced pulmonary artery and human pulmonary artery endothelial cells (HPAECs). ConclusionRg1 improves hypoxia-induced pulmonary vascular endothelial dysfunction through TXNIP/NLRP3 pathway-modulated oxidative stress, inflammation and mitophagy.

Levosimendan in patients with low-cardiac-output syndrome after cardiac surgery: Substudy of the multicenter randomized CHEETAH trial

ObjectiveTo test the hypothesis that levosimendan administration to patients with low-cardiac-output syndrome after cardiac surgery is associated with improved long-term (5-year follow-up) outcome. DesignSingle-center subanalysis of the multicenter randomized CHEETAH trial. SettingCardiac surgery department of a tertiary hospital. ParticipantsA total of 134 adult patients requiring hemodynamic support for cardiac index <2.5 L/min/m2 after cardiac surgery with cardiopulmonary bypass (CPB). InterventionsPatients were randomized (1:1 ratio) to receive levosimendan (continuous infusion with starting dose of 0.05 μg/kg/min) or placebo, in addition to standard inotropic care. Measurements and Main ResultsThe primary endpoint was long-term mortality (1-5 years) after randomization. Secondary outcomes were the following: hemodynamic parameters, need for inotropic support (VIS), acute kidney injury (AKI), need for renal-replacement therapy, duration of mechanical ventilation, ICU and hospital stay, 30-day mortality. No significant between-group difference in long-term mortality (5-year) was observed (hazard ratio, 1.59; 95% CI, 0.81 to 3.11; P = 0.17). There were no significant differences in secondary outcomes, except for the difference in the mean pulmonary artery pressure at 4-6 hours after randomization, which was lower in the levosimendan group (24 [21.8, 28] mmHg versus placebo 26 [22.2, 33] mmHg, p = 0.019). ConclusionsAmong patients requiring hemodynamic support after cardiac surgery with CPB, perioperative levosimendan infusion does not affect long-term survival (1-5 years) compared with placebo. Levosimendan also had no effect on major clinical outcomes such as AKI, ICU stay, hospital stay, 30-day mortality.

EP.06G.12 The Fibrosis Around the Pulmonary Artery Is Associated with Difficulty in Dissection During Surgery after Systemic Therapy

EP.06G.12 The Fibrosis Around the Pulmonary Artery Is Associated with Difficulty in Dissection During Surgery after Systemic Therapy

Successful treatment of large hemoptysis and pseudoaneurysm of the pulmonary artery associated to oesophagomediastinal fistula with amphotericin B cholesterol sulfate complex: A case report.

Oesophagomediastinal fistula is uncommon. Oesophageal fistulas, may manifest as recurrent pneumonias. While pulmonary infections can lead to pulmonary artery pseudoaneurysms (PAPs), particularly in fungal infections. PAPs pose a rupture risk, potentially causing life-threatening hemoptysis. We report a unique case of a 45-year-old male who presented with sudden cough, dyspnea, and hemoptysis. Bronchoscopy triggered massive hemoptysis, necessitating emergency embolization. Persistent hemoptysis prompted further imaging, revealing an aneurysmal dilation located next to the spine and infectious lesions, suggesting an oesophagomediastinal fistula. After initiating therapy with Amphotericin B Cholesterol Sulfate Complex and fistula closure, the patient's hemoptysis resolved, with imaging resolution of the PAP. Long-term Voriconazole therapy ensured continued improvement. This case highlights the rarity and severity of such fistulas may be associated with fungal infections and PAPs, emphasizing the importance of prompt recognition, aggressive treatment for favourable outcomes.

The role of the TAPSE/sPAP ratio as a predictor of mortality in pulmonary arterial Hypertension: its value for patient risk stratification

BackgroundThe tricuspid annular plane systolic excursion and systolic pulmonary artery pressure (TAPSE/sPAP) ratio has been proposed as an indicator of ventriculo-arterial coupling, predicting right ventricular failure (RVF) and mortality in patients with pulmonary arterial hypertension (PAH). ObjectiveTo evaluate the usefulness of the TAPSE/sPAP ratio in predicting outcomes and improving risk stratification in patients with PAH. Methods156 patients with PAH were included. Clinical, functional, echocardiographic, and haemodynamic variables, along with the TAPSE/sPAP ratio, were analysed based on etiological PAH subgroups and outcomes. Additional statistical measures, such as the area under the curve (AUC), net reclassification index (NRI), and integrated discrimination improvement, assessed the predictive ability of TAPSE/sPAP in combination with the ESC/ERS risk score, and other risk assessment strategies (COMPERA and Reveal Lite 2). ResultsMost patients were female (86.5%), with a median age of 45.5 (IQR: 29–58) years. The TAPSE/sPAP ratio for the whole group was 0.26 (IQR: 0.190–0.347) mm/mmHg, which was similar among different aetiologies, but different between deceased and surviving patients (0.14 vs. 0.27 mm/mmHg, respectively, P<0.001). A TAPSE/sPAP ratio <0.18 mm/mmHg independently predicted mortality (AUC: 0.859, 95% CI: 0.766– 0.952; P<0.001). Integration with the ESC/ERS risk score improved predicted mortality (AUC: 0.87 vs. 0.75, p=0.002) and risk stratification, reclassifying 14.28% of events and 36.92% of non-events, with an NRI of 39.4% (P<0.001). Likewise, integration with other scores improved predicted ability of COMPERA and REVEA Lite2; COMPERA+TAPSE/sPAP (AUC: 0.837 vs 0.742; p=0.005) and REVEAL Lite 2 +TAPSE/sPAP (AUC: 0.840 vs. 0.713; p<0.001). ConclusionsA TAPSE/sPAP ratio <0.18 mm/mmHg predicts mortality in PAH. The combination of the TAPSE/sPAP ratio with the ESC/ERS risk score improved risk stratification, and reclassification emphasizing the potential of ESC/ERS+TAPSE/sPAP as a valuable tool for risk assessment and clinical decision-making in PAH patients. Integration of TAPSE/sPAP ratio with other scores (COMPERA and (REVEAL Lite 2) also improved the risk stratification and reclassification of these risk scores.

PPARγ/ETV2 axis regulates endothelial-to-mesenchymal transition in pulmonary hypertension.

Endothelial-to-mesenchymal transition (EndoMT) plays an important role in pulmonary hypertension (PH) but the molecular mechanisms regulating EndoMT remain to be defined. We demonstrate that the axis of the transcription factors PPARγ (Peroxisome Proliferator-Activated Receptor gamma) and ETV2 (ETS variant 2) play important roles in the pathogenesis of PH. Decreased levels of the expression of PPARγ and ETV2 along with reduced endothelial and increased EndoMT markers are consistently observed in lungs and pulmonary artery endothelial cells (PAECs) of idiopathic pulmonary arterial hypertension patients, in hypoxia-exposed mouse lungs, human PAECs, and in induced-EndoMT cells. Etv2 +/- mice spontaneously developed PH and right ventricular hypertrophy (RVH), associated with increased EndoMT markers and decreased EC markers. Interestingly, chronic hypoxia exacerbated right ventricular systolic pressure and RVH in Etv2 +/- mice. PPARγ transcriptionally activates the ETV2 promoter. Consistently, while mice overexpressing endothelial PPARγ increases the expression of ETV2 and endothelial markers with reduced EndoMT markers, endothelial PPARγ KO mice show decreased ETV2 expression and enhanced EndoMT markers. Inducible overexpression of ETV2 under induced-EndoMT cell model reduces number of cells with mesenchymal morphology and decreases expression of mesenchymal markers with increased EC makers, compared to control. Therefore, our study suggests that PPARγ-ETV2 signaling regulates PH pathogenesis through EndoMT.

Current Overview of the Biology and Pharmacology in Sugen/Hypoxia-Induced Pulmonary Hypertension in Rats.

The Sugen 5416/hypoxia (Su/Hx) rat model of pulmonary arterial hypertension (PAH) demonstrates most of the distinguishing features of PAH in humans, including increased wall thickness and obstruction of the small pulmonary arteries along with plexiform lesion formation. Recently, significant advancement has been made describing the epidemiology, genomics, biochemistry, physiology, and pharmacology in Su/Hx challenge in rats. For example, there are differences in the overall reactivity to Su/Hx challenge in different rat strains and only female rats respond to estrogen treatments. These conditions are also encountered in human subjects with PAH. Also, there is a good translation in both the biochemical and metabolic pathways in the pulmonary vasculature and right heart between Su/Hx rats and humans, particularly during the transition from the adaptive to the nonadaptive phase of right heart failure. Noninvasive techniques such as echocardiography and magnetic resonance imaging have recently been used to evaluate the progression of the pulmonary vascular and cardiac hemodynamics, which are important parameters to monitor the efficacy of drug treatment over time. From a pharmacological perspective, most of the compounds approved clinically for the treatment of PAH are efficacious in Su/Hx rats. Several compounds that show efficacy in Su/Hx rats have advanced into phase II/phase III studies in humans with positive results. Results from these drug trials, if successful, will provide additional treatment options for patients with PAH and will also further validate the excellent translation that currently exists between Su/Hx rats and the human PAH condition.