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BACKGROUND: Pulmonary hypertension (PH) represents an important phenotype in heart failure with preserved ejection fraction (HFpEF). However, management of PH-HFpEF is challenging because mechanisms involved in the regulation of PH-HFpEF remain unclear. METHODS: We used a mass spectrometry-based comparative plasma proteomics approach as a sensitive and comprehensive hypothesis-generating discovery technique to profile proteins in patients with PH-HFpEF and control subjects. We then validated and investigated the role of one of the identified proteins using in vitro cell cultures, in vivo animal models, and independent cohort of human samples. RESULTS: Plasma proteomics identified high protein abundance levels of B2M (β2-microglobulin) in patients with PH-HFpEF. Interestingly, both circulating and skeletal muscle levels of B2M were increased in mice with skeletal muscle SIRT3 (sirtuin-3) deficiency or high-fat diet-induced PH-HFpEF. Plasma and muscle biopsies from a validation cohort of PH-HFpEF patients were found to have increased B2M levels, which positively correlated with disease severity, especially pulmonary capillary wedge pressure and right atrial pressure at rest. Not only did the administration of exogenous B2M promote migration/proliferation in pulmonary arterial vascular endothelial cells but it also increased PCNA (proliferating cell nuclear antigen) expression and cell proliferation in pulmonary arterial vascular smooth muscle cells. Finally, B2m deletion improved glucose intolerance, reduced pulmonary vascular remodeling, lowered PH, and attenuated RV hypertrophy in mice with high-fat diet-induced PH-HFpEF. CONCLUSIONS: Patients with PH-HFpEF display higher circulating and skeletal muscle expression levels of B2M, the magnitude of which correlates with disease severity. Our findings also reveal a previously unknown pathogenic role of B2M in the regulation of pulmonary vascular proliferative remodeling and PH-HFpEF. These data suggest that circulating and skeletal muscle B2M can be promising targets for the management of PH-HFpEF.

Chronic thromboembolic pulmonary hypertension (CTEPH) develops due to the accumulation of blood clots in the lung vasculature that obstructs flow and increases pressure. The mechanobiological factors that drive progression of CTEPH are not understood, in part because mechanical and hemodynamic changes in the small pulmonary arteries due to CTEPH are not easily measurable. Using previously published hemodynamic measurements and imaging from a large animal model of CTEPH, we applied a subject-specific one-dimensional (1D) computational fluid dynamic (CFD) approach to investigate the impact of CTEPH on pulmonary artery stiffening, time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) in extralobar (main, right, and left) pulmonary arteries and intralobar (distal to the extralobar) arteries. Our results demonstrate that CTEPH increases pulmonary artery wall stiffness and decreases TAWSS in extralobar and intralobar arteries. Moreover, CTEPH increases the percentage of the intralobar arterial network with both low TAWSS and high OSI, quantified by the novel parameter φ , which is related to thrombogenicity. Our analysis reveals a strong positive correlation between increases in mean pulmonary artery pressure (mPAP) and φ from baseline to CTEPH in individual subjects, which supports the suggestion that increased φ drives disease severity. This subject-specific experimental-computational framework shows potential as a predictor of the impact of CTEPH on pulmonary arterial hemodynamics and pulmonary vascular mechanics. By leveraging advanced modeling techniques and calibrated model parameters, we predict spatial distributions of flow and pressure, from which we can compute potential physiomarkers of disease progression. Ultimately, this approach can lead to more spatially targeted interventions that address the needs of individual CTEPH patients.

AIMS: Pulmonary hypertension (PH) is a pulmonary vascular disease characterized by a high mortality rate. Pulmonary arterial endothelium cells (PAECs) serve as a primary sensor of various environmental cues, such as shear stress and hypoxia, but PAEC dysfunction may trigger vascular remodelling during the onset of PH. This study aimed to illustrate the role of Sirtuin 7 (SIRT7) in endothelial dysfunction during PH and explore the potential therapeutic strategy for PH. METHODS AND RESULTS: SIRT7 levels were measured in human and murine experimental PH samples. Bioinformatic analysis, immunoprecipitation, and deacetylation assay were used to identify the association between SIRT7 and Krüpple-like factor 4 (KLF4), a key transcription factor essential for endothelial cell (EC) homeostasis. Sugen5416 + hypoxia (SuHx)-induced PH mouse models and cell cultures were used for the study of the therapeutic effect of SIRT7 for PH. SIRT7 level was significantly reduced in lung tissues and PAECs from PH patients and the SuHx-induced PH mouse model as compared with healthy controls. Pulmonary endothelium-specific depletion of Sirt7 increased right ventricular systolic pressure and exacerbated right ventricular hypertrophy in the SuHx-induced PH model. At the molecular level, we identified KLF4 as a downstream target of SIRT7, which deacetylated KLF4 at K228 and inhibited the ubiquitination-proteasome degradation. Thus, the SIRT7/KLF4 axis maintained PAEC homeostasis by regulating proliferation, migration, and tube formation. PAEC dysfunction was reversed by adeno-associated virus type 1 vector-mediated endothelial overexpression of Sirt7 or supplementation with nicotinamide adenine dinucleotide (NAD)+ intermediate nicotinamide riboside which activated Sirt7; both approaches successfully reversed PH phenotypes. CONCLUSION: The SIRT7/KLF4 axis ensures PAEC homeostasis, and pulmonary endothelium-specific SIRT7 targeting might constitute a PH therapeutic strategy.

Pulmonary arterial hypertension (PAH) is a devastating and progressive disease with limited treatment options. Endothelial dysfunction plays a central role in the development and progression of PAH, yet the underlying mechanisms are incompletely understood. The endosome-lysosome system is important to maintain cellular health, and the small GTPase RAB7 regulates many functions of this system. Here, we explored the role of RAB7 in endothelial cell (EC) function and lung vascular homeostasis. We found reduced expression of RAB7 in ECs from patients with PAH. Endothelial haploinsufficiency of RAB7 caused spontaneous pulmonary hypertension (PH) in mice. Silencing of RAB7 in ECs induced broad changes in gene expression revealed via RNA-Seq, and RAB7-silenced ECs showed impaired angiogenesis and expansion of a senescent cell fraction, combined with impaired endolysosomal trafficking and degradation, suggesting inhibition of autophagy at the predegradation level. Furthermore, mitochondrial membrane potential and oxidative phosphorylation were decreased, and glycolysis was enhanced. Treatment with the RAB7 activator ML-098 reduced established PH in rats with chronic hypoxia/SU5416. In conclusion, we demonstrate for the first time to our knowledge the fundamental impairment of EC function by loss of RAB7, causing PH, and show RAB7 activation to be a potential therapeutic strategy in a preclinical model of PH.

Background Methods Results Conclusion The impact of continuous flow resulting from contemporary left ventricular assist devices (LVAD) on renal vascular physiology is unknown. Renal resistive index (RRI) reflects arterial compliance, as well as renal vascular resistance, contributed by afferent and efferent arteriolar tone, the renal interstitium as well as renal venous pressures.Prospective, single center study with renal Doppler evaluation at baseline (pre‐implant) and at 3‐months support. Outcomes assessed include need for post‐operative renal replacement therapy (RRT), worsening renal function (WRF) defined as persistent increase from pre‐implant KDIGO chronic kidney disease stage, right ventricular (RV) failure, and survival to transplantation.Pre‐implant RRI did not predict cardiorenal outcomes including right heart failure, need for renal replacement therapy or worsening renal function. Post‐implant RRI was significantly lower than pre‐implant RRI, with a distinct Doppler waveform characteristic of continuous flow. Post‐implant renal end‐diastolic velocity, but not RRI, correlated strongly with LVAD flow (Spearman rho −0.99, p < 0.001), with trend toward correlation with mean arterial pressure (Spearman's rho 0.63, p = 0.129). There was a negative correlation between post‐implant RRI and mean pulmonary artery pressure (Spearman's rho −0.81, p = 0.049), likely driven by elevated pulmonary capillary wedge pressure (Spearman's rho −0.83, p = 0.058).The hemodynamic contributors to RRI in LVAD supported patients are complex. Higher mean pulmonary artery and pulmonary capillary wedge pressures seen in lower RRI may reflect a smaller difference in systolic and diastolic flow. Future simultaneous Doppler assessment of the LVAD outflow graft and RRI may help understand the hemodynamic interactions contributing to this index. [ABSTRACT FROM AUTHOR]

A fifteen-month-old Pembroke Welsh corgi with respiratory distress, exercise intolerance, and moderate regenerative anemia was referred to The Norwegian University of Life Sciences, Small Animal Hospital. Hematology revealed moderate regenerative anemia without evidence of hemolysis. Thoracic radiographs showed a generalized mixed interstitial to alveolar lung pattern and enlarged pulmonary arteries. Changes suggestive of moderate pulmonary hypertension were noted on echocardiography. Baermann fecal diagnostic flotation identified large numbers of Angiostrongylus vasorum larvae, and the AngioDetect serological antigen test was positive. The dog was treated with a two-week course with fenbendazole (51 mg/kg q24h po) and topical imidacloprid/moxidectin (250 mg/62.5 mg) and a one-week course with sildenafil (0.45 mg/kg q12h po). Complete clinical, clinicopathological and echocardiographic resolution was observed after only four weeks. Rapid improvement of echocardiographic abnormalities in cases with suspected pulmonary hypertension is not usually reported in cases with angiostrongylosis. Infection with A. vasorum should be considered in dogs with respiratory signs and bleeding tendencies, even in countries with no endemic history or reported cases. [ABSTRACT FROM AUTHOR]

Objective: This study aims to present the midterm outcomes of surgical correction of the anomalous left coronary artery from the pulmonary artery (ALCAPA). Methods: This is a retrospective study of patients undergoing anomalous origin of the LCA from the pulmonary artery repair between 2010 and 2019. Results: Forty-nine patients (20 boys and 29 girls) underwent ALCAPA repair. Patients were divided into two groups based on their age at ALCAPA repair: infant (< 1 year of age: n = 24) and non-infant (≧ 1 year of age: n = 25). Median age at time of repair was 23 months(7-60months). LCA reimplantation was performed in 47 patients, and Takeuchi repair was performed in 2 patients. Hospital mortality in the infant group was 8.2% (4 of 49). Infant group had significantly lower LVEF in pre-operation (p < 0.05), but there was not significantly different between the two groups about LVEF at discharge. The median follow-up duration was 43(18–85)months. The freedom from reoperation was not significantly different between two groups (infants vs. non-infants: 68.8% vs. 87.5% at 10 years; p = 0.096). Conclusions: Surgical treatment of ALCAPA had an excellent early and midterm outcomes. Left ventricular dysfunction in pre-operation was the main risk of mortality in-hospital. The freedom from reoperation did not differ significantly between infant group and non-infant group. [ABSTRACT FROM AUTHOR]

Background: There is no consensus regarding the choice of anesthetic method for patients with pulmonary hypertension (PH). We report two cases in which neuraxial anesthesia was safely performed without general anesthesia during open abdominal surgery in patients with severe PH. Case presentation: Case 1: A 59-year-old woman had an atrial septal defect and a huge abdominal tumor with a mean pulmonary arterial pressure (PAP) of 39 mmHg and pulmonary vascular resistance (PVR) of 3.5 Wood units. Case 2: A 23-year-old woman who had hereditary pulmonary artery hypertension (mean PAP, 65 mmHg; PVR, 16.45 Wood units). Both patients underwent open abdominal surgery under neuraxial anesthesia without circulatory collapse with intraoperative administration of vasoconstrictors. Conclusion: Although anesthetic care must be personalized depending on the pathology and severity of PH, neuraxial anesthesia may be an option for patients with severe PH undergoing abdominal surgery. [ABSTRACT FROM AUTHOR]

We previously reported pulmonary arterial remodelling and active endothelial-to-mesenchymal transition (EndMT) in smokers and patients with early chronic obstructive pulmonary disease (COPD). In the present study, we aimed to evaluate the role of different drivers of EndMT. Immunohistochemical staining for EndMT drivers, TGF-β1, pSMAD-2/3, SMAD-7, and β-catenin, was performed on lung resections from 46 subjects. Twelve were non-smoker-controls (NC), six normal lung function smokers (NLFS), nine patients with small-airway diseases (SAD), nine mild-moderate COPD-current smokers (COPD-CS) and ten COPD-ex-smokers (COPD-ES). Histopathological measurements were done using Image ProPlus softwarev7.0. We observed lower levels of total TGF-β1 (P<0.05) in all smoking groups than in the non-smoking control (NC). Across arterial sizes, smoking groups exhibited significantly higher (P<0.05) total and individual layer pSMAD-2/3 and SMAD-7 than in the NC group. The ratio of SAMD-7 to pSMAD-2/3 was higher in COPD patients compared with NC. Total β-catenin expression was significantly higher in smoking groups across arterial sizes (P<0.05), except for COPD-ES and NLFS groups in small and medium arteries, respectively. Increased total β-catenin was positively correlated with total S100A4 in small and medium arteries (r = 0.35, 0.50; P=0.02, 0.01, respectively), with Vimentin in medium arteries (r = 0.42, P=0.07), and with arterial thickness of medium and large arteries (r = 0.34, 0.41, P=0.02, 0.01, respectively). This is the first study uncovering active endothelial SMAD pathway independent of TGF-β1 in smokers, SAD, and COPD patients. Increased expression of β-catenin indicates its potential interaction with SMAD pathway, warranting further research to identify the deviation of this classical pathway [ABSTRACT FROM AUTHOR]

Hypoxia-induced pulmonary artery hypertension (HPH) is a complication of chronic hypoxic lung disease and the third most common type of pulmonary artery hypertension (PAH). Epigenetic mechanisms play essential roles in the pathogenesis of HPH. N6-methyladenosine (m6A) is an important modified RNA nucleotide involved in a variety of biological processes and an important regulator of epigenetic processes. To date, the precise role of m6A and regulatory molecules in HPH remains unclear. HPH model and pulmonary artery smooth muscle cells (PASMCs) were constructed from which m6A changes were observed and screened for AlkB homolog 5 (Alkbh5). Alkbh5 knock-in (KI) and knock-out (KO) mice were constructed to observe the effects on m6A and evaluate right ventricular systolic pressure (RVSP), left ventricular and septal weight [RV/(LV + S)], and pulmonary vascular remodeling in the context of HPH. Additionally, the effects of Alkbh5 knockdown using adenovirus were examined in vitro on m6A, specifically in PASMCs with regard to proliferation, migration and cytochrome P450 1A1 (Cyp1a1) mRNA stability. In both HPH mice lung tissues and hypoxic PASMCs, a decrease in m6A was observed, accompanied by a significant up-regulation of Alkbh5 expression. Loss of Alkbh5 attenuated the proliferation and migration of hypoxic PASMCs in vitro, with an associated increase in m6A modification. Furthermore, Alkbh5 KO mice exhibited reduced RVSP, RV/(LV + S), and attenuated vascular remodeling in HPH mice. Mechanistically, loss of Alkbh5 inhibited Cyp1a1 mRNA decay and increased its expression through an m6A-dependent post-transcriptional mechanism, which hindered the proliferation and migration of hypoxic PASMCs. The current study highlights the loss of Alkbh5 impedes the proliferation and migration of PASMCs by inhibiting post-transcriptional Cyp1a1 mRNA decay in an m6A-dependent manner. [Display omitted] • The Alkbh5 was upregulated in HPH and resulted in m6A methylation. • Loss of Alkbh5 attenuates the proliferation and migration of PASMCs. • Loss of Alkbh5 attenuates PASMCs remodeling is Cyp1a1 dependent. [ABSTRACT FROM AUTHOR]

Myxopapillary ependymomas (MPEs) are rare spinal cord tumors with low rates of metastasis outside of the neuraxis. Gross total resection of MPEs can significantly improve progression-free survival; however, adjunctive treatment remains unstandardized. A 29-year-old female with a history of spina bifida occulta surgical correction and lower back pain presented with dyspnea and tachycardia. A large pulmonary artery mass was discovered consistent with pulmonary thromboembolism. It was subsequently determined to be an intravascular metastasis secondary to sacral MPE. Standardization of MPE treatment and clinical suspicion of spinal neoplasm in the setting of chronic back pain with undetermined origin are of value. [ABSTRACT FROM AUTHOR]

This study assesses the safety and efficacy of particle embolization during bronchial artery embolization (BAE) in patients with shunts between bronchial and non-bronchial systemic arteries and the pulmonary artery. In this retrospective, single-center study, we analyzed 312 BAE procedures performed from June 2020 to April 2023. The patient cohort had shunts between bronchial and non-bronchial systemic arteries and the pulmonary artery. We meticulously collected and examined comprehensive data, including clinical characteristics, computed tomography (CT) imaging, and embolization procedural details. Vascular shunts were identified in 49 patients. The etiologies of hemoptysis included post-TB sequelae (42.8%), bronchiectasis (26.5%), active TB (12.2%), aspergilloma (8.1%), bacterial pneumonia (4.1%), lung cancer (4.1%), and non-tuberculous mycobacterial infection (2%). The technical success rate of the procedures was 98%, with 149 out of 152 identified vessels successfully embolized. All patients experienced cessation or significant reduction of hemoptysis within 24 hours following the procedure. The clinical success rates were 97.9% at one month, 93.9% at six months, and 89.8% at one year. No shunt-related complications were detected. BAE with particle embolization is a safe and effective treatment for hemoptysis, particularly in cases with complex shunts between bronchial and non-bronchial systemic arteries and the pulmonary artery. • Chronic inflammation as a risk factor for recurrent hemoptysis. • Chronic inflammation leads to vascular shunts. • At one year, BAE achieved 89.8% clinical success in shunt patients. • BAE offers safe, effective hemoptysis treatment for patients with vascular shunts. [ABSTRACT FROM AUTHOR]

Background: Macitentan, either as monotherapy or part of combination therapy, improved clinical outcomes in patients with pulmonary artery hypertension (PAH) in clinical trials. Evidence on the effectiveness and safety of macitentan administered in real-world clinical practice in China is limited. Methods: This real-world, retrospective, multicenter chart review study was conducted at seven hospitals in China. Adult patients with a diagnosis of PAH who initiated macitentan and had medical assessments at 3–7 months after macitentan initiation were included. The primary outcomes were changes in the World Health Organization functional class (WHO-FC), 6-min walk distance (6MWD), and N-terminal pro-B-type natriuretic peptide (NT-proBNP)/B-type natriuretic peptide from baseline to first follow-up visit (months 3–7). Serious adverse events (SAEs) and adverse drug reactions (ADRs) of macitentan were collected. Results: From 30 August 2021 to 31 March 2022, 214 eligible patients were included in the safety analysis set and 105 patients were included in the analysis of effectiveness. At the first follow-up visit compared with baseline, significant changes in WHO-FC were observed (p =.04), 93.5% patients had their WHO-FC improved (25.8%) or maintained (67.7%). 6MWD changed by a mean (standard deviation [SD]) of 45.0 (81.4) meters (p <.001), with 94.7% having their 6MWD improved (34.7%) or maintained (60.0%). The mean (SD) of NT-proBNP decreased from 1667.4 (3233.0) ng/L to 1090.0 (2230.1) ng/L (p <.001). In the safety analysis set, 24 (11.2%) patients experienced at least one ADR and/or SAE. ADRs and SAEs were reported in 11 (5.1%) and 18 (8.4%), respectively. No deaths or unexpected safety events were observed. Conclusion: This study provided real-world evidence on the clinical benefits and good tolerance of macitentan in Chinese patients with PAH treated in routine clinical practice. [ABSTRACT FROM AUTHOR]

[Display omitted] • We introduced a novel chamber attention network (CAN) that utilizes the Grad-CAM technique to assess the relevance of different chambers in identifying PAH. • The attention vector generated by the chamber attention module provides a quantitative measure of the chambers' importance in PAH diagnosis, which aligns well with clinical knowledge and enhances the model's interpretability. • Our CAN model achieved outstanding performance on a large training-validation dataset consisting of 13912 individual subjects. • Evaluation on an external test dataset from a different hospital demonstrated the superior generalization ability of our CAN model. Accurate identification of pulmonary arterial hypertension (PAH) in primary care and rural areas can be a challenging task. However, recent advancements in computer vision offer the potential for automated systems to detect PAH from echocardiography. Our aim was to develop a precise and efficient diagnostic model for PAH tailored to the unique requirements of intelligent diagnosis, especially in challenging locales like high-altitude regions. We proposed the Chamber Attention Network (CAN) for PAH identification from echocardiographic images, trained on a dataset comprising 13,912 individual subjects. A convolutional neural network (CNN) for view classification was used to select the clinically relevant apical four chamber (A4C) and parasternal long axis (PLAX) views for PAH diagnosis. To assess the importance of different heart chambers in PAH diagnosis, we developed a novel Chamber Attention Module. The experimental results demonstrated that: 1) The substantial correspondence between our obtained chamber attention vector and clinical expertise suggested that our model was highly interpretable, potentially uncovering diagnostic insights overlooked by the clinical community. 2) The proposed CAN model exhibited superior image-level accuracy and faster convergence on the internal validation dataset compared to the other four models. Furthermore, our CAN model outperformed the others on the external test dataset, with image-level accuracies of 82.53% and 83.32% for A4C and PLAX, respectively. 3) Implementation of the voting strategy notably enhanced the positive predictive value (PPV) and negative predictive value (NPV) of individual-level classification results, enhancing the reliability of our classification outcomes. These findings indicate that CAN is a feasible technique for AI-assisted PAH diagnosis, providing new insights into cardiac structural changes observed in echocardiography. [ABSTRACT FROM AUTHOR]

BACKGROUND: STIM1 (stromal interaction molecule 1) regulates store-operated calcium entry and is involved in pulmonary artery vasoconstriction and pulmonary artery smooth muscle cell proliferation, leading to pulmonary arterial hypertension (PAH). METHODS: Bioinformatics analysis and a 2-stage matched case-control study were conducted to screen for noncoding variants that may potentially affect STIM1 transcriptional regulation in 242 patients with idiopathic PAH and 414 healthy controls. Luciferase reporter assay, real-time quantitative polymerase chain reaction, western blot, 5-ethynyl-2'-deoxyuridine (EdU) assay, and intracellular Ca2+ measurement were performed to study the mechanistic roles of those STIM1 noncoding variants in PAH. RESULTS: Five noncoding variants (rs3794050, rs7934581, rs3750996, rs1561876, and rs3750994) were identified and genotyped using Sanger sequencing. Rs3794050, rs7934581, and rs1561876 were associated with idiopathic PAH (recessive model, all P<0.05). Bioinformatics analysis showed that these 3 noncoding variants possibly affect the enhancer function of STIM1 or the microRNA (miRNA) binding to STIM1. Functional validation performed in HEK293 and pulmonary artery smooth muscle cells demonstrated that the noncoding variant rs1561876-G (STIM1 mutant) had significantly stronger transcriptional activity than the wild-type counterpart, rs1561876-A, by affecting the transcriptional regulatory function of both hsa-miRNA-3140-5p and hsa-miRNA-4766-5p. rs1561876-G enhanced intracellular Ca2+ signaling in human pulmonary artery smooth muscle cells secondary to calcium-sensing receptor activation and promoted proliferation of pulmonary artery smooth muscle cells under both normoxia and hypoxia conditions, suggesting a possible contribution to PAH development. CONCLUSIONS: The potential clinical implications of the 3 noncoding variants of STIM1, rs3794050, rs7934581, and rs1561876, are 2-fold, as they may help predict the risk and prognosis of idiopathic PAH and guide investigations on novel therapeutic pathway(s). [ABSTRACT FROM AUTHOR]

Background: Pulmonary artery involvement (PAI) is not rare in Takayasu arteritis (TA). Persistently elevated pulmonary arterial pressure in TA‐PAI patients leads to pulmonary hypertension (PH), and eventually cardiac death. Thus, the early detection of right ventricular dysfunction before the onset of PH is important. Purpose: To explore the potential of right ventricular global peak longitudinal and circumferential strain (RVGLS and RVGCS, respectively) in detecting right ventricular myocardial damage in TA‐PAI patients without PH. Study Type: Retrospective. Population: One hundred and six TA patients (39.6 ± 13.9 years), of whom 52 were non‐PAI and 54 were PAI patients (36 without PH and 18 with PH), along with 58 sex‐ and age‐matched healthy volunteers (HVs) (36.7 ± 13.2 years). The involved arteries were validated by aorta magnetic resonance (MR) angiography and pulmonary artery computed tomography angiography. Field Strength/Sequence: 3 T/Cine imaging sequence with a steady‐state free precession readout. Assessment: Cardiac MRI‐derived parameters measured by two radiologists independently were compared among HVs, and TA patients with and without PAI. In addition, these indices were further compared among HVs, and TA‐PAI patients with and without PH. Statistical Tests: Student's t test, one‐way ANOVA analysis, Pearson and Spearman correlation analysis, and reproducibility analysis. A P‐value of <0.05 was considered statistically significant. Results: Although the TA‐PAI patients without PH had a similar RV ejection fraction (RVEF) with HV (P = 0.348), RVGLS (non‐PH 20.6 ± 3.7% vs. HV 24.0 ± 3.1%) was significantly lower and RVGCS (non‐PH 14.8 ± 3.9% vs. HV 13.0 ± 2.7%) higher. The TA‐PAI patients with PH had significantly poorer RVGLS (PH 13.5 ± 3.8% vs. non‐PH 20.6 ± 3.7%) and RVGCS (PH 10.9 ± 3.2% vs. non‐PH 14.8 ± 3.9%) than those without PH. Data Conclusion: Right ventricular dysfunction was detected in the TA‐PAI patients without PH. MR‐feature tracking may be an effective method for detecting early cardiac damage in the TA‐PAI patients without PH. Level of Evidence: 3 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

The great artery relationship in transposition of great arteries (TGA) is based on the degree of resorption and growth of subsemilunar conus. In transposition of great arteries, the spatial relationship of the great arteries can be variable. Commonly, the aorta will be related right and anterior to pulmonary artery (D‐TGA). Less commonly, the aorta can be related left and anterior (SDL‐TGA), side‐by‐side, and antero‐posterior to pulmonary artery. Four fetuses with concordant atrioventricular and discordant ventriculoarterial connection with various great arteries relationship were presented in this imaging essay. [ABSTRACT FROM AUTHOR]

Aims Evaluation of left and right ventricular (RV) longitudinal systolic function may enhance risk stratification following aortic valve replacement (AVR). The study objective was to evaluate the changes in left and RV longitudinal systolic function and RV–pulmonary artery (RV–PA) coupling from baseline to 30 days and 1 year after AVR. Methods and results Left ventricular (LV) longitudinal strain (LS), tricuspid annulus plane systolic excursion (TAPSE), and RV–PA coupling were evaluated in patients from the PARTNER 2A surgical AVR (SAVR) arm (n = 985) and from the PARTNER 2 SAPIEN 3 registry (n = 719). TAPSE and RV–PA coupling decreased significantly following SAVR, but remained stable following TAVR. Lower LV LS, TAPSE, or RV–PA coupling at baseline was associated with increased risk of the composite of death, hospitalization, and stroke at 5 years [adjusted hazard ratios (HRs) for LV LS < 15%: 1.24, 95% confidence interval (CI) 1.05–1.45, P = 0.001; TAPSE < 14 mm: 1.44, 95% CI 1.21–1.73, P < 0.001; RV–PA coupling < 0.55 mm/mmHg: 1.32, 95% CI 1.07–1.63, P = 0.011]. Reduced TAPSE at baseline was the most powerful predictor of the composite endpoint at 5 years. Patients with LV ejection fraction <50% at baseline had increased risk of the primary endpoint with SAVR (HR: 1.34, 95% CI 1.08–1.68, P = 0.009) but not with TAVR (HR: 1.12, 95% CI 0.88–1.42). Lower RV–PA coupling at 30 days showed the strongest association with cardiac mortality. Conclusion SAVR but not TAVR was associated with a marked deterioration in RV longitudinal systolic function and RV–PA coupling. Lower TAPSE and RV–PA coupling at 30 days were associated with inferior clinical outcomes at 5 years. In patients with LVEF < 50%, TAVR was associated with superior 5-year outcomes. [ABSTRACT FROM AUTHOR]

Aims Although several studies have shown that the right ventricular to pulmonary artery (RV-PA) coupling, assessed by the ratio between tricuspid annular plane systolic excursion and systolic pulmonary artery pressure (TAPSE/sPAP) using echocardiography, is strongly associated with cardiovascular events, its prognostic value is not established in acute coronary syndrome (ACS). We aimed to assess the in-hospital prognostic value of TAPSE/sPAP among patients hospitalized for ACS in a retrospective analysis from the prospective ADDICT-ICCU study. Methods and results A total of 481 consecutive patients hospitalized in intensive cardiac care unit [mean age 65 ± 13 years, 73% of male, 46% ST-elevation myocardial infarction (STEMI)] for ACS [either STEMI or non-STEMI (NSTEMI)] with TAPSE/sPAP available were included in this prospective French multicentric study (39 centres). The primary outcome was in-hospital major adverse cardiovascular events (MACEs) defined as all-cause death, resuscitated cardiac arrest, or cardiogenic shock and occurred in 33 (7%) patients. Receiver operating characteristic curve analysis identified 0.55 mm/mmHg as the best TAPSE/sPAP cut-off to predict in-hospital MACEs. TAPSE/sPAP <0.55 was associated with in-hospital MACEs, even after adjustment with comorbidities [odds ratio (OR): 19.1, 95% confidence interval (CI) 7.78–54.8], clinical severity including left ventricular ejection fraction (OR: 14.4, 95% CI 5.70–41.7), and propensity-matched population analysis (OR: 22.8, 95% CI 7.83–97.2, all P < 0.001). After adjustment, TAPSE/sPAP <0.55 showed the best improvement in model discrimination and reclassification above traditional prognosticators (C-statistic improvement: 0.16; global χ 2 improvement: 52.8; likelihood ratio test P < 0.001) with similar results for both STEMI and NSTEMI subgroups. Conclusion A low RV-PA coupling defined as TAPSE/sPAP ratio <0.55 was independently associated with in-hospital MACEs and provided incremental prognostic value over traditional prognosticators in patients hospitalized for ACS. Trial Registration ClinicalTrials.gov Identifier: NCT05063097 [ABSTRACT FROM AUTHOR]

Background: Percutaneous pulmonary valve implantation (PPVI) is a recognized alternative treatment to surgery for patients with dysfunctional right ventricular outflow tracts. Patient selection is essential to avoid serious complications from attempted treatment, such as rupture or dissection, especially of the calcified outflow tracts. We describe a case with an unexpected rupture of a calcified homograft valve and main pulmonary artery, which was treated successfully by emergency implantation of a self-expanding Venus P-Valve (Venus MedTech, Hangzhou, China) without the need for pre-stenting with a covered stent. Case details: A 13-year-old boy had two previous operations of tetralogy of Fallot, one a total repair and the other a homograft valved conduit for pulmonary regurgitation. He presented with dyspnea and severe right ventricular outflow tract obstruction (RVOTO) and had a calcified outflow tract and main pulmonary artery. In the catheter laboratory, a non-compliant balloon dilation resulted in a contained rupture of the conduit. The patient remained hemodynamically stable, and the rupture was treated with a self-expandable Venus P-Valve without the need for a covered stent combined with a balloon-expandable valve or a further surgical procedure. Discussion: Preprocedural evaluation with an inflating balloon is necessary to examine tissue compliance and determine suitability for PPVI. However, this condition is accompanied by a risk of conduit rupture. Risk factors of this complication are calcification and homograft use. These ruptures are mostly controlled with a prophylactic or therapeutic covered stent, with a low rate of requiring surgery. However, there are severe ruptures which lead to hemothorax and death. In the available literature, there was no similar reported case of conduit rupture, which a self-expandable Pulmonary valve stent has managed. It seems that fibrosis and collagen tissue around the heart, formed after open surgeries, can contribute to the control of bleeding in these cases. Conclusion (clinical Learning Point): The suitability of patients for the PPVI procedure should be examined more carefully, specifically patients with homograft and calcification in their conduit. Furthermore, conduit rupture might be manageable with self-expandable artificial pulmonary valves, specifically in previously operated patients, and the applicability of this hypothesis is worth examining in future research. [ABSTRACT FROM AUTHOR]

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA syndrome) is a rare congenital coronary abnormality carrying a poor prognosis. We present a clinical case series of ALCAPA-related anterior mitral valve leaflet prolapse and discuss its mechanism as a key to suspicion of ALCAPA syndrome. [ABSTRACT FROM AUTHOR]

Background: Hemoptysis resulting from rupture of the pulmonary artery pseudoaneurysm (PAP) is massive and fatal, while factor contributing to the rupture of pseudoaneurysm remains elusive. This study aimed to elucidate the clinical and radiological features of PAP and identify the risk factors associated with rupture. Methods: Patients who developed hemoptysis with PAP were collected from January 2019 to December 2022 retrospectively. Clinical data of the demographic characteristics, radiological findings, treatment strategies, and prognosis were collected. A comparative analysis was performed on the characteristics in the ruptured and non-ruptured cases. Results: A total of 58 PAPs were identified in the 50 patients. The most common causes were infection (86%) and cancer (8%). The PAPs were located predominantly in the upper lobes of both lungs, and 57 (99.3%) were distributed in the segmental or subsegmental pulmonary arteries. The median diameter was 6.1(4.3–8.7) mm. A total of 29 PAPs were identified adjacent to pulmonary cavitations, with the median diameter of the cavity being 18.9 (12.4–34.8) mm. Rupture of pseudoaneurysm occurred in 21 cases (42%). Compared to unruptured group, the ruptured group had a significantly higher proportion of massive hemoptysis (57.1% vs. 6.9%, p < 0.001), larger pseudoaneurysm diameter (8.1 ± 3.2 mm vs. 6.0 ± 2.3 mm, p = 0.012), higher incidence of pulmonary cavitation (76.2% vs. 44.8%, p = 0.027), and larger cavitation diameters (32.9 ± 18.8 mm vs. 15.7 ± 8.4 mm, p = 0.005). The mean pulmonary artery pressure (mPAP) in the ruptured group was also significantly higher than that in the unruptured group [23.9 ± 7.4 mmHg vs. 19.2 ± 5.0 mmHg, p = 0.011]. Endovascular treatment was successfully performed in all 21 patients with ruptured PAP, of which the clinical success rate was 96.0%. Five patients experienced recurrent hemoptysis within one year. Conclusions: Massive hemoptysis, pseudoaneurysm diameter, pulmonary cavitation, and elevated mPAP were the risk factors for rupture of pseudoaneurysm. Our findings facilitate early identification and timely intervention of PAP at high risk of rupture. [ABSTRACT FROM AUTHOR]

Background: Obstetric ultrasound is considered important for determining gestational age, identifying single or multiple pregnancies, locating the placenta and fetal anomalies and monitoring fetal growth and pregnancy-related complications in order to improve patient management. Objectives: To explore health professionals' perspectives on different aspects of obstetric ultrasound in Tanzania regarding self-reported skills in performing ultrasound examinations and what could improve access to and utilization of obstetric ultrasound in the clinical setting. Design: Cross-sectional study. Material and Methods: Data was collected between November and December 2017 using a questionnaire based on previous qualitative research results from the CROss Country UltraSound Study (CROCUS Study). Seventeen healthcare facilities in 5 urban and semiurban municipalities in the Dar-es-Salaam region were included, with 636 health professionals participating (physicians, n = 307 and midwives/nurses, n = 329). Results: Most health professionals (82% physicians, 81% midwives/nurses) believed that obstetric ultrasound was decisive in the clinical management of pregnancy. Results indicate proficiency gaps across disciplines: 51% of physicians and 48.8% of midwives/nurses reported no or low-level skills in assessing cervical length. Similarly, deficiencies were observed in evaluating the four-chamber view of the fetal heart (physicians: 51%, midwives/nurses: 61%), aorta, pulmonary artery (physicians: 60.5%, midwives/nurses: 65%) and Doppler assessments (umbilical artery: physicians 60.6%, midwives/nurses 56.1%). Compared to midwives/nurses, physicians were significantly more likely to agree or strongly agree that utilization would improve with more ultrasound machines (odds ratio (OR) 2.13; 95% confidence intervals (CI) 1.26–3.61), better quality of ultrasound machines (OR 2.27; 95% CI 1.10–4.69), more training for health professionals currently performing ultrasound (OR 2.11; 95% CI 1.08–4.17) and more physicians trained in ultrasound (OR 2.51; 95% CI 1.30–4.87). Conclusions: Improving the provision of obstetric ultrasound examinations in Tanzania requires more and better-quality ultrasound machines, enhanced training for health professionals and an increased number of physicians trained in ultrasound use. To further increase the accessibility and utilization of obstetric ultrasound in maternity care in Tanzania, it is essential to provide training for midwives in basic obstetric ultrasound techniques. Plain language summary: A study reporting on health professionals' insights and skills regarding pregnancy scans in Tanzania This study, conducted in Tanzania, explores health professionals' perspectives on obstetric ultrasound, an important component believed to increase antenatal care attendance in low-income countries. The research was carried out through a cross-sectional study involving 636 health professionals, primarily physicians and midwives/nurses, to assess their self-reported skills in performing obstetric ultrasound examinations and identify factors that could enhance access to and utilization of obstetric ultrasound in clinical settings. The findings highlight that most health professionals view obstetric ultrasound as crucial in managing pregnancy. However, there is a notable discrepancy in the perceived skills between physicians and midwives/nurses, especially in basic obstetric ultrasound examinations. A majority of health professionals reported either no skills or low-level skills in assessing various aspects like cervical length, fetal heart (four-chamber views), aorta, pulmonary artery and Doppler (umbilical artery). The study suggests that improving access and utilization of obstetric ultrasound could be achieved through increased availability of quality ultrasound machines and enhanced training. Physicians expressed a stronger belief in the positive impact of more ultrasound machines, better machine quality, additional training for current ultrasound examiners and more physicians trained in ultrasound. The data underscores the potential for enhancing obstetric ultrasound provision in Tanzania by investing in better technology, providing more training for healthcare professionals and increasing the number of physicians skilled in ultrasound use. Furthermore, the study recommends targeted training for midwives to enhance their proficiency in basic obstetric ultrasound, ultimately contributing to improved accessibility and utilization of obstetric ultrasound in maternity care in Tanzania. [ABSTRACT FROM AUTHOR]

Background: Despite recent advances the prognosis of pulmonary hypertension remains poor and warrants novel therapeutic options. Extensive studies, including ours, have revealed that hypoxia-induced pulmonary hypertension is associated with high oxidative stress. Cerium oxide nanozyme or nanoparticles (CeNPs) have displayed catalytic activity mimicking both catalase and superoxide dismutase functions and have been widely used as an anti-oxidative stress approach. However, whether CeNPs can attenuate hypoxia-induced pulmonary vascular oxidative stress and pulmonary hypertension is unknown. Results: In this study, we designed a new ceria nanozyme or nanoparticle (AuCeNPs) exhibiting enhanced enzyme activity. The AuCeNPs significantly blunted the increase of reactive oxygen species and intracellular calcium concentration while limiting proliferation of pulmonary artery smooth muscle cells and pulmonary vasoconstriction in a model of hypoxia-induced pulmonary hypertension. In addition, the inhalation of nebulized AuCeNPs, but not CeNPs, not only prevented but also blunted hypoxia-induced pulmonary hypertension in rats. The benefits of AuCeNPs were associated with limited increase of intracellular calcium concentration as well as enhancement of extracellular calcium-sensing receptor (CaSR) activity and expression in rat pulmonary artery smooth muscle cells. Nebulised AuCeNPs showed a favorable safety profile, systemic arterial pressure, liver and kidney function, plasma Ca2+ level, and blood biochemical parameters were not affected. Conclusion: We conclude that AuCeNPs is an improved reactive oxygen species scavenger that effectively prevents and treats hypoxia-induced pulmonary hypertension. [ABSTRACT FROM AUTHOR]

Background: The importance of high-resolution computed tomography (HRCT) in the diagnosis of idiopathic interstitial pneumonia (IIP) is being recognized more and more. Pulmonary arterial hypertension is common in patients with idiopathic pulmonary fibrosis, the presence of PAH is linked to higher mortality rates and might explain why some people who otherwise have normal pulmonary function are displaying symptoms of deterioration. The aim of this work was to find out the potency of integration of high-resolution computed tomography (HRCT) scoring system with pulmonary artery systolic pressure (PASP) for ascertaining the disease severity of patients with idiopathic pulmonary fibrosis and to predict the prognosis for proper management, along with incorporation of the key disparity of different HRCT scoring systems for the ILD. Results: This prospective study included 80 patients, who came with idiopathic pulmonary fibrosis. A strong positive correlation (r = 0.989) was noted between total lung zone HRCT score and PASP, pulmonary artery size, grades of dyspnea and PCO2. Nonetheless, total lung zone HRCT score proved to have good correlation and inversely proportional to (r = − 0.71) 6MWT, PO2, SPO2, FVC and FEV1/FVC. We utilized a ROC curve to identify the optimal cutoff value in HRCT scoring systems, for detecting pulmonary hypertension associated with the IPF. The sensitivity and specificity of Warrick score cutoff value was higher compared to that of the HRCT scoring system-based grading scale. Both HRCT scoring systems attained high correlation coefficient factors with various incorporated parameters in the study. Conclusion: We can safely say that in order to reveal the severity and prognosis of idiopathic pulmonary fibrosis, a high-resolution computed tomography scoring system should be incorporated with echocardiography measurement of pulmonary artery systolic pressure —which proved to be the most potent predictive factor; especially when measured after a specific HRCT score cutoff value—followed by (FEV1/FVC), the 6MWT and the severity of dyspnea. Their integration collectively will aid in precise management and follow-up of IPF cases. Both HRCT scoring systems proved to be potent and perfect for short-term interval follow-up, yet the Warrick score was easier and faster to use and attained relatively increased sensitivity and specificity for the cutoff value of the pulmonary hypertension detection compared to the HRCT scoring system-based grading scale. [ABSTRACT FROM AUTHOR]

Background and Aims In patients with chronic heart failure (HF), the MONITOR-HF trial demonstrated the efficacy of pulmonary artery (PA)-guided HF therapy over standard of care in improving quality of life and reducing HF hospitalizations and mean PA pressure. This study aimed to evaluate the consistency of these benefits in relation to clinically relevant subgroups. Methods The effect of PA-guided HF therapy was evaluated in the MONITOR-HF trial among predefined subgroups based on age, sex, atrial fibrillation, diabetes mellitus, left ventricular ejection fraction, HF aetiology, cardiac resynchronization therapy, and implantable cardioverter defibrillator. Outcome measures were based upon significance in the main trial and included quality of life-, clinical-, and PA pressure endpoints, and were assessed for each subgroup. Differential effects in relation to the subgroups were assessed with interaction terms. Both unadjusted and multiple testing adjusted interaction terms were presented. Results The effects of PA monitoring on quality of life, clinical events, and PA pressure were consistent in the predefined subgroups, without any clinically relevant heterogeneity within or across all endpoint categories (all adjusted interaction P -values were non-significant). In the unadjusted analysis of the primary endpoint quality-of-life change, weak trends towards a less pronounced effect in older patients (P interaction =.03; adjusted P interaction =.33) and diabetics (P interaction =.01; adjusted P interaction =.06) were observed. However, these interaction effects did not persist after adjusting for multiple testing. Conclusions This subgroup analysis confirmed the consistent benefits of PA-guided HF therapy observed in the MONITOR-HF trial across clinically relevant subgroups, highlighting its efficacy in improving quality of life, clinical, and PA pressure endpoints in chronic HF patients. [ABSTRACT FROM AUTHOR]

Pulmonary artery stenosis represents a group of disorders involving main, branch or peripheral pulmonary arteries with pain, dyspnea, hemoptysis or even no symptoms. Early diagnosis and timely intervention are crucial for reducing mortality, but timely diagnosis is challenging due to the non-specific symptoms. Computed tomography pulmonary angiography (CTPA) is useful in the diagnosis because it can provide more details about abnormal changes in the lumen, vessel wall and adjacent mediastinal structures. Congenital and acquired pulmonary artery anomalies have some characteristics on CTPA, which can be useful for differential diagnosis. Awareness of these conditions is important for radiologists. This pictorial review provides an overview of CTPA imaging features of pulmonary artery stenosis. [ABSTRACT FROM AUTHOR]

Background: Myopathy, lactic acidosis and inherited sideroblastic anemia (MLASA) are a group of rare intriguing disorders with wider pathophysiological implications. One of the causes of MLASA is the mutation in PUS1 gene that encodes for pseudouridine synthase. This PUS1 mutation results in MLASA in which anemia and myopathy predominate. Severe pulmonary arterial hypertension has not been previously reported in patients with PUS1 gene mutation. Case report: A 17 year old girl with congenital sideroblastic anemia presented with worsening of breathlessness. Severe pulmonary artery hypertension was documented on investigations. A homozygous variant in exon 3 of gene PUS1,(chromosome 12:g.131932301 C > T c.430 C > T) was found on sanger sequencing. Conclusion: We document severe pulmonary arterial hypertension in a patient of congenital sideroblastic anemia from PUS1 gene. We hypothesis that cross talk with TGFb pathways might occur in PUS1 mutation, and that might cause severe PAH. This observation might have therapeutic implications. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusion Despite the available treatments, pulmonary arterial hypertension (PAH) prognosis is poor.We aimed to investigate the effects of the alamandine (ALA), melatonin (MEL), and ALA + MEL in PAH.The rats were randomly divided into Control (n = 10), monocrotaline (MCT) (n = 12), ALA (n = 12), MEL (n = 12), and ALA + MEL (n = 12) groups. PAH was induced by MCT. The ALA, MEL, and ALA + MEL groups received 50 μg/kg/day ALA, 10 mg/kg/day MEL, and ALA + MEL, respectively, for 35 days. Echocardiographic and hemodynamic measurements and tissue analyses (morphometric, histopathological, ELISA, and western blot) were performed.Monotherapies, especially MEL, reduced the right ventricular (RV) systolic pressure. Only MEL increased the pulmonary artery acceleration time. MCT increased the RV/left ventricle (LV) + interventricular septum (IVS) ratio. While ALA and ALA + MEL slightly decreased the RV/(LV + IVS), MEL significantly restored it. MCT increased the tunica intima‐media (TIM) thickness, PCNA and α‐SMA of pulmonary arterioles, histopathological score (HS) (inflammatory infiltration etc.) of the lung, and RV. All treatments reduced the TIM thickness (especially MEL), PCNA, and α‐SMA. All treatments significantly decreased the HS of the lung; however, MEL and ALA + MEL produced greater benefits. All treatments attenuated the HS of RV. MCT caused a significant increase in lung lysyl oxidase (LOX) activity. All treatments restored the LOX; however, MEL and ALA + MEL provided greater improvement. While lung Nrf‐2 was increased in MCT‐treated rats, MEL reduced it.ALA, MEL, and ALA + MEL attenuate PAH and protect RV via antiproliferative, anti‐remodeling, antihypertrophic, anti‐inflammatory, and free radical scavenging (only MEL) capabilities. Overall, MEL produced the best outcomes. [ABSTRACT FROM AUTHOR]

Background: Bronchial bifurcation abnormalities are often discovered incidentally on chest computed tomography or bronchoscopy. As this condition is asymptomatic, it has little effect on the disease course of patients with lung cancer. However, this abnormality must be considered when performing lung resection. Case presentation: Patient 1 was a 73-year-old man with suspected simultaneous triple lung cancers [cT1c (3) N0M0, Stage IA3] in the right and left upper lobes. He was initially scheduled to undergo right upper lobectomy and systematic nodal dissection. Chest computed tomography revealed a displaced B3 that arose from the right middle lobe bronchus. V1+2 was transected first, followed by the superior truncus of the pulmonary artery, and B1+2, respectively. After the branches of V3 were ligated, B3 was identified smoothly. Finally, the incomplete interlobar fissure between the upper and middle lobes was separated using an auto-stapler. No vascular abnormalities were observed. Patient 2 was a 62-year-old woman with suspected lung cancer (cT1cN0M0, Stage IA3) in the right upper lobe, and was scheduled to undergo right upper lobectomy and lobe-specific nodal dissection. Chest computed tomography revealed a right top pulmonary vein and a displaced B1 that arose from the right main bronchus independently. Because V1+3 was resected simultaneously during upper and middle lobe resection during robot-assisted thoracic surgery, the procedure was cool-converted to video-assisted thoracic surgery. An independently A1 was observed, followed by A2b and A3, which branched off as a common stem. A right top pulmonary vein was smoothly detected. Each blood vessel was transected using an auto-stapler. B2+3 was transected first using an auto-stapler, followed by B1. Conclusions: The displaced anomalous bronchus is often accompanied by pulmonary arterial or venous abnormalities and an incomplete interlobar fissure. A "hilum first, fissure last" technique is often useful. Preoperative evaluation and surgical planning are important. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is a chronic progressive vascular disease characterized by abnormal pulmonary vascular resistance and pulmonary artery pressure. The major structural alteration during PH is pulmonary vascular remodelling, which is mainly caused by the imbalance between proliferation and apoptosis of pulmonary vascular cells. Previously, it was thought that apoptosis was the only type of programmed cell death (PCD). Soon afterward, other types of PCD have been identified, including autophagy, pyroptosis, ferroptosis and necroptosis. In this review, we summarize the role of the above five forms of PCD in mediating pulmonary vascular remodelling, and discuss their guiding significance for PH treatment. The current review could provide a better understanding of the correlation between PCD and pulmonary vascular remodelling, contributing to identify new PCD‐associated drug targets for PH. [ABSTRACT FROM AUTHOR]

This work presents the results of the characterization of two 1 × 5 mm2 miniaturized rectennas developed for medical applications. They have been designed for relatively high voltage and high-power applications, given the size of the rectennas. Both rectennas were tested in open-air conditions and surrounded by pork fat and muscle tissues, whose properties are similar to those of the human body. The resonant frequencies of the rectennas were found, and the incident electric field on the rectennas tests was increased. The first chip showed a maximum output voltage of 5.29 V and a maximum output power of 0.056 mW, at 1.446 GHz, under an incident field on the rectenna of 340 V/m, and the second chip, 4.62 V and 4.27 mW, at 1.175 GHz, under 535 V/m. The second rectenna can provide an output power greater than 5 mW. The rectennas presented in this article are beyond the state of the art, as they can deliver about three times more power and voltage than those of similar dimensions reported in the literature. Based on the test results, the efficiency of the rectennas was analyzed at different locations of the human body, considering different thicknesses of tissues with high and low water content. Finally, potential applications are described in which the rectennas could power implantable medical devices or microsurgery tools, for example, pulmonary artery pressure monitors. [ABSTRACT FROM AUTHOR]

BACKGROUND: Endothelial cell (EC) apoptosis and proliferation of apoptosis-resistant cells is a hallmark of pulmonary hypertension (PH). Yet, why some ECs die and others proliferate and how this contributes to vascular remodeling is unclear. We hypothesized that this differential response may: (1) relate to different EC subsets, namely pulmonary artery (PAECs) versus microvascular ECs (MVECs); (2) be attributable to autophagic activation in both EC subtypes; and (3) cause replacement of MVECs by PAECs with subsequent distal vessel muscularization. METHODS: EC subset responses to chronic hypoxia were assessed by single-cell RNA sequencing of murine lungs. Proliferative versus apoptotic responses, activation, and role of autophagy were assessed in human and rat PAECs and MVECs, and in precision-cut lung slices of wild-type mice or mice with endothelial deficiency in the autophagy-related gene 7 (Atg7EN-KO). Abundance of PAECs versus MVECs in precapillary microvessels was assessed in lung tissue from patients with PH and animal models on the basis of structural or surface markers. RESULTS: In vitro and in vivo, PAECs proliferated in response to hypoxia, whereas MVECs underwent apoptosis. Single-cell RNA sequencing analyses support these findings in that hypoxia induced an antiapoptotic, proliferative phenotype in arterial ECs, whereas capillary ECs showed a propensity for cell death. These distinct responses were prevented in hypoxic Atg7EN-KO mice or after ATG7 silencing, yet replicated by autophagy stimulation. In lung tissue from mice, rats, or patients with PH, the abundance of PAECs in precapillary arterioles was increased, and that of MVECs reduced relative to controls, indicating replacement of microvascular by macrovascular ECs. EC replacement was prevented by genetic or pharmacological inhibition of autophagy in vivo. Conditioned medium from hypoxic PAECs yet not MVECs promoted pulmonary artery smooth muscle cell proliferation and migration in a platelet-derived growth factor-dependent manner. Autophagy inhibition attenuated PH development and distal vessel muscularization in preclinical models. CONCLUSIONS: Autophagic activation by hypoxia induces in parallel PAEC proliferation and MVEC apoptosis. These differential responses cause a progressive replacement of MVECs by PAECs in precapillary pulmonary arterioles, thus providing a macrovascular context that in turn promotes pulmonary artery smooth muscle cell proliferation and migration, ultimately driving distal vessel muscularization and the development of PH. [ABSTRACT FROM AUTHOR]

Background: Previous research has revealed the potential impact of circadian rhythms on pulmonary diseases; however, the connection between circadian rhythm-associated Thyrotroph Embryonic Factor (TEF) and Pulmonary Arterial Hypertension (PAH) remains unclear. We aim to assess the genetic causal relationship between TEF and PAH by utilizing two sets of genetic instrumental variables (IV) and publicly available Pulmonary Arterial Hypertension Genome-Wide Association Studies (GWAS). Methods: Total of 23 independent TEF genetic IVs from recent MR reports and PAH GWAS including 162,962 European individuals were used to perform this two-sample MR study. Gain- and loss-of-function experiments were used to demonstrate the role of TEF in PAH. Results: Our analysis revealed that as TEF levels increased genetically, there was a corresponding increase in the risk of PAH, as evidenced by IVW (OR = 1.233, 95% CI: 1.054–1.441; P = 0.00871) and weighted median (OR = 1.292, 95% CI for OR: 1.064–1.568; P = 0.00964) methods. Additionally, the up-regulation of TEF expression was associated with a significantly higher likelihood of abnormal circadian rhythm (IVW: P = 0.0024733, β = 0.05239). However, we did not observe a significant positive correlation between circadian rhythm and PAH (IVW: P = 0.3454942, β = 1.4980398). In addition, our in vitro experiments demonstrated that TEF is significantly overexpressed in pulmonary artery smooth muscle cells (PASMCs). And overexpression of TEF promotes PASMC viability and migratory capacity, as well as upregulates the levels of inflammatory cytokines. Conclusion: Our analysis suggests a causal relationship between genetically increased TEF levels and an elevated risk of both PAH and abnormal circadian rhythm. Consequently, higher TEF levels may represent a risk factor for individuals with PAH. [ABSTRACT FROM AUTHOR]

Objective: Congenital defects/diseases. Background: Pulmonary artery sling (PAS) is an anatomical vascular anomaly due to the origin of the left pulmonary artery from the right pulmonary artery, which runs posteriorly between the esophagus and trachea, resulting in compression of adjacent structures. Accurate evaluation for malformation of the pulmonary artery and severity of airway obstruction is essential to surgical strategy. This report presents the diagnosis and surgical management of pulmonary artery sling in a 12-year-old boy. Case Report: A 12-year-old boy had chest tightness and wheezing after exercise for 6 years. He was diagnosed with PSA based on findings from imaging tests, demonstrating the left pulmonary artery originated from the middle of the right pulmonary artery and the tracheal carina was located at the site of the T6 thoracic vertebra. The main bronchus and esophagus were compressed by the left pulmonary artery due to its ectopic origin. Then, after comprehensive preoperative assessment, the patient underwent surgical repair of PAS. Conclusions: This report highlights the importance of pulmonary artery sling diagnosis, imaging, and surgical planning, and the role of a multidisciplinary team in preoperative and postoperative patient management. An individualized strategy based on the preoperative assessment, intraoperative coordination among cardiologists, surgeons, and perfusionists, and careful postoperative management are the core elements for successful PAS repair. [ABSTRACT FROM AUTHOR]

Pulmonary artery aneurysm (PAA) in Behcet's disease is a rare yet potentially life-threatening manifestation, often presenting as haemoptysis. We present a case report of a 33-year-old male with recurrent haemoptysis and a history of oral and genital ulcers, diagnosed with Behcet's disease complicated by PAA. Diagnostic workup, including imaging and laboratory tests, confirmed the diagnosis, leading to prompt initiation of immunosuppressive therapy and meticulous follow-up. The patient showed significant clinical improvement with reduced ulcer severity and no new episodes of haemoptysis during one-year follow-up. Our case underscores the importance of early recognition, multidisciplinary management, and close monitoring to optimize outcomes in Behcet's disease with pulmonary involvement. A comprehensive literature review further elucidates the clinical nuances, diagnostic challenges, and therapeutic strategies associated with this rare manifestation, highlighting the need for collaborative care and tailored interventions to mitigate complications and improve patient prognosis. Key clinical message Behcet's disease can present with pulmonary artery aneurysm, necessitating vigilant monitoring and prompt intervention to prevent severe complications like haemoptysis. Multidisciplinary collaboration is vital for tailored management and improved patient outcomes. [ABSTRACT FROM AUTHOR]

The article describes the case of a seven-day old neonate with prenatal diagnosis of congenital pulmonary airway malformation and was diagnosed with anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA), a rate congenital heart disease. It describes the patient's echocardiographic results and cites possible complications from extracorporeal membrane exygenation (ECMO). It refers to coronary reimplantation as the most common surgical strategy for ARCAPA.

Chronic hypoxia plays a central role in diverse pulmonary pathologies, but its effects on longitudinal changes in the biomechanical behavior of proximal pulmonary arteries remain poorly understood. Similarly, effects of normoxic recovery have not been well studied. Here, we report hypoxia-induced changes in composition, vasoactivity, and passive biaxial mechanics in the main branch pulmonary artery of male C57BL/6J mice exposed to 10% FiO2 for 1, 2, or 3 weeks. We observed significant changes in extracellular matrix, and consequently wall mechanics, as early as 1 week of hypoxia. While circumferential stress and stiffness returned toward normal values by 2–3 weeks of hypoxia, area fractions of cytoplasm and thin collagen fibers did not return toward normal until after 1 week of normoxic recovery. By contrast, elastic energy storage and overall distensibility remained reduced after 3 weeks of hypoxia as well as following 1 week of normoxic recovery. While smooth muscle and endothelial cell responses were attenuated under hypoxia, smooth muscle but not endothelial cell responses recovered following 1 week of subsequent normoxia. Collectively, these data suggest that homeostatic processes were unable to preserve or restore overall function, at least over a brief period of normoxic recovery. Longitudinal changes are critical in understanding large pulmonary artery remodeling under hypoxia, and its reversal, and will inform predictive models of vascular adaptation. [ABSTRACT FROM AUTHOR]

Aims: Heart failure (HF), a global pandemic affecting millions of individuals, calls for adequate predictive guidance for improved therapy. Congestion, a key factor in HF‐related hospitalizations, further underscores the need for timely interventions. Proactive monitoring of intracardiac pressures, guided by pulmonary artery (PA) pressure, offers opportunities for efficient early‐stage intervention, since haemodynamic congestion precedes clinical symptoms. Methods: The BioMEMS study, a substudy of the MONITOR‐HF trial, proposes a multifaceted approach integrating blood biobank data with traditional and novel HF parameters. Two additional blood samples from 340 active participants in the MONITOR‐HF trial were collected at baseline, 3‐, 6‐, and 12‐month visits and stored for the BioMEMS biobank. The main aims are to identify the relationship between temporal biomarker patterns and PA pressures derived from the CardioMEMS‐HF system, and to identify the biomarker profile(s) associated with the risk of HF events and cardiovascular death. Conclusion: Since the prognostic value of single baseline measurements of biomarkers like N‐terminal pro‐B‐type natriuretic peptide is limited, with the BioMEMS study we advocate a dynamic, serial approach to better capture HF progression. We will substantiate this by relating repeated biomarker measurements to PA pressures. This design rationale presents a comprehensive review on cardiac biomarkers in HF, and aims to contribute valuable insights into personalized HF therapy and patient risk assessment, advancing our ability to address the evolving nature of HF effectively. [ABSTRACT FROM AUTHOR]

Background/Objectives: The literature reports high complication rates in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who undergo balloon pulmonary angioplasty (BPA), especially in patients with poor pulmonary hemodynamics. Here, we describe the complications of BPA based on the new definitions. Methods: All patients with CTEPH who completed BPA treatment before 15 September 2023 were selected from the CTEPH database. Peri-procedural complications were collected and classified according to the 2023 consensus paper on BPA treatment. Complications were analyzed in subgroups of patients with pulmonary vascular resistance (PVR), ≤ or >6.6 WU, and mean pulmonary artery pressure (mPAP), ≤ or >45 mmHg, at first BPA. Results: In this analysis, 87 patients (63% women; mean age 61.1 ± 14.0 years; 62% on dual PH targeted medical therapy) underwent 426 (mean 4.9 ± 1.6 per patient) BPAs. Only non-severe complications occurred in 14% of BPA treatments and in 47% of the patients; 31% patients had a thoracic complication. The thoracic complications were mild (71%) or moderate (29%). Patients with a PVR > 6.6 WU (n = 8) underwent more BPA treatments (6.6 ± 1.5 versus 4.6 ± 1.5, p = 0.002), had more complications (88% versus 41% of patients, p = 0.020), and had more thoracic complications (17% vs. 7% of BPAs, p = 0.013) than patients with PVR ≤ 6.6 WU. Patients with mPAP > 45 mmHg (n = 13) also had more BPA treatments (6.5 ± 1.7 versus 4.6 ± 1.4, p < 0.001), more complications (77% versus 44% of patients, p = 0.027) and more thoracic complications (14% versus 8% of BPAs, p = 0.039) than patients with mPAP ≤ 45 mmHg. Conclusions: Complications occurred in 14% of BPAs and were mostly mild. Patients with severe pulmonary hemodynamics suffered more (thoracic) complications. [ABSTRACT FROM AUTHOR]

Background: The safety and impact of sodium glucose transporter 2 inhibitors (SGLT2‐I) in patients with left ventricular assist devices (LVAD) are unknown. Methods: A retrospective analysis of all consecutive patients who underwent LVAD Heart Mate 3 (HM3) implantation at a single medical center and received SGLT2‐I therapy following surgery was conducted. LVAD parameters, medical therapy, laboratory tests, echocardiography, and right heart catheterization (RHC) study results were recorded and compared before and after initiation of SGLT2‐I. Results: SGLT2‐I medications were initiated in 29 (21%) of 138 patients following HM3 implantation (23 (79%) received Empagliflozin and 6 (21%) Dapagliflozin). The mean age at the time of LVAD implantation was 62 ± 6.7 years, 25 (86%) were male, and 23 (79%) had diabetes mellitus. The median time from HM3 implantation to SGLT2‐I initiation was 108 days, IQR (26–477). Following SGLT2‐I therapy, the daily dose of furosemide decreased from 47 to 23.5 mg/day (mean difference = 23.5 mg/d, 95% CI 8.2–38.7, p = 0.004) and significant weight reduction was observed (mean difference 2.5 kg, 95% CI 0.7–4.3, p = 0.008). Moreover, a significant 5.6 mm Hg reduction in systolic pulmonary artery pressure (sPAP) was measured during RHC (95% CI 0.23–11, p = 0.042) in a subgroup of 11 (38%) patients. LVAD parameters were similar before and after SGLT2‐I initiation (p > 0.2 for all). No adverse events were recorded during median follow‐up of 354 days, IQR (206–786). Conclusion: SGLT2‐I treatment is safe in LVAD patients and might contribute to reduction in patients sPAP. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is a progressive cardiovascular disease, which may lead to severe cardiopulmonary dysfunction. As one of the main PH disease groups, pulmonary artery hypertension (PAH) is characterized by pulmonary vascular remodeling and right ventricular dysfunction. Increased pulmonary artery resistance consequently causes right heart failure, which is the major reason for morbidity and mortality in this disease. Although various treatment strategies have been available, the poor clinical prognosis of patients with PAH reminds us that further studies of the pathological mechanism of PAH are still needed. Inflammation has been elucidated as relevant to the initiation and progression of PAH, and plays a crucial and functional role in vascular remodeling. Many immune cells and cytokines have been demonstrated to be involved in the pulmonary vascular lesions in PAH patients, with the activation of downstream signaling pathways related to inflammation. Consistently, this influence has been found to correlate with the progression and clinical outcome of PAH, indicating that immunity and inflammation may have significant potential in PAH therapy. Therefore, we reviewed the pathogenesis of inflammation and immunity in PAH development, focusing on the potential targets and clinical application of anti-inflammatory and immunosuppressive therapy. [ABSTRACT FROM AUTHOR]

Background: Knowledge of the anatomy of pulmonary arteries is essential in many invasive procedures concerning pulmonary circulation. In the diagnosis and treatment of chronic thromboembolic pulmonary hypertension (CTEPH), two-dimensional (2D) pulmonary angiography is used. Recognizing the topographic course of the pulmonary arteries and understanding the status in three dimensions (3D) is paramount. This study aimed to evaluate and describe the branching variant of pulmonary arteries in a single case, as well as morphological parameters of the segmental arteries, like length, diameter and branching angles. Methods: One pair of embalmed human cadaver lungs was dissected by a scalpel and surgical forceps and was measured up to the subsegmental arteries. Results: The diameters (ranging from 3.04 to 9.29 mm) and lengths (ranging from 9.09 to 53.91 mm) of the pulmonary segmental arteries varied. The proximal branching angles were wide and close to perpendicular, while distally, the angles between the segmental and subsegmental arteries were narrower (30–45°). Upon evaluating the branching, rare variations were identified and delineated, notably in the lower lobes of both lungs. Conclusions: Utilizing knowledge and data in clinical settings is instrumental for effectively diagnosing and treating CTEPH. Further research is required to explore the complications in invasive procedures related to various anatomical variations. [ABSTRACT FROM AUTHOR]

Introduction: This study investigated the clinical and radiological characteristics and demographics of patients who developed pulmonary embolism (PE) after Coronavirus disease-2019 (COVID-19) vaccination. Methods: The cases of PE were analyzed retrospectively. Data on clinical, demographic, and radiologic characteristics, laboratory findings, Pulmonary Embolism Severity Index (PESI) scores, early mortality scores, PE severity classes, and risk categories for early mortality (low-risk, intermediate-high-risk, intermediate-low-risk and high-risk) were collected from patient files as defined in the European Society of Cardiology guidelines. Patients were divided into two groups: those who had received a COVID-19 vaccine (group 1) and those who had not (group 2). Patients who developed PE within 1 month after vaccination were analyzed separately. Results: A total of 97 patients were included in the study, of whom 61 (62.9%) patients were female. Seventy-five (77.3%) study patients with PE had a history of COVID-19 vaccination (group 1), and 22 (22.7%) had never been vaccinated (group 2). Five (6.6%) patients had received a vaccine within 1 month before PE developed. No significant differences were found between groups 1 and 2 regarding demographics, clinical and radiologic characteristics, laboratory findings, PESI scores, early mortality scores, and PE severity classes (p>0.05), except for mean pulmonary artery pressures. The mean age of patients who developed PE within 1 month after vaccination was 74.6 years, and 80% of these patients were female. The average time to PE after vaccination was 22.2 days, and the mean PESI score was 86.6. Two patients (40%) were in the low-risk category for early mortality and one patient (20%) was in the intermediate/high-risk category. Conclusion: Overall, the characteristics of patients who developed PE after COVID-19 vaccination were comparable to those of patients who had not received a vaccine injection. No statistically significant increases in the incidence of PE were observed within the first month after being vaccinated. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatic heart disease with persistent atrial fibrillation (RHD‐AF) is associated with increased morbidity. However, there is no standardized approach for the maintenance of sinus rhythm (SR) in them. We aimed to determine the utility of a stepwise approach to achieve SR in RHD‐AF. Methods: Consecutive patients with RHD‐AF from July 2021 to August 2023 formed the study cohort. The stepwise approach included pharmacological rhythm control and/or electrical cardioversion (Central illustration). In patients with recurrence, additional options included AF ablation or pace and ablate strategy with conduction system pacing or biventricular pacing. Clinical improvement, NT‐proBNP, 6‐Minute Walk Test (6MWT), heart failure (HF) hospitalizations, and thromboembolic complications were documented during follow‐up. Results: Eighty‐three patients with RHD‐AF (mean age 56.13 ± 9.51 years, women 72.28%) were included. Utilizing this approach, 43 (51.81%) achieved and maintained SR during the study period of 11.04 ± 7.14 months. These patients had improved functional class, lower NT‐proBNP, better distance covered for 6MWT, and reduced HF hospitalizations. The duration of AF was shorter in patients who achieved SR, compared to those who remained in AF (3.15 ± 1.29 vs 6.93 ± 5.23, p = 0.041). Thirty‐five percent (29) maintained SR after a single cardioversion over the study period. Only one underwent AF ablation. Of the 24 who underwent pace and ablate strategy, atrial lead was implanted in 22 (hybrid approach), and 50% of these achieved and maintained SR. Among these 24, none had HF hospitalizations, but patients who maintained SR had further improvement in clinical and functional parameters. Conclusions: RHD‐AF patients who could achieve SR with a stepwise approach, had better clinical outcomes and lower HF hospitalizations. [ABSTRACT FROM AUTHOR]

Mediastinal diffuse large B‐cell lymphoma (DLBC) may manifest in different presentations including systemic symptoms and local mass symptoms. We report two cases of diffuse large B‐cell lymphoma presenting with pulmonary artery compression symptoms. The first case is of a 38‐year‐old Asian man which mimicked pulmonary embolism, and the second one is of a 27‐year‐old Asian woman who presented with fainting and respiratory symptoms due to local mass effect. Both cases were significantly improved after treatment. Local mass effect symptoms may be the first clinical presentation in DLBC lymphoma and should not be overlooked. [ABSTRACT FROM AUTHOR]

A 2-year-old castrated Russian Blue cat presented with inappetence, depression, and labored respirations. Radiography findings suggested left lung atelectasis; however, the ultrasonography findings did not indicate lung atelectasis. The left pulmonary artery (PA) was abnormally small on echocardiography; further, there were no other cardiac anomalies. Computed tomography revealed an abnormally small left PA and left lung. Furthermore, bronchiectasis and tree-in-bud patterns were observed in the lung lobes. Based on these findings, the cat was diagnosed with isolated left PA hypoplasia, presumed left lung hypoplasia, and feline chronic bronchial disease. Early diagnosis of this disease is important because it can cause serious complications, including recurrent respiratory infection, bronchiectasis, massive hemoptysis, and pulmonary hypertension. [ABSTRACT FROM AUTHOR]