Pulmonary Hypertension Research Articles

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Development and Evaluation of a Deep Learning-Based Pulmonary Hypertension Screening Algorithm Using a Digital Stethoscope.

Despite the poor outcomes related to the presence of pulmonary hypertension, it often goes undiagnosed in part because of low suspicion and screening tools not being easily accessible such as echocardiography. A new readily available screening tool to identify elevated pulmonary artery systolic pressures is needed to help with the prognosis and timely treatment of underlying causes such as heart failure or pulmonary vascular remodeling. We developed a deep learning-based method that uses phonocardiograms (PCGs) for the detection of elevated pulmonary artery systolic pressure, an indicator of pulmonary hypertension. Approximately 6000 PCG recordings with the corresponding echocardiogram-based estimated pulmonary artery systolic pressure values, as well as ≈169 000 PCG recordings without associated echocardiograms, were used for training a deep convolutional network to detect pulmonary artery systolic pressures ≥40 mm Hg in a semisupervised manner. Each 15-second PCG, recorded using a digital stethoscope, was processed to generate 5-second mel-spectrograms. An additional labeled data set of 196 patients was used for testing. GradCAM++ was used to visualize high importance segments contributing to the network decision. An average area under the receiver operator characteristic curve of 0.79 was obtained across 5 cross-validation folds. The testing data set gave a sensitivity of 0.71 and a specificity of 0.73, with pulmonic and left subclavicular locations having higher sensitivities. GradCAM++ technique highlighted physiologically meaningful PCG segments in example pulmonary hypertension recordings. We demonstrated the feasibility of using digital stethoscopes in conjunction with deep learning algorithms as a low-cost, noninvasive, and easily accessible screening tool for early detection of pulmonary hypertension.

Elevated Lp(a) and its association with cardiac fibrosis in group II pulmonary hypertension patients.

Group II Pulmonary Hypertension (PH) secondary to Heart Failure with preserved Ejection Fraction (HFpEF) is associated with significant morbidity and mortality. Lipoprotein(a) [Lp(a)] is a novel biomarker implicated in cardiovascular pathology, yet its role in myocardial fibrosis within this population remains underexplored. This study investigates the association between elevated Lp(a) levels and cardiac fibrosis to improve understanding of its prognostic and diagnostic utility. This retrospective cohort study included 100 patients with Group II PH secondary to HFpEF. Serum Lp(a) levels were quantified using enzymatic assays, and myocardial fibrosis was assessed using Cardiac Magnetic Resonance Imaging (CMR) techniques, including T1 mapping and late gadolinium enhancement (LGE). Statistical models adjusted for confounding factors. Elevated Lp(a) levels were significantly associated with increased myocardial extracellular volume (31% vs. 27%, p < 0.01), prolonged native T1 times, and increased odds of myocardial scar formation. Structural cardiac changes correlated with Lp(a) concentrations. Elevated Lp(a) is a key marker of myocardial fibrosis and structural remodeling in Group II PH secondary to HFpEF. Routine Lp(a) measurement may enhance risk stratification and inform therapeutic strategies.

P16INK4a promoted progress of MCT induced pulmonary hypertension via maintaining redox balance and autophagy pathway.

Pulmonary arterial hypertension (PAH) is a disease characterized by increased pulmonary vascular resistance and elevated pulmonary arterial pressure. Currently, pathogenesis of PAH remains poorly understood, and therapeutic options are limited. In this study, we aimed to explore role of p16INK4A (p16) in the development of PAH using mouse model induced by monocrotaline (MCT). We utilized p16 knockout mice to investigate protective effects on PAH pathophysiology. Histopathological analysis, Western blotting, and transcriptomic profiling revealed that p16 knockout significantly reduced pathological changes associated with MCT-induced PAH, including vascular remodeling and pulmonary fibrosis. These effects were correlated with enhanced autophagy and balanced oxidative stress response following p16 deletion. Transcriptome analysis indicated that the regulatory impact of p16 on autophagy and oxidative stress was primarily mediated through its modulation of oxidative phosphorylation and glutathione metabolic pathways. Our findings provide new insights in PAH pathogenesis and suggest that targeting p16 may offer novel therapeutic approach for treating PAH. These results highlighted that p16 could be a therapeutic target for modulating autophagy and oxidative stress in PAH, paving the way for future research in this area.

Targeted FTO knockout in endothelial cells Boosts adhesion and lowers inflammatory infiltration to alleviate pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a syndrome characterized by increased pulmonary vascular resistance and elevated pulmonary artery pressure, ultimately leading to right heart failure and even death. Increasing evidence implicates the fat mass and obesity-associated protein (FTO) in various metabolic and inflammatory pathways; however, its role in pulmonary endothelial function and PAH remains largely unexplored. In this study, we examined the effects of endothelial cell-specific FTO knockout on PAH development. Our results indicate that the absence of FTO in endothelial cells mitigates hypoxia-induced PAH. Mechanistically, FTO deletion reduces endothelial cell adhesion and inflammatory cell infiltration. Single-cell RNA sequencing revealed disruptions in key inflammatory and adhesion pathways, including TNF-α/NF-κB signaling and VCAM1 expression. These findings suggest that targeting endothelial FTO could be a novel therapeutic strategy for PAH by modulating endothelial adhesion and inflammatory responses.

Tianlong Kechuanling Decoction Attenuates Pulmonary Hypertension by Inhibiting Endothelial-to-Mesenchymal Transition.

Pulmonary hypertension (PH) is a serious and progressive disease, posing a significant challenge to patient survival and quality of life. However, current treatments have limited effectiveness. Tianlong Kechuanling (TL) is a traditional Chinese medicine (TCM) compound formulation commonly used in clinical practice for the treatment of pulmonary heart disease, but its underlying mechanism is unknown. This study aimed to validate the mitigating effect of TL on PH and to further investigate its mechanism. A rat model of PH was induced by SU5416 combined with hypoxia (SuHx). The effects of TL on PH were evaluated through right ventricular systolic pressure (RVSP), Right ventricular hypertrophy index (RVHI) and histopathological analysis. The serum levels of HIF-1α, VEGFA in rats were detected by ELISA; VEGFR2, Vimentin and CD31 were detected by immunohistochemistry to explore the mechanism of action of TL. Human pulmonary artery endothelial cells (HPAECs) were induced by hypoxia, and the effects of TL were confirmed by RT-PCR and Western Blotting. Liquid chromatography-mass spectrometry (LC-MS) analysis was used to identify the chemical composition of TL. TL ameliorated PH through modulation of the HIF-1α/VEGFA pathway and endothelial-to-mesenchymal transition (End-MT). The study also identified the key chemical components responsible for these effects. The study demonstrates that TL can improve PH by inhibiting End-MT, supporting the further development of TL as an effective therapeutic option for PH.

Smooth Muscle Cell-Specific LKB1 Protects Against Sugen 5416/Hypoxia-induced Pulmonary Hypertension through Inhibition of BMP4.

Pulmonary hypertension (PH) is a life-threatening syndrome associated with hyperproliferation of pulmonary artery smooth muscle cells (PASMCs), which exhibit features similar to those of cancer cells. Currently, there is no curative treatment for PH. LKB1 is known as a tumor suppressor gene with an antiproliferative effect on cancer cells. However, its role and mechanism in the development of PH remain unclear. Gain- and loss-of-function strategies were used to elucidate the mechanisms of LKB1 in regulating the occurrence and progression of PH. Sugen 5416/hypoxia (SuHx) PH model was utilized for invivo study. We observed a decreased expression of LKB1 not only in the lung vessels of the SuHx mouse model but also in human PASMCs (HPASMCs) exposed to hypoxia. Smooth muscle-specific LKB1 knockout significantly aggravated SuHx-induced PH in mice. RNA-sequencing analysis revealed a substantial increase in bone morphogenetic protein 4 (BMP4) in the aortas of LKB1SMKO mice compared with controls, identifying BMP4 as a novel target of LKB1. LKB1 knockdown in HPASMCs cultured under hypoxic conditions increased BMP4 protein level and HPASMC proliferation and migration. The coimmunoprecipitation analysis revealed that LKB1 directly modulates BMP4 protein degradation through phosphorylation. Therapeutically, suppressing BMP4 expression in smooth muscle cells alleviates PH in LKB1SMKO mice. Our findings demonstrate that LKB1 attenuates PH by enhancing the lysosomal degradation of BMP4, thus suppressing the proliferation and migration of HPASMCs. Modulating the LKB1-BMP4 axis in smooth muscle cells could be a promising therapeutic strategy of PH.

Echocardiographic evaluation of the size of the main pulmonary artery and right pulmonary artery in dogs with pulmonary hypertension.

Evaluating the size of the pulmonary artery (PA) is key for the echocardiographic assessment of pulmonary hypertension (PH) in dogs. To compare the diagnostic accuracy of the main PA (MPA) and right PA (RPA) sizes for the echocardiographic detection of PH in dogs, and to evaluate differences between precapillary and postcapillary PH dogs. Four hundred four dogs; 136 controls and 268 with PH. Prospective, multicenter, observational study. The MPA, maximum and minimum RPA diameter were normalized to body weight (MPA_N, RPAmax_N, and RPAmin_N). The MPA was also indexed to the ascending aorta (MPA/AO), while the RPA size was indexed to the aortic annulus (RPAmax/Aod and RPAmin/Aod). The right pulmonary artery distensibility index (RPADi) was also calculated. The diagnostic accuracy of PA parameters for PH was assessed through the receiver operating characteristic curve analysis and area under the curve (AUC). Measurement variability was assessed trough the coefficient of variation (CV). The RPADi, RPAmin_N, and RPAmin/Aod showed similar diagnostic accuracy for the detection of PH (AUC = 0.975, AUC = 0.971, and AUC = 0.953, respectively), higher than MPA/AO (AUC = 0.926), MPA_N (AUC = 0.880), RPAmax_N (AUC = 0.814), and RPAmax/Aod (AUC = 0.803; P < .05). Aside from RPAmax variables, no differences were found between precapillary and postcapillary PH. RPA size parameters showed lower CVs in comparison to MPA/AO and RPADi. Although MPA/AO showed an excellent sensitivity and specificity for the detection of PH, the RPAmin exhibited a higher diagnostic accuracy and less measurement variability, thus could represent a new useful parameter for the detection of PH in dogs.

A simple HPLC-UV method for monitoring therapeutic adherence in pulmonary arterial hypertension.

A considerable percentage of ineffective treatment in pulmonary arterial hypertension (PAH) may be related to subtherapeutic dosage or non-adherence. The aim of the study was to develop a simple analytical method suitable for plasma determination of selected drugs: riociguat (RIO), bosentan (BOS) and macitentan (MAC) administered to PAH patients. An isocratic HPLC-UV system (Spectra Physics - Shimadzu) with a manual injector (50μL loop) was applied. Chromatographic analysis was performed using a Suplecosil LC-CN column (150×4.6mm, 5μm) protected with a Supelguard precolumn at room temperature. The separation was carried out using the mobile phase: CH3CN:H2O:0.5M KH2PO4:85% H3PO4 (172:324.2:3.7:0.1, v/v) at a flow rate of 1.8mL/min. Ethyl acetate (4mL) was used for 10-min liquid-liquid extraction from 0.4mL alkalized plasma sample. Detection was performed at λ=245nm chosen as a compromise between signal intensity and matrix interference. The analytes were eluted at retention times of 4.4min (RIO), 5.4min (BOS), 8.9min (MAC) and 7.8min for gallopamil (internal standard, GAL). The method was found linear and calibrated in the ranges: 5-1000ng/mL for RIO, 10-2000ng/mL for BOS and 20-2000ng/mL for MAC, with r2 of 0.9991 for RIO, 0.9983 for BOS, and 0.9949 for MAC, respectively. Within the given ranges, the method ensured reliable results with the required precision and accuracy: ≤15% (≤20% for LLOQ). There was no significant carryover effect. The method has been successfully used in pilot study on adherence in patients treated for PAH, enabling monitoring of RIO, BOS and MAC. Drug concentrations were assessed in samples taken before (C0) and 3h after drug administration (C3). For RIO, BOS and MAC, the developed method was suitable for both C0 and C3 samples, allowing steady-state drug determination if used. The presented method can be recommended to laboratories equipped with basic HPLC apparatus as an attractive analytical tool for both TDM and adherence studies.

Angiopoietin-2 and D-dimer add prognostic information to clinical risk in pulmonary arterial hypertension

Thrombosis and endothelial injury are pathologic hallmarks of pulmonary arterial hypertension (PAH). We aimed to evaluate whether markers of endothelial dysfunction and coagulation in the blood would provide insight into disease activity, treatment response, and outcomes in PAH. MethodsWe prospectively collected baseline and 3-month follow-up blood samples from treatment-naïve PAH patients (n=22) and those who had a clinical indication to intensify therapy (n=19). In addition, we recruited 12 healthy people and clinically stable PAH patients (n=45) as controls who had two blood samples collected twice within 14 days. We generated platelet-free plasma and measured D-dimer, angiopoietin-2, thrombin time, soluble P-selectin, von Willebrand factor, and vascular endothelial growth factor. We assessed treatment response with Reveal Lite 2 scores (all patients had NT-pro-BNP, 6-minute-walk, and functional class assessment at both visits) and followed clinical outcomes for 3 years. ResultsAngiopoietin-2 levels were elevated and fell with response to effective therapy (drop in Reveal Lite 2 score). At follow-up, persistently elevated angiopoietin-2 levels predicted clinical events and even identified low-risk participants who subsequently had events. D-dimer levels were also elevated in PAH patients but didn’t change in response to therapy. Several other abnormalities in endothelial and platelet activation were identified (including elevated soluble P-selectin, elevated von Willebrand factor, and elevated vascular endothelial growth factor) but these did not change with treatment or predict outcome. ConclusionsAngiopoietin-2 and D-dimer are elevated in PAH patients and may add prognostic information to routine clinical assessment.

Predictors of in-hospital early mortality following valve-in-valve transcatheter aortic valve replacement.

There is an increasing preference of utilizing valve-in-valve transcatheter aortic valve replacement (ViV TAVR) after bioprosthetic valve failure. However, updated large-scale analysis investigating early-mortality after the patients underwent ViV TAVR is limited. This study aimed to assess in-hospital early mortality and analyze the factors associated with in-hospital early mortality among patients who underwent ViV TAVR. Using the all-payer, nationally representative National Readmission Database, our study included patients aged 18years or older who had ViV TAVR between 2017 and 2020. We categorized the cohort into two groups depending on the occurrence of in-hospital early mortality (death within 30days after the procedure). Based on the ICD-10, we identified the trend of in-hospital early mortality after ViV TAVR and further analyzed the significant factors associated with it. After adjustment, a total of 11,009 patients who had ViV TAVR were included in this study. 329 (3.0%) had in-hospital early mortality and 10,680 (97.0%) without. There was a decreasing trend in in-hospital early mortality from 3.3% in 2017 to 1.0% in 2020, but it was insignificant (p=0.71). In multivariable analysis, the independent factors associated with in-hospital early mortality were chronic liver disease (adjusted odds ratio [aOR]: 3.62; 95% confidence interval [CI]: 1.96-6.71, p<0.01), coagulation disorder (aOR: 1.77; CI: 1.16-2.68, p<0.01) and pulmonary hypertension (aOR: 1.78; CI: 1.18-2.68, p<0.01). Among patients who died during early readmission following ViV TAVR, the most common cardiac cause and non-cardiac cause of readmission were heart failure (15.4%) and infection (23.1%), respectively. The in-hospital early mortality following ViV TAVR was low at 3.0%. The independent factors associated with in-hospital early mortality post-procedurally were chronic liver disease, coagulation disorder, and pulmonary hypertension.

TGFBI regulates pulmonary vascular remodeling through endothelial-to-mesenchymal transition in pulmonary arterial hypertension

TGFBI regulates pulmonary vascular remodeling through endothelial-to-mesenchymal transition in pulmonary arterial hypertension

Left Atrial Markers in Diagnosing and Prognosticating Non-Ischemic Cardiomyopathies: Ready for Prime Time?

The left atrium (LA) is pivotal in cardiac hemodynamics, serving as a dynamic indicator of left ventricular (LV) compliance and diastolic function. The LA undergoes structural and functional adaptations in response to hemodynamic stress, infiltrative processes, myocardial injury, and arrhythmic triggers. Remodeling of the LA in response to these stressors directly impacts pulmonary circulation, eventually leading to pulmonary capillary involvement, pulmonary artery hypertension, and eventually right ventricular failure. LA dysfunction and fibrosis also contribute to the future risk of atrial arrhythmias and mitral regurgitation. The parameters of LA size and function are being recognized as robust markers for the progression of several cardiac pathologies as well as important tools for prognostication. In this article, we briefly describe the different modalities and markers used to evaluate LA pathology in patients with nonischemic cardiomyopathies (NICM). We then provide an overview of the studies that compared the association of the different LA parameters with disease severity and future prognosis. We also identify the gaps in knowledge before these LA parameters make a case for clinical adoption.

Connexin 43 Affects Pulmonary Artery Reactivity via Changes in Nitric Oxide Production and Influences Proliferative and Migratory Responses in Mouse Pulmonary Artery Fibroblasts

Pulmonary hypertension (PH) is a complex condition characterized by pulmonary artery constriction and vascular remodeling. Connexin 43 (Cx43), involved in cellular communication, may play a role in PH development. Cx43 heterozygous (Cx43+/−) mice show partial protection against hypoxia-induced pulmonary remodeling, with prior research highlighting its role in rat pulmonary artery fibroblast (PAF) proliferation and migration. However, inhibiting Cx43 may compromise nitric oxide (NO)-mediated vascular relaxation. This study evaluated the effects of Cx43 on mouse PAF (MPAF) proliferation, migration, NO-dependent and independent pulmonary vascular relaxation, and NO synthesis. Proliferation and migration were assessed in Cx43+/− MPAFs under normoxic and hypoxic conditions. Vascular responses were analyzed in intra-lobar pulmonary artery rings with acetylcholine (ACh), SNAP, and U46619, while NO production was measured in lung tissue. Both genetic knockdown and pharmacological inhibition of Cx43 significantly reduced serum-induced proliferation but not migration under normoxia, while 37,43Gap27 inhibited hypoxia-induced proliferation and migration. The effects of genetic knockdown and pharmacological inhibition of Cx43 on vascular reactivity were also investigated. NO-dependent and independent relaxations and NO production were reduced in Cx43+/− mice by 37,43Gap27. In conclusion, while Cx43 inhibition may protect against PAF proliferation and migration, it could also impair pulmonary vascular relaxation, at least in part through a reduction in NO signaling. Further studies are needed to fully understand the mechanisms by which Cx43 influences NO signaling.