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Background: Pulmonary hypertension (PH) results in increased right ventricular (RV) afterload, leading to RV dysfunction and failure. The mechanisms underlying maladaptive RV remodeling are poorly understood. In this study, we investigated the multiscale and mechanistic nature of RV free-wall (RVFW) biomechanical remodeling and its correlations with RV function adaptations., Methods: Mild and severe models of PH, consisting of a hypoxia model in Sprague-Dawley rats (n=6 each, control and PH) and a Sugen-hypoxia model in Fischer rats (n=6 each, control and PH), were used. Organ-level function, tissue-level stiffness, and microstructure were quantified through in vivo and ex vivo measures, respectively. Multiscale analysis was used to determine the association between fiber-level remodeling, tissue-level stiffness and anisotropy, and organ-level dysfunction., Results: Decreased RV-pulmonary artery coupling correlated strongly with RVFW stiffening but showed a weaker association with the loss of RVFW anisotropy. Machine-learning classification identified the range of adaptive and maladaptive RVFW stiffening. Multiscale modeling revealed that increased collagen fiber tautness was a key remodeling mechanism that differentiated severe from mild stiffening. Myofiber orientation analysis indicated a shift away from the predominantly circumferential fibers observed in healthy RVFW specimens, leading to a significant loss of tissue anisotropy., Conclusions: Multiscale biomechanical analysis indicated that, although hypertrophy and fibrosis occur in both mild and severe PH, certain fiber-level remodeling events, including increased tautness of collagen fibers and significant reorientations of myofibers, contributed to excessive biomechanical maladaptation of the RVFW leading to severe RV-pulmonary artery uncoupling. Collagen fiber remodeling and the loss of tissue anisotropy can provide an improved understanding of the transition from adaptive to maladaptive RV remodeling.

Purpose: We compared adults with mitral stenosis (MS) to 8 controls (CONT) to see how pulmonary impedance and wave reflections differ at baseline and after balloon valvuloplasty., Methods: We separated the MS patients into groups according to mean pulmonary artery pressure: moderate (MOD; ≤ 26 mmHg, n = 21) and high (HIGH; > 26 mmHg, n = 33). We made baseline high-fidelity measurements in all patients, in the MS groups after vasodilation with nitroprusside, immediately and 4 months after balloon valvuloplasty., Results: Comparing MOD vs CONT, using the Kruskal-Wallis test with Bonferroni correction, reveals evidence for higher baseline input resistance (R) (489 vs 205 dyne-sec/cm 5 , P = 0.07); first harmonic of impedance modulus (Z 1 ) (97.3 vs 27.6 dyne-sec/cm 5 , P = 0.01); first zero crossing of impedance phase angle (F 0 ) (4.49° vs 2.19°, P = 0.02) but no difference in wave reflection index (P b /P f ). Baseline HIGH vs CONT comparisons reveal stronger evidence and larger differences than MOD for R (995 vs 205, P < 0.001); Z 1 (151 vs 27.6, P < 0.001); F 0 (5.25 vs 2.19, P < 0.001); as well as P b /P f (0.69 vs 0.42, P < 0.001). Responses to nitroprusside and valvuloplasty are also greater in the HIGH than MOD, but the HIGH parameters still differ from the CONT. Four months after valvuloplasty there is evidence for reverse remodeling in both groups. Further analyses reveal that sinus rhythm and younger age are potentially important factors for remodeling., Conclusion: MS causes alterations in pulmonary hemodynamics that differ according to pressure levels. These changes are only partially reversed immediately after valvuloplasty. There is evidence for reverse remodeling 4 months afterwards., Competing Interests: Declarations. Conflict of interest: No conflicts of interest, financial or otherwise, are declared by the authors. Ethical Approval: Each person (his/her parents if they were under age 21) gave informed consent for the investigative portion of the study. All studies in the controls and in patients with MS were performed in accordance with institutional guidelines for human research under separate protocols approved by the Institutional Review Board of the Veterans General Hospital, Taipei, Taiwan and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards., (© 2024. The Author(s).)

Background: Pulmonary hypertension (PH) involves increased arterial stiffness and reduced vascular tone, affecting pulmonary arterial wave reflections. The Reflection Index (RI) may provide insights into these changes., Objective: This study examines the utility of RI in PH patients by correlating it with key right heart catheterization (RHC) parameters., Methods: Patients who underwent RHC with a preliminary diagnosis of PH, including those with normal RHC findings and those diagnosed with Group 1 and Group 4 PH, were included in the study. RI was defined as the ratio of systolic to diastolic pressure differences from pulmonary arterial waveforms and compared with hemodynamic, clinical, and echocardiographic parameters., Results: The study included 115 patients (mean age 53.92 ± 16.43 years; 43.5% male). RI showed significant correlations with key RHC parameters, such as sPAP (r=0.359, p<0.001), dPAP (r=0.322, p<0.001), mPAP (r=0.339, p<0.001), PVR (r=0.431, p<0.001), and pSO2 (r=-0.243, p=0.011). Among echocardiographic measures, RI correlated with TRV (r=0.377, p<0.001) and echo sPAP (r=0.359, p<0.001). In multivariable analysis, RI (OR:1.032, p=0.003) and NT-proBNP (OR:1.004, p=0.049) remained significant predictors of PH. ROC analysis demonstrated the moderate predictive power for RI (AUC=0.806, p<0.001), with 76.4% sensitivity and 78.5% specificity at a cut-off of 232.05., Conclusion: RI is a valuable parameter for assessing pulmonary arterial stiffness and vascular tone in patients with PAH and CTEPH. Significant correlations were observed with key hemodynamic parameters, including PVR and mPAP. Additionally, RI demonstrated moderate predictive power for PH. These findings highlight the potential of RI as an independent marker of vascular health, providing direct insights into the pulmonary arterial bed., Competing Interests: Declaration of competing interest All authors declare that they do not have conflict of interest. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. This article does not contain any studies with animal subjects performed by any of the authors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Coronary-to-coronary fistulas are rare anomalies, often detected incidentally. These fistulas may involve complex vascular connections around major cardiac structures, such as the pulmonary artery. Functional assessments help determine clinical significance, with management typically involving observation for asymptomatic patients, while symptomatic cases may require intervention to prevent complications., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

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

This study investigated the sexual dimorphism in right ventricle (RV) remodeling in right heart failure susceptible Fischer CDF rats using the pulmonary artery banding (PAB) model. Echocardiography and hemodynamic measurements were performed in adult male and female Fischer CDF rats at 1- or 2-wk post-PAB. RV systolic pressure and RV hypertrophy were significantly elevated in PAB rats compared with sham control at 1- and 2-wk post-PAB; however, no differences were observed between male and female rats. Increase in cardiomyocyte cross-sectional area and RV end-diastolic diameter was observed in male rats compared with female rats at 2-wk post-PAB. Conversely, higher fractional area change and cardiac index were observed in female rats compared with male rats at 2-wk post-PAB. To explore the mechanisms, a focused PCR array was performed and higher expression of angiogenic genes, including sphingosine kinase-1 ( Sphk1 ), was observed in the RV of female rats compared with male rats. Consistent with the higher angiogenic gene expression, female rats had a higher RV vascular density at 2-wk post-PAB compared with male rats. Female RV endothelial cells (RVECs) had better angiogenic ability compared with male cells that was potentiated by estradiol. Furthermore, effect of estradiol on RVECs was inhibited by Sphk1 inhibitor (PF-543). Together, female Fischer CDF rats develop adaptive RV remodeling post-PAB compared with maladaptive remodeling in male rats. Moreover, the adaptive remodeling in female rats is associated with better RV angiogenic response that may result from better angiogenic ability of female RVECs and proangiogenic effects of estradiol through Sphk1. NEW & NOTEWORTHY Female patients with pulmonary hypertension have better right ventricular adaptation compared with male. These sex differences were modeled in right heart failure susceptible Fischer CDF rat using pulmonary artery banding model. Preservation of right ventricular function in female rats is linked to better right ventricular angiogenic response that involves higher intrinsic angiogenic ability of female right ventricular endothelial cells together with the proangiogenic effects of female sex hormone estradiol through sphingosine kinase-1.

Objectives: There are limited data evaluating the echocardiographic parameters of risk in tricuspid regurgitation (TR) patients. We sought to evaluate the incremental prognostic value of quantitative right ventricle (RV) function and RV-pulmonary artery (RV-PA) coupling to an established clinical risk score in TR patients., Methods: We retrospectively identified patients with moderate or greater TR from January 1, 2019, to June 30, 2019. Univariable and multivariable Cox proportional hazards regressions were used to test the association of right ventricular free wall strain (RVFWS), RVFWS indexed to right ventricular systolic pressure (RVSP), and the Tricuspid Regurgitation Impact on Outcomes (TRIO) risk score with mortality. A novel TRIO-RV risk score was developed by incorporating RVFWS/RVSP into the clinical TRIO risk score., Results: Among 417 patients, age 73 ± 11.5 years, 47% female, the TRIO score was 3.5 ± 2. The TRIO score was low risk in 213 (51%), intermediate risk in 162 (39%), and high risk in 42 (10%). During a median follow-up of 3.96 years (interquartile range, 1.66-4.34 years), death occurred in 157 patients (38%). The baseline TRIO risk category was associated with mortality (P < .001). After adjustment by TRIO risk score, both RVFWS <18.6% (adjusted hazard ratio, 3.08; 95% CI, 2.01-4.72; P < .001) and RVFWS/RVSP <0.43 %/mm Hg (adjusted hazard ratio, 2.76; 95% CI, 1.75-4.35, P < .001) remained significantly correlated with mortality. With the addition of RVFWS/RVSP, 151 (40%) patients with low- and intermediate-risk TRIO scores were reclassified to a higher-risk TRIO-RV score. The chi-square value increased in sequential models predictive of mortality for the TRIO score alone, the TRIO score plus RVFWS <18.6%, and the TRIO score plus RVFWS/RVSP <0.43 %/mm Hg (model chi-square 38.3, 72.2, and 82.3, respectively)., Conclusions: Quantitative parameters of RV function are associated with mortality in TR patients even after correction for an existing clinical risk score. Incorporating RVFWS/RVSP into the TRIO clinical risk score, the TRIO-RV score, reclassifies a substantial number of low- and intermediate-risk patients into higher-risk categories and improves risk stratification., Competing Interests: Conflicts of Interest None., (Copyright © 2024 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Abstract: Pulmonary vascular remodeling and arterial hypertension (PAH) correlate with increased platelet-derived growth factor activity and elevated KIT expression. Imatinib has emerged as a potential therapeutic agent for PAH. The purpose of this systematic review and meta-analysis was to assess the effectiveness of imatinib in the treatment of PAH. A literature search was conducted with the PubMed, Embase, Web of Science, and Cochrane Library to obtain randomized controlled trials where the efficacy of imatinib and placebo in patients with PAH was compared. Three randomized controlled trials that involved 262 patients were finally included in this study. Results showed that imatinib significantly improved 6-minute walk distance (mean difference [MD] = 42.76, 95% confidence interval [CI], 9.20-76.32, P = 0.01), reduced pulmonary vascular resistance (MD = -396.68, 95% CI, -474.50 to -318.85, P < 0.00001), and lowered mean pulmonary arterial pressure (MD = -7.29, 95% CI, -13.97 to -0.61, P = 0.03) in patients with PAH. No significant difference was found between the imatinib and placebo groups in terms of mortality (odds ratio = 1.25, 95% CI, 0.49-3.18) or adverse events (odds ratio = 1.82, 95% CI, 0.76-4.36, P = 0.18). Despite the significant improvement of key hemodynamic parameters, there was no advantage in reducing clinical adverse events or mortality. The prolonged efficacy and safety of imatinib in patients with PAH warrant further studies., Competing Interests: The authors report no conflicts of interest., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hypoxia is associated with the onset of cardiovascular diseases including cardiac hypertrophy and pulmonary hypertension. HIF2 (hypoxia inducible factor 2) signaling in the endothelium mediates pulmonary arterial remodeling and subsequent elevation of the right ventricular systolic pressure during chronic hypoxia. Thus, novel therapeutic opportunities for pulmonary hypertension based on specific HIF2 inhibitors have been proposed. Nevertheless, HIF2 relevance beyond the pulmonary endothelium or in the cardiac adaptation to hypoxia remains elusive. Wt1 (Wilms tumor 1) lineage contributes to the heart and lung vascular compartments, including pericytes, endothelial cells, and smooth muscle cells., Methods: Here, we describe the response to chronic hypoxia of a novel HIF2 mutant mouse model in the Wt1 lineage ( Hif2/Wt1 cKO [conditional knockout]), characterizing structural and functional aspects of the heart and lungs by means of classical histology, immunohistochemistry, flow cytometry, echocardiography, and lung ultrasound analysis., Results: Hif2/Wt1 cKO is protected against pulmonary remodeling and increased right ventricular systolic pressure induced by hypoxia, but displays alveolar congestion, inflammation, and hemorrhages associated with microvascular instability. Furthermore, lack of HIF2 in the Wt1 lineage leads to cardiomegaly, capillary remodeling, right and left ventricular hypertrophy, systolic dysfunction, and left ventricular dilation, suggesting pulmonary-independent cardiac direct roles of HIF2 in hypoxia. These structural defects are partially restored upon reoxygenation, while cardiac functional parameters remain altered., Conclusions: Our results indicate that cardiopulmonary HIF2 signaling prevents excessive vascular proliferation during chronic hypoxia and define novel protective roles of HIF2 to warrant stable microvasculature and organ function., Competing Interests: None.

Introduction: Right heart catheterization (RHC) is the diagnostic standard for establishing residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). A potential non-invasive alternative diagnostic test could be electrocardiography (ECG)-derived ventricular gradient optimized for right ventricular pressure overload (VG-RVPO)., Methods: We studied 66 CTEPH patients who underwent PEA. A subgroup of 20 patients also had a cardiac MRI before and after PEA. The diagnostic performance of the VG-RVPO for the detection of residual PH as well as the potential to replace RHC were assessed. Different cut-off values to define a normal VG-RVPO were evaluated. Also, we evaluated the association between mean pulmonary artery pressure (mPAP) and CMR derived indexed right ventricular (RV) mass and the VG-RVPO., Results: During follow-up, 28 patients had residual PH (42%). A decrease in VG-RVPO after PEA was associated with decrease in mPAP or indexed RV mass post PEA (r = 0.55, p < 0.05 and r = 0.64, p < 0.05, respectively). If a normal VG-RVPO would exclude residual PH, the need for RHC would be reduced with 15-48%, but up to 36% of the CTEPH patients with residual PH would have been missed as they had a normal VG-RVPO., Conclusion: Although there was an association between the change in VG-RPVO and changes in mPAP or indexed RV mass, our study demonstrated that VG-RPVO has limited value in excluding the presence of residual PH post-PEA as up to 36% of the CTEPH patients with residual PH would have been missed if residual PH would have been excluded based on a normal VG-RVPO., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright: © 2025 Luijten et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Endothelial dysfunction is a pivotal initiating factor in vascular remodeling in pulmonary hypertension. EGLN3, a hypoxia response factor, plays a significant role in cell proliferation and angiogenesis, which are closely related to the pathophysiological conditions of pulmonary hypertension. This study investigates the potential involvement of EGLN3 in the injury response of pulmonary vascular endothelial cells and its contribution to the development of pulmonary arterial hypertension. Research has demonstrated that in patients with pulmonary arterial hypertension and various animal models of the condition, EGLN3 expression is upregulated in the remodeled pulmonary artery endothelium. Notably, the endothelial cell-specific knockout of EGLN3 can decelerate the progression of pulmonary arterial hypertension, whereas its overexpression has the opposite effect. Mechanistic analyses reveal that under hypoxic conditions, JUN initiates the transcription of EGLN3 by binding to its promoter region. Subsequently, EGLN3 interacts with HUR to enhance the stability of EGFR mRNA, thereby activating the PI3K/AKT and MAPK signaling pathways, which ultimately results in endothelial cell damage, proliferation, and migration. These findings suggest that EGLN3 is a critical gene for maintaining endothelial function and vascular homeostasis and holds promise as a novel therapeutic target for the treatment of pulmonary hypertension., Competing Interests: Declarations. Ethics approval and consent to participate: The ethics committee of the First Affiliated Hospital at Jinzhou Medical University approved the study protocol regarding tissue donation; also, written informed consent was obtained from either the patients involved or their appointed next of kin (2024216). Additionally, the Research Ethics Committee at Jinzhou Medical University granted approval for all animal experiments and methodologies (2021083001). The Laboratory Animal Science Department facilitated the procurement of Sprague–Dawley rats. Strict compliance with the established protocols for the care and use of laboratory animals was maintained throughout all experimental processes. Consent for publication: All authors consent to the publication of this manuscript. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background and Objectives : The pulmonary artery pulsatility index (PAPi) is an emerging marker of right ventricular (RV) injury but has not been well investigated in acute pulmonary embolism (PE) or chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to investigate its discriminatory capabilities and ability to detect therapeutic effects in acute PE and CTEPH. Materials and Methods : This was a secondary analysis of data from both experimental studies of autologous PE and human studies of acute PE and CTEPH. PAPi was calculated and compared in (1) PE versus sham and (2) before and after interventions aimed at reducing RV afterload in PE and CTEPH. The correlations between PAPi, cardiac output, and RV to pulmonary artery coupling were investigated. Results : PAPi did not differ between animals with acute PE versus sham, nor was it affected by clot burden ( p = 0.673) or at a 30-day follow-up ( p = 0.242). Pulmonary vasodilatation with oxygen was associated with a reduction in PAPi (4.9 [3.7-7.8] vs. 4.0 [3.2-5.6], p = 0.016), whereas positive inotropes increased PAPi in the experimental PE. In humans, PAPi did not change consistently with interventions. Balloon pulmonary angioplasty did not significantly increase PAPi (6.5 [4.3-10.7] vs. 9.8 [6.8-14.2], p = 0.1) in patients with CTEPH, and a non-significant reduction in PAPi (4.3 ± 1.6 vs. 3.3 ± 1.2, p = 0.074) was observed in patients with acute PE who received sildenafil. PAPi did not correlate well with cardiac output or measures of RV to pulmonary artery coupling in either species. Conclusions : PAPi did not detect acute, experimental PE or changes as a result of therapeutic interventions in patients with hemodynamically stable acute PE or CTEPH. However, it did change with pharmacological interventions in the experimental PE. Further research should establish its utility in detecting and monitoring RV injury in different clinical phenotypes of acute PE and CTEPH.

Pulmonary arterial hypertension is a disease of the pulmonary vasculature, resulting in elevated pressure in the pulmonary arteries and disrupting the physiological coordination between the right heart and the pulmonary circulation. Exercise intolerance is one of the primary symptons of pulmonary arterial hypertension, significantly impacting the quality of life. The pathophysiology of exercise intolerance in pulmonary arterial hypertension is complex and likely multifactorial. Although the significance of right ventricle impairment and perfusion/ventilation mismatch is widely acknowledged, recent studies suggest pathophysiology of the skeletal muscle contributes to reduced exercise capacity in pulmonary arterial hypertension, a concept explored herein.

Background: The current study sought to determine the prevalence of elevated estimated pulmonary artery systolic pressure (ePASP) in clinically stable children and adults with sickle cell disease)SCD(worldwide., Methods: The studies included were identified through a search of databases such as PubMed, Scopus, Science Direct, Web of Science, and Embase, as well as Google Scholar engine, adhering to specific inclusion and exclusion criteria. Heterogeneity among the primary study results was assessed using the I-squared index, while publication bias was evaluated through funnel plots, Egger's test, and trim and fill analysis. All statistical analyses were conducted using R software, version 4.3.0., Results: 79 primary studies were included, comprising 6,256 children (<18 years old) and 6,582 adults (≥18 years old) with SCD from 22 countries. The prevalence of elevated ePASP was found to be 21.8% (95% confidence interval [CI]: 18.46 to 25.07) in children and 30.6% (95% CI: 27.1 to 34.1) in adults. The prevalence of elevated ePASP among studies with severe SCD genotypes including HbSS and HbS/β0 was found to be 19.45% (95% CI: 14.95 to 23.95) in children and 29.55% (95% CI: 24.21 to 34.89) in adults. Furthermore, sex-specific prevalence among SCD patients with elevated ePASP indicated the highest prevalence in male children at 60.35% (95% CI: 54.82 to 65.88) and adult female patients at 54.41% (95% CI: 47.3 to 61.5). A comparative analysis of the mean values of clinical and laboratory results revealed significant differences in several characteristics, including age, oxygen saturation, hemoglobin levels, fetal hemoglobin, white blood cell counts, platelet counts, and reticulocyte counts between patients with elevated ePASP and those without, in both children and adult SCD populations., Conclusion: Our findings regarding clinically stable SCD patients highlight a high prevalence of elevated ePASP., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Ghazaiean et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: COVID-19 can cause acute pulmonary hypertension (PH), worsening outcomes in critically ill elderly patients. Point-of-care ultrasound (POCUS), assessing right ventricular hemodynamics, predicts short-term outcomes. This study examines the long-term impact of acute PH on mortality in elderly COVID-19 patients., Methods: This retrospective long-term study analyzed data from patients over 70 years old with severe COVID-19 pneumonia admitted to a mixed 25-bed, level 3 intensive care unit (ICU). POCUS focused on systolic pulmonary artery pressure (sPAP) at admission. Mortality was evaluated 1000 days post-admission., Results: The study included 130 patients, comprising 30 long-term survivors and 100 non-survivors, with a cumulative long-term mortality rate of 77%. Non-survivors had significantly higher sPAP values (39.1 ± 12.8 vs. 30.4 ± 9.2, p = 0.04), which were associated with long-term mortality in survival analysis., Conclusion: Acute pulmonary hypertension (PH), reflected by elevated systolic pulmonary artery pressure (sPAP), is strongly associated with long-term mortality in elderly critically ill COVID-19 patients. Early assessment of sPAP via POCUS may help identify high-risk patients and guide management strategies to improve outcomes.

Background: Data regarding the association of pulmonary hypertension (PH) and outcomes in patients undergoing transcatheter tricuspid valve edge-to-edge repair (T-TEER) are scarce., Objectives: The aims of this study were: 1) to investigate the impact of PH on outcomes after T-TEER; and 2) to shed further light on the role of precapillary- and postcapillary PH in patients undergoing T-TEER for relevant tricuspid regurgitation (TR)., Methods: The study included patients from EuroTR (European Registry of Transcatheter Repair for Tricuspid Regurgitation; NCT06307262) who underwent T-TEER for relevant TR from 2016 until 2023 with available invasive evaluation of systolic pulmonary artery pressure (sPAP) using right heart catheterization. Study endpoints were procedural TR reduction, improvement in NYHA function class, and a combined endpoint of death or heart failure hospitalization (HFH) at 2 years., Results: Among a total of 1,230 patients (mean age 78.6 ± 7.0 years, 51.4% women), increasing sPAP was independently associated with increasing rates of 2-year death or HFH (HR: 1.027; 95% CI: 1.003-1.052; P = 0.030; median survival follow-up 343 days [Q1-Q3: 114-645 days]). No significant survival differences were observed for patients with pre- vs postcapillary PH. Sensitivity analysis revealed an sPAP value of 46 mm Hg as the optimized threshold for the prediction of death or HFH. Being observed in 526 patients (42.8%), elevated sPAP (>46 mm Hg) was associated with more severe heart failure symptoms at baseline and follow-up. Importantly, NYHA functional class significantly improved and TR severity was significantly reduced irrespective of PH., Conclusions: PH is an important outcome predictor in patients undergoing T-TEER for relevant TR. In contrast to previous studies, no significant differences were observed for patients with precapillary and postcapillary PH in terms of survival free from HFH., Competing Interests: Funding Support and Author Disclosures Dr Stolz has received speaker honoraria from Edwards Lifesciences. Dr Kresoja has received travel expenses from Edwards Lifesciences. Dr von Stein has received lecture honoraria from Edwards Lifesciences. Dr Rottbauer has received speaker honoraria from Edwards Lifesciences and Abbott. Dr Denti has served as a consultant for InnovHeart, Picardia, HVR, and Approxima; and has received speaker honoraria from Abbott and Edwards Lifesciences. Dr Rassaf has received speaker honoraria and consulting fees from AstraZeneca, Bayer, Pfizer, and Daiichi-Sankyo. Dr Barreiro-Perez has received speaker fees from Abbott Vascular, Edwards Lifesciences, and Venus Medtech. Dr Adamo has received consulting fees in the past 3 years from Abbott Structural Heart and Edwards Lifesciences. Dr von Bardeleben has received institutional grants from and has served as a speaker for Abbott Vascular and Edwards Lifesciences. Dr Toggweiler has received personal honoraria from Medtronic, Boston Scientific, Biosensors, Abbott Vascular, Medira, Shockwave Medical, Teleflex, atHeart Medical, Cardiac Dimensions, Polares Medical, Amarin, Sanofi, AstraZeneca, ReCor Medical, and Daiichi-Sankyo; has received institutional research grants from Edwards Lifesciences, Boston Scientific, Fumedica, Novartis, and Boehringer Ingelheim; and holds equity in Hi-D Imaging. Dr Metra has received consulting fees in the past 3 years from Abbott Structural Heart, AstraZeneca, Bayer, Boehringer Ingelheim, Edwards Lifesciences, and Roche Diagnostics. Dr Geisler has received speaker honoraria and research grants from AstraZeneca, Bayer, Bristol Myers Squibb/Pfizer, Ferrer/Chiesi, Medtronic, and Edwards Lifesciences (all unrelated to this study). Dr Estévez-Loureiro has received speaker fees from Abbott Vascular, Edwards Lifesciences, Boston Scientific, and Venus Medtech. Dr Lüdike has received speaker honoraria and consulting fees from AstraZeneca, Bayer, Pfizer, and Edwards Lifesciences; and has received research honoraria from Edwards Lifesciences. Dr Maisano has received grant and/or research institutional support from Abbott, Medtronic, Edwards Lifesciences, Biotronik, Boston Scientific, NVT, Terumo, and Venus Medtech; has received consulting fees and personal and institutional honoraria from Abbott, Medtronic, Edwards Lifesciences, Xeltis, Cardiovalve, Occlufit, Simulands, Mtex, Venus Medtech, Squadra, and Valgen; has received royalty income from and holds intellectual property rights with Edwards Lifesciences; and is a shareholder (including share options) in Magenta, Transseptal Solutions, and 4Tech. Dr Praz has received travel expenses from Edwards Lifesciences, Abbott Vascular, Polares Medical, Medira, and Siemens Healthineers. Dr Kessler has received speaker honoraria from Edwards Lifesciences and Abbott. Dr Kalbacher has received personal fees from Abbott Medical, Edwards Lifesciences, Pi-Cardia, and Medtronic. Dr Rudolph has received research grants from Abbott Medical, Boston Scientific, and Edwards Lifesciences. Dr Iliadis has received consultant fees and travel expenses from Abbott Medical and Edwards Lifesciences. Dr Lurz has received institutional grants from Edwards Lifesciences and honoraria from Innoventrics. Dr Hausleiter has received research grant support and speaker honoraria from Edwards Lifesciences. Dr Sticchi has served on an advisory board for Edwards Lifesciences. Dr Tarantini has received speaker fees for Abbott Vascular and Edwards Lifesciences. Dr Karam has received consultant fees from Edwards Lifesciences, Boston Scientific, and Medtronic; and has received proctor fees from Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary arterial hypertension (PAH) is an incurable disease initiated by endothelial dysfunction, secondary to vascular inflammation and occlusive pulmonary arterial vascular remodeling, resulting in elevated pulmonary arterial pressure and right heart failure. Previous research has reported that dysfunction of type 2 bone morphogenetic protein receptor (BMPR2) signaling pathway in endothelium is inclined to prompt inflammation in PAH models, but the underlying mechanism of BMPR2 deficiency-mediated inflammation needs further investigation. This study was designed to investigate whether BMPR2 deficiency contributes to pulmonary arterial hypertension via the NLRP3 (NOD-like receptor family protein 3)/GSDME (gasdermin E)-mediated pyroptosis pathway., Methods and Results: NLRP3 knockout or short hairpin RNA interference of GSDME was performed in PAH animal models to investigate its effect on PAH progression. In addition, the effects of BMPR2 deficiency and restoration of BMPR2 by BMP9 (bone morphogenetic protein 9) or FK506 on pyroptosis were explored both in animal and cell models. Knockout of NLRP3 or short hairpin RNA interference of GSDME in animal models can alleviate the development of pyroptosis, accompanied with improved endothelial integrity, vascular remodeling, and right ventricular systolic pressure. Blocking BMPR2 is sufficient to induce NLRP3 upregulation and release of inflammatory factor IL-1β (interleukin-1β) in pulmonary arterial endothelial cells. Moreover, BMPR2 deficiency can induce GSDME-mediated pyroptosis through NLRP3 activation in 2 animal models, whereas activation of BMPR2 signaling by FK506 or BMP9 can reverse these phenotypes., Conclusions: These findings provide evidence that loss of BMPR2 signaling promotes endothelial cell pyroptosis by enhancing NLRP3/GSDME signaling in PAH. Our findings may provide new insights to explore the inflammatory mechanism of PAH treatment.

Background: 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., Methods: 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., Results: 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., Conclusions: 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.

Background: Riociguat and balloon pulmonary angioplasty (BPA) improve hemodynamics in inoperable chronic thromboembolic pulmonary hypertension. Importantly, comparative effects of riociguat and BPA on different components of right ventricular (RV) afterload and function remain not fully elucidated., Methods: We conducted a post hoc analysis including patients from the RACE trial (Riociguat Versus Balloon Pulmonary Angioplasty in Non-Operable Chronic Thromboembolic Pulmonary Hypertension) with complete data for the primary end point assessment (49 riociguat and 51 BPA). Symptomatic patients with a residual pulmonary vascular resistance >4 WU received add-on riociguat after BPA (n=18) or add-on BPA after riociguat (n=36) and were included in an ancillary 26-week follow-up study with hemodynamic reassessment at week 52., Results: Cardiac output, stroke volume, and RV afterload improved significantly with riociguat and BPA, and the relative changes in RV afterload from baseline to week 26 were more pronounced in the BPA group (all P <0.001). Change in RV afterload was primarily mediated by decreased mean pulmonary arterial pressure in the BPA group, while increased cardiac output was the main driver in the riociguat group. Key parameters of RV function (RV stroke work and right atrial pressure) improved only in the BPA group. The ancillary follow-up study confirmed that relative change in RV afterload from week 26 to week 52 was more pronounced with add-on BPA, and improved RV function was only observed in the add-on BPA group., Conclusions: Both riociguat and BPA are effective in improving RV afterload in inoperable chronic thromboembolic pulmonary hypertension. However, BPA provided a more substantial impact on RV afterload reduction, and RV function only improved with BPA., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02634203., Competing Interests: Dr Gerges has received compensation for scientific symposia from AstraZeneca, AOPHealth, Cordis, Janssen, and Merck Sharp & Dohme (MSD); speaker fees from AOPHealth, AstraZeneca, Janssen, and Ferrer; and an educational grant from AOPHealth. Dr Jevnikar has received speaker fees from Janssen. Dr Savale has received compensation for scientific symposia from Janssen and MSD, speaker fees from Janssen, and has served as an advisory board member for Janssen. Dr Beurnier has received speaker fees from AstraZeneca and Sanofi Aventis. Dr Sitbon has received speaker fees from AOPHealth, Janssen, Ferrer, and MSD; consultancy fees from Acceleron, Altavant, AOPHealth, Ferrer, Gossamer Bio, Janssen, and MSD, research grants from Acceleron, AOPHealth, Janssen, and MSD; and has served as an advisory board member for Altavant, Gossamer Bio, Janssen, and MSD. Dr Fadel has received speaker fees from MSDe. Dr Boucly has received compensation for scientific symposia from Janssen and MSD; speaker fees from Janssen, MSD, AOPHealth, and Ferrer; and research grants from Acceleron, Janssen, and MSD. Dr Simonneau has received speaker and consultancy fees from Janssen, Bayer, GlaxoSmithKline, MSD, and Pfizer; research grants from Janssen; and has served as a steering committee member for Janssen. Dr Humbert has received speaker fees from Janssen and MSD; consultancy fees from Acceleron, Aerovate, Altavant, AOPHealth, Bayer, Chiesi, Ferrer, Janssen, MSD, MorphogenIX, Shou Ti, Tiakis, and United Therapuetics; research grants from Acceleron, AOPHealth, Janssen, MSD, and Shou Ti; and has served as an advisory board member for Acceleron, Altavant, Janssen, MSD, and United Therapeutics. Dr Montani has received speaker fees from Bayer, Janssen, and MSD; consultancy fees from Acceleron, Janssen, and MSD; and research grants from Acceleron, Janssen, and MSD. Dr Jaïs has received speaker fees from Janssen and MSD; and research grants from Acceleron, Bayer, Janssen, and MSD. The other authors report no conflicts.

Purpose: The impact of donor pulmonary hemodynamics as assessed by mean pulmonary artery pressure (mPAP) and transpulmonary gradients (TPG) on the clinical outcome of heart transplant (HT) recipients is unknown. We compared outcomes of adult HT recipients as stratified by donor pulmonary hemodynamics in the contemporary era in the United States., Methods: We reviewed adult donor hearts (age ≥ 18 years) which were offered for transplantation between January 2010 and March 2023 in the UNOS database with available right heart catheterization (RHC) data. Adjusted Cox regression was performed to evaluate the relationship between 30-day and 1-year mortality after HT and donor mPAP, TPG, and mean arterial pressure (MAP). Each hemodynamic parameter was modeled as a quadratic polynomial to not assume a linear relationship with mortality., Results: 2038 HT recipients with complete donor RHC were included: 58 % were on inotrope support. Elevated mPAP (≥25 mmHg), TPG (≥15), and PVR (≥1.5) were present in 416 (20.4 %), 179 (8.8 %), and 2038 (100 %), respectively. No significant association was found between donor mean PAP (HR 1.47, 95 % CI 0.80-2.67), donor TPG (HR 0.47, 95 % CI 0.20-1.08), and donor PVR (HR 1.69, 95 % CI 0.77-3.72) and 30-day mortality. Similarly, no significant association was found between donor mPAP (HR 1.33, 95 % CI 0.90-1.95), donor TPG (HR 0.65, 95 % CI 0.37-1.12), and donor PVR (HR 1.38, 95 % CI 0.83-2.32) and 1-year mortality., Conclusions: Donor pulmonary pressures did not impact post-heart transplant survival in adult recipients. Donors with abnormal pulmonary hemodynamics remain viable donor hearts for transplantation., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Pulmonary stenosis (PS) is common in congenital heart disease and an integral finding in Tetralogy of Fallot (TOF). Pulmonary regurgitation (PR) is more commonly found following surgery in repaired TOF. We aimed to evaluate the haemodynamic effects of PS and PR on cardiac physiology in a porcine model using cardiac magnetic resonance-based feature tracking (CMR-FT) deformation imaging., Methods: CMR-FT was performed in 14 pigs before and 10-12 weeks after surgery. Surgery included either pulmonary artery banding to simulate PS (n = 7), or an incision to the pulmonary valve to simulate PR (n = 7). CMR-FT assessment included left and right ventricular global longitudinal (LV/RV GLS) and LV circumferential (GCS) strain and strain rates (SR) as well as left and right atrial reservoir/conduit/booster pump (LA/RA Es, Ee, Ea) strain and SR., Results: RV GLS was significantly reduced following PS compared to PR induction (PS -7.51 vs. PR -23.84, p < 0.001). RV GLS improved after induction of PR (before - 20.50 vs. after - 23.84, p = 0.018) as opposed to PS (before - 11.73 vs. after - 7.51, p = 0.128). Similarly, RA Es (PS 14.22 vs. PR 27.34, p = 0.017) and Ee (PS 8.65 vs. PR 20.51, p = 0.004) were decreased in PS compared to PR with detrimental impact of PS (Es before 23.20 vs. after 14.22, p = 0.018, Ee before 15.04 vs. after 8.65, p = 0.028) but not PR (Es before 31.65 vs. after 27.34, p = 0.176, Ee before 20.63 vs. after 20.51, p = 0.499)., Conclusions: In a porcine model of RV pressure vs. volume overload, increased after- but not preload shows detrimental impact on RV and RA physiology., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Disclosures: None. Grants: The study was funded by grants from the University of Nebraska Foundation and Children’s Hospital and Medical Center Foundation and partially supported by the German Research Foundation (DFG, Grant GO1067/6-1-KU1329/10 − 1, Berlin, Germany., (© 2024. The Author(s).)

Background: Right ventricular-to-pulmonary artery (RV-PA) coupling has recently been shown to be associated with outcome in valvular heart disease. However, longitudinal data on RV dysfunction and reverse cardiac remodeling in patients following transcatheter edge-to-edge mitral valve repair (M-TEER) are scarce., Methods: Consecutive patients with primary as well as secondary mitral regurgitation (MR) were prospectively enrolled and had comprehensive echocardiographic and invasive hemodynamic assessment at baseline. Kaplan-Meier estimates and multivariable Cox-regression analyses were performed, using a composite endpoint of heart failure hospitalization and death., Results: Between April 2018 and January 2021, 156 patients (median 78 y/o, 55% female, EuroSCORE II: 6.9%) underwent M-TEER. On presentation, 64% showed impaired RV-PA coupling defined as tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) ratio < 0.36. Event-free survival rates at 2 years were significantly lower among patients with impaired coupling (57 vs. 82%, p < 0.001), both in patients with primary (64 vs. 91%, p = 0.009) and secondary MR (54 vs. 76%, p = 0.026). On multivariable Cox-regression analyses adjusted for baseline, imaging, hemodynamic, and procedural data, TAPSE/PASP ratio < 0.36 was independently associated with outcome (adj.HR 2.74, 95% CI 1.17-6.43, p = 0.021). At 1-year follow-up, RV-PA coupling improved (TAPSE: ∆ + 3 mm, PASP: ∆ - 10 mmHg, p for both < 0.001), alongside with a reduction in tricuspid regurgitation (TR) severity (grade ≥ II: 77-54%, p < 0.001)., Conclusions: TAPSE/PASP ratio was associated with outcome in patients undergoing M-TEER for primary as well as secondary MR. RV-PA coupling, alongside with TR severity, improved after M-TEER and might thus provide prognostic information in addition to established markers of poor outcome., Competing Interests: Declarations. Conflict of interest: V. Dannenberg received consulting fees from Abbott, and educational grants from Edwards Lifesciences. J. Mascherbauer received proctor fees from Abbott and Edwards Lifesciences, consulting fees from Boston Scientific, Edwards Lifesciences, and Shockwave Medical, and educational grants from Abbott, Boston Scientific, and Edwards Lifesciences. The remaining authors have nothing to disclose., (© 2023. The Author(s).)

Severe vitamin D (vitD) deficiency is a very common condition in patients with pulmonary arterial hypertension (PAH), and it is a predictor of poor prognosis. There is emerging evidence suggesting a connection between the insufficient response to phosphodiesterase-5 inhibitors (PDE5i) and vitD deficiency in patients with PAH. In the present translational study, vitD deficiency was induced in Wistar rats by exposure to vitD-free diet for 5 wk and followed by Su5416 administration and hypoxia (10%) for 3 wk, a standard experimental model of PAH. Then, rats were randomized to either 1 ) the PDE5i tadalafil and continuing vitD-free diet or 2 ) tadalafil plus a single dose of vitD and standard diet for 4 wk. VitD supplementation improved exercise capacity and right ventricular function and decreased systolic right ventricular pressure, right atrial hypertrophy, right ventricular hypertrophy, and pulmonary arterial remodeling. VitD improved the ex vivo endothelium-dependent response to acetylcholine, indicating an improvement in NO bioavailability, which also resulted in an acute ex vivo response to sildenafil. Thus, the restoration of vitD, by rescuing endothelial function and PDE5i effectiveness, significantly improved the histological, hemodynamic, and functional features of rats with PAH. VitD may be especially beneficial for PDE5i-treated patients with PAH. NEW & NOTEWORTHY Severe vitamin D deficiency is very prevalent in patients with pulmonary arterial hypertension. We show that addition of vitamin D to the standard PDE5 inhibitor tadalafil increases its therapeutic efficacy in pulmonary hypertensive rats that were deficient in vitamin D.

The development of right heart failure (RHF) in patients with advanced heart failure following left ventricular assist device (LVAD) implantation remains difficult to predict. We proposed a novel composite hemodynamic index-the right ventricular-arterial compliance index (RVACi), derived from pulmonary artery pulse pressure (PAPP), ejection time (ET), heart rate (HR), and cardiac output (CO), with and expressed as mm Hg·s/L. We then conducted a retrospective, single-center analysis comparing the predictive value of RVACi for the development of RHF or unplanned right ventricular (RV) mechanical circulatory support following LVAD implantation against existing hemodynamic indices. One hundred patients were enrolled after screening 232 patients over a 10 year period, with 74 patients having complete hemodynamic data for RVACi calculation. There was good correlation between pulmonary arterial capacitance ( R ² = 0.48) and pulmonary vascular resistance ( R ² = 0.63) with RVACi, but not RV stroke work index or pulmonary artery pulsatility index. Reduced baseline RVACi (52 ± 23 vs . 92 ± 55 mm Hg·s/L; p = 0.02) was the strongest hemodynamic predictor of unplanned RV mechanical circulatory support requirement in patients following LVAD insertion. Composite pulsatile hemodynamic indices including RVACi may provide additional insight over existing hemodynamic indices for the prediction of RHF and need for RV mechanical circulatory support., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Objective: Few reliable tools exist to predict weaning patient outcomes from venoarterial extracorporeal membrane oxygenation (ECMO; VA-ECMO). Pulmonary artery pulse pressure indexed on right atrial pressure (PAPi) reflects the ventricle-pulmonary coupling and may be representative of right ventricular recovery. Radial artery pulse pressure (rPP) may be representative of left ventricular recovery. We intended to explore the usefulness of these indices in the weaning from VA-ECMO., Design: Retrospective cohort study., Setting: Single center in a tertiary university hospital., Participants: Patients benefiting from a VA-ECMO for all-cause refractory cardiogenic shock between 2017 and 2021. Non-inclusion criteria were minor/pregnant patients and ECMO within 48 hours. Univariate and multivariate logistic regression analyses explored the relationship between PAPi and rPP with weaning success., Interventions: We explored the association between the pulmonary artery pulse pressure indexed on PAPi, rPP, and the success of weaning from VA-ECMO., Measurements and Main Results: We included 124 patients for rPP analysis and 82 patients for PAPi analysis. Higher rPP and PAPi (50.43 v 26.3 mmHg, p < 0.001: 1.78 v 0.88, p < 0.001, respectively) and shorter ECMO duration were associated with weaning success. Areas under ROC for rPP and PAPi were 0.85 and 0.88. The combination of rPP ≥ 40 mmHg and PAPi ≥ 1.09 predicted weaning with a sensitivity of 0.94, specificity of 1.00, positive predictive value of 1.00, and negative predictive value of 0.84., Conclusion: Higher PAPi and rPP were predictors of successful weaning from VA-ECMO in this retrospective study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Ineffective right ventricular (RV) adaptation to increasing pulmonary arterial (PA) afterload in pulmonary vascular disease (PVD) significantly contributes to morbidity and mortality. Pulmonary vascular disease in systemic sclerosis (SSc) arises through various mechanisms, yet detecting abnormal contractile response remains challenging. Here we examine whether echocardiographic RV-PA coupling metrics correlate with invasive pressure-volume (PV) loops, enhancing the prediction of adverse clinical outcomes in SSc-PVD patients., Methods: Prospectively enrolled patients with SSc-PVD with paired echocardiogram and PV loops were included. Linear regression and receiver-operating curve analysis were used to assess the relationship between tricuspid annular plane systolic excursion/PA systolic pressure (PASP), fractional area change/PASP, tissue Doppler velocityS'/PASP, and RV free wall strain (RVFWS)/PASP and coupling thresholds defined by end-systolic to end-arterial elastance (Ees/Ea), obtained by the multibeat method. The contribution of right atrial strain (RAS) to RV-PA coupling parameters was also investigated. Kaplan-Meier analysis was used to identify the relationship between coupling ratios and composite outcomes including clinical worsening, lung transplant, and death., Results: Forty-two patients with SSc were studied, 91% female, with a mean age of 59 ± 12 years and varying degrees of PVD: mean pulmonary artery pressure 29.5 ± 12.8 mm Hg, PVR 4.7 ± 4.2 WU, and PCWP 10.3 ± 4.1 mm Hg. Echocardiographic coupling metrics including tricuspid annular plane systolic excursion/PASP, fractional area change/PASP, tissue Doppler velocity S'/PASP, RVFWS global and RVFWS basal /PASP, and RAS reservoir /PASP were linearly associated with Ees/Ea. At cut points obtained through receiver-operating curve analysis, all ratios were predictive of RV-PA uncoupling, defined by Ees/Ea, and composite outcomes. Additionally, RAS reservoir /RVFWS correlated with Ees/Ea even after adjustment for PASP, suggesting that diminished RAS further impacts RV performance and coupling., Conclusion: Echocardiographic RV-PA coupling ratios strongly correlate with invasive Ees/Ea and predict adverse clinical outcomes in SSc patients across the spectrum of PVD. Further, we demonstrate how RAS impacts RV performance. These findings may refine risk stratification and prognostication in this at-risk cohort., Competing Interests: Disclosures Dr. Tedford is the cochair of the PH due to left heart disease task force for 7th World Symposium on Pulmonary Hypertension and deputy editor for the Journal of Heart and Lung Transplantation. He reports general disclosures to include consulting relationships with and receiving honoraria from Abbott, Acorai, Aria CV Inc., Acceleron/Merck, Alleviant, Boston Scientific, Cytokinetics, Edwards LifeSciences, Endotronix, Gradient, Medtronic, Morphic Therapeutics, Restore Medical, and United Therapeutics. Dr. Tedford serves on the steering committee for Abbott, Edwards, Endotronix, and Merck as well as a research advisory board for Abiomed. He also does hemodynamic core lab work for Merck. The remaining authors have nothing to disclose., (Copyright © 2024 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

To evaluate dual-layer dual-energy computed tomography (dlDECT)-based characterization of thrombus composition for differentiation of acute pulmonary embolism (PE) and chronic thromboembolic pulmonary hypertension (CTEPH). This retrospective single center cohort study included 49 patients with acute PE and 33 patients with CTEPH who underwent CT pulmonary angiography on a dlDECT from 06/2016 to 06/2022. Conventional images), material specific images (virtual non-contrast [VNC], iodine density overlay [IDO], electron density [ED]), and virtual monoenergetic images (VMI 50KeV ) were analyzed. Regions-of-interest (ROIs) were manually placed in pulmonary artery thrombi, and morphological imaging characteristics for acute and chronic PE were assessed. Area under the receiver operating characteristics curve (AUC) of ROI measurements, morphological imaging features, and their combination in distinguishing between acute PE and CTEPH were evaluated. Compared to PE, thrombi in patients with CTEPH had lower attenuation on conventional images (Median [inter-quartile range]: 40 [35-47] HU vs 64 [52-83] HU) and VMI 50keV reconstructions (59 [46-72] HU vs 101 [80-123] HU) as well as decreased iodine uptake (IDO: 0.5 [0.2-1.0] vs 1.2 [0.5-1.8]; p for all < 0.001). Conventional images and VMI 50keV reconstructions were the most accurate for differentiating between acute and chronic thrombi (conventional: AUC 0.92, 95% CI 0.86-0.98; VMI 50keV : AUC 0.91, 95% CI 0.85-0.97). Main pulmonary artery (MPA) diameter combined with thrombus attenuation significantly increased the AUC compared to MPA diameter alone (p = 0.002 respectively). Thrombi in patients with CTEPH exhibit lower attenuation and reduced contrast enhancement. Analyzing attenuation in pulmonary thrombi may add diagnostic information to established morphological parameters in differentiating acute PE from CTEPH., Competing Interests: Declarations. Competing interest: Roman Johannes Gertz was supported by the Cologne Clinician Scientist Program (CCSP)/Faculty of Medicine/University of Cologne. Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) (Project No. 413543196). Roman Johannes Gertz, Nils Große Hokamp, Lenhard Pennig and David Maintz are on speaker’s bureau of Philips Healthcare. Florian Johannes Fintelmann is a speaker and consultant for Boston Scientific, a consultant for BD, and has received research funding from Pfizer. Roman Johannes Gertz and Lenhard Pennig are on speaker´s bureau of Guerbet GmbH. Simon Lennartz is a member of Editorial Board of Radiology and a Senior Deputy Editor of Radiology in Training. Jan Robert Kroeger received honoraria for scientific lectures from GE Healthcare and honoraria for clinical advisory board membership from Siemens Healthineers. Ethical approval: This study was approved by the local institutional review board (Ethics Committee of the Faculty of Medicine from the University of Cologne, Cologne, Germany). The necessity for informed consent was waived due to the retrospective design of the study. All clinical investigations were conducted in accordance with the Declaration of Helsinki., (© 2024. The Author(s).)

Lowering mean pulmonary arterial pressure (mPAP) without reducing cardiac output is essential in treating pulmonary hypertension (PH). Isosorbide dinitrate (ISDN) potentially achieves this in post-capillary PH but can decrease cardiac output and blood pressure (BP), especially in pre-capillary PH. However, post-capillary PH and pre-capillary PH can overlap, and their clear discrimination is difficult. The aim of the study was to examine to what extent bolus ISDN injection reduces mPAP and BP, and changes mixed venous oxygen saturation (SvO 2 ), an indicator of cardiac output in PH with various cardiopulmonary comorbidities in the context of treatment modifications. We retrospectively examined the hemodynamic effects of bolus ISDN injection in patients with PH who underwent right heart catheterization and their subsequent treatment modification. Our sample comprised 13 PH patients. In seven with pre-capillary PH, ISDN significantly lowered mPAP from the median 34 (interquartile range 32-39) to 28 (28-30) mmHg and the mean BP (mBP) from 90 (79-92) to 72 (68-87) mmHg. In six with post-capillary PH, ISDN lowered mPAP from 40 (29-44) to 27 (23-31) mmHg and mBP from 91 (87-110) to 87 (82-104) mmHg. There was a significant decrease in SvO 2 from 69.8% (64.9%-78.1%) to 63.9% (60.5%-71.5%) in pre-capillary PH, but not in post-capillary PH including combined post- and pre-capillary PH and some patients showed a large increase in SvO 2 . In all patients showing an SvO 2 increase, diuretics or hemodialysis were up-titrated or continued. Bolus ISDN injection lowered mPAP. However, in pre-capillary PH, it caused a significant decrease in SvO 2 and a notable reduction in blood pressure. In post-capillary PH, including combined post- and pre-capillary PH, it clarified whether systemic preload and afterload reduction increased or decreased SvO 2 in each patient, which may aid in treatment modification., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflicts of interest concerning this study., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Purpose: To report a case of an asymptomatic patient with a pulmonary aneurysmal arterio-venous malformation successfully treated with a vascular plug., Case Report: An active 30-year-old male patient, residing at 3000 ft above sea level was referred due to an incidental finding on a CT scan of a 37 mm vascular mass localized in the lower lobe of the right lung, which corresponded to a pulmonary arteriovenous malformation with a single feeding artery. The patient was treated with an Amplatzer vascular plug, which effectively excluded the afferent vessel. An angio CT at 19 months follow-up revealed a hypodense residual mass of 9.0 mm in diameter with no arterial filling or venous drainage. The patient is fully active and remains asymptomatic at 24 months follow-up., Conclusion: An unusual case of a pulmonary aneurysmal arteriovenous malformation successfully treated with a vascular plug is presented, highlighting the efficiency of this procedure., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Pulmonary artery stenosis, neoaortic dilatation, and neoaortic valve insufficiency are among the most frequent complications of the arterial switch operation for repair of dextro-transposition of the great arteries (d-TGA). It remains difficult to predict which patients will require great arterial reintervention., Objective: We aimed to characterize hemodynamics within the great arteries using 4D flow MRI in patients with d-TGA after the arterial switch operation., Materials and Methods: Patients with d-TGA after the arterial switch operation and controls with normal cardiac anatomy who underwent 4D flow MRI between 2012 and 2024 were included in this IRB-approved retrospective cohort study. Controls included patients undergoing MRI for other indications who consented or assented to the addition of a 4D flow sequence, as well as patients who underwent clinically indicated 4D flow MRI and were found to have normal cardiac anatomy and function. Velocity, stasis, kinetic energy, energy loss, wall shear stress, and pulse wave velocity were quantified in the aorta and pulmonary arteries. To compare each parameter between d-TGA patients and controls, unpaired t-tests were used for normally distributed data and Mann-Whitney tests for non-normal data. P < 0.05 was significant., Results: Patients with d-TGA after the arterial switch operation (15.7 years ± 2.4, 2 females) demonstrated significantly higher maximum and mean velocity, maximum and mean kinetic energy, energy loss, and maximum and mean wall shear stress within the pulmonary arteries (P < 0.0001 for all parameters) compared with age-matched controls (15.5 years ± 2.4, 14 females). Aortic maximum (P = 0.001) and mean (P = 0.048) velocity, maximum (P = 0.0008) and mean (P = 0.003) kinetic energy, energy loss (P < 0.0001), maximum wall shear stress in five of six regions (range P < 0.0001 to P = 0.002), and mean wall shear stress in three regions (range P = 0.005 to P = 0.03) were significantly higher in patients with d-TGA after the arterial switch operation patients compared with age-matched controls., Conclusion: Patients with d-TGA after the arterial switch operation demonstrate hemodynamic abnormalities within the great arteries, which may provide insight into the mechanisms underlying postoperative consequences of the arterial switch operation., Competing Interests: Declarations. Conflicts of interest: None, (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Abstract: Pulmonary arterial hypertension (PAH) is a cardiopulmonary vascular condition with an unclear pathogenesis. Targeting endoplasmic reticulum (ER) stress has been suggested as a novel treatment approach for PAH, but the mechanisms involving ER stress-related genes in PAH are not well understood. Microarray data for PAH and ER stress-related genes were analyzed. Differential and Venn analyses identified 17 differentially expressed ER stress-related genes in PAH. Candidate drugs targeting these genes were predicted using the CMap database. A protein-protein interaction (PPI) network was constructed, and hub genes (LCN2, IGF1, VCAM1, EDN1, HMOX1, TLR4) with complex interplays were identified using the STRING database and Cytoscape plugins. The clinical diagnostic performance of the hub genes was evaluated using ROC curves. The GeneMANIA Web site was utilized to predict enriched pathways associated with the hub genes and their functionally similar genes. MiRNAs and transcription factors targeting the hub genes were predicted using the Networkanalyst Web site. The immune levels in control samples and PAH samples were assessed using various algorithms. Nine drug candidates were found to potentially target the identified ER stress-related genes. The hub genes and their correlated genes were significantly enriched in immune-related pathways. The PAH group showed increased immune cell infiltration, indicating a heightened immune response. This study sheds light on the role of ER stress-associated hub genes in PAH and proposes potential drugs targeting these genes. These findings provide valuable insights into PAH mechanisms and support the exploration of ER stress as a therapeutic target., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Bronchial stenosis associated with bronchial anastomosis dehiscence after lung transplantation is a catastrophic complication following lung transplantation with a paucity of therapeutic solutions., Purpose: To describe an adaptation of the parallel stent grafting technique in the pulmonary arterial territory to treat this challenging situation., Research Design: This is a case report of a 52-year-old patient who presented bronchus stenosis and bronchial anastomosis dehiscence after lung transplantion. Bronchial stenting and lung retransplantation were contraindicated. Therefore, an endovascular approach using pulmonary artery endograft placement to prevent bleeding during repeated right bronchial balloon dilation was propposed. The technique consists of the deployment of an aortic extender endoprosthesis in the right main pulmonary artery and a balloon expandable stent in the upper lobe pulmonary artery (using a parallel graft configuration) through the common femoral and right internal jugular veins, respectively. Intraoperative transesophageal echocardiogram and one-lung ventilatory ventilation are needed., Results: The patient underwent a new bronchoscopy 16 days after the procedure, that showed epithelization at the previous eroded zone, enabling bronchocopic balloon dialtion to be safely performed. A post-operative contrast-enhanced CT scan revealed an adequate positioning of the stent grafts. Despite all eforts, the patient succumbed to ventilator associated pneumonia on postoperative day 108., Data Analysis: The technique's advantages include its feasibility even in situations in which other techniques may be contraindicated and its potential use in emergencies. Its limitations include the need for experienced interventionists to perform it, and the potential risk of acute tricuspid regurgitation., Conclusion: This study illustrates the early feasibility of the parallel stent grafting technique applied to the pulmonary artery territory. However, it's safety profile regarding infectious risk was not demontrated., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The aim of the study was to evaluate the association between the tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (sPAP) ratio and estimated glomerular filtration rate (eGFR) and their association with mortality in the European Scleroderma Trials and Research (EUSTAR) cohort., Methods: Patients with systemic sclerosis (SSc) from the EUSTAR database with TAPSE, sPAP, and parameters required to calculate eGFR were included. Logistic regression and Cox regression analysis were performed to evaluate TAPSE/sPAP as a risk factor for chronic kidney disease (CKD) and overall survival., Results: A total of 2,370 patients with SSc were included; 284 (12%) patients had CKD stage 3a-5. TAPSE/sPAP (odds ratio [OR] 0.479; 95% CI 0.310-0.743; P < 0.001), arterial hypertension (OR 3.118; 95% CI 2.173-4.475; P < 0.001), diastolic dysfunction (OR 1.670; 95% CI 1.148-2.428; P < 0.01), and N-terminal pro-B-type natriuretic peptide (OR 1.165; 95% CI 1.041-1.304; P < 0.01) were associated with CKD stage 3a-5. TAPSE/sPAP ≤0.32 mm/mm Hg (hazard ratio [HR] 3.589; 95% CI 2.236-5.761; P < 0.001), eGFR <60 mL/min per 1.73 m 2 (HR 2.818; 95% CI 1.777-4.468; P < 0.001), and age (HR 1.782; 95% CI 1.348-2.356; P < 0.001) were the most significant predictive factors for all-cause mortality. A total of 276 patients with SSc had pulmonary hypertension (PH) confirmed by right-sided heart catheterization, with 69 (25%) having CKD stage 3a-5. No difference was found in eGFR between patients with PH with reduced or normal cardiac index., Conclusion: Reduced TAPSE/sPAP ratio is independently associated with CKD. TAPSE/sPAP ratio ≤0.32 mm/mm Hg and eGFR <60 mL/min per 1.73 m 2 are prognostic factors for all-cause mortality. In patients with SSc with PH, eGFR is independent by reduced cardiac output., (© 2023 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: Right ventricular-to-pulmonary artery (RV-PA) coupling is an important predictor of long-term survival following transcatheter edge-to-edge repair. However, its impact on survival in patients undergoing indirect mitral annuloplasty is unknown. The study aimed to assess the impact of baseline RV-PA coupling on survival following indirect mitral annuloplasty in heart failure patients., Methods: Patients were classified according to baseline RV-PA coupling: TAPSE (tricuspid annular plane systolic excursion)/PASP (pulmonary artery systolic pressure) > 0.55 (group 1), ≤ 0.55 ≥ 0.32 (group 2) and ≤ 0.32 (group 3). Clinical follow-up and RV function were assessed 3 and 12 months following indirect annuloplasty., Results: A TAPSE/PASP > 0.55 was found in 19 patients, while 47 patients showed a TAPSE/PASP ≤ 0.55 > 0.32 and 26 a TAPSE/PASP ≤ 0.32. A significant reduction in vena contracta and regurgitant volume compared to baseline was found in all groups at 3-months and 12-months follow-up. One-year mortality was significantly increased in group 3 compared to the other groups (group 1: 0.95, group 2: 0.91, group 3: 0.77; Log-Rank test p = 0.018). In groups 2 and 3 the TAPSE/PASP significantly improved during the 12-months follow-up, while it remained unchanged in group 1 (group 1: baseline = 0.71 ± 0.03, 12-months = 0.67 ± 0.01; group 2: baseline = 0.43 ± 0.06, 12-months: 0.56 ± 0.04; group 3: baseline = 0.25 ± 0.06, 12-months: 0.4 ± 0.03; p < 0.001)., Conclusions: RV-PA uncoupling before indirect mitral annuloplasty is associated with poor survival. However, Carillon device implantation improved right heart function and RV-PA coupling in patients with severe RV dysfunction at baseline. Therefore, Carillon device implantation can be a valuable option for transcatheter treatment of patients with FMR and right heart failure., (© 2024 The Author(s). Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Endothelial cell-selective adhesion molecule (ESAM) is a member of tight junction molecules, highly abundant in the heart and the lung, and plays a role in regulating endothelial cell permeability. We previously reported that mice with genetic ESAM deficiency ( ESAM -/- ) exhibit coronary microvascular dysfunction leading to the development of left ventricular diastolic dysfunction. Here, we hypothesize that ESAM -/- mice display impairments in the pulmonary vasculature, affecting the overall pulmonary vascular resistance (PVR). We utilized ESAM -/- mice and employed isolated, ventilated, and perfused whole lung preparation to assess PVR independently of cardiac function. PVR was assessed in response to stepwise increases in flow, and also in response to perfusion of the endothelium-dependent agonist, bradykinin, the thromboxane analog, U46619, and the nitric oxide (NO) donor sodium nitroprusside (SNP). We found that PVR, at every applied flow rate, is significantly elevated in ESAM -/- mice compared with WT mice. Bradykinin-induced reduction in PVR and U46619-induced increase in PVR were both diminished in ESAM -/- mice, whereas SNP-induced responses were similar in wild-type (WT) and ESAM -/- mice. Inhibition of NO synthase with N (ω)-nitro-l-arginine methyl ester increased agonist-induced PVR in WT but not in ESAM -/- mice. Pulmonary arteries isolated from ESAM -/- mice exhibited a reduced level of phospho-Ser473-Akt and phospho-Ser1177-eNOS. Furthermore, in human lung microvascular endothelial cells cultured under flow conditions, we found that siRNA-mediated knockdown of ESAM impaired fluid shear stress-induced endothelial cell alignment. Thus, we suggest that ESAM plays an important role in the endothelium-dependent, flow/shear stress- and vasoactive agonist-stimulated, and NO-mediated maintenance of PVR in mice. NEW & NOTEWORTHY Our study reveals a novel role for ESAM in contributing to the maintenance of pulmonary vascular resistance under normal physiological conditions. Employing mice with global genetic deficiency of ESAM and using isolated whole lung preparation, we show significant impairments in nitric oxide-mediated pulmonary artery function. In vitro cell culture studies demonstrate impaired fluid shear stress-induced cell alignment in human lung endothelial cells after siRNA-mediated ESAM knockdown.

Aims: Intra-aortic balloon pump (IABP) devices are commonly used in patients with heart failure related cardiogenic shock (HF-CS), including those with out-of-proportion right ventricular (RV) dysfunction. Pulmonary artery pulsatility index (PAPi) is a haemodynamic surrogate for RV performance. We aimed to assess short-term haemodynamic changes in patients with HF-CS following IABP support stratified by baseline PAPi., Methods and Results: This is a single-centre study of 67 consecutive patients with HF-CS who underwent IABP placement between 2020 and 2022. The primary aim was haemodynamic changes of specific variables on pulmonary artery catheter monitoring over 72 h following IABP placement. Secondary aims were clinically significant changes in diuretic regimens, changes in inotropes or vasopressors at 72 h following IABP, along with clinical outcomes. Prior to IABP placement, 57% of the total cohort (median age 59 years [48, 69], 31% female) had Society of Cardiovascular Angiography and Interventions Stage C HF-CS. Thirty-eight (56%) patients had a PAPi <2.0. Following 72 h of IABP support, the PAPi <2.0 group had an observed significant decrease in central venous pressure (CVP; 20 to 12 mmHg, P < 0.001) and mean pulmonary artery pressure (mPAP; 37.5 to 28.5 mmHg, P = 0.001), and an increase in PAPi (1 to 1.6, P = 0.001). No significant change in cardiac index (CI; 2 to 2.1 L/min/m 2 , P = 0.31) was observed. The PAPi ≥2.0 group (N = 29) had no observed significant change in CVP (10 to 8 mmHg, P = 0.47), or PAPi (2.6 to 2.8, P = 0.92), but there was a significant improvement in CI (1.9 to 2.5 L/min/m 2 , P = 0.004) along with reduction in mPA (37 to 29 mmHg, P = 0.03). The PAPi <2.0 group had a significant increase in diuretic requirement (52.6% vs. 20.7%, P = 0.01) and numerically greater addition of inotropes/vasopressors (47.3% vs. 34.4%, P = 0.07) compared with the PAPi ≥2.0 group at 72 h following IABP placement. Significantly more patients in the PAPi ≥2.0 group underwent left ventricular assist device (55.2% vs. 26.3%, P = 0.02), with no overall significant differences observed in escalation to veno-arterial extracorporeal membrane oxygenation, 30-day mortality, renal replacement therapy post-IABP, or rates of heart transplantation., Conclusions: IABP devices in those with HF-CS and low or abnormal PAPi may provide modest short-term haemodynamic benefits without significant improvement in CI, along with greater need for adjustment in medical therapeutics to achieve haemodynamic optimization., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Computational modeling indicated that pathological high shear stress (HSS; 100 dyn/cm 2 ) is generated in pulmonary arteries (PAs; 100-500 µm) in congenital heart defects causing PA hypertension (PAH) and in idiopathic PAH with occlusive vascular remodeling. Endothelial-to-mesenchymal transition (EndMT) is a feature of PAH. We hypothesize that HSS induces EndMT, contributing to the initiation and progression of PAH., Methods: We used the Ibidi perfusion system to determine whether HSS applied to human PA endothelial cells (ECs) induces EndMT when compared with physiological laminar shear stress (15 dyn/cm 2 ). The mechanism was investigated and targeted to prevent PAH in a mouse with HSS induced by an aortocaval shunt., Results: EndMT, a feature of PAH not previously attributed to HSS, was observed. HSS did not alter the induction of transcription factors KLF (Krüppel-like factor) 2/4, but an ERG (ETS-family transcription factor) was reduced, as were histone H3 lysine 27 acetylation enhancer-promoter peaks containing ERG motifs. Consequently, there was reduced interaction between ERG and KLF2/4, a feature important in tethering KLF and the chromatin remodeling complex to DNA. In PA ECs under laminar shear stress, reducing ERG by siRNA caused EndMT associated with decreased BMPR2 (bone morphogenetic protein receptor 2), CDH5 (cadherin 5), and PECAM1 (platelet and EC adhesion molecule 1) and increased SNAI1/2 (Snail/Slug) and ACTA2 (smooth muscle α2 actin). In PA ECs under HSS, transfection of ERG prevented EndMT. HSS was then induced in mice by an aortocaval shunt, causing progressive PAH over 8 weeks. An adeno-associated viral vector (AAV2-ESGHGYF) was used to replenish ERG selectively in PA ECs. Elevated PA pressure, EndMT, and vascular remodeling (muscularization of peripheral arteries) in the aortocaval shunt mice were markedly reduced by ERG delivery., Conclusions: Pathological HSS reduced lung EC ERG, resulting in EndMT and PAH. Agents that upregulate ERG could reverse HSS-mediated PAH and occlusive vascular remodeling resulting from high flow or narrowed PAs., Competing Interests: J. Körbelin is an inventor on, and received royalties for, a patent on the capsid-modified AAV-ESGHGYF vector, assigned to Boehringer Ingelheim International GmbH (“Peptides Having Specificity for the Lungs”; US20230181683A1). J.M. Engreitz is a consultant and equity holder in Martingale Labs, Inc, and has received materials from 10× Genomics unrelated to this study. The other authors report no conflicts.

Background: Right ventricular (RV) dysfunction in patients undergoing transcatheter aortic valve implantation (TAVI) for aortic stenosis (AS) has long been disregarded. We aimed to assess the predictive value of RV to pulmonary artery coupling (RV/PAc), defined as tricuspid annular plane systolic excursion to systolic pulmonary artery pressure, on mortality in different flow types of AS after TAVI., Methods: All patients undergoing TAVI for AS at our centre between 2018 and 2020 were assessed; 862 patients were analysed. The cohort was dichotomized using a ROC analysis (cut-off 0.512 mm/mmHg), into 429 patients with preserved and 433 patients with reduced RV/PAc., Results: Reduced RV/PAc was associated with male sex and a higher rate of comorbidities. Short-term VARC-3 endpoints and NYHA classes at follow-up were comparable. Reduced RV/PAc was associated with higher 2-year all-cause mortality (35.0% [30.3-39.3%] vs. 15.4% [11.9-18.7%], hazard ratio 2.5 [1.9-3.4], p < 0.001). Cardiovascular mortality was almost tripled. Results were consistent after statistical adjustment and in a multivariate model. Sub-analyses of AS flow types revealed lower RV/PAc in classical and paradoxical low-flow low-gradient AS, with the majority having reduced RV/PAc (74% and 59%). RV/PAc retained its predictive value in these subgroups., Conclusions: RV dysfunction defined by low RV/PAc is a strong mortality predictor after TAVI independent of flow group. It should be incorporated in future TAVI risk assessment., Competing Interests: Declarations. The study has been conducted in accordance to the ethical standards laid out in the 1964 Declaration of Helsinki and its amendments. All patients gave their informed consent to the inclusion in the study. Conflict of interest: JS received speaker honoraria from AstraZeneca. MO received speaker honoraria and travel compensations from Abbott Medical, AstraZeneca, Abiomed, Bayer vital, BIOTRONIK, Bristol-Myers Squibb, CytoSorbents, Daiichi Sankyo Germany, Edwards Lifesciences Services, and Sedana Medical. JH received research support Abbott Vascular and Edwards Lifesciences. DB received speaker honoraria from Abbott Vascular. SD received speaker honoraria from AstraZeneca. All other authors declare to not have any conflicts of interests., (© 2024. The Author(s).)

Background: Echocardiographic tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary arterial pressure (sPAP) ratio is a noninvasive surrogate for right ventricle (RV)-pulmonary arterial (PA) coupling. It has been related to outcome in patients with moderate to severe pulmonary hypertension (PH)., Research Question: Is RV-PA coupling of prognostic relevance in patients with suspected PH, but only normal or mildly elevated mean pulmonary arterial pressure (mPAP), and is it associated with impaired exercise capacity and exercise hemodynamics?, Study Design and Methods: Patients with mPAP of < 25 mm Hg who underwent echocardiography and exercise right heart catheterization in our PH clinic were analyzed retrospectively. Mild PH was defined as mPAP of 21 to 24 mm Hg and exercise PH (EPH) was defined as a mPAP to cardiac output (CO) slope of > 3 mm Hg/L/min. Multivariate analysis was performed to identify independent predictors for clinical worsening (CW), defined by disease-related hospitalization, transplantation, or death., Results: Two hundred thirty-seven patients (155 female with median age, 64 years [interquartile range (IQR), 54-73 years]; no PH: n = 147; mild PH: n = 90; EPH: n = 202) were included. During the observation time of 63 months (IQR, 29-104 months), 36 patients died and 126 clinical worsening events occurred. TAPSE to sPAP ratio was an age- and sex-independent predictor of mortality (hazard ratio [HR], 0.09; 95% CI, 0.01-0.62; P = .014) and clinical worsening (HR, 0.05; 95% CI, 0.35-0.78; P = .002). TAPSE to sPAP ratio also was correlated significantly to 6-min walk distance (r = 0.33; P < .001) and exercise hemodynamics (mPAP to CO slope: r ρ  = -0.56; P < .001). The best multivariate predictive model for clinical worsening in this population consisted of TAPSE to sPAP ratio (HR, 0.71; 95% CI, 0.53-0.95; P = .021), N-terminal pro-brain natriuretic peptide (HR, 1.15; 95% CI, 0.99-1.34; P = .065), and 6-min walk distance (HR, 0.998; 95% CI, 0.995-1.00; P = .042)., Interpretation: Our results indicate that in patients with suspected PH, but normal or only mildly elevated resting mPAP, TAPSE to sPAP ratio is an independent predictor of outcome. In addition, it is associated significantly with exercise capacity and exercise hemodynamics and may be a helpful tool in the prediction of future clinical worsening of this patient population., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: T. J. reports personal fees and nonfinancial support from Janssen, Ferrer, MSD, and Boehringer Ingelheim and personal fees from Roche, outside the submitted work; V. F. reports personal fees and nonfinancial support from Janssen and Chiesi, and nonfinancial support from Boehringer Ingelheim, AstraZeneca, MSD, and Ferrer, outside the submitted work; K. Z. reports grants from Max Kade Foundation, Cardiovascular Medical Research, and Education Fund, personal fees from MSD, Janssen, and Ferrer, and other from Ferrer, outside the submitted work; H. O. reports grants and personal fees from MSD and Iqvia, personal fees from Janssen, Ferrer, Mondial, and MedUpdate, grants and nonfinancial support from Ludwig Boltzmann Institute for Lung Vascular Research, outside the submitted work; G. K. reports grants, personal fees and nonfinancial support from Janssen, Boehringer-Ingelheim, MSD, AOP, and Chiesi, outside the submitted work, personal fees from Bayer, Ferrer, GSK, and AstraZeneca; P. D. reports personal fees from Actelion, Janssen, Ferrer, GSK, and Chiesi and nonfinancial support from Actelion, AstraZeneca, Boehringer Ingelheim, GSK, MSD, Novartis, Menarini, Ferrer and Chiesi, outside, the submitted work. None declared (A. A., N. J., A. E., M. R., K. T)., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Right ventricular (RV) hemodynamic performance determines the prognosis of patients with RV pressure overload. Using ultrafast ultrasound, natural wave velocity (NWV) induced by cardiac valve closure was proposed as a new surrogate to quantify myocardial stiffness., Objectives: This study aimed to assess RV NWV in rodent models and children with RV pressure overload vs control subjects and to correlate NWV with RV hemodynamic parameters., Methods: Six-week-old rats were randomized to pulmonary artery banding (n = 6), Sugen hypoxia-induced pulmonary arterial hypertension (n = 7), or sham (n = 6) groups. They underwent natural wave imaging, echocardiography, and hemodynamic assessment at baseline and 6 weeks postoperatively. The authors analyzed NWV after tricuspid and after pulmonary valve closure (TVC and PVC, respectively). Conductance catheters were used to generate pressure-volume loops. In parallel, the authors prospectively recruited 14 children (7 RV pressure overload; 7 age-matched control subjects) and compared RV NWV with echocardiographic and invasive hemodynamic parameters., Results: NWV significantly increased in RV pressure overload rat models (4.99 ± 0.27 m/s after TVC and 5.03 ± 0.32 m/s after PVC in pulmonary artery banding at 6 weeks; 4.89 ± 0.26 m/s after TVC and 4.84 ± 0.30 m/s after PVC in Sugen hypoxia at 6 weeks) compared with control subjects (2.83 ± 0.15 m/s after TVC and 2.72 ± 0.34 m/s after PVC). NWV after TVC correlated with both systolic and diastolic parameters including RV dP/dt max (r = 0.75; P < 0.005) and RV Ees (r = 0.81; P < 0.005). NWV after PVC correlated with both diastolic and systolic parameters and notably with RV end-diastolic pressure (r = 0.65; P < 0.01). In children, NWV after both right valves closure in RV pressure overload were higher than in healthy volunteers (P < 0.01). NWV after PVC correlated with RV E/E' (r = 0.81; P = 0.008) and with RV chamber stiffness (r = 0.97; P = 0.03)., Conclusions: Both RV early-systolic and early-diastolic myocardial stiffness show significant increase in response to pressure overload. Based on physiology and our observations, early-systolic myocardial stiffness may reflect contractility, whereas early-diastolic myocardial stiffness might be indicative of diastolic function., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Pulmonary hypertension (PH) is associated with morbidity and mortality in patients with interstitial lung disease (ILD). Several prediction models have been proposed to predict PH in ILD patients. We sought to discern how previously described prediction models perform in predicting PH in patients with ILD., Methods: Patients with ILD who completed a baseline right heart catheterization, from Inova Fairfax Hospital, Northwestern Memorial Hospital, and Asan Medical Center in Korea were enrolled. The performance of various prediction models (FORD model, the FORD calculator, the PH-ILD Detection tool, and the mean pulmonary artery pressure prediction model) were assessed using receiver operating characteristic (ROC) curves and area under the receiver operating characteristic curve (AUROC). There were four definitions of pulmonary hypertension against which the models were evaluated., Results: There were a total of 192 patients with ILD, of whom 32.8% (n = 63/192) met the modified 5th world symposium on PH definition of precapillary PH. Among the models assessed, the FORD calculator had an AUROC (0.733) that was marginally highest. Subgroup analysis revealed that the FORD index had the highest AUROC (0.817) in patients with idiopathic pulmonary fibrosis, while the FORD calculator had the highest AUROC (0.751) in patients with non-IPF ILD., Conclusion: The FORD model can be used to predict group 3 PH in both IPF patients and non-IPF ILD patients. It could serve as a tool for ILD patient selection for right heart catheterization as well as an enrichment tool for clinical trials targeting the pulmonary vasculature., Competing Interests: Declarations. Conflict of interest: SDN is a consultant and is on the speakers bureau for both Boehringer-Ingelheim and United Therapeutics. He has also received research funding from both Companies. He is also on the steering committee for IPF studies by Tvardi and Avalyn Pharma. CSK is a speaker for and has served on advisory boards for United Therapeutics and served on advisory boards for Merck and Jannsen. RT served on advisory boards for TFF and is a speaker for Boehringer Ingelheim. None of the other investigators have any conflicts of interest with regards to this study., (© 2025. The Author(s).)

The initiation of sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment was shown to reduce pulmonary artery pressure (PAP) in New York Heart Association (NYHA) class III heart failure (HF) patients with an implanted PAP sensor. We aimed to investigate the impact of SGLT2-I initiation on pulmonary vascular resistance (PVR), pulmonary capillary wedge pressure (PCWP), pulmonary arterial capacitance (PAC), and right ventricle (RV) to PA (RV-PA) coupling in a pilot cohort of HF with preserved/mildly reduced ejection fraction (HFpEF/HFmrEF) patients and whether PVR and PCWP can be serially calculated non-invasively using PAP sensor data during follow-up., Methods: Right heart catheterization parameters (PVR, PCWP, and PAC) were obtained at sensor implantation and echocardiographic assessments (E/E', RV-PA coupling, and RV cardiac output) were made at baseline and every 3 months. SGLT2 inhibition was initiated after 3 months of telemedical care. Three methods for calculating PVR and PCWP were compared using Bland-Altman plots and Spearman's correlation., Results: In 13 HF patients (mean age 77 ± 4 years), there were no significant changes in PAP, PVR, PCWP, RV-PA coupling, or PAC over 9 months (all p -values > 0.05), including after SGLT2-I initiation. PVR values were closely correlated across the three methods (PVR New and PVR New Tedford (r = 0.614, p < 0.001), PVR Echo and PVR New Tedford (r = 0.446, p = 0.006), and PVR Echo and PVR New (r = 0.394, p = 0.016)), but PCWP methods lacked reliable association (PCWP Echo and PCWP New (r = 0.180, p = 0.332)., Conclusions: No changes in cardiopulmonary hemodynamics were detected after hemodynamic telemonitoring either prior to or following SGLT2-I initiation. Different PVR assessment methods yielded comparable results, whereas PCWP methods were not associated with each other. Further investigations with larger cohorts including repeated right heart catheterization are planned.

Objective: Impaired right ventricular (RV)-pulmonary arterial (PA) coupling, calculated by measuring the tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP), can be used as an early indicator of right ventricular dysfunction (RVD) in patients with heart failure with a reduced ejection fraction (HFrEF). Patients suffering from HFrEF experience improvements in left ventricular (LV) function through the administration of sacubitril/valsartan therapy. In addition, the albumin-bilirubin (ALBI) score was associated with the fluid overload status and adverse clinical outcomes in patients with heart failure. This study aimed to assess whether angiotensin receptor-neprilysin inhibitor (ARNI) affects the TAPSE /PASP in patients with HFrEF, and whether there is a correlation between changes in the ALBI score and ARNI treatment., Methods: A retrospective observational study was conducted on 305 patients with HFrEF and RVD who were hospitalized between June 2020 and December 2021. One year after treatment, laboratory test results, ALBI score, transthoracic echocardiography (TTE), New York Heart Association classification, Minnesota Living with Heart Failure Questionnaire scores and changes in relevant variables were reevaluated., Results: Compared to before sacubitril/valsartan treatment, the ALBI was found to be significantly reduced after one year of follow-up (-2.42 ± 0.37 vs. -2.51 ± 0.32, p < 0.001). Additionally, A significant improvement was demonstrated in the following echocardiography parameters assessing RV function after 1 year of treatment with sacubitril/valsartan: TAPSE (15 ± 1 vs. 18 ± 2 mm, p < 0.001), PASP (45 ± 8 vs. 40 ± 9 mmHg, p < 0.001), pulmonary artery diastolic pressure (PADP) (22 ± 4 vs. 19 ± 4 mmHg, p < 0.001), RV-PA coupling (0.35 ± 0.08 vs. 0.48 ± 0.12, p < 0.001), and RV s'(8.7 ± 2.2 vs. 9.5 ± 2.6 cm/s, p < 0.001). Multivariate analysis showed that the improvement of RV-PA coupling was associated with baseline PASP (r: -0.45, p < 0.001) and PADP (r: -0.45, p < 0.001)., Conclusions: Sacubitril/valsartan improves RV-PA conjugation in patients with RVD and HFrEF, and has a positive impact on the ALBI score by improving liver function in patients with HFrEF., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Aims: This study explores the clinical application of lung ultrasound scoring(LUS) combined with echocardiography in assessing right heart function in patients undergoing maintenance hemodialysis(MHD) and those with elevated pulmonary artery systolic pressure(PASP), as well as the correlation between LUS and right ventricular(RV) function., Methods: Eighty five patients who underwent MHD combined with elevated PASP, at the First Central Hospital of Baoding City were selected. Divided into three groups based on PASP, and perform echocardiography and lung ultrasound examinations. Compare the right heart function parameters and LUS among the three groups. Using Pearson correlation analysis to examine the relationship between LUS and right heart function parameters. Perform multivariate logistic regression analysis to identify predictive factors for RV systolic dysfunction. A receiver operating characteristic (ROC) curve and calculate the area under the curve(AUC) to compare the diagnostic efficacy of various parameters., Results: Patients undergoing MHD exhibited varying degrees of reduced left ventricular (LV) and RV systolic function. Correlation analysis revealed that Tricuspid annular plane systolic excursion (TAPSE), Fractional area change (FAC), and Tricuspid annular peak systolic velocity(S') were negatively correlated with LUS(r = -0.81, -0.86, -0.69), while Right ventricular free wall longitudinal strain(RVFWLS) was positively correlated with LUS (r = 0.85, P < 0.05). The ROC curve indicated that the combination of LUS and RVFWLS had the highest area under the curve (AUC = 0.963), followed by the combination of LUS and TAPSE (AUC = 0.847), LUS and FAC(AUC = 0.937), and LUS combined with S'(AUC = 0.940). All combinations demonstrated higher AUC values than the individual indicators., Conclusions: Patients with MHD combined with elevated PASP, the RV function parameters are associated with LUS, which may serve as a valuable reference indicator for assessing RV function. The use of LUS to evaluate right heart function in these patients, alongside traditional two-dimensional parameters, holds significant clinical value., Competing Interests: Declarations. Ethics approval and consent to participate: Informed consent was obtained from all subjects and all methods were carried out in accordance with relevant guidelines and regulation. All subjects provided written informed consent prior to participation in the study. This study protocol was approved by the Ethics Committee of the Baoding No.1 Central Hospital ([2023]123). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

This study introduced a novel dual fixation method for the pulmonary vasculature and lung tissue in pulmonary hypertension (PH) rats, addressing the limitations of traditional fixation methods that failed to accurately preserve the in vivo status of pulmonary vascular morphology. The modified method involved a dual fixation process, combining individualized ventilation support and vascular perfusion to simulate the respiratory motion, pulmonary artery pressure and right ventricular output of the rat under in vivo conditions. Utilizing a monocrotaline-induced PH rat model, this study compared the dual fixation with the traditional immersion fixation, focusing on the quantitative assessment of alveolar expansion degree, capillary patency, endothelial cell quantity and wall thickness of pulmonary vein and artery. The results demonstrated that the dual fixation is superior in maintaining the authenticity and integrity of lung tissue and more sensitive in the evaluation of pulmonary artery hypertrophy, providing a more reliable representation of pulmonary vascular remodeling associated with PH., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: In developing countries evidences regarding pulmonary hypertension (PH) in rheumatic heart disease (RHD) patients are lacking, despite being responsible for significant morbidity and mortality. As a result, identifying the factors that influence PH is crucial to improve the quality of care., Objective: To determine prevalence of pulmonary hypertension and its associated factors among rheumatic heart disease patients at the public hospitals of Bahir Dar city, Ethiopia., Methods: An institution based prospective cross-sectional study was conducted among RHD patients who had follow up at the two public hospitals of Bahir Dar city from January 2022 to December 2023. It involved 310 patients selected by systematic random sampling technique. Pretested, structured, and interviewer-administered questionnaires were used to collect sociodemographic and diseases related parameters.Transthoracic echocardiography by cardiologist was used to assess PH. Data were entered using Epidata Manager version 4.6 and analyzed using SPSS version 27. Multivariate logistic regression analysis was used to identify determinants of PH, considering with a p-value of < 0.05 as statically significant, with a 95% confidence interval., Results: The mean systolic pulmonary arterial pressure (sPAP) of the participants was 50.2 mmHg [SD ± 25.0 mmHg]. The prevalence of PH among RHD patients was 56.5% (95% CI 50.9 - 61.9) from which 51.4% had severe PH. Severe mitral valve stenosis (AOR 7.8, 95% CI 2.4-25.7), duration of illness ≥ 3 years (AOR 7.7, 95% CI 2.1-28.5), and diuretics use (AOR 5.6, 95% CI 2.2-14.3) were factors associated with PH. In contrast, valvular intervention (AOR 0.06, 95% CI 0.01-0.29) and LVEF ≥ 50% (AOR 0.14, 95% CI 0.02-0.81) were found to be protective factors., Conclusions: The prevalence of PH among RHD patients in Ethiopia is high and it's associated with delayed presentation & complications. Special attention should be paid to early surgical or percutaneous valvular intervention for those who have indication, before they develop permanent cardiac remodeling and LVFE become reduced. As a result, access to valvular intervention need to be addressed to improve PH related morbidity & mortality among RHD patients in Ethiopia., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted according to declarations of Helsinki. Ethical clearance was approved by the Research Ethical Review Board of College of Medicine and Health Sciences, Bahir Dar university (protocol number 802/2023). Written informed consent was obtained from the participants including legal guardians and or parents, and patient data confidentiality was respected at all levels from patient interview, chart retrieving and data analysis which was handled by the investigators. During the data collection process, those patients who were found to have pulmonary hypertension were linked to the treating physicians for any farther management. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Pulmonary artery smooth muscle cell (PASMC) dysfunction is the central pathogenic mechanism in pulmonary hypertension (PH). This study explored the mechanism of action of RUNX1, a potential therapeutic target for PH, in PASMCs. A PH mouse model was used to investigate the impacts of RUNX1 knockdown on hemodynamics, right ventricular hypertrophy (RVH), and pulmonary artery remodeling (hematoxylin-eosin [H&E] staining). Isolated PASMCs were transfected with RUNX1- or chromobox 5 (CBX5)-related vectors and then subjected to cell function assays. Immunoprecipitation was used to detect molecular binding and ubiquitination. RUNX1 knockdown reduced right ventricular systolic pressure (RVSP), RVH, and pulmonary artery remodeling in mice with PH. Knockdown of RUNX1 or CBX5 suppressed proliferation, invasion, and migration and stimulated apoptosis in PASMCs under hypoxia. RUNX1 enhanced ubiquitin-specific protease 15 (USP15) promoter activity. USP15 bound to CBX5 and reduced CBX5 ubiquitination, thereby promoting CBX5 expression. CBX5 overexpression promoted the proliferation and movement of hypoxic PASMCs with reduced RUNX1 expression and decreased their apoptosis. In conclusion, RUNX1 knockdown inhibits USP15 transcription to promote the ubiquitination and degradation of CBX5, thereby alleviating PH in mice and reducing hypoxia-induced PASMC dysfunction.

Background: Pulmonary endarterectomy (PEA) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH), while balloon pulmonary angioplasty (BPA) is an alternative for inoperable patients. We aimed to compare right ventricular (RV) remodelling and late survival after PEA and BPA., Methods: In this prospective observational cohort study, we performed echocardiography at baseline and follow-up in patients with CTEPH treated with PEA (n=54) or BPA (n=44) between 2011 and 2022., Results: Follow-up echocardiography was performed at 5 months (IQR 4-7) after PEA and 3 months (IQR 2-4) after the last BPA. Both groups showed significant improvements in left ventricular end-systolic eccentricity index, RV basal diameter and RV fractional area change (RV FAC). Tricuspid regurgitation pressure decreased by 26±18 mm Hg after PEA and 13±21 mm Hg after BPA (p=0.02 for between-group difference). Tricuspid annular systolic excursion (TAPSE) decreased by 4±5 mm after PEA but increased by 1±4 mm after BPA (p<0.001). The TAPSE/systolic pulmonary artery pressure ratio improved similarly in both groups. Five-year survival was 96% (95% CI 86% to 99%) for PEA and 79% (95% CI 61% to 89%) for BPA (p=0.25). Change in RV FAC was an independent predictor of survival (HR 0.9, 95% CI 0.82 to 0.99, p=0.03)., Conclusions: Both PEA and BPA led to significant RV reverse remodelling, with no clear evidence of a difference in survival rates. Improvement in RV function, particularly RV FAC, was associated with better outcomes, highlighting the importance of RV recovery in CTEPH treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Introduction Acute heart failure (AHF) is a life-threatening condition that requires swift diagnosis and tailored management to enhance patient outcomes. In the pursuit of more precise prognostic indicators, Tricuspid Annular Plane Systolic Excursion (TAPSE) and Pulmonary Arterial Systolic Pressure (PASP) have emerged as potential significant advancements. The TAPSE/PASP ratio, a novel parameter, has recently gained attention as a promising predictor of outcomes in acute heart failure., Aim: This study delves into the significance of TAPSE/PASP as a predictive tool, shedding light on its potential to revolutionize the landscape of AHF management., Methods: We included 152 patients with AHF. Echocardiographic evaluation for left ventricle systolic and diastolic function was performed at the time of admission. RV functions were evaluated by calculating the following (TAPSE, PASP, TAPSE/PASP ratio). Data were analyzed to find the predictors of mortality and/or rehospitalization., Results: The TAPSE/PASP ratio emerged as a significant independent predictor of clinical outcomes in AHF patients (HR=2.6; 95%CI: 1.04-6.47; p=0.04). Furthermore, it was the sole predictor of rehospitalization for AHF (HR=3.97; 95%CI: 1.38-11.40; p=0.01). It also independently predicted all-cause mortality in AHF, with an HR of 2.73 (95% CI: 1.25-9.12; p=0.03). When evaluating its predictive accuracy, the TAPSE/PASP ratio with a cutoff value <0.35 mm/mmHg demonstrated a sensitivity of 65%, specificity of 70%, and an area under the receiver operating characteristic curve of 0.70 for forecasting adverse outcomes., Conclusion: The non-invasive TAPSE/PASP ratio is an independent predictor of mortality and /or rehospitalization in patients with acute heart failure.

Purpose: This study aims to determine the outcomes of maintaining antegrade pulmonary blood flow (APBF) during the bidirectional cavopulmonary shunt (BCPS) procedure in patients with single ventricle physiology undergoing staged palliative surgeries., Methods: A systematic search of electronic databases was conducted and focused on studies comparing pulsatile BCPS (with APBF) with non-pulsatile BCPS (without APBF). Outcomes were categorized into early (post-BCPS) and late (pre-Fontan). Data were analyzed using Mantel-Haenszel random effects model with odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs). The study protocol was registered in the PROSPERO (CRD42024586369)., Results: A total of 17 studies with 2504 patients were included. There was no significant difference in 30-day mortality (OR 1.11, 95% CI: 0.61-2.04, p = 0.73), but pulsatile BCPS led to a higher rate of prolonged chest drainage (OR 2.45, 95% CI: 1.43-4.20, p <0.001). Pulsatile BCPS resulted in significantly higher SaO 2 in both post-BCPS (MD 3.33%, 95% CI: 2.70-3.97, p <0.001) and pre-Fontan (MD 2.91%, 95% CI: 2.51-3.31, p <0.001). The Nakata index was also higher in the pulsatile group (MD 30.67, 95% CI: 16.68-44.65, p <0.001)., Conclusions: Pulsatile BCPS can optimize pre-Fontan hemodynamics by improving oxygenation and pulmonary artery development. However, the increased risk of prolonged chest drainage requires careful patient selection and monitoring.