Current in vivo imaging techniques for cardiopulmonary vascular evaluation in Sprague-Dawley (SD) rats face limitations, including structural disruption, inadequate contrast filling, and invasiveness. This study develope...Current in vivo imaging techniques for cardiopulmonary vascular evaluation in Sprague-Dawley (SD) rats face limitations, including structural disruption, inadequate contrast filling, and invasiveness. This study developed a reliable, minimally invasive computed tomography angiography (CTA) technique via jugular vein catheterization for enhanced cardiopulmonary vascular imaging in live SD rats. Jugular vein catheterization was performed in 22 anesthetized healthy male SD rats (320-480 g), followed by dual-source CT angiography with iopamidol contrast. Three-dimensional vascular reconstruction was performed, and pulmonary artery width alongside left and right ventricular diameters was measured. CT-derived measurements were compared with ultrasound data using Bland-Altman analysis. CTA achieved clear visualization of pulmonary arteries, cardiac chambers, and aortic structures, demonstrating complete contrast filling and anatomical detail. Three-dimensional reconstructions precisely delineated mediastinal and vascular relationships. Pulmonary artery widths measured by CT and ultrasound showed strong agreement ( > 0.05), validating reliability. Jugular catheterization enabled stable contrast delivery with minimal trauma. Jugular vein catheterization combined with CT angiography provides a safe, accurate, and minimally invasive method for in vivo cardiopulmonary vascular imaging in SD rats. This technique offers high anatomical resolution, compatibility with hemodynamic assessments, and reduced experimental trauma, establishing this approach as a valuable tool for cardiopulmonary disease model research. CT-derived measurements were compared with ultrasound data using Bland-Altman analysis. CTA achieved clear visualization of cardiac chambers and pulmonary arteries, demonstrating complete contrast filling and anatomical detail. Three-dimensional reconstructions precisely delineated mediastinal and vascular relationships. Pulmonary artery widths measured by CT and ultrasound showed strong agreement ( > 0.05), validating reliability. Jugular catheterization enabled stable contrast delivery with minimal trauma. Jugular vein catheterization combined with CT angiography provides a safe, accurate, and minimally invasive method for in vivo cardiopulmonary vascular imaging in SD rats. This technique offers high anatomical resolution, compatibility with hemodynamic assessments, and reduced experimental trauma, establishing this approach as a valuable tool for cardiopulmonary disease model research.
This letter to the editor revisits the origins of high-dose calcium channel blocker use in pulmonary arterial hypertension (PAH) in light of bedside vasoreactivity testing, reaffirming its present-day relevance for a sel...This letter to the editor revisits the origins of high-dose calcium channel blocker use in pulmonary arterial hypertension (PAH) in light of bedside vasoreactivity testing, reaffirming its present-day relevance for a selected subgroup. Integrating historical insights with modern tools, the authors highlight: the "responder" phenotype as an expression of precision medicine; ion channels as pathobiological targets; the value of real-world registries and benchmarks for high-quality care pathways; attention to special contexts (interstitial lung disease in connective-tissue diseases, and sex differences in diastolic dysfunction/HFpEF). In sum, we propose a personalized approach that pairs careful high-dose titration in appropriate candidates with molecular phenotyping and standardized follow-up.
Platelets have emerged as immune-inflammatory cells that may contribute to the pathogenesis and prognosis of pulmonary arterial hypertension (PAH), although their clinical relevance remains uncertain. We retrospectively...Platelets have emerged as immune-inflammatory cells that may contribute to the pathogenesis and prognosis of pulmonary arterial hypertension (PAH), although their clinical relevance remains uncertain. We retrospectively evaluated platelet indices in 243 patients with PAH from a tertiary referral center and compared them with 50 normopressoric controls undergoing right heart catheterization. Platelet count, mean platelet volume (MPV), and survival outcomes were analyzed. PAH patients exhibited significantly lower platelet counts compared with controls (203,666 ± 90,466 vs. 246,025 ± 126,778/µL; < 0.001). MPV was also reduced in idiopathic PAH compared with controls (9.8 ± 1.68 vs. 10.44 ± 1.25 fL; < 0.05). Survival analysis demonstrated that PAH patients with platelet counts within the normal range (150,000-450,000/µL) had significantly better outcomes than those with thrombocytopenia ( < 0.05). These findings suggest that alterations in platelet indices may reflect disease severity and prognosis in PAH. While exploratory and subject to potential confounders such as connective tissue disease, the results reinforce the potential role of platelets as biomarkers in pulmonary vascular disease and highlight the need for further mechanistic and longitudinal studies.
Acute chest syndrome in sickle cell disease (SCD) carries high morbidity and mortality, with up to 15% of patients requiring invasive mechanical ventilation. However, the rates and mechanisms of ventilator-induced lung i...Acute chest syndrome in sickle cell disease (SCD) carries high morbidity and mortality, with up to 15% of patients requiring invasive mechanical ventilation. However, the rates and mechanisms of ventilator-induced lung injury (VILI) in SCD remain poorly understood. We hypothesized individuals with SCD are protected from VILI in a caveolin-1 (Cav-1) dependent manner. SCD mice and control littermates underwent either spontaneous tidal breathing or high tidal volume mechanical ventilation for 4 h (VILI model), or received intratracheal -derived lipopolysaccharide (LPS) or sterile phosphate-buffered saline and recovered for 16 h (LPS model). Bronchoalveolar lavage (BAL) samples were analyzed for inflammatory cytokine profiles and lung tissues were used for histology and Western blot. SCD mice were protected from VILI but were more susceptible to LPS-induced lung injury, as evidenced by higher BAL fluid total protein concentrations, polymorphonuclear cell infiltration and total cell count. Inflammatory cytokine profiles differed significantly in BAL fluid: IL-6, KC and MIP-2 levels were attenuated in the SCD-VILI model, while TNF-α levels were significantly increased after LPS exposure. Cav-1 expression was reduced at baseline in SCD mice and further decreased after exposure to VILI when compared to control animals. Phosphorylated Cav-1 expression increased, leading to depletion of total Cav-1 in the SCD-VILI model. These data suggest SCD mice are protected from VILI, but not LPS-induced lung injury. These differences appear to be mediated by distinct inflammatory cytokine profiles and expression of Cav-1. Further studies are needed to explore differences in lung injury patterns in patients with SCD.
Using lung immunohistochemistry and stereology, platelets were found to accumulate and co-localize with leukocytes, particularly monocytes, within the mural and adventitial space of remodeled vessels of patients with pul...Using lung immunohistochemistry and stereology, platelets were found to accumulate and co-localize with leukocytes, particularly monocytes, within the mural and adventitial space of remodeled vessels of patients with pulmonary arterial hypertension. The presumed signaling between these cell types invites further studies into the role of platelet-monocyte aggregates in pulmonary hypertension.
Pulmonary Hypertension (PH) is a critical disease characterized by increased pulmonary arterial pressure and the development of vascular resistance, which can lead to fatal outcomes if left untreated. Cardiovascular and...Pulmonary Hypertension (PH) is a critical disease characterized by increased pulmonary arterial pressure and the development of vascular resistance, which can lead to fatal outcomes if left untreated. Cardiovascular and Respiratory Nurses (CRNs) play a significant role in the management of PH; however, there is a lack of sufficient studies examining their role competence. This study aimed to investigate the role competencies of CRNs regarding PH. This cross-sectional and descriptive study was conducted at Istanbul Yedikule Chest Diseases Hospital with the participation of 85 CRNs. Data were collected using a personal characteristics form and Pulmonary Hypertension Inventory of the Rol Competence (PHIRC). Data analysis was performed using Mann-Whitney U, Kruskal-Wallis, Chi-Square, and post hoc Bonferroni tests. Among the nurses, 76.5% held a bachelor's degree, and 78.9% were working in clinical settings. The CRNs scored above mean level in all sub-dimensions of the PHIRC. The moderate scores for knowledge and symptom management, risk factors awareness of CRNs, and symptom identification, and the total score were 12.75 ± 1.92, 11.52 ± 1.91, 10.34 ± 2.48, and 34.67 ± 5, respectively. A significant increase in the role competence was observed as the frequency of encountering PH patients increased ( < 0.05). The findings of this study indicate that CRNs had above-moderate role competence regarding PH management. Additionally, nurses who frequently encountered PH patients demonstrated higher role competence, which may be related to maintaining active knowledge. Nurses in their first year of practice had higher knowledge levels, highlighting the necessity of periodic and high-quality training programs and courses on PH.
The natural history of late-onset pulmonary arterial hypertension (PAH) with features of venous/capillary involvement and the associations with rare variants in PAH genes are not well known. We report a case of a female...The natural history of late-onset pulmonary arterial hypertension (PAH) with features of venous/capillary involvement and the associations with rare variants in PAH genes are not well known. We report a case of a female patient who developed severe PAH at the age of 70. Two years before, lung histology was obtained showing features of pulmonary veno-occlusive disease. Genetic testing revealed that the patient was harbouring two rare genetic variants in the and genes. She received a triple combination therapy alongside diuretics and survived remarkable 8 years after the PAH diagnosis.
Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension that is caused by persistent obstruction of the pulmonary arteries by organized thrombi and associated microvascular disease. Pulm...Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension that is caused by persistent obstruction of the pulmonary arteries by organized thrombi and associated microvascular disease. Pulmonary endarterectomy (PEA) is the gold standard treatment, but the extent of small vessel remodeling, which strongly influences treatment outcomes, remains difficult to quantify pre-operatively. We developed a multiscale, structure-based model of the pulmonary circulation using patient-specific vascular geometries from CT pulmonary angiography (CTPA) and haemodynamic data from right heart catheterization (RHC). Eleven CTEPH patients were included. The model estimated individual remodeling burden by fitting simulated to measured preoperative mean pulmonary artery pressure (mPAP). PEA was simulated by removing flow obstructions to predict Postoperative mPAP and pulmonary vascular resistance (PVR), both under pre- and post-PEA boundary conditions. Model predictions of post-PEA mPAP and PVR were in reasonable agreement with measured outcomes, especially when Postoperative boundary conditions were applied. Predicted changes in mPAP (∆mPAP) strongly correlated with clinical values ( = 0.81, = 0.002), improving further with post-PEA flow parameters ( = 0.84, = 0.001). The model captured variable haemodynamic responses to PEA, even among patients with similar Postoperative mPAP. This preliminary investigation demonstrates the feasibility of personalized computational modeling to non-invasively estimate the extent of microvascular disease and simulate postsurgical haemodynamic outcomes in CTEPH. The findings support the potential for this approach to serve as a clinical decision-making tool, with future validation in larger cohorts and integration of spatial remodeling and longitudinal data.
Treatment options for acute pulmonary embolism (PE) have evolved rapidly, with an increasing number of interventional options, necessitating interhospital transfer for consideration of advanced therapies and optimal care...Treatment options for acute pulmonary embolism (PE) have evolved rapidly, with an increasing number of interventional options, necessitating interhospital transfer for consideration of advanced therapies and optimal care. Utilizing the National PERT Consortium database, this study analyzed 12,346 patients from 35 institutions between October 16, 2015 and June 1, 2024. Patients were categorized as directly presenting to a PERT hospital or transferred from a referring hospital. Demographics, clinical presentations, treatments, and outcomes were compared. Multivariable logistic regression was used to evaluate the association between transfer status and outcomes. Transferred patients ( = 3277) were younger, more frequently White, more often obese, and had lower malignancy rates. They were more likely to be classified as high-risk PE (16.7% vs. 13.8%, < 0.01) and intermediate-high risk PE (55.9% vs. 54.3%, < 0.01). Transferred patients more frequently received advanced therapies, including ECMO (2.8% vs. 1.1%, < 0.01), surgical embolectomy (2.0% vs. 0.8%, < 0.01), systemic thrombolysis (5.3% vs. 3.8%, < 0.001), and catheter-based interventions (32.3% vs. 17.1%, < 0.01). After adjustment, transfer was associated with lower odds of 30-day mortality (OR 0.82, 95% CI 0.69-0.98), 1-year mortality (OR 0.77, 95% CI 0.67-0.89), and in-hospital mortality (OR 0.78, 95% CI 0.65-0.97), with no significant difference in major bleeding risk. Subgroup analysis showed mortality benefits were most evident among intermediate-low and high-risk patients. In conclusion, acute PE patients transferred to PERT hospitals were more likely to receive advanced therapies and had improved short- and long-term survival, with no increase in bleeding risk, despite presenting with higher clinical severity.
Mechanical ventilation (MV), though life-saving in acute respiratory distress syndrome (ARDS), can cause ventilator-induced lung injury (VILI). MicroRNA-24 (miR-24) has been implicated in regulating inflammation and apop...Mechanical ventilation (MV), though life-saving in acute respiratory distress syndrome (ARDS), can cause ventilator-induced lung injury (VILI). MicroRNA-24 (miR-24) has been implicated in regulating inflammation and apoptosis, but its role in VILI remains unexplored. Therefore, our study aimed to explore the role of mechanism of miR-24 in VILI. MiR-24 expression was analyzed in MV-induced ARDS rat models (GSE57223), plasma from ARDS patients, and cyclic stretch (CS)-treated alveolar epithelial cells. Functional studies included intratracheal delivery of miR-24-agomir in rats with VILI and transfection of miR-24 mimic in CS-exposed cells. Inflammatory cytokines, oxidative stress markers, apoptosis, and mitochondrial dysfunction were assessed using ELISA, RT-qPCR, TUNEL, JC-1 staining, and ATP assays. BOK was identified as a target of miR-24 via bioinformatics, luciferase reporter, and RNA pull-down assays. Rescue experiments using BOK overexpression vectors (pcDNA3.1/BOK) were conducted in both models to confirm functional interaction. MiR-24 was significantly downregulated in ARDS patients and VILI models and positively correlated with oxygenation index. Overexpression of miR-24 attenuated MV- and CS-induced inflammation, oxidative damage, and mitochondrial apoptosis dysfunction. BOK was confirmed as a direct target of miR-24; its expression was upregulated in ARDS and VILI and inversely correlated with miR-24 levels. Silencing of BOK attenuated MV-induced inflammation, oxidative damage, and apoptosis in rats. Importantly, BOK overexpression reversed the protective effects of miR-24 both in vivo and in vitro, confirming its role as a key downstream effector. Receiver operating characteristic (ROC) analysis showed that miR-24 had good diagnostic potential (AUC = 0.834). Overall, MiR-24 protects against MV-induced lung injury by targeting BOK and modulating key injury pathways. The miR-24/BOK axis offers a promising therapeutic avenue for ARDS-associated VILI.
Pulmonary perfusion assessment is essential for the management of chronic thromboembolic pulmonary hypertension (CTEPH). Lung perfusion scintigraphy and contrast-enhanced CT are occasionally limited by the need for radio...Pulmonary perfusion assessment is essential for the management of chronic thromboembolic pulmonary hypertension (CTEPH). Lung perfusion scintigraphy and contrast-enhanced CT are occasionally limited by the need for radionuclides or allergy to the contrast agents. Dynamic chest radiography (DCR) can evaluate the pulmonary perfusion non-invasively using conventional X-ray technology. We validated pulmonary perfusion measurements using DCR by comparing them with those obtained using perfusion scintigraphy in CTEPH. Thirty-three patients with CTEPH who underwent both DCR and lung perfusion scintigraphy within 1-month interval from December 2019 to December 2022 were included. DCR was performed with patients in both standing and supine positions. To assess lung perfusion, each lung was divided into six fields (right and left; upper, middle, and lower). The blood flow rates per field were quantified by using analysis software as 100% of the sum of the six sites. The correlation between blood flow rates of each area in DCR and perfusion scintigraphy was evaluated using intraclass correlation coefficients (ICC). DCR showed a strong correlation with pulmonary perfusion scintigraphy in both standing (ICC(2,1) = 0.86; confidence interval [CI], 0.81-0.89) and supine (ICC(2,1) = 0.82; CI, 0.77-0.86) positions. When analyzed by region, all regions except the left lower lung showed significant correlations with perfusion scintigraphy findings. Intra- and intra-inspector reliabilities at both positions were excellent. The quantitative assessment of lung perfusion using DCR is reliable in patients with CTEPH. However, perfusion in the left lower lung was underestimated using DCR.
DeSanti E, Jankowich M, Choudhary G
… +14 more, Morrison A, Stanley ZK, Garshick E, Moy ML, Kang M, Wongtrakool C, Sadikot RT, Dempsey EC, Griffith M, Ha DM, Schmid CH, Goldstein RH, Rounds S, BETTER COPD‐PH Study Group
Dyspnea, a debilitating symptom of COPD, worsens health-related quality of life (HRQL), reduces daily physical activity, increases health care utilization, and is more closely associated with survival than airflow limita...Dyspnea, a debilitating symptom of COPD, worsens health-related quality of life (HRQL), reduces daily physical activity, increases health care utilization, and is more closely associated with survival than airflow limitation. Thus, having treatments that reduce dyspnea in COPD is important. Pulmonary hypertension (PH) is a common complication of COPD that is associated with severe dyspnea, more frequent COPD exacerbations, and increased mortality. Multiple causes of PH, including a reduction in bioavailable vasodilator nitric oxide (NO), are associated with COPD (COPD-PH). Phosphodiesterase type-5 inhibitor (PDE5i) therapy restores NO signaling and improves hemodynamics and dyspnea in patients with Group 1 Pulmonary Arterial Hypertension, but has not been proven effective in COPD-PH. In a prior study (ClinicalTrials. gov identifier: NCT01862536), we investigated effects of 12 months of oral PDE5i therapy with tadalafil on 6-min walk distance (6MWD) in a multi-center, randomized, placebo-controlled trial funded by the Department of Veterans Affairs. While tadalafil did not change 6MWD at 12 months, the treatment group experienced clinically meaningful improvements in patient-reported dyspnea and HRQL at 6 months. Because of the importance of mitigating dyspnea in COPD-PH, we developed a new study protocol examining the effect of PDE-5i therapy in COPD-PH, with a reduction in dyspnea the primary outcome. In the current study (NCT05937854), we will conduct a prospective, randomized, double-blind, multi-center clinical trial to evaluate the effects of 6 months of maximally tolerated therapy with tadalafil (target dose 40 mg/day) versus placebo on dyspnea, as measured by University of California San Diego Shortness of Breath Questionnaire.
Geller A, Martinez Manzano JM, Kosak Lopez E
… +10 more, Wattanachayakul P, Malin J, Leguizamon R, John TA, Khan R, McLaren I, Prendergast A, Jarrett SA, Lo KB, Witzke C
Identifying noninvasive measures to assess intravascular volume status and risk stratify patients with pulmonary hypertension (PH) and chronic kidney disease (CKD) is needed. We assessed the predictive value of estimated...Identifying noninvasive measures to assess intravascular volume status and risk stratify patients with pulmonary hypertension (PH) and chronic kidney disease (CKD) is needed. We assessed the predictive value of estimated plasma volume status (ePVS) using the Strauss-derived Duarte formula in PH-CKD patients. This single-center retrospective cohort analysis included patients with PH and CKD Stage 3b (CKD3b), Stage 4 (CKD4), or Stage 5 (CKD5) who underwent right heart catheterization from 2018 to 2023. Patients were categorized into low ePVS (< 6.2) and high ePVS (≥ 6.2) using Youden's statistics. We used the Cox-proportional hazards model, adjusting for age, sex, and body mass index, to investigate the association between high ePVS and major adverse cardiovascular events (MACE) and all-cause mortality within 1 year after ePVS measurement date. Of 305 patients with PH-CKD, 30% ( = 91) had low ePVS, and 70% ( = 215) had high ePVS. Compared to the low ePVS group, patients with high ePVS had higher left ventricular ejection fraction, right atrial pressure, pulmonary artery wedge pressure, and cardiac index, lower pulmonary vascular resistance, worse kidney function, and more chronic anemia. Among patients with precapillary or Cpc-PH, high ePVS was associated with a greater incidence of 1-year all-cause mortality (adjusted HR = 2.11, 95% CI 1.06-4.22 = 0.034). Among PH-CKD patients, high ePVS was associated with hyperdynamic circulation, worse kidney function, and anemia. High ePVS was associated with greater 1-year all-cause mortality among patients with a precapillary PH component.
Pulmonary hypertension (PH) in children requires complex medical management. Health-related quality of life (HRQoL) remains understudied in this population. During an 8-month period children and parents attending PH outp...Pulmonary hypertension (PH) in children requires complex medical management. Health-related quality of life (HRQoL) remains understudied in this population. During an 8-month period children and parents attending PH outpatient appointments completed the generic PedsQL (measuring physical, emotional, social, and school functioning). Parents completed the Hospital Anxiety and Depression scale, a validated measure of anxiety and depression, about their own mental health. Clinical data were extracted from the medical notes. Analyses explored relationships between clinical factors, parental mental health and HRQoL and compared scores with published norms. Parents of 94 of 98 (96%) eligible children with PH and 48 of 54 (89%) eligible children aged ≥ 5 years completed the PedsQL. All HRQoL scores were significantly below healthy norms, with 49% scoring > 2 S.D. below normative means. Physical HRQoL was associated with disease severity and survival outcomes. Multiple regression analyses showed age, learning disability, functional class, and parental depression explained 38% of parent-reported HRQoL variance (F(6, 86) = 7.67; < 0.001) while learning disability explained 33% of child-reported variance (F(3, 45) = 6.78; < 0.001). These findings support routine HRQoL evaluation and development of disease-specific measures for paediatric PH.
Porto-pulmonary hypertension (PoPH) represents a rare but significant form of pulmonary arterial hypertension (PAH) in children. Despite its clinical importance, systematic analyses of paediatric presentations and outcom...Porto-pulmonary hypertension (PoPH) represents a rare but significant form of pulmonary arterial hypertension (PAH) in children. Despite its clinical importance, systematic analyses of paediatric presentations and outcomes remain limited. We analysed the United Kingdom National Registry for Paediatric Pulmonary Hypertension (2001-2022) identifying children with PoPH through standardised diagnostic criteria including cardiac catheterisation and cross-sectional imaging. In our cohort of 12 patients (58% female, median age 4 years, range: 3 months-12 years), congenital porto-systemic shunts (CPSS) were the predominant pathology (58%). We found a high prevalence of genetic abnormalities (50%) and congenital heart disease (50%). Haemodynamic assessment revealed evidence of pulmonary vascular disease (mean pulmonary artery pressure 38 mmHg, range 20-52 mmHg; mean pulmonary vascular resistance index 6.1 WU·m², range 4.2-9.0 WU·m²) without vaso-reactivity. Over a median follow-up of 8.2 years, three patients achieved resolution of pulmonary hypertension after definitive treatment of underlying liver pathology. Four deaths occurred during follow-up: three from progressive PAH and one unrelated death that occurred 2 years following PAH resolution. Our analysis reveals distinctive features of paediatric PoPH, including predominant CPSS aetiology, and earlier age of onset than previously reported. Multi-modality imaging proved essential for diagnosis, as initial ultrasound missed CPSS in 5/7 cases. The variable treatment outcomes emphasise the importance of individualised therapeutic approaches and sustained clinical surveillance.