Pulmonary Circulation最新文献

Selexipag is an oral selective agonist of the prostacyclin receptor approved to treat adults with pulmonary arterial hypertension (PAH). Selexipag is initiated at a dose of 200 μg twice daily (bid) and usually titrated up by 200 μg bid weekly (per label) or more slowly (e.g., every other week in real-world clinical practice) to the highest tolerated individualized dose (ID) ranging from 200 to 1600 µg bid. In the Phase 3 GRIPHON trial, selexipag delayed disease progression and reduced risk of PAH-related hospitalization compared with placebo; the effect was consistent across three prespecified ID groups: low (200-400 µg bid), medium (600-1000 µg bid), and high (1200-1600 µg bid). This study evaluated patient outcomes across selexipag dose ranges in real-world practice. Data were analyzed from 1186 US adult patients with PAH on selexipag from the Komodo closed-claims database (2015‒2022). Of these, 634 (53.5%) patients completed titration and reached their selexipag ID (43.8% high ID, 29.8% medium ID, 26.3% low ID). Subsequently, 72.4% of patients in the low ID group had dose adjustments compared with 61.9% (medium ID) and 34.5% (high ID; standardized mean difference 0.63). There were no significant differences in patient outcomes, i,e, persistence (time to discontinuation) and risk of all-cause and PAH-related hospitalization across ID groups. The findings in this diverse, real-world population of patients with PAH reinforced an individualized approach to the dosing scheme to maximize benefit-risk and achieve the highest tolerated dose with selexipag similar to findings from the GRIPHON trial and other studies.

Carnitine is required to transport fatty acid across the mitochondrial membrane to undergo beta oxidation. In addition to disorders of fatty acid metabolism, a relative carnitine deficiency has been reported in pulmonary arterial hypertension (PAH). Here we performed an observational study in which food and supplement consumption were collected in an observation period followed by open label administration of a carnitine supplement to determine feasibility of increasing plasma carnitine levels in humans PAH. We confirmed that relative carnitine deficiency in PAH is not due to reduced dietary consumption and that plasma levels of carnitine can be increased in PAH patients with supplementation that is well tolerated.

The prognostic significance of pretransplant N-terminal pro-brain (B)-type natriuretic peptide (NT-proBNP) level has not been investigated in lung transplant recipients. The electronic files of 173 patients with chronic lung disease who underwent lung transplantation in 2018-2022 at a tertiary medical center were retrospectively reviewed. Right heart catheterization (RHC) and NT-proBNP determination were performed preoperatively in all cases. Pretransplant demographic, clinical, and laboratory data were compared between posttransplant survivors and nonsurvivors. Correlations of NT-proBNP values with lung function and RHC parameters and all-cause mortality were analyzed. NT-proBNP level correlated positively with mean pulmonary artery pressure (R = 0.51, p < 0.001) and pulmonary vascular resistance (PVR) (R = 0.45, p = 0.0013), and negatively with diffusing lung capacity for carbon monoxide (R = -0.25, p = 0.0017), cardiac index (R = -0.26, p = 0.001), and cardiac output (R = -0.23, p = 0.004). Over a median follow-up time of 23.22 months, 74 patients died. On univariate analysis, mortality was significantly associated with higher log-NT-proBNP (hazard ratio [HR] = 0.54, 95% confidence interval [CI] 1.15-2.05, p = 0.016), older age at transplant registration (HR = 1.033, 95% CI 1.009-1.058, p = 0.0068), higher PVR (HR 1.15, 95% CI 1.07-1.23, p = 0.015), and lower cardiac output (HR = 0.62, 95% CI 0.42-0.92, p = 0.045). On multivariate analysis adjusted for age, sex, and body mass index, mortality significance was maintained only for higher log-NT-proBNP (HR = 1.54, 95% CI 1.12-2.11, p = 0.007). Among lung transplant recipients, pretransplant NT-proBNP levels correlated well with RHC parameters and were strongly associated with posttransplantation mortality. Assessment of NT-proBNP may improve risk stratification of lung transplant candidates.

Various erythropoietic abnormalities are highly prevalent among patients with pulmonary arterial hypertension (PAH) and associated with worse disease severity. Given the poorly understood yet important roles of dysregulated erythropoiesis and iron metabolism in PAH, we sought to further characterize the hematologic and iron profiles in PAH and their relationship to PAH severity. We recruited 67 patients with PAH and 13 healthy controls. Hemodynamics attained within 1 year of blood sample collection were available for 36 patients. Multiple hematologic, iron, and inflammatory parameters were evaluated for their association with hemodynamics. The subset with hemodynamic data consisted of 29 females (81%). The most common etiologies were idiopathic PAH (47%) and connective tissue disease-related PAH (33%). 19 (53%) had functional class 3 or 4 symptomatology, and 12 (33%) were on triple pulmonary vasodilator therapy. Immature reticulocyte fraction (IRF) had significant positive correlations with mean pulmonary artery (PA) pressure (mPAP) (0.59, p < 0.001), pulmonary vascular resistance (0.52, p = 0.001), and right atrial pressure (0.46, p = 0.005), and significant negative correlations with cardiac index (-0.43, p = 0.009), PA compliance (PAC) (-0.60, p < 0.001), stroke volume index (SVI) (-0.57, p < 0.001), and mixed venous oxygen saturation (-0.51, p = 0.003). IRF correlated with markers of iron deficiency (ID) and erythropoiesis. On multivariable linear regression, IRF was associated with elevated mPAP and reduced SVI and PAC independent of EPO levels, transferrin saturation, and soluble transferrin receptor levels. We identified IRF as a novel and potent biomarker of PAH hemodynamic severity, possibly related to its associations with erythropoiesis, ID, and tissue hypoxia.

The PEGASUS study is the first multicentric and prospective assessment of the safety of air travel flying in pulmonary hypertension (PH) (NCT03051763). Data of air travel from 60 patients with PH was available. No severe adverse events occurred. Nine patients self-reported mild adverse events during flight (13%), while after landing, 12 patients reported events (20%). Solely one patient (2%) had an adverse event leading to medical consultation. In patients with PH and World Health Organization functional classes II and III, air travel was safe.

Hemoptysis is a frequently encountered manifestation in cases of acute pulmonary thromboembolism (PTE), significantly impacting clinical decision-making. Despite its clinical relevance, studies focusing on patients with acute PTE and hemoptysis are notably scarce. In this retrospective study, we examined data from hospitalized patients with acute PTE at Peking Union Medical College Hospital (PUMCH) between January 2012 and October 2020. Among the 896 patients analyzed, 105 (11.7%) presented with hemoptysis. Patients with hemoptysis were younger, had higher RRs, and frequently reported chest pain, predominantly showing a negative sPESI score. A significant association with autoimmune diseases was observed (39.0% vs. 16.1%; p < 0.001), along with higher occurrences of pulmonary infections (29.5%), lung cancer (21.0%), and chronic heart failure (16.2%). Hemoptysis in PTE is multifactorial; 51.4% of cases were PTE-related, with 85.2% experiencing mild hemoptysis. Among patients with disease-related hemoptysis (13.3%), 90.9% with massive hemoptysis had underlying diseases, predominantly lung cancer. In 35.2% of cases, the cause of hemoptysis remained undetermined, with vasculitis accounting for 29.7%. Anticoagulation strategies varied with the severity of hemoptysis; 82.9% with mild and only 27.3% with massive hemoptysis received therapeutic-dose anticoagulation. Multivariate analysis identified massive hemoptysis as the most significant determinant of anticoagulation decisions. Patients with massive hemoptysis had the poorest outcomes, with an in-hospital mortality rate of 36.4% and 72.7% receiving reduced or no anticoagulation.

Selexipag is indicated for the treatment of pulmonary arterial hypertension (PAH), including PAH associated with connective tissue disease (CTD), and further insights into the management of selexipag-treated PAH-CTD patients in clinical settings are needed. These analyses of the ongoing, multicenter, prospective EXPOSURE (EUPAS19085) study describe characteristics, treatment patterns, tolerability, and outcomes of PAH-CTD patients initiating selexipag in Europe/Canada. All analyses were descriptive, with idiopathic PAH patients who typically display better prognosis included for context. Six hundred ninety-eight selexipag-treated patients had follow-up information; 178 (26%) had PAH-CTD. The median age was 68 years, patients were predominantly female (88%), and with WHO functional class III symptoms (63%); the median time since diagnosis was 1.7 years. There were 5% patients at low, 25% intermediate-low, 40% intermediate-high, and 30% high risk of 1-year mortality, according to the ESC/ERS 4-strata risk score. Most (80%) initiated selexipag as a triple oral therapy, and most of these (62%) remained on triple therapy 6 months post-baseline. Over a median (Q1-Q3) selexipag exposure period of 8.6 (2.5-17.2) months, 79 (44%) patients discontinued selexipag; 36 (20%) due to tolerability/adverse events. Sixty (34%) patients were hospitalized at least once; 120 hospitalizations occurred, with 49 (48%) deemed PAH-related. Survival at 1 year was 85%, and at 2 years was 71%; 29 (16%) patients died. These results describe the use of combination therapy with selexipag for patients with PAH-CTD. These findings suggest an opportunity to optimize the benefits of selexipag among patients with PAH-CTD by moving from escalating after years in response to clinical deterioration to escalating sooner to prevent clinical deterioration.

The objective of this study is to provide a positron emission tomography (PET) imaging modality targeting vascular endothelial growth factor receptors (VEGFR) for the early noninvasive detection and assessment of pulmonary arterial hypertension (PAH) severity. To validate the effectiveness of the [¹⁸F]VEGFR PET tracer, we utilized a monocrotaline (MCT)-induced PAH rat model. Molecular optical imaging, using a Cy5.5-conjugated VEGFR targeting agent, was employed to demonstrate the uptake of the agent at pulmonary arterioles, correlating with the onset and progression of PAH. Histological examinations of the MCT-PAH rat lung revealed a significant correlation between VEGFR2 expression and the pathogenesis of PAH. Molecular optical imaging demonstrated heightened uptake of the Cy5.5-conjugated VEGFR targeting agent at pulmonary arterioles, corresponding with the onset and progression of PAH. [¹⁸F]VEGFR PET showed increased lung uptake detectable in early-stage PAH before increase in pulmonary artery pressures, and this uptake correlated with increased PAH severity. Moreover, when compared to [¹⁸F]FDG PET, [¹⁸F]VEGFR PET exhibited markedly lower background cardiac signal, enhancing imaging sensitivity for lung abnormalities. Our study provides a compelling evidence for the potential utility of the innovative [¹⁸F]VEGFR PET tracer, in non-invasively detecting early signs of PAH, and monitoring its progression. The observed correlations between VEGFR2 expression, molecular optical imaging results, and [¹⁸F]VEGFR PET findings support the use of this tracer for early detection, and assessment of PAH severity. The lower background cardiac signal observed with [¹⁸F]VEGFR PET further enhances its imaging sensitivity, emphasizing its potential clinical significance.