Integrating routine mental health support in pulmonary hypertension care is not just a matter of efficiency but also of recognition, equity, and epistemic justice. We provide evidence supporting the Generalised Anxiety Disorder-2 questionnaire and the Patient Health Questionnaire-2 as practical, psychometrically sound, and low-burden entry points for screening anxiety and depression.

ABSTRACTPulmonary arterial hypertension (PAH) is a life‐threatening disease of the pulmonary arteries. Progressively increasing pulmonary artery pressure may lead to fatal failure of the right ventricle, necessitating aggressive drug treatment. Sotatercept, a novel drug for PAH‐targeted therapy, shows promising results in clinical trials. Nevertheless, efficacy in the heterogeneous PAH population and long‐term outcomes have yet to be investigated. This case report illustrates the life‐changing effects of sotatercept in a patient with heritable PAH associated with a TBX4 mutation. Our patient faced near immobility, oxygen dependency, and was listed for lung transplantation in November 2023. Following sotatercept administration from July 2024 onward, she started sporting activities and has been removed from the transplantation waiting list. Thereby, this case illustrates an exceptional response to sotatercept in a patient with TBX4‐associated heritable PAH. Positive effects persist 1 year after initiation without significant side effects.

ABSTRACTCatheter‐directed intervention (CDI) in patients presenting with pulmonary embolism (PE) is suggested to improve in‐hospital outcomes. We aimed to compare the effect of early versus late initiation of CDI on in‐hospital outcomes. A systematic review and meta‐analysis were conducted according to PRISMA guidelines. A comprehensive search of PubMed, Scopus, Web of Science, and Embase databases was performed from inception to May 2025. Data extraction was conducted independently by multiple reviewers. Statistical analysis was performed using R software version 4.3.2, and odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) were combined using a random‐effects model. Six studies, including 53,472 patients, were included. Early intervention before 24 h significantly reduced mortality (OR 0.61, 95% CI [0.44–0.84]; I² = 0%). Moreover, Early intervention before 24 h significantly reduced the all‐cause readmission in patients with acute PE (OR = 0.81 (95% CI: [0.73, 0.89]; I² = 0%). There was no significant difference in risk of major bleeding in early vs late intervention (OR = 0.82; 95% CI: [0.48, 1.39]; I² = 69.3%). Also, early intervention before 24 h significantly reduced the length of hospital stay (LOS) (MD = –3.11 days (95% CI: [–4.33, –1.89]; I² = 0%). This meta‐analysis showed that early CDI, particularly within 24 h of presentation, is associated with a significant reduction in both mortality and all‐cause readmission in patients with acute PE, without increasing the risk of bleeding. These findings support the concept of “time‐is‐myocardium” and reinforce the need for structured protocols that enable early therapeutic intervention. Further randomized controlled trials are needed to confirm these findings and to establish the optimal timing for this potentially life‐saving therapy.

ABSTRACTPatients with pulmonary arterial hypertension (PAH) experience long delays in diagnosis; however, little is known about the time between diagnosis and initiation of guideline‐recommended optimal treatment. Immediate therapy is imperative for optimizing patient outcomes, as much of the pulmonary vasculature has already deteriorated by the time of diagnosis. This study used real‐world U.S. data to investigate the time from the most recent right heart catheterization (RHC) to initiation of the first PAH‐specific treatment. Adults with PAH were identified in the Komodo Health database using claims for RHC, pulmonary hypertension diagnostic codes, and PAH medications (1/1/2016–4/1/2024). Time from RHC to medication dispensing was examined and categorized by initial treatment regimen (monotherapy, dual therapy, and triple therapy). Baseline characteristics and treatment patterns were assessed. Among 7952 patients, the median time from most recent RHC to first PAH medication was 43.0 days. Most patients (77.7%) initially received monotherapy, with 20.0% and 2.3% receiving upfront dual and triple therapy, respectively. Cardiac comorbidities were present in most patients (85.8%). Among 2965 (48.0%) upfront monotherapy users who added another treatment during follow‐up, the median time to dual therapy was 39 days. Of those who escalated to dual therapy, 567 (19.1%) eventually escalated to triple therapy, with a median time from dual therapy to triple therapy of 62 days. In real‐world practice, delays between PAH diagnosis and initiation of optimal therapy remain significant, and barriers to access should be addressed.

ABSTRACTThe typical pathology of pulmonary hypertension (PH) is characterized by pulmonary vasoconstriction and irreversible pulmonary vascular remodeling. Vascular remodeling is the process of structural changes and cellular rearrangement of blood vessels due to injury and is a significant factor in conditions such as PH. Echinacoside (ECH) is a phenylethanol glycoside from Tibetan herbs, and our previous study found that ECH modulated calcium channels on pulmonary artery smooth muscle cells (PASMCs) and improved pulmonary vasoconstriction. To investigate the role of ECH in improving pulmonary vascular remodeling in PH, we constructed hypoxia‐induced hypoxic pulmonary hypertension (HPH) and MCT‐induced pulmonary arterial hypertension (PAH) models. Transcriptomic analysis revealed significant enrichment of Cav1.2, Cav3.2, and PKC/MAPK signaling pathways in PAH rats. ECH effectively inhibited Cav1.2 and Cav3.2 protein and mRNA expression, as well as the phosphorylation levels of PKC/MAPK, in HPH and PAH. In addition, ECH effectively reduced mean pulmonary artery pressure (mPAP) and right ventricular hypertrophy index (RVHI) and improved pulmonary vascular remodeling in HPH and PAH rats. In short, we found that ECH improved pulmonary vascular remodeling by modulating Cav1.2 and Cav3.2/PKC/MAPK pathways. Furthermore, this improvement was effective in both HPH and PAH.

Guidelines recommend different approaches to investigate for pulmonary hypertension (PH) by transthoracic echocardiography (TTE). We used data from the CIPHER study (NCT04193046) to prospectively evaluate TTE detection of PH. Participants newly referred to PH clinics who underwent right heart catheterization (RHC) within 6 weeks and TTE within 60 days of enrolment (blinded central TTE reading) were classified by TTE probability of PH applying (i) the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) TTE algorithm or (ii) right ventricular systolic pressure (RVSP) > 40 mmHg. For calculation of sensitivity and specificity, 'non-assessable' patients (peak tricuspid regurgitation velocity [TRV] missing or ≤ 2.8 m/s with missing data on other echocardiographic signs) and patients with missing RVSP were counted as PH-negative. Performance was measured against RHC-confirmed diagnosis of mean pulmonary artery pressure > 20 mmHg. Of 475 patients included, 345 (73%) had PH. Using the ESC/ERS algorithm, PH probability was high, intermediate, low and non-assessable for 198, 104, 22 and 151 patients and PH prevalence was 98%, 75%, 23%, and 44%, respectively. Seventy-threepatients were missing RVSP and 292 had RVSP > 40 mmHg. The two TTE approaches achieved similar results: sensitivity was 79%-77%, specificity was 78%-79%. This prospective study of patients newly referred to PH centres for RHC found similar sensitivity and specificity when using either RVSP > 40 mmHg or the 2015 ESC/ERS TTE algorithm. Among patients who were low-probability or non-assessable by ESC/ERS algorithm, 42% had PH, highlighting the persistent need for additional non-invasive investigative tools.

ABSTRACT Pulmonary artery pressures (PAPs) often become abnormal during exercise in patients with systemic sclerosis (SSc). This study sought to determine whether exercise‐induced pulmonary hypertension (EIPH) assessed by exercise stress echocardiography (ESE) would be associated with subsequent increases in resting PAPs in patients with SSc. Patients with SSc who underwent serial echocardiography > 6 months apart were retrospectively screened ( n = 543). Of those, patients undergoing ESE were divided based on the presence of EIPH, defined as estimated mean PAP (mPAP) > 30 mmHg during exercise and a mPAP/cardiac output (CO) > 3 mmHg/L/min. Patients who did not undergo ESE and had a mPAP < 20 mmHg were selected as controls ( n = 198). The primary endpoint was a longitudinal change in sPAP from baseline to last follow‐up echocardiography. Compared to controls and patients with non‐EIPH ( n = 71), those with EIPH ( n = 56) had a higher sPAP at baseline (22 ± 4 mmHg, 28 ± 6 mmHg, and 31 ± 6 mmHg, p < 0.0001). Over a median follow‐up duration of 2.4 years, a longitudinal change in resting sPAP from baseline to follow‐up echocardiography was higher in patients with EIPH than those without (+ 1.2 mmHg vs. −1.0 mmHg, p = 0.048). In a sensitivity analysis excluding 30 patients who received pulmonary vasodilators or heart failure medications after baseline echocardiography, the difference in sPAP change over time between the two groups increased further (+ 2.2 mmHg in the EIPH group vs. −1.6 mmHg in the non‐EIPH group, p = 0.0008). In conclusion, echocardiography‐derived EIPH was associated with a longitudinal increase in sPAP, supporting ESE as a non‐invasive tool for risk stratification in SSc‐PH.

Reflux of contrast medium into the inferior vena cava (IVC) on computed tomography pulmonary angiogram (CTPA) is an independent risk factor for mortality in patients with acute pulmonary embolism (PE). This study's aim was to determine if reflux into the IVC correlates with objective scores of clinical risk in acute PE. Patient-level data were collected for adults diagnosed with acute PE by CTPA at University of California, San Diego Health between January 1 and June 30, 2023. Contrast reflux into the IVC was graded on a 4-point scale. The primary endpoint was the correlation between reflux severity and risk for clinical deterioration as measured by the National Early Warning Score (NEWS). The secondary endpoint was interobserver reliability grading reflux amongst 16 reviewers. Fifty-six subjects with acute PE were included. Extent of contrast reflux into the IVC correlated with NEWS (Spearman's ρ 0.2932; p = 0.028). Subjects with grade 3 reflux had increased NEWS (7.80) compared to those with reflux grades 0 (3.63; p = 0.014) or 1 (4.29; p = 0.05). NEWS was elevated in those with contrast below the diaphragm compared to those without when grading was pooled (p = 0.036). Interobserver reliability for reflux grading was "moderate" (κ = 0.58), yet increased to "almost perfect" (κ = 0.87) for pooled grading. Contrast reflux into the IVC during acute PE correlates with risk for clinical deterioration, as reflected by NEWS. Simplification of grading to contrast above or below the diaphragm improves reliability without compromising this relationship.

Exercise testing has long been essential for evaluating diagnosis, prognosis, and functional status in pulmonary hypertension (PH). Recent advances have clarified its role in defining reference values and prognostic markers. Nonetheless, substantial knowledge gaps persist regarding the implementation of invasive cardiopulmonary exercise testing (iCPET) and its potential to inform pathophysiology and therapeutic decision-making. This statement addresses the knowledge gaps that hinder the application of iCPET and exercise right heart catheterization (RHC) in the assessment of PH. We present research priorities and scenarios in which these tests may clarify drug mechanisms and support PH subphenotyping. An international, multidisciplinary task force of cardiology and pulmonology experts reviewed the literature and formulated consensus recommendations through iterative discussions.

ABSTRACTTotal anomalous pulmonary venous connection (TAPVC) is a rare but life‐threatening congenital heart defect that requires surgical correction. The sutureless technique has been developed as an alternative to conventional repair to minimize postoperative complications. This meta‐analysis evaluates and compares the efficacy and safety of the two surgical approaches. A comprehensive literature search was conducted in PubMed, EMBASE, the Cochrane Library, and major Chinese databases for studies published between January 2010 and December 2024. Five retrospective comparative studies including a total of 1,327 patients met the inclusion criteria. Data were analyzed using RevMan version 5.4. Primary outcome measures included the incidence of postoperative pulmonary venous obstruction (PVO), reoperation due to PVO, total postoperative mortality, and late mortality. A random‐effects model was applied to all analyses to account for anticipated clinical heterogeneity. A subgroup analysis based on TAPVC anatomical type was also performed. The meta‐analysis demonstrated that the sutureless technique was associated with a significantly lower postoperative PVO rate (Odds Ratio [OR] = 0.46; 95% Confidence Interval [CI]: 0.28–0.77; p = 0.047) and a reduced reoperation rate due to PVO (OR = 0.25; 95% CI: 0.08–0.77; p = 0.049) compared with conventional surgery. Subgroup analysis indicated that the reduction in postoperative PVO was most evident among patients with infracardiac‐type TAPVC. No statistically significant differences were observed in total postoperative mortality (OR = 0.66; 95% CI: 0.35–1.24; p > 0.05) or late mortality (OR = 0.37; 95% CI: 0.13–1.06; p > 0.05). Across all outcomes, heterogeneity was low to moderate (I² < 50%). Major limitations of this study include the retrospective design of all included studies, small sample sizes for certain analyses, variability in study methodology, and possible publication bias. The sutureless technique appears to be a safe and effective alternative to conventional surgery for primary TAPVC repair. It significantly reduces postoperative PVO and the need for reoperation, with the greatest benefit observed in high‐risk subtypes such as infracardiac TAPVC. However, given that all available evidence is derived from retrospective studies of moderate quality, further large‐scale prospective investigations are required to validate these findings and assess long‐term outcomes.