In patients with pulmonary arterial hypertension (PAH), limited real-world data are available on persistence to oral treprostinil therapy, particularly while transitioning from parenteral prostacyclins. We compared persi...In patients with pulmonary arterial hypertension (PAH), limited real-world data are available on persistence to oral treprostinil therapy, particularly while transitioning from parenteral prostacyclins. We compared persistence to oral treprostinil and total daily dose (TDD) achieved among patients with PAH initiating oral treprostinil de novo or while transitioning from parenteral prostacyclins using two real-world datasets: specialty pharmacy shipment records (Analysis 1) and ADAPT registry (Analysis 2). In Analysis 1, patients receiving oral treprostinil in 2017, 2020, and 2023 were included. In Analysis 2, de-identified data of patients enrolled in ADAPT from July 2017 to January 2022 were included. We conducted descriptive analyses and quantified persistence to oral treprostinil and TDD. In Analysis 1, the proportion of transition patients increased (24%-41%) from 2017 to 2023, whereas the proportion of de novo patients decreased (76%-59%). For the overall population, the mean initial oral treprostinil dose increased over the 3 years (6.0-8.9 mg TDD). The majority (61%) of patients transitioning to oral treprostinil were persistent with therapy at 12 months compared with de novo patients (47%). In Analysis 2, approximately 93% of transition patients and 77% of de novo patients were persistent on oral treprostinil therapy at 12 months. These analyses suggest that patients with PAH are increasingly being initiated on oral treprostinil while transitioning from parenteral prostacyclin rather than initiating de novo. Patients transitioning to oral treprostinil achieved and maintained higher TDD of oral treprostinil and persisted on oral treprostinil therapy longer than de novo patients.
Landmark trials of sotatercept in pulmonary arterial hypertension (PAH) excluded patients with significant cardiopulmonary comorbidities. To evaluate the real-world effectiveness and safety of sotatercept in patients wit...Landmark trials of sotatercept in pulmonary arterial hypertension (PAH) excluded patients with significant cardiopulmonary comorbidities. To evaluate the real-world effectiveness and safety of sotatercept in patients with Group I PAH and cardiopulmonary comorbidities. We conducted a single-center prospective observational study of adults with PAH on stable background therapy who initiated sotatercept between August 2024 and April 2025. Clinical, echocardiographic, and adverse event data were collected at baseline, 3 months, and 6 months. Forty-five patients (mean age 59.1 years old; 88.8% female) were included. Common comorbidities include CAD (44.7%), HTN (40.4%), ILD (23.4%), and COPD (12.7%). Most patients were on triple background pulmonary vasodilator therapy (63.8%). At 6-month follow-up, oxygen requirement at rest improved from 4.64 to 3.20 L/min ( = 0.001), 6MWD increased by 20 meters (310.5 ± 142.4 m to 330.4 ± 132.3 m, = 0.01). REVEAL Lite 2 scores improved, with over half the cohort achieving or maintaining low risk status. Adverse effects were mild, including epistaxis and increased hematocrit. Sotatercept appears safe and clinically beneficial in PAH patients with cardiopulmonary comorbidities.
Pulmonary arterial hypertension (PAH) is a progressive disease with significant morbidity and mortality. Due to nonspecific symptoms, diagnosis can be challenging and subject to substantial delays. Using data from Mayo C...Pulmonary arterial hypertension (PAH) is a progressive disease with significant morbidity and mortality. Due to nonspecific symptoms, diagnosis can be challenging and subject to substantial delays. Using data from Mayo Clinic's electronic health records, we looked at causes of delayed diagnosis and whether earlier diagnosis means better outcomes. This retrospective cohort study included adults with PAH confirmed by right heart catheterization (RHC) between 2015 and 2019. Univariate and multivariate analyses evaluated the association of 229 clinical and laboratory features with time to PAH diagnosis and survival outcomes. Early diagnosis was defined as < 6 months and a delayed diagnosis as ≥ 22.2 months from an eligible event. Survival probability was determined using Kaplan-Meier analysis. The study enrolled 160 patients. The most common initial PAH symptoms were dyspnea (42.5%) and fatigue (16.9%). It took a median of 7, 13, 26, and 123 days from eligible event to the first X-ray, electrocardiogram, echocardiogram, and RHC, respectively. Factors most closely associated with delayed diagnosis were chronic obstructive pulmonary disease, normal creatinine, high systolic blood pressure, acute respiratory infection, normal iron, normal diastolic blood pressure, and being male aged 18.5 to < 25 years. Compared with delayed diagnosis patients (22.6%), more early diagnosis patients saw a pulmonologist (35.3%) before another provider. After 5 years, 73% of patients in the early diagnosis and 31% in the delayed diagnosis group were still alive. This study identified factors associated with a delayed diagnosis of PAH and found that earlier diagnosis and treatment initiation were associated with significantly improved survival.
This study quantified prior authorization (PA)-insurance-required approval-burden for pediatric pulmonary hypertension (PH) at an accredited center. Among 53 patients, 72% of 283 prescriptions between 2021 and 2023 requi...This study quantified prior authorization (PA)-insurance-required approval-burden for pediatric pulmonary hypertension (PH) at an accredited center. Among 53 patients, 72% of 283 prescriptions between 2021 and 2023 required PA, with non-FDA-approved medications showing highest volume. Despite 97% approval and all patients ultimately obtaining medication, delays (mean 4.2 days), repeat requests (39%), and reliance on patient assistance programs created significant administrative burden. Results highlight the need for policy reform to ensure timely, equitable access to essential therapies.
Assessing operability in late-presenting ventricular septal defects (VSD) with pulmonary arterial hypertension (PAH) is complex. Although a comprehensive assessment is often recommended, pulmonary vascular resistance ind...Assessing operability in late-presenting ventricular septal defects (VSD) with pulmonary arterial hypertension (PAH) is complex. Although a comprehensive assessment is often recommended, pulmonary vascular resistance index (PVRI) is the cornerstone of most decisions. PVRI-based operability assessment, nonetheless, is not infallible. Cases with PVRI much higher than operability cut-offs have done well, while some with lower PVRI have experienced late recurrence of PAH. We propose the Diastolic Pulmonary Shunt Index (DiPSI), defined as the diastolic pulmonary gradient (DPG = PADP - PAWP) divided by Qp/Qs, as an adjunct to aid clinical judgment. DiPSI, by offering a physiologically grounded, flow-adjusted index, may help clarify borderline cases, providing a more nuanced assessment of operability in late presenters with large VSD than PVRI alone.
Pulmonary hypertension (PH) significantly impacts outcomes in heart failure with preserved ejection fraction (HFpEF), especially with right ventricular dysfunction (RVD), yet effective treatments are limited. This study...Pulmonary hypertension (PH) significantly impacts outcomes in heart failure with preserved ejection fraction (HFpEF), especially with right ventricular dysfunction (RVD), yet effective treatments are limited. This study retrospectively evaluated sacubitril-valsartan's effects on pulmonary pressures, RV function, and clinical outcomes in 20 severe HFpEF-PH patients. Significant improvements were observed over a median 397-day follow-up. Sacubitril-valsartan notably reduced RV systolic pressure (RVSP) by 27.50 mmHg ( < 0.0001) and peak tricuspid regurgitation (TR) velocity by 0.825 m/s ( < 0.0001). TR severity improved significantly ( = 0.0426). RV dimensions decreased significantly (basal: = 0.0083; mid-cavity: = 0.0025). RV-pulmonary arterial coupling (TAPSE/RVSP) improved from 0.27 to 0.47 ( < 0.0001), and NYHA functional class improved from mean III to II ( = 0.0164). Systolic blood pressure also decreased by 24.0 mmHg ( < 0.0001). Diastolic function parameters (E velocity, E/e', LAVI) did not show significant changes. These findings suggest that sacubitril-valsartan could improve pulmonary pressures, RV dimensions, RV-PA coupling, TR severity, and functional status in HFpEF-PH patients, supporting its potential therapeutic role.
Budhram B, Alrasheed SK, Rashad M
… +18 more, Chandy G, Dvorkin-Gheva A, Fox GA, Foxall J, Gardner A, Helmersen D, Hirani N, Kemp K, Kularatne M, Langleben D, Lesenko L, Provencher S, Spence E, Swiston JR, Thakrar M, Wadden D, Weatherald J, Hambly N
Transition from parenteral prostanoids to oral selexipag may be considered in select patients with pulmonary arterial hypertension (PAH) to reduce the therapeutic burden imposed on patients and caregivers, but its safety...Transition from parenteral prostanoids to oral selexipag may be considered in select patients with pulmonary arterial hypertension (PAH) to reduce the therapeutic burden imposed on patients and caregivers, but its safety and efficacy remain uncertain. A retrospective cohort study was conducted involving adult patients with PAH who transitioned from parenteral prostanoids to selexipag at Canadian tertiary referral centers between January 2016 and November 2020. The primary outcome was transition failure at 12 months, defined as a composite of death or PAH-related worsening. Baseline predictors of transition failure were identified using univariate Cox regression, with follow-up data collected up to 36 months post-transition or until site-specific data submission, occurring between May 2021 and February 2023. At 12 months post-transition, 11 of 36 patients (31%) experienced transition failure, including 4 deaths, all classified as high-risk pre-transition. Of the 25 patients (69%) who successfully transitioned, only one (4%) experienced transition failure over the subsequent observation period (median follow-up 28 months). Pre-transition variables protective against transition failure included a right atrial pressure (RAP) < 8 mmHg (HR 0.290, 95% CI 0.084-0.999, = 0.049), absence of hospitalizations in the year preceding transition (HR 0.239, 95% CI 0.064-0.885, = 0.032), lower brain natriuretic peptide (< 50 pg/mL)/N-terminal pro-B-type natriuretic peptide (< 300 pg/mL) levels (HR 0.174, 95% CI 0.045-0.676, = 0.011), and REVEAL 2.0 score < 7 (HR 0.162, 95% CI 0.049-0.541, = 0.003). These findings suggest that transition from parenteral prostanoids to selexipag carries the risk of clinical deterioration and should only be considered in carefully selected, low-risk patients.
Pulmonary arterial hypertension (PAH) is a pulmonary disease associated with alterations in gut microbiota. We aimed to identify potential diagnostic genes causally associated with gut microbiota and PAH. Mendelian rando...Pulmonary arterial hypertension (PAH) is a pulmonary disease associated with alterations in gut microbiota. We aimed to identify potential diagnostic genes causally associated with gut microbiota and PAH. Mendelian randomization (MR) was performed to screen gut microbiota causally associated with PAH and to identify gut microbiota-related genes. A regulatory network was constructed to reveal the relationships among genes, gut microbiota and PAH. Diagnostic genes were screened and used to construct a diagnostic model for PAH. Characteristics of immune infiltration and diagnostic gene expression in each cell type were evaluated at the transcriptome and single-cell levels. Family. Porphyromonadaceae and genus. Eubacteriumfissicatena were risk factors for PAH, whereas phylum. Actinobacteria, class. Bacilli, genus. Erysipelatoclostridium, and genus. Ruminococcaceae were protective factors for PAH. The gene-gut microbiota-PAH network showed causal associations among six gut microbiota taxa, 13 PAH-associated genes and PAH. Copper metabolism MURR1 domain (COMMD) containing 10 (COMMD10), FES proto-oncogene, tyrosine kinase (FES), nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1), solute carrier family 22 member 4 (SLC22A4), and synaptogyrin 1 (SYNGR1) were identified as diagnostic genes, with Area Under Curve (AUC) values ranging from 0.79 to 0.99. The abundances of activated B cells, activated CD8 T cells, eosinophils, mast cells, and T helper cells were increased, whereas the abundances of activated dendritic cells (DCs), gamma delta T cells, MDSCs, macrophages, neutrophils, plasmacytoid DCs, and regulatory T cells were decreased in PAH. NUCKS1 was expressed in each cell type and was lower in T/NK and NK cells. The study deepens the understanding of PAH pathogenesis, and may provide diagnostic targets for PAH.
Pulmonary artery wedge pressure is a crucial measurement for differentiating between hemodynamic categories of pulmonary hypertension (PH), particularly Groups 1 and 2. In this prospective study, we analyzed the diagnost...Pulmonary artery wedge pressure is a crucial measurement for differentiating between hemodynamic categories of pulmonary hypertension (PH), particularly Groups 1 and 2. In this prospective study, we analyzed the diagnostic utility of checking wedge oxygen saturation to confirm wedge position during right heart catheterization in patients referred for PH.
Pulmonary Arterial Hypertension (PAH) is a rare, chronic and progressive disease affecting the heart and lungs. Endothelin receptor antagonist (ERA) + phosphodiesterase type 5 inhibitor (PDE5i) treatment is recommended f...Pulmonary Arterial Hypertension (PAH) is a rare, chronic and progressive disease affecting the heart and lungs. Endothelin receptor antagonist (ERA) + phosphodiesterase type 5 inhibitor (PDE5i) treatment is recommended for all PAH patients. The two approved PDE5is are tadalafil and sildenafil. To determine the efficacy and safety outcomes for tadalafil and sildenafil as monotherapies or in combination with ERAs for treating PAH, from randomized controlled trials (RCTs) and real-world evidence studies (RWEs) identified by a systematic literature review (SLR). MEDLINE, Embase and Cochrane Libraries were searched in May 2024. Relevant outcomes included 6-min walk distance (6MWD), pulmonary vascular resistance (PVR) and safety. This report includes studies where patients were treated with either sildenafil or tadalafil. Fifteen RCTs and three RWEs investigated tadalafil (tadalafil 40 mg or 20 mg once daily) or sildenafil (20 mg three times a day). Mean 6MWD change from baseline (CFB) in patients receiving tadalafil or sildenafil monotherapy were comparable, however, in combination with an ERA, tadalafil may be more effective. Generally, there was more data for tadalafil + ERAs, showing marked improvement in mean PVR CFB, compared with patients receiving sildenafil. Conclusions on safety were limited. Risk of bias in RCTs was generally low but moderate in RWEs. Two studies reported patients who switched from sildenafil to tadalafil treatment, treatment transition was feasible. Although comparable when used as monotherapy, this qualitative analysis suggests that tadalafil + ERA combination therapy may have more favorable 6MWD improvements than sildenafil + ERA combination therapy.
Pulmonary arterial hypertension (PAH) is a life-threatening condition with no cure, making research into its underlying mechanisms critical. The platelet-derived growth factor (PDGF) signaling pathway plays a crucial rol...Pulmonary arterial hypertension (PAH) is a life-threatening condition with no cure, making research into its underlying mechanisms critical. The platelet-derived growth factor (PDGF) signaling pathway plays a crucial role in vascular remodeling, a key factor in PAH progression. Anti-PDGF receptor therapies, such as imatinib, show promise but are associated with significant side effects. Recent research identified PDGF-D as a new risk gene in idiopathic PAH, highlighting the need for further investigation into the PDGF pathway in the disease. In this study, we investigated PDGF-D, a specific PDGFRβ ligand, as a potential therapeutic target. RNA-Seq data from healthy lungs indicated that PDGF-D is predominantly expressed in inflammatory cells, whereas in vascular lesions of idiopathic PAH patients, PDGF-D was produced by various cell types. In vitro, PDGF-D induced mitogenic effects on pulmonary arterial smooth muscle cells. However, genetic deletion of PDGF-D in the chronic hypoxia mouse model of pulmonary hypertension showed no significant impact on vascular muscularization, hemodynamic parameters, or right ventricular hypertrophy. But, the absence of hypoxia-induced upregulation and the lack of increased expression of PAH-regulated genes, and , in PDGF-D-deficient mice, suggests activation of alternative mechanisms. MicroRNA analyses revealed PDGF-d-related alterations in the expression of miR-21 and miR-451, both important regulators in PAH, further supporting the notion that PDGF-D plays a unique role in PAH development. Taken together, our data suggest that PDGF-D may target a distinct population of PDGFRβ-expressing cells, separate from those stimulated by PDGF-B, positioning PDGF-D as a potentially unique and compelling therapeutic target for PAH.
Pericardial effusion (PEF) in PAH may be a marker of worsening disease or associated with autoimmune conditions. Sotatercept was not initially reported as associated with the development or progression of PEF. We describ...Pericardial effusion (PEF) in PAH may be a marker of worsening disease or associated with autoimmune conditions. Sotatercept was not initially reported as associated with the development or progression of PEF. We describe PAH patients taking sotatercept who were found to have new or worsening PEF and examine associated comorbidities.
High-risk acute pulmonary embolism (PE) is associated with significant in-hospital mortality. Large-Bore Mechanical Thrombectomy (LBMT) is a treatment option for acute PE, but data on its efficacy in high-risk PE was lim...High-risk acute pulmonary embolism (PE) is associated with significant in-hospital mortality. Large-Bore Mechanical Thrombectomy (LBMT) is a treatment option for acute PE, but data on its efficacy in high-risk PE was limited. This prospective case series reported the outcomes of 14 patients with high-risk PE treated using a novel multipurpose mechanical aspiration system (MMAS). Most patients were in hemodynamic decompensation, requiring inotropic or mechanical circulatory support. The mean procedural time was 73.5 ± 39.2 min. Complete procedural success was achieved in 78.6% of the cases, while two patients required bailout therapies. The mean pulmonary arterial pressure decreased by 27.2%, and the right-ventricle/left-ventricle ratio normalized in 85.7% of patients. The primary endpoint-in-hospital mortality-was 0%, while the major bleeding rate was 27.2%. These findings suggest that MMAS is a safe and effective intervention for acute high-risk PE.
Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism that is characterized by chronic obstruction of pulmonary arteries because of organized thrombi. Pulmonary endarterectomy (PEA...Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism that is characterized by chronic obstruction of pulmonary arteries because of organized thrombi. Pulmonary endarterectomy (PEA) is the primary treatment of choice for CTEPH, which aims to clear the pulmonary arteries as completely as possible to decrease right ventricular afterload, thereby improving pulmonary hypertension (PH). PEA is a complex surgical procedure involving cardiopulmonary bypass and deep hypothermic circulatory arrest. Although it provides excellent outcomes, it is associated with frequent complications, including lung reperfusion injury, endobronchial hemorrhage, and persistent PH. Therefore, patients with CTEPH need to be referred to specialized centers. Germany performs approximately 150 PEA procedures annually. However, in Japan, the availability of PEA facilities is limited. The present study aims to delineate the differences in CTEPH management between Japan and Germany, evaluate the underlying reasons for the limited implementation of PEA in Japan, and underscore the need for specialized assessment and referral of patients who are eligible for PEA. The limited utilization of PEA in Japan appears to be attributable not to underestimation of the procedure itself, but rather to anatomical and institutional constraints.
Pulmonary arterial hypertension (PAH) is a chronic, progressive, and ultimately life-threatening disease characterized by vascular remodeling and increasing pulmonary vascular resistance. Despite significant advances in...Pulmonary arterial hypertension (PAH) is a chronic, progressive, and ultimately life-threatening disease characterized by vascular remodeling and increasing pulmonary vascular resistance. Despite significant advances in diagnostic tools and therapeutic strategies, clinical intervention often begins only when patients become symptomatic-typically at New York Heart Association (NYHA) functional class II or higher. Paradoxically, while early detection of PAH is strongly encouraged to preempt irreversible vascular, cardiac, and multisystem damage, treatment remains largely restricted to those already exhibiting symptoms. Patients in NYHA class I, though experiencing pathophysiological progression, are systematically excluded from approved pharmacological therapies. This disjunction represents not only a clinical and ethical conundrum but also a conceptual paradox: why invest in early diagnosis if early treatment is withheld? Emerging evidence on various chronic diseases, including cancer, infectious diseases like HIV and hepatitis, and even other cardiovascular diseases, underscores the benefits of initiating treatment before the onset of symptoms. In contrast, the current approach to PAH inadvertently promotes a nihilistic "wait and see" policy, exposing asymptomatic patients to preventable deterioration. Herein, we call for a reassessment of clinical guidelines, regulatory frameworks, and access policies with the goal of better aligning them with the biological realities of PAH. While we advocate for a paradigm shift toward the inclusion of NYHA class I patients in treatment strategies, we explicitly acknowledge the current limitations of the evidence base and emphasize the need for ongoing, high-quality research including counterarguments and the practical challenges of early treatments.
Children with single ventricle heart disease (SVHD) demonstrate decreased arginine/NO metabolism following Stage 2 (Glenn) palliation, associated with poor postoperative outcomes. It is unknown if arginine dysregulation...Children with single ventricle heart disease (SVHD) demonstrate decreased arginine/NO metabolism following Stage 2 (Glenn) palliation, associated with poor postoperative outcomes. It is unknown if arginine dysregulation persists at Stage 3 (Fontan). The purpose of this study is to quantify circulating arginine metabolites in children undergoing Fontan palliation for SVHD to evaluate the relationship between metabolite concentrations and outcomes. Prospective cohort study of children undergoing Fontan operation ( = 82) and similar age healthy controls ( = 49). We measured circulating arginine metabolites pre- and post-op by tandem mass spectrometry. Postoperative outcomes included length of stay (LOS) and pleural drainage. Pre-op cases showed lower arginine, argininosuccinate, cysteine, NMMA, higher glutathione, and lower arginine/ADMA, arginine/citrulline, and arginine/ornithine ratios compared to controls. Post-op cases experienced progressively decreasing citrulline concentration and higher arginine/ADMA, arginine/citrulline, and arginine/ornithine ratios compared to pre-op. In uncorrected analysis, postoperative decreased citrulline level (31.4% and 33.9% longer LOS for 50% decrease in [citrulline] at 2 and 24 h, respectively) was associated with longer LOS. Decreased arginine/ADMA and arginine/ornithine ratios were significantly associated with longer LOS and greater pleural drainage. Arginine metabolism is altered in children with SVHD in both the pre- and post-Stage 3 period. Patients with greater postoperative derangements, including lower arginine/ADMA and arginine/ornithine ratios, experienced more morbidity. We speculate that alterations in arginine metabolism may be a modifiable risk factor for adverse post-Stage 3 outcomes in SVHD.