Schistosomiasis-associated pulmonary arterial hypertension (Sch-PAH) is one of the most frequent etiologies of pulmonary arterial hypertension in Brazil and globally. The disease is a complication of hepatosplenic schist...Schistosomiasis-associated pulmonary arterial hypertension (Sch-PAH) is one of the most frequent etiologies of pulmonary arterial hypertension in Brazil and globally. The disease is a complication of hepatosplenic schistosomiasis characterized by portal hypertension, egg deposition, and granuloma formation in the pulmonary arteries leading to inflammation, vascular remodeling, increased pulmonary vascular resistance, and progressive right heart failure. During the Infection in Pulmonary Vascular Disease (iPVD) consortium meeting during the Pulmonary Vascular Research Institute (PVRI) annual meeting in January 2025, in Rio de Janeiro, Brazil, a dedicated symposium entitled schistosomiasis-associated pulmonary vascular disease in Latin America addressed the most relevant aspects of the epidemiology, diagnosis, and prevention of Sch-PAH in Brazil. This review summarizes the main discussed topics and serves as a call to increase efforts to understand the disease burden better and enhance diagnostic proficiency.
Eisenmenger syndrome (ES) represents an advanced stage of pulmonary arterial hypertension (PAH) associated with congenital heart disease. It is characterized by elevated pulmonary vascular resistance, with a right-to-lef...Eisenmenger syndrome (ES) represents an advanced stage of pulmonary arterial hypertension (PAH) associated with congenital heart disease. It is characterized by elevated pulmonary vascular resistance, with a right-to-left shunt and resting hypoxemia. ES is associated with high morbidity and mortality. Sotatercept, an activin-signaling inhibitor recently approved for PAH, has demonstrated meaningful hemodynamic and clinical benefits; however, post-approval experience has raised concern for an association with pericardial effusion. We report a 21-year-old woman with ES secondary to an unrepaired patent ductus arteriosus, who developed a hemodynamically significant pericardial effusion 84 days after initiating sotatercept. She presented with tamponade physiology requiring urgent pericardiocentesis and drain placement. An extensive evaluation revealed no obvious alternative etiology. A review of the published literature identified 39 cases of pericardial effusion associated with sotatercept, with more than half occurring in patients with connective tissue-associated PAH. This case highlights potential susceptibility in complex physiologic states such as ES and emphasizes the importance of close surveillance.
Portopulmonary hypertension (PoPH) is a subtype of pulmonary arterial hypertension (PAH) associated with portal hypertension, occurring in 2%-6% of cirrhotic patients. Although guidelines recommend routine echocardiograp...Portopulmonary hypertension (PoPH) is a subtype of pulmonary arterial hypertension (PAH) associated with portal hypertension, occurring in 2%-6% of cirrhotic patients. Although guidelines recommend routine echocardiography before transplantation, the prevalence, and outcomes of PAH-specific therapy in cirrhotic patients remain unclear. We retrospectively analyzed 4,113 cirrhotic patients who underwent transthoracic echocardiography (TTE) between 2008 and 2019 using the Chang Gung Research Database. Patient characteristics, medication, echocardiographic findings, right heart catheterization (RHC) results and clinical outcome were collected from medical records and retrospectively analyzed by the investigators. Among 3243 patients with completed TTE, 709 (21.9%) had elevated tricuspid regurgitation peak gradient (TRPG ≥ 35 mmHg), suggesting pulmonary hypertension. There were 52 patients underwent RHC at our center, of whom 46 (88.5%) fulfilled hemodynamic criteria for PoPH. Additionally, seven patients with externally confirmed PoPH were included, yielding 53 patients in the final analysis. Among them, 13 patients received PAH-specific therapy with significant TRPG reduction but shorter mean survival (median survival 22.6 vs 78.9 months, = 0.037) than those without therapy. Among patients under PAH-specific therapy, those who had higher baseline TRPG (≧ 50 mmHg), mPAP (≧ 40 mmHg) and pulmonary vascular resistance (≧ 2 Wood Units) were noted with better survival. PoPH is not rare in patients with liver cirrhosis. Exploratory subgroup analyses suggest that selected patients with severe hemodynamic impairment may potentially benefit from PAH-specific therapy; however, these findings require validation in larger prospective studies.
Right ventricle (RV) dysfunction is central to pulmonary arterial hypertension (PAH) yet its molecular mechanisms remain unclear. This study aimed to identify biomarkers and therapeutic targets for RV remodeling in PAH....Right ventricle (RV) dysfunction is central to pulmonary arterial hypertension (PAH) yet its molecular mechanisms remain unclear. This study aimed to identify biomarkers and therapeutic targets for RV remodeling in PAH. The dataset GSE240941 have 39 RV tissue samples, including normal RV, compensated RV (comRV), and decompensated RV (decomRV). Differential analysis revealed no significant gene differences between comRV and normal RV tissues but identified 2384 different expression genes between decomRV and normal RV tissues. Weighted gene co-expression network analysis (WGCNA) highlighted the Coral2 module as strongly associated with decomRV remodeling (cor = 0.51, = 0.01). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of Coral2 module identified potential mechanisms and 78 hub genes (|MM | > 0.80 and |GS | > 0.50). Among these hub genes, CDK2, ITGB3, and RUNX1 emerged as key candidates through further filtering and CytoHubba analysis. While all three genes showed elevated expression in the training set, only RUNX1 was significantly upregulated in the validation dataset (GSE120852). RT-qPCR and western blot from RV tissue of monocrotaline-induced pulmonary hypertension rats showed that RUNX1 was significantly elevated in RV tissue. Immunofluorescence indicated that RUNX1 was primarily localized in the nucleus. Receiver operating characteristic curve analysis demonstrated the ability of CDK2, ITGB3, and RUNX1 to differentiate decomRV remodeling in training dataset and validating dataset. Based on the results of WGCNA and preliminary validation from animal experiments, RUNX1 may be a potential biomarker for RV failure in the context of PAH.
Patients with chronic thromboembolic pulmonary disease (CTEPD) without resting pulmonary hypertension (PH) frequently experience dyspnea which is not explained by stationary assessment and therefore requires cardiopulmon...Patients with chronic thromboembolic pulmonary disease (CTEPD) without resting pulmonary hypertension (PH) frequently experience dyspnea which is not explained by stationary assessment and therefore requires cardiopulmonary exercise testing for further diagnostic insight. Ventilatory inefficiency in CTEPD is commonly identified; however, consensus definitions are lacking. Upright iCPET and careful definition of ventilatory inefficiency (i.e., lack of reduction in VD/VT with exercise) may allow optimal characterization of patients with chronic thromboembolic disease and specifically helps correctly identify patients with preload insufficiency who may otherwise be misclassified or undiagnosed.
Twelve patients with severe pulmonary hypertension (PH) who had a pulmonary artery-to-descending aorta (Potts) shunt were treated with the novel PH drug sotatercept for an average of 12 months. Overall, the group showed...Twelve patients with severe pulmonary hypertension (PH) who had a pulmonary artery-to-descending aorta (Potts) shunt were treated with the novel PH drug sotatercept for an average of 12 months. Overall, the group showed significant improvement in a number of clinical parameters with no serious complications. Thus, a trial of sotatercept could be considered prior to an invasive intervention in patients with severe PH. Similarly, it may also be useful in patients with Eisenmenger-like physiology.
Pulmonary arterial hypertension (PAH) patients frequently present with cardiometabolic comorbidities and experience substantial hematologic and cardiovascular events. In a retrospective U.S. linked claims-EHR cohort ( = ...Pulmonary arterial hypertension (PAH) patients frequently present with cardiometabolic comorbidities and experience substantial hematologic and cardiovascular events. In a retrospective U.S. linked claims-EHR cohort ( = 16,749), hypertension, heart failure, diabetes, and CKD were common. Incidence rates (per 100 person-years) for thrombocytopenia and major bleeding were 8.2 and 7.3, respectively.
Accurate measurement of cardiopulmonary hemodynamics and exercise capacity is vital for PAH diagnosis and management. Terminal digit bias in clinical measures introduces non-differential error. Remote monitoring using im...Accurate measurement of cardiopulmonary hemodynamics and exercise capacity is vital for PAH diagnosis and management. Terminal digit bias in clinical measures introduces non-differential error. Remote monitoring using implanted devices eliminated this bias, demonstrating its potential to enhance accuracy in both clinical practice and research by reducing variability in observer-reported data.
Pulmonary arterial hypertension (PAH) is characterized by excessive pulmonary vasoconstriction and vascular remodelling, with mutations in bone morphogenetic protein receptor type 2 (BMPR2) being the most common genetic...Pulmonary arterial hypertension (PAH) is characterized by excessive pulmonary vasoconstriction and vascular remodelling, with mutations in bone morphogenetic protein receptor type 2 (BMPR2) being the most common genetic alteration associated with the disease. While inflammatory mediators like interleukin-6 (IL-6) and the iron-regulatory hormone hepcidin have been implicated in vascular remodelling, their interaction with BMPR2 signalling remains poorly understood. This study investigated how IL-6 and hepcidin influence BMPR2 expression and downstream signalling in human pulmonary arterial endothelial cells (hPAECs). Using qPCR and Western blot analyses, we demonstrated that both IL-6 and hepcidin significantly reduced BMPR2 mRNA and protein levels in hPAECs. Intriguingly, despite this reduction, SMAD1/5 phosphorylation remained active, suggesting compensatory signalling through alternative receptor complexes. Treatment with IL-6 and hepcidin upregulated inhibitors of differentiation (ID) protein expression, mimicking the effects observed with BMPR2 knockdown. These findings reveal a novel regulatory axis involving IL-6, hepcidin, and BMPR2 in PAH pathogenesis, where IL-6 and hepcidin promote vascular remodelling through both BMPR2-dependent and independent mechanisms. These results suggest that therapeutic strategies targeting this axis, particularly those aimed at rebalancing BMP/TGF-β signalling, may hold promise for treating PAH.
Pediatric idiopathic pulmonary arterial hypertension (IPAH) refractory to maximal medical therapy is associated with high morbidity and mortality, and therapeutic options remain limited. We describe a 12-year-old girl wi...Pediatric idiopathic pulmonary arterial hypertension (IPAH) refractory to maximal medical therapy is associated with high morbidity and mortality, and therapeutic options remain limited. We describe a 12-year-old girl with end-stage IPAH who developed acute decompensated right heart failure despite triple combination therapy, including high-dose prostacyclin. Escalation to intravenous epoprostenol failed to result in clinical or hemodynamic improvement. Following multidisciplinary discussion, ethical approval, and informed consent, sotatercept was initiated under compassionate use. Sotatercept therapy resulted in rapid and marked clinical recovery, including improvement in World Health Organization functional class (WHO FC) from IV to II, substantial increase in 6-min walk distance, normalization of NT-proBNP levels, and significant echocardiographic and invasive hemodynamic improvement. This case highlights the potential role of sotatercept as a rescue therapy in pediatric IPAH refractory to conventional treatment.
Eisenmenger syndrome represents a complex and severe form of pulmonary arterial hypertension (PAH) associated with congenital heart disease. Sotatercept, a first-in-class activin-signaling inhibitor, offers a novel thera...Eisenmenger syndrome represents a complex and severe form of pulmonary arterial hypertension (PAH) associated with congenital heart disease. Sotatercept, a first-in-class activin-signaling inhibitor, offers a novel therapeutic approach in the treatment of PAH, and has emerged as a promising therapeutic agent. However, patients with Eisenmenger syndrome were not included in its pivotal trials. Therefore, data regarding its effect in this patient cohort is lacking. We present two cases of patients with Eisenmenger syndrome treated with sotatercept. Sotatercept improved the subjective and objective exercise capacity in both patients without any significant adverse side effects.
Cullen O, Ross L, Fairley JL
… +11 more, Spencer LW, Mitchell AM, Rowe SJ, Janssens K, Bekhuis Y, Foulkes SJ, D'Ambrosio P, Calvo-Lopez M, Newcomb K, La Gerche A, Burns AT
Accurate resting oxygen consumption (rVO) quantification is critical for Fick-derived cardiac output calculations. Yet, clinical practice predominantly uses empirical estimations, which can be inaccurate. We evaluated th...Accurate resting oxygen consumption (rVO) quantification is critical for Fick-derived cardiac output calculations. Yet, clinical practice predominantly uses empirical estimations, which can be inaccurate. We evaluated the established rVO₂ prediction equations against direct metabolic cart measurements in systemic sclerosis patients, revealing significant discordances with potential diagnostic implications.
Patients 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 ther...Patients 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.
Pulmonary arterial hypertension (PAH) is a rare and progressive disease resulting in increased workload of the right ventricle (RV). Despite advances in therapies, PAH remains highly morbid from a progressive vasculopath...Pulmonary arterial hypertension (PAH) is a rare and progressive disease resulting in increased workload of the right ventricle (RV). Despite advances in therapies, PAH remains highly morbid from a progressive vasculopathy and RV failure. For patients admitted to hospital with RV failure, transplant remains the only option for a select few. Sotatercept, a novel activin signaling inhibitor approved for the treatment of PAH, has demonstrated significant improvement in clinical outcomes across a wide spectrum of disease severity. However, descriptions of its use to treat acute RV failure in an intensive care unit (ICU) setting are limited. We report a case of cardiogenic shock and respiratory failure secondary to decompensated PAH requiring veno-arterial extracorporeal membrane oxygenation (VA ECMO), with rapid improvement following sotatercept initiation.
Remote 6-min walk testing (6MWT) has been shown to be safe in pulmonary hypertension, but limited data exist on its longitudinal durability and relationship to supervised in-clinic testing. Cardiac Effort (CE), defined a...Remote 6-min walk testing (6MWT) has been shown to be safe in pulmonary hypertension, but limited data exist on its longitudinal durability and relationship to supervised in-clinic testing. Cardiac Effort (CE), defined as total heartbeats divided by walk distance, provides physiologic context beyond distance alone. We evaluated the longitudinal performance of a home-based 6MWT and CE performed on a modified indoor walking space using a wearable chest sensor and compared results with in-clinic testing over 8 weeks. This single-center prospective study was conducted with institutional review board approval. Participants with PH performed supervised in-clinic and unsupervised home 6MWTs at baseline and Week 8. A chest-based wearable sensor recorded acceleration and heart rate data to estimate walk distance and calculate CE. Mixed-effects repeated-measures models were used to compare sensor-estimated and directly observed walk distance and CE in the clinic and at home over time. Agreement was assessed using Bland-Altman analyses, intraclass correlation coefficients (ICC), and Spearman correlations. Twenty-nine participants were enrolled, and no adverse events occurred. Sensor-estimated 6MWT distance and CE demonstrated minimal bias and excellent agreement with directly observed in-clinic measurements (6MWD bias 0.04%, ICC 0.995; CE bias -0.04%, ICC 0.995). Home-based 6MWD was approximately 40 m lower than supervised clinic testing. Mixed-effects models showed similar longitudinal changes between home and clinic testing. Changes in home 6MWD and CE correlated with corresponding in-clinic changes (6MWD: = 0.40, = 0.045; CE: = 0.42, = 0.03). Home-based 6MWT and CE obtained using a wearable chest sensor provide a safe, feasible method for remote functional assessment in PH that tracks with in-clinic testing. Frequent home assessment may facilitate earlier detection of clinical change, support therapeutic titration, and expand access to standardized physiologic monitoring.
This study analyzed the US Open Payments and Medicare Part D databases from 2014 to 2022 to assess associations between industry-physician payments and PAH therapy prescribing. Among 5502 pulmonologist-, cardiologist- an...This study analyzed the US Open Payments and Medicare Part D databases from 2014 to 2022 to assess associations between industry-physician payments and PAH therapy prescribing. Among 5502 pulmonologist-, cardiologist- and pediatrician-prescribers of PAH therapies, drug-specific industry payments were associated with dose-response increases in Medicare spending.
Bunclark K, Newman J, Ghani H
… +15 more, Munagala S, Otter E, Fischer G, Kurzyna M, Meszaros G, Stone M, Moledina S, Howard L, Gin-Sing W, Ferrari P, Beghetti M, Toshner M, Granato M, PH GPS Consortium, Pepke-Zaba J
In this first global study of patient perspectives in Group 2 and 3 PH, we demonstrate that those with Group 3 PH report significantly greater adverse impacts on physical and mental wellbeing than those in Group 2 or Gro...In this first global study of patient perspectives in Group 2 and 3 PH, we demonstrate that those with Group 3 PH report significantly greater adverse impacts on physical and mental wellbeing than those in Group 2 or Group 1, despite a lower treatment side-effect profile.
Quyam S, Drumm S, Mungala S
… +15 more, Bunclark K, Fischer G, Otter E, Ghani H, Gin-Sing W, Howard L, Kurzyna M, Ferrari P, Macdonald L, Newman J, Stone M, Toshner M, Pepke-Zaba J, Beghetti M, Moledina S
The Pulmonary Hypertension Global Patient Survey (PH GPS) provides the first international examination of experiences among children with pulmonary hypertension (PH) and their caregivers. Through an online survey distrib...The Pulmonary Hypertension Global Patient Survey (PH GPS) provides the first international examination of experiences among children with pulmonary hypertension (PH) and their caregivers. Through an online survey distributed via PH associations across 32 countries, we collected responses from 136 caregivers about diagnostic journeys, treatment experiences, healthcare access and research participation. Qualitative analysis revealed challenges around the 'invisible' nature of PH, with caregivers describing how schools and communities sometimes doubted their child's limitations in the absence of visible symptoms, adding to family burden. Quantitative findings demonstrated extensive caregiver burden with 40% providing constant care while facing significant employment consequences, including leaving work altogether, reduced hours, or career changes. Although 78.8% of children accessed specialist centres, significant barriers persisted: 41.2% encountered diagnostic delays exceeding 6 months, 34.8% travelled over 2 h for appointments and 27.7% received no healthcare cost reimbursement. Treatment experiences revealed 37.7% of children experienced side effects, yet only one-third discussed changes with their clinical teams, reflecting pragmatic decisions within limited therapeutic options. Research participation was low (19.2%), though families with trial experience showed greater willingness for future participation, compared to those without experience (70.8% vs. 49.5%). Barriers centred on awareness gaps (16.4%), safety concerns (14.5%), and age-related considerations (10.9%), distinct from adult PH populations where logistical challenges predominate. These findings demonstrate that paediatric care must extend beyond medical management to address family needs including social-work assistance for benefits navigation, flexible care delivery models incorporating telemedicine, pro-active communication about treatment tolerability and research protocols designed with families from inception.
Bunclark K, Newman J, Ghani H
… +15 more, Munagala S, Otter E, Fischer G, Kurzyna M, Meszaros G, Stone M, Moledina S, Howard L, Gin-Sing W, Ferrari P, Beghetti M, Toshner M, Granato M, PH GPS Consortium, Pepke-Zaba J
The Pulmonary Hypertension (PH) Global Patient Survey provides the first truly international description of the symptomatic burden of PH and its treatment on patient's health-related quality of life (HRQoL). From 3329 ad...The Pulmonary Hypertension (PH) Global Patient Survey provides the first truly international description of the symptomatic burden of PH and its treatment on patient's health-related quality of life (HRQoL). From 3329 adult responses across 88 countries, the "invisible" nature of PH is an over-arching theme, with repercussions on socialisation, relationships and employment. Emotional burden is common with 35.6% feeling misunderstood, 33.4% angry or frustrated and 32.0% isolated. A reduced capacity for paid employment, in combination with healthcare/medication costs and difficulty in accessing social and financial support, compound societal exclusion and isolation. Physical limitations are almost universally reported (78.6%) with poor sleep quality (42.3%) the greatest factor in physical well-being. Treatment side-effects are common (46.7%), are greatest with parenteral therapies, but improve with age. Women of child-bearing age bear the brunt of PH physical and psychological burden, compounded by inconsistent messages from specialist services surrounding pregnancy and contraception. Patient-reported outcome measures (PROM) accurately reflect impacts from PH but are underutilised in clinical practice. Many respondents would like to be better able to discuss their emotional symptoms with their PH specialist (but often find a lack of empathy). Psychological support is a highly requested, but frequently unmet, need reinforcing the importance of holistic care models and multiagency working in managing patients with PH.