Contemporary Hospitalization and Mortality Burden in Real-world US Pulmonary Arterial Hypertension Patients

Authors: A Ravichandran, et al.

This real-world US study evaluated the current burden of pulmonary arterial hypertension (PAH) using claims data from 2017-2024. A total of 2,712 patients met the inclusion criteria, including 2,072 newly treated patients and 1,079 patients with PAH-related hospitalization. The mean age of the study population was 62 years, with women accounting for 69% of the participants. Over a mean follow-up period of 2.2 years, 56.2% experienced at least one all-cause hospitalization, while 44.9% had at least one hospitalization related to PAH. Among the PAH-hospitalized cohort (mean age 63 years; 67% women), patients averaged 1.5 PAH-related admissions per year and a median time interval of 1.2 years before re-hospitalization. More than half of the PAH-related hospitalizations (57.2%) required intensive care unit (ICU) stay, and 9.8% required mechanical ventilation. Among newly treated patients, mortality remained high despite available therapies. Mortality rates were 9.7% at 1 year, 19.6% at 2 years, and 25.2% at 3 years after treatment initiation.

Overall, these findings demonstrate that PAH remains associated with a substantial burden of hospitalization, re-hospitalization, and mortality in real-world clinical practice. Despite advances in PAH therapies, these findings underscore the ongoing unmet need for improved disease management.

Right in Front but Left Out: Ongoing Gaps in the Recognition and Management of Group 3 Pulmonary Hypertension in Patients with Honeycombing

Authors: I Guet-Cruza, et al.

This retrospective review evaluated recognition and management patterns of pulmonary hypertension (PH) and fibrotic lung disease in patients with CT chest reports showing honeycombing. Using natural language processing, 100 patients with honeycombing identified on CT imaging during 2024 were reviewed. Among these patients, 51 were evaluated by a pulmonologist. Of these, 38 patients (75%) were also seen by a cardiologist and all underwent echocardiography. Echocardiographic findings suggestive of PH, including reduced right ventricular systolic function, right-sided chamber enlargement, or elevated right ventricular systolic pressure (RVSP), were identified in 74% (28/38) of patients. However, only 18% (7/38) had a documented PH diagnosis, and none received PH-specific treatment. Most patients (92%; 35/38) had preserved left ventricular ejection fraction (≥50%), suggesting normal left sided function. From the pulmonary evaluation, 45% (17/38) had documented fibrotic lung disease, including idiopathic pulmonary fibrosis (IPF), progressive pulmonary fibrosis (PPF), interstitial lung disease (ILD), or pulmonary fibrosis. Despite this, only 18% (3/17) were treated with antifibrotic therapy.

Overall, the study highlights significant under-recognition and under-management of group 3 PH and fibrotic lung disease in patients with honeycombing on CT imaging, despite evaluation by pulmonologists. Closer collaboration between pulmonologists and cardiologists is critical for early diagnosis, prompt referral, and optimal treatment of these patients.

Comparing Safety Profiles Across Pulmonary Arterial Hypertension Therapeutic Classes: A Meta-Analysis of Randomized Controlled Trials

Authors: M Abdullah, et al.

This meta-analysis evaluated the safety profiles of different drug classes used in pulmonary arterial hypertension (PAH), including endothelin receptor antagonists (ERAs), phosphodiesterase-5 inhibitors (PDE5i), prostacyclin-pathway agents, soluble guanylate cyclase (sGC) stimulators, and activin-pathway agents. A total of 23 randomized controlled trials (RCTs) conducted between 1996 and 2024, involving approximately 5,800 patients with WHO Group 1 PAH, were included. The most commonly reported adverse events (AEs) across 23 RCTs were peripheral edema (about 19%), anemia (about 8%), hypotension/syncope (about 6%), and AE-related treatment discontinuation (about 5%). ERAs showed the highest pooled risk of peripheral edema (RR 1.46; 95% CI 1.25-1.72) and hepatic enzyme elevation (RR 2.05; 95% CI 1.40-3.00). PDE5i and sGC stimulators were associated with increased hypotension or syncope (RR 1.31; 95% CI 1.08-1.60) but demonstrated favorable hepatic safety profiles. Prostacyclin-pathway agents were linked to more gastrointestinal and headache-related AEs, while hepatic adverse events were less frequent. Activin-pathway agents demonstrated dose-dependent anemia (RR 1.35; 95% CI 1.10-1.68) and mild bleeding tendency. Significant heterogeneity was observed between drug classes (p<0.01). The analysis identified distinct toxicity signatures for each mechanistic pathway, including fluid retention and hepatic enzyme elevation with ERAs, hypotension with PDE5i/sGC stimulators, and hematologic toxicity with activin-pathway therapies that may shape monitoring.

Overall, this meta-analysis provides a comprehensive safety map of PAH pharmacotherapies. This enables individualised, risk-adjusted treatment selection and monitoring based on class-specific adverse event profiles, as well as the informed use of PAH therapies in patients receiving multidrug regimens.

The Incremental Shuttle Walk Test — A Practical Surrogate for VO2 Peak in Pulmonary Hypertension

Authors: E Cerrone, et al.

This study aimed to evaluate whether the incremental shuttle walking test (ISWT) could serve as a practical surrogate for peak oxygen consumption (VO2 peak) measured by cardiopulmonary exercise testing (CPET) in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). A total of 107 patients from the ASPIRE registry were included, of whom 57% had PAH and 43% had CTEPH. The mean age was 52 (+/- 15) years, and 62% were male. Mean pulmonary arterial pressure (mPAP) was 37(+/-13.7) mmHg, median pulmonary vascular resistance (PVR) was 4.2(2.7-7) Wood units and mean pulmonary artery wedge pressure (PAWP) was 10.1(+/- 3.1) mmHg. Mean incremental shuttle walk test distance (ISWTD) was 498(+/-257) meters, while mean VO2 peak was 17.5(+/- 5.2) mL/kg/min. A strong positive linear relationship was observed between VO2 peak and ISWTD (Pearson’s r=0.78; p=0.001). Linear regression analysis showed that VO2 peak was the main determinant of ISWTD, explaining about 60% of its variance (R²=0.607). Adjustment for demographic factors, type of diagnosis, and hemodynamic severity did not significantly increase the variance (adjusted R²=0.603). Each 1 mL/kg/min increase in VO2 peak was associated with an approximately 37-meter increase in ISWTD in this cohort.

Overall, the findings suggest that the ISWT may be a useful and practical field measure of peak aerobic capacity in patients with PAH and CTEPH.

Impact of Switching from Ambrisentan to Bosentan on Clinical and Risk Profiles in Pulmonary Arterial Hypertension: Insights from the Action Study

Authors: I Nascimento, et al.

This real-world retrospective single-center study evaluated short-term clinical outcomes after switching from ambrisentan to bosentan in patients with Group 1 pulmonary arterial hypertension (PAH) during a nationwide ambrisentan shortage in Brazil. A total of 72 adult patients were included. The mean age of the study population was 49.8 ± 14.6 years, with females accounting for 83.3% of the participants. The average time since diagnosis was 5.0 ± 4.2 years. Idiopathic PAH was the most common subtype (52.8%), followed by connective tissue disease-associated PAH (15.3%). Patients were receiving either dual combination therapy (51.4%) or triple combination therapy (48.6%). Following the switch to bosentan, 6-minute walk distance significantly declined from 419.5 meters to 386.5 meters (p=0.010). B- Type natriuretic peptide (BNP) levels increased modestly from a median of 99 pg/mL to 135 pg/mL, (p=0.097). No significant overall change was observed in WHO functional class (p = 0.91); however, a modest shift toward higher functional classes was noted, with 10 patients (14%) worsening. Risk status worsened after switching therapy. According to COMPERA 2.0 (n=72), the proportion of low-risk patients decreased from 41.7% to 25.0%, while it increased from 20.8% to 23.6% and 0% to 4.2% for intermediate-high and high-risk categories respectively (p=0.0018). As per REVEAL Lite 2, low-risk patients decreased from 55.6% to 38.9%, while high-risk patients increased from 13.9% to 25.0% (p<0.0001). Clinical decompensation occurred in 31.9%(n=23) of patients and was defined as early worsening with deterioration in class, dyspnea or syncope. Patients who decompensated had higher baseline right atrial pressure(12.3+/- 4.6vs 9.6+/- 4.8 mmHg; p=0.011). No significant differences in cardiac index, pulmonary vascular resistance, or mixed venous oxygen saturation was observed. Hepatotoxicity was reported in one patient (1.4%) with complete recovery observed after bosentan discontinuation.

Overall, short-term switching from ambrisentan to bosentan was associated with worsening exercise capacity and risk profile. Patients with elevated baseline right atrial pressure were more likely to experience clinical decompensation. These findings suggest potential differences in efficacy between the two ERAs that should be considered when making treatment switches and underscores the importance of close clinical monitoring during ERA transitions.

The Potential Role of Sildenafil in the Management of Acute Right Ventricular Dysfunction Following Pulmonary Embolism

Authors: S Shiv Priya, et al.

This case report describes a previously healthy 26-year-old man who developed right heart dysfunction following acute pulmonary embolism (PE) and was successfully treated with sildenafil. The patient developed diarrhea and dehydration during travel in Egypt and later experienced calf pain following his return flight to London. Initial computed tomography pulmonary angiography (CTPA) showed bilateral central pulmonary emboli involving the main pulmonary arteries, and anticoagulation therapy was started. However, due to lack of clinical improvement, he was referred for further management 10 days later. Repeat CTPA demonstrated disease progression with complete occlusion of the left lower lobe pulmonary artery and a large area of infarction. Transthoracic echocardiography showed a dilated right ventricle with impaired radial function, although longitudinal systolic function was preserved (pulmonary artery systolic pressure was 31 mmHg and right atrial pressure was 10-15 mmHg. The patient was treated with heparin and antibiotics. Thrombolysis or thrombectomy was not performed because the thrombi had likely been present for approximately two weeks and there was significant infarction of the left lower lobe. Sildenafil was initiated at 25 mg three times daily and later increased to 50 mg. Following clinical improvement, patient, was transitioned to rivaroxaban, and discharged. At 3-month follow-up, repeat CTPA showed no evidence of pulmonary embolism, and echocardiography demonstrated normal right ventricular function, including fractional area change of 48% and tricuspid annular plane systolic excursion of 2.9 cm. Sildenafil was subsequently discontinued, and the patient remained well at 1 year after discharge

This case suggests that sildenafil may have a role in selected patients with acute right ventricular dysfunction associated with pulmonary embolism.

Echo to Right Heart Catheterization: Assessing Bottlenecks in Pre-Capillary Pulmonary Hypertension Diagnosis

Authors: J W Leclair, et al.

This retrospective study evaluated echocardiographic features associated with delays in diagnosing precapillary pulmonary hypertension (PH). The Mass General Brigham Research Patient Data Registry (RPDR) was retrospectively reviewed to identify patients who had undergone at least one echocardiogram and a right heart catheterization (RHC) within six months of the echocardiographic assessment. A custom artificial intelligence–based data extraction pipeline was used to process unstructured RHC and echocardiography reports systematically. Demographic, hemodynamic, and echocardiographic data were extracted for 3,537 patients with paired RHC and echocardiographic evaluations, and the dataset was further analyzed to identify patients meeting hemodynamic criteria for pre-capillary pulmonary hypertension.

Among patients with paired RHC and echocardiographic studies performed between 2010 and 2023, 741 of 3,537 patients (21%) met the criteria of pre-capillary pulmonary hypertension by RHC and had normal to mildly enlarged left atrial size. The average tricuspid regurgitant velocity (TRV) on echocardiogram, was 3.13 m/s. A statistically significant correlation was observed between TRV and mean pulmonary arterial pressure (mPAP) (R = 0.639). Patients with TRV <3.4 m/s had a significantly longer time to diagnostic RHC compared to those with TRV ≥3.4 m/s (36 days vs 29 days; p=0.04). Time from echocardiography to diagnostic catheterization was similar between patients with normal and mildly enlarged left atrial size (35 days vs 33 days; p=0.28). No significant difference in time to diagnostic RHC was observed between patients aged <65 years and those aged ≥65 years (35 days vs 32 days; p=0.29). The study also found that patients obtaining echocardiograms after 2017 had a significantly longer interval between echocardiography and diagnostic RHC compared to before 2017(38 vs 28 days; p=0.003).

Overall, lower TRV on echocardiography was associated with longer time to diagnostic RHC in patients with precapillary PH. In contrast, advanced age and mild left atrial enlargement, factors associated with HFpEF and other cardiac comorbidities were not associated with delayed diagnosis.

Pulmonary Hypertension in Patients with Interstitial Lung Disease: Abbreviated Screening Tool for Early Detection

Authors: C Dagher, et al.

Pulmonary hypertension (PH) is a serious complication of interstitial lung disease (ILD) and is associated with higher morbidity and mortality. Early detection is important for guiding further evaluation, treatment decisions, and consideration for lung transplantation. A previously developed PH-ILD Detection Tool using eight clinical, physiologic, and imaging variables distinguishing patients into low, intermediate or high-risk groups has shown good performance but may be difficult to use in routine practice. This study aimed to develop a simplified screening tool using easily available clinical data. A retrospective cohort of 154 patients with ILD who underwent right heart catheterization (RHC) between October 2016 and February 2022 was analyzed. Within the original eight-variable PH-ILD Detection Tool, a simplified 3-point score was derived from three variables: (1) physical examination signs suggestive of PH, (2) diffusing capacity for carbon monoxide (DLCO) < 40% predicted, and (3) use of supplemental oxygen. Each variable was assigned 1 point (score range: 0–3). Overall prevalence of PH in the cohort was 48.1%. PH prevalence increased with higher scores: 14.3% (score 0), 58.1% (score 1), 79.0% (score 2), and 87.2% (score 3). Using a cutoff ≥2, the tool showed sensitivity of 90%, specificity of 58%, positive predictive value (PPV) of 78%, and negative predictive value (NPV) of 79%. At a cutoff of 3, sensitivity was 54%, specificity 88%, PPV 87%, and NPV 56%. Receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.74 (95% confidence interval: 0.65–0.82; p < 0.001), indicating significant ability to distinguish ILD patients with and without PH.

Overall, the simplified 3-point screening tool including physical examination findings, DLCO <40%, and supplemental oxygen use, demonstrated meaningful accuracy in detecting PH among ILD patients and may help support early identification and prompt referral for confirmatory testing, improving management of PH-ILD.

Evaluating Non-invasive Predictors of Pre- and Post-capillary Pulmonary Hypertension

Authors: I Jackson, et al.

Pulmonary hypertension (PH) is a disorder characterized by elevated pulmonary arterial pressure, resulting in substantial morbidity and mortality. It is classified as pre-capillary PH (due to dysfunction within the arterial vasculature), post-capillary PH (due to left-sided cardiac pressure elevation), or mixed PH.  While a diagnosis of pre-capillary PH typically prompts initiation of PH-specific vasodilator therapy, identifying post-capillary PH is less likely to alter treatment, as management primarily focuses on treating the underlying left-sided cardiac dysfunction. Right heart catheterization (RHC) is required for definitive diagnosis and classification but is invasive and not always accessible. Hence, this study aimed to evaluate whether non-invasive tests could help differentiate pre-capillary from post-capillary to guide whether pursuing RHC will be beneficial. This retrospective study included 79 patients diagnosed with PH confirmed by RHC in the past two years. Based on 2022 European Respiratory Society (ERS) guidelines, patients were classified as pre-capillary, post-capillary, or mixed PH; post-capillary and mixed PH were combined into one group for analysis due to small sample size. Clinical variables, serum biomarkers, and echocardiographic parameters were assessed using logistic regression. Among 79 patients, 58.2% had pre-capillary PH, while 41.8% had post-capillary or mixed PH. A 10% increase in percent-predicted distance on the six-minute walk test (6MWT) was associated with 52% higher odds of having post-capillary or mixed PH (95% confidence interval [CI]: 3%–124%; p=0.037). A 0.1-unit increase in mitral E/A ratio was associated with 15% higher odds of post-capillary or mixed PH (95% CI: 1%–32%; p=0.043). Patients with elevated tricuspid regurgitation (TR) velocity and abnormal tricuspid annular plane systolic excursion (TAPSE) demonstrated a non-statistically significant trend towards having pre-capillary PH.

Overall findings suggest that non-invasive assessments may help predict pre-capillary PH from post-capillary or mixed PH. A lower percent-predicted 6MWT was associated with pre-capillary PH and may support the decision to pursue RHC and initiate PH-specific therapy. In contrast, evidence of diastolic dysfunction, reflected by a higher E/A ratio, may indicate that management should initially focus on underlying left-sided cardiac disease before considering invasive evaluation with RHC. Although higher TR velocity and TAPSE showed a trend toward pre-capillary PH, these associations did not reach statistical significance, potentially due to the limited sample size and reduced statistical power of the study.

ATS 2026, May15 –20, Orlando, Florida