Assessment Of Pulmonary Arterial Hypertension Research Articles

Equivalency of Multiple Biomarkers to Clinical Pulmonary Arterial Hypertension Survival Risk Models

Risk assessment in pulmonary arterial hypertension (PAH) is fundamental to guiding treatment and improved outcomes. Clinical models are excellent at identifying high-risk patients but leave uncertainty amongst moderate risk patients. Can a multiple blood biomarker model of PAH, using previously described biomarkers, improve risk discrimination over current models? Using multiplex ELISA, we measured NT-proBNP, ST2, IL-6, Endostatin, Galectin-3, HDGF, and IGF binding proteins (IGFBP1-7) in train (n=1623), test (n=696) and validation (n=237) cohorts. Clinical variables, biomarkers were evaluated by principal component analysis. NT-proBNP was not included to develop an NT-proBNP independent model. Unsupervised k-means clustering classified subjects into clusters. Transplant-free survival by cluster was examined using Kaplan-Meier and Cox proportional hazard regressions. Hazard by cluster was compared to NT-proBNP, REVEAL, and ESC/ERS Risk models alone, and combined clinical and biomarker models. The algorithm generated 5 clusters with good risk discrimination using 6 biomarkers, weight, height, and age at PAH diagnosis. In the test and validation cohorts the biomarker model alone performed equivalent to REVEAL (AUC 0.74). Adding the biomarker model to the ESC/ERS, and REVEAL scores improved the ESC/ERS and REVEAL scores. The best overall model was the biomarker model adjusted for NT-proBNP with the best C-statistic, AIC, and calibration for the adjusted model compared to either the biomarker or NT-proBNP model alone. A multi-biomarker model alone was equivalent to current PAH clinical mortality risk prediction models and improved performance when combined, and added to NT-proBNP. Clinical risk scores offer excellent predictive models but require multiple tests; adding blood biomarkers to models can improve prediction or enable more frequent, non-invasive monitoring of risk in PAH to support therapeutic decision making.

Early detection of pulmonary arterial hypertension through [18F] positron emission tomography imaging with a vascular endothelial receptor small molecule.

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.

Frequency, characteristics and risk assessment of pulmonary arterial hypertension with a left heart disease phenotype.

To obtain real-world evidence about the features and risk stratification of pulmonary arterial hypertension (PAH) with a left heart disease (LHD) phenotype (PAH-LHD). By reviewing the records of consecutive incident PAH patients at 7 tertiary centers from 2001 to 2021, we selected 286 subjects with all parameters needed to determine risk of death at baseline and at first follow-up with COMPERA and COMPERA 2.0 scores. Fifty seven (20%) had PAH-LHD according to the AMBITION definition. Compared with no-LHD ones, they were older, had higher BMI, more cardiovascular comorbidities, higher E/e' ratio and left atrial area, but lower BNP concentrations and better right ventricular function and pulmonary hemodynamics. Survival was comparable between PAH-LHD and no-LHD patients, although the former were less commonly treated with dual PAH therapy. Both COMPERA and COMPERA 2.0 discriminated all-cause mortality risk of PAH-LHD at follow-up, but not at baseline. Risk profile significantly improved during follow-up only when assessed by COMPERA 2.0. At multivariable analysis with low-risk status as reference, intermediate-high and high-risk, but not LHD phenotype, were associated with higher hazard of all-cause mortality. Results were comparable in secondary analyses including patients in the last 10years and atrial fibrillation and echocardiographic abnormalities as additional criteria for PAH-LHD. In real life, PAH-LHD patients are frequent, have less severe disease and are less likely treated with PAH drug combinations than no-LHD. TheCOMPERA 2.0 model may be more appropriate to evaluate their mortality risk during follow-up and how it is modulated by therapy.

Risk Assessment in Pulmonary Arterial Hypertension.

Risk Assessment in Pulmonary Arterial Hypertension.

Explanatory deep learning to predict elevated pulmonary artery pressure in children with ventricular septal defects using standard chest x-rays: a novel approach.

Early risk assessment of pulmonary arterial hypertension (PAH) in patients with congenital heart disease (CHD) is crucial to ensure timely treatment. We hypothesize that applying artificial intelligence (AI) to chest x-rays (CXRs) could identify the future risk of PAH in patients with ventricular septal defect (VSD). A total of 831 VSD patients (161 PAH-VSD, 670 nonPAH-VSD) was retrospectively included. A residual neural networks (ResNet) was trained for classify VSD patients with different outcomes based on chest radiographs. The endpoint of this study was the occurrence of PAH in VSD children before or after surgery. In the validation set, the AI algorithm achieved an area under the curve (AUC) of 0.82. In an independent test set, the AI algorithm significantly outperformed human observers in terms of AUC (0.81 vs. 0.65). Class Activation Mapping (CAM) images demonstrated the model's attention focused on the pulmonary artery segment. The preliminary findings of this study suggest that the application of artificial intelligence to chest x-rays in VSD patients can effectively identify the risk of PAH.

Echocardiographic Assessment of Pulmonary Arterial Hypertension Following Inhaled Nitric Oxide in Infants with Severe Bronchopulmonary Dysplasia

Objectives: Inhaled nitric oxide (iNO) is an effective pulmonary vasodilator. However, the efficacy of iNO in former premature infants with established bronchopulmonary dysplasia (BPD) has not been studied. This study aimed to determine the efficacy of iNO in reducing pulmonary artery pressure in infants with severe BPD as measured by echocardiography. Study Design: Prospective, observational study enrolling infants born at less than 32 weeks gestation and in whom (1) iNO therapy was initiated after admission to our institution, or (2) at the outside institution less than 48 h before transfer and received an echocardiogram prior to iNO initiation, and (3) had severe BPD. Data were collected at three time-points: (1) before iNO; (2) 12–48 h after initiation of iNO; and (3) 48–168 h after initiation of iNO. The primary outcome was the effect of iNO on pulmonary artery pressure measured by echocardiography in patients with severe BPD between 48 and 168 h after initiating iNO therapy. Results: Of 37 enrolled, 81% had echocardiographic evidence of pulmonary arterial hypertension (PAH) before iNO and 56% after 48 h of iNO (p = 0.04). FiO2 requirements were significantly different between time-points (1) and (3) (p = 0.05). There were no significant differences between Tricuspid Annular Plane Systolic Excursion (TAPSE) Z-Scores, time to peak velocity: right ventricular ejection time (TPV:RVET), and ventilator changes. Conclusions: Although we found a statistically significant reduction of PAH between time-point (1) and (3), future trials are needed to further guide clinical care.

Risk assessment in pulmonary arterial hypertension: A step towards clinical implementation based on the 2022 ESC/ERS pulmonary hypertension guidelines.

Risk assessment in pulmonary arterial hypertension: A step towards clinical implementation based on the 2022 ESC/ERS pulmonary hypertension guidelines.

PH Professional Network: Real-World Implementation: Nursing Role in Balancing the Art and Science of PAH Risk Assessment

Comprehensive serial risk assessment in pulmonary arterial hypertension has shown to determine prognosis, monitor disease progression, and guide treatment decisions. The treatment goal is to achieve a low-risk status, which is associated with lower mortality rate. However, use of formal risk assessment in clinical practice has been inconsistent due to numerous barriers related to the multivariable nature of the scores. This publication reviews strategies to increase risk evaluation in daily clinical practice, while emphasizing the role of the RN and APRN in implementing risk assessment calculation and skillful communication to the patient-family dyad to promote open dialogue with shared decision making and improved patient outcomes.

Incremental value of cardiopulmonary exercise testing in intermediate-risk pulmonary arterial hypertension.

Risk assessment in pulmonary arterial hypertension (PAH) is essential for prognostication. However, the majority of patients end-up in an intermediate risk status, offering insufficient guidance in clinical practice. The added value of cardiopulmonary exercise testing in this setting remains undefined. Two independent cohorts with idiopathic PAH at intermediate risk were used to develop (n=124) and externally validate (n=143) the prognostic model. Cross-validation on the overall population was used to strengthen the results of the analysis. Risk assessment was based on the simplified version of the ESC/ERS guidelines score. Discrimination and calibration were assessed. A risk score was constructed based on the beta-coefficient of the cross-validated model, including the stroke volume index (SVI) and the peak oxygen uptake (VO2 peak). Patients were grouped based on cutoff values of the risk score allowing the highest discrimination in the overall cohort. Group 1, score ≤2 (101 patients) with VO2 peak ≥14 ml/kg/min and SVI >30 ml/m2; Group 2, score between 2 and 5 (112 patients) with VO2 peak between 9 and 14 ml/kg/min, and SVI between 20 and 50 ml/m2; Group 3, score >5 (46 patients) with VO2 peak <10 ml/kg/min and SVI <30 ml/m2. The event-free survival rates at 1, 2 and 3 years, were 96%, 83% and 79% for Group 1, respectively; 82%, 67% and 52% for Group 2; 69%, 50% and 41% for Group 3. Combinations of VO2 peak and SVI may provide important information to further stratify intermediate-risk prevalent patients with idiopathic PAH.

PREVALENCE OF PULMONARY HYPERTENSION IN CHRONIC KIDNEY DISEASE

Background: Pulmonary hypertension (PH) is a recently recognized complication of chronic kidney disease (CKD), especially in end-stage renal disease. Cardiovascular disease is the most important cause of morbidity and mortality in CKD. This study was done to assess the prevalence of Pulmonary Hypertension in CKD patients and to assess the severity of Pulmonary Hypertension in different stages of CKD. The studyMaterials And Methods: was performed on 140 patients. At M. L. N. medical college prayagraj. All patients were evaluated by clinical, laboratory and imaging. All patients were subjected to echocardiography for assessment of Pulmonary arterial Hypertension. A totalResults: of 140 patients were included. Mean age of statics was 55.61±11.65 years. Male: Female was 2.33:1. Out of 140 study subjects, PH was found in 45 patients (32.1%.). Amongst which 26 had mild PH, 13 moderate and 6 had severe PH. Prevalence of Severe PH was signicantly higher in stage 5 CKD subjects (23.5%) compared to stage 3(1.3%) &amp; 4(2.3%). As CKD progressesConclusion: the prevalence and severity of PH increases.

Risk Assessment in Pulmonary Arterial Hypertension (PAH): Insights from the Inspire Study with LIQ861

<h3>Purpose</h3> The objective of this analysis was to assess for risk status improvement in PAH patients receiving inhaled dry powder treprostinil (LIQ 861) in the INSPIRE study. <h3>Methods</h3> INSPIRE was a Phase 3, open-label, multicenter study of WHO Group I PAH patients to evaluate the long-term safety and tolerability of LIQ861. Patients with New York Heart Association functional class (NYHA FC) II or III were transitioned to LIQ861 after receiving a stable dose of Tyvaso® for ≥3 months (Transition) or were started on LIQ861 as prostacyclin-naïve patients in addition to background therapy with an ERA and/or PDE5i. Transition patients received an initial dose of LIQ861 that was comparable to their Tyvaso® dose. Add-On patients initiated LIQ861 at a dose of 26.5 mcg 4 times/day. Dose increments in both groups were by 26.5 mcg as tolerated and as per the treating physicians' discretion. Three risk variables (NYHA FC, 6MWD and NT-pro BNP) were measured at baseline and during LIQ861 treatment. The percent of patients who achieved low-risk (NYHA FC: I-II; 6-minute walk distance (6MWD) >440m; N-terminal pro-brain natriuretic peptide (NT-pro BNP) <300ng/liter) were assessed at Baseline, Month 2, Month 4, and Month 8 in Transition, Add-On, and Overall Groups. <h3>Results</h3> A total of 121 patients were enrolled (55 Transition; 66 Add-On) in the trial. Overall, 51% of patients met 2 or 3 low risk variables at Baseline (n=120). At Month 2 (n=103), Month 4 (n=99) and Month 8 (n=91) there were 65%, 63% and 76% of patients who met 2 or 3 low risk variables respectively (Figure 1). Overall, a larger percentage of patients met 2 or 3 PAH low-risk variables at Month 8 than at Baseline. The percentage of patients increased from 51% at Baseline to 76% overall, and the shift was more pronounced in the Add-On Group (from 42% to 73%) than the Transition Group (62% to 79%). <h3>Conclusion</h3> In WHO group 1 PAH patients, LIQ861 was shown to improve risk stratification using the French non-invasive criteria.

Regular Risk Assessment in Pulmonary Arterial Hypertension - A Whistleblower for Hidden Disease Progression.

Despite developments in the treatment of pulmonary arterial hypertension, timely treatment is seldom achieved, and hidden progression is not uncommonly disguised as a seemingly "stable" condition. Appropriate risk assessment tools facilitate goal-oriented treatment strategies. This article aimed to review the development of these risk assessment tools including early assessment equations/scores, European guidelines-based risk assessment scores, and tools derived from the United States nationwide registry. A stepwise and regular approach with these assessment tools in clinical practice is highly recommended for timely treatment escalation to stop disease progression early. In this review, a practical and recommended algorithm of these assessment tools is also provided.

198 Intrapulmonary shunt assessment in pulmonary arterial hypertension

Abstract Aims Pulmonary arterial hypertension (PAH) is a rare, progressive disease with a poor prognosis. It is characterized by the presence of mean pulmonary arterial pressure (mPAP) ≥25 mmHg along with a pulmonary arterial wedge pressure (PAWP) ≤15 mmHg and pulmonary vascular resistance (PVR) &amp;gt;3 Wood units at right heart catheterization, in the absence of other causes of pre-capillary PH such as PH due to lung diseases, chronic thromboembolic PH, or other rare diseases. Hypoxaemia is a frequent finding in patients with PAH and could be related to ventilation–perfusion mismatch, reduced diffusing capacity, decreased cardiac output, or the opening of intrapulmonary (IP) or intracardiac shunt. Purpose of the present study is to detect IP shunts in PAH patients and its determinants. Methods and results We retrospectively enrolled 29 PAH patients, collecting clinical parameters, haemodynamic and blood gas analysis at baseline and after specific therapies at follow-up. Shunt fraction was calculated by the formula (Cc—Ca)/(Cc—Cv) during oxygen supplementation (FiO2 100%). Intracardiac defects were excluded by echo contrast examination. As expected, after treatments our results showed a significant decrease of PAPm (−7.2 ± 11.6 mmHg) and a significant decrease of PVR (−2.1 ± 3.9 WU). However, it was reported a statistically significant decrease in Hb value (−1.2 ± 1.7 g/dl), in SpO2 (−2.1 ± 3.8%) and in the alveolar–arterial oxygen gradient (a-ADO2) (+54.5 ± 113.1 mmHg). 6MWT and NYHA decreased at follow-up but not statistically significance was detected. IP shunt increase was detected at follow-up after specific treatments (delta Shunt +6.9 ± 6.5%). At multivariate analysis delta PVR remains the only independent determinants of delta Shunts with a significative increment of shunts when PVR are reduced by more than three WU. Conclusions Specific PAH treatments determine a decrease of PVR, but a reverse correlation with IP shunt was noticed. Increase of IP shunt could be not a favourable clinical feature. In fact high IP shunt fraction could determine hypoxaemia and the need of a chronic oxygen supply therapy. Although a not statistically significant decrease of 6MWT and NYHA was found, it is reasonable that a long-standing hypoxaemia could reduce the aerobic function capacity. Ours results unfortunately were deeply influenced by the loss of a great part of elective patients during the pandemic, with the most part of data coming from patients needing hospitalization. This could explain why the delta shunt fraction is higher than expected.

150 Incremental value of cardiopulmonary exercise testing in intermediate-risk pulmonary arterial hypertension

Abstract Aims Risk assessment in pulmonary arterial hypertension (PAH) is essential for prognostication. However, the majority of patients end-up in an intermediate risk status despite targeted-therapy, offering insufficient guidance in clinical practice. The added value of cardiopulmonary exercise testing (CPET) in this setting remains undefined. Methods and results Two independent cohorts with idiopathic PAH at intermediate risk were used to develop (n = 124) and externally validate (n = 143) the prognostic model. Risk assessment was based on the simplified version of the ESC/ERS guidelines score. The same definition of clinical worsening (CW) was used for both cohorts. Discrimination and calibration were assessed. Seventy-four derivation cohort patients experienced CW (51.2%) during a median of 34 months. Stroke volume index (SVI) and 6-min walk-distance (6MWD) were independent predictors of CW. With addition of CPET variables, SVI and VO2 peak independently improved the power of the prognostic model, determined by the integrated discrimination integral (IDI) index. ROC-derived cut-off values for SVI and VO2 peak were 34 and 14 ml/kg/min, respectively. Forty-eight validation cohort patients experienced CW (33.5%) during a median of 27 months follow-up. Different combinations of cut-off values of SVI and VO2 peak defined three meaningful groups showing good discrimination and calibration. The event-free survival rates at 1, 2, and 3 years were, respectively, 96%, 89%, and 89% for high SVI/high VO2 peak combination; 85%, 73%, and 61% for high SVI/low VO2 peak; and 80%, 70%, and 56% for low SVI/low VO2 peak. Conclusions Combinations of VO2 peak and SVI during follow-up is important in the prognostication of intermediate-risk prevalent patients with idiopathic PAH.

A pragmatic approach to risk assessment in pulmonary arterial hypertension using the 2015 European Society of Cardiology/European Respiratory Society guidelines

ObjectiveTo optimise treatment of patients with pulmonary arterial hypertension (PAH), the 2015 European Society of Cardiology/European Respiratory Society guidelines recommend using risk stratification, with the aim of patients achieving low-risk...

What's new in pulmonary hypertension clinical research: lessons from the best abstracts at the 2020 American Thoracic Society International Conference.

In this conference paper, we review the 2020 American Thoracic Society International Conference session titled, “What’s New in Pulmonary Hypertension Clinical Research: Lessons from the Best s”. This virtual mini-symposium took place on 21 October 2020, in lieu of the annual in-person ATS International Conference which was cancelled due to the COVID-19 pandemic. Seven clinical research abstracts were selected for presentation in the session, which encompassed five major themes: (1) standardizing diagnosis and management of pulmonary hypertension, (2) improving risk assessment in pulmonary arterial hypertension, (3) evaluating biomarkers of disease activity, (4) understanding metabolic dysregulation across the spectrum of pulmonary hypertension, and (5) advancing knowledge in chronic thromboembolic pulmonary hypertension. Focusing on these five thematic contexts, we review the current state of knowledge, summarize presented research abstracts, appraise their significance and limitations, and then discuss relevant future directions in pulmonary hypertension clinical research.

The Evolution of Risk Assessment in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a chronic debilitating disease that carries an unacceptably high morbidity and mortality rate despite improved survival with modern therapies. The combination of several modifiable and nonmodifiable variables yields a robust risk assessment across various available clinical calculators. The role of risk calculation is integral to managing PAH and aids in the timely referral to expert centers and potentially lung transplantation. Studies are ongoing to determine the role of risk calculators in the framework of clinical trials and to elucidate novel markers of high risk in PAH.

Role of Plasma Connective Tissue Growth Factor Levels in Assessment of Pulmonary Arterial Hypertension in Children with Congenital Heart Disease

Abstract Background: To investigate plasma Connective Tissue Growth Factor (CTGF) levels in Pulmonary Arterial Hyper-tension (PAH) associated with Congenital Heart Disease (PAH-CHD) in children and the relationships of CTGF with hemodynamic parameters. Plasma CTGF levels were calculated in 30 children with PAH-CHD and 30 health volunteers, using the subtraction method. Aim of Study: To assess plasma Connective Tissue Growth Factor (CTGF) levels in children with CHD and study its role in assessment of PAH that can be promising diagnostic and prognostic biomarkers for PAH in children with CHD. Patients and Methods: Our study was conducted in Pedi-atric Cardiology Clinic and Cardiology Catheter Laboratory of Ain Shams University Pediatric Hospital, in the period from Jan. 2019 to May 2020, including 30 patient and 30 healthy controls of matched age and sex. Results: The patients with PAH, 17 were acyanotic and 13 were cyanotic. The health control group and patient groups did not differ significantly in terms of age, gender and BSA (p>0.05). Height, weight and BMI were significantly lower in PAH-CHD group compared with the HCG (p 0.05). In addition, CTGF levels were higher in PAH-CHD group than health control group. Depicts that, PAH-CHD group had higher PASP, PADP, RVSP, mPAP, Qp, Rp and Rp/Rs (p < 0.01). Conclusion: Plasma CTGF levels could be a promising diagnostic biomarker for PAH-CHD in children.

Current advances in cardiac magnetic resonance imaging in systemic sclerosis.

Systemic sclerosis (SSc) is a systemic autoimmune disorder characterized by inflammation, fibroproliferative vasculopathy, and progressive fibrosis. Cardiac involvement is common in SSc and may affect the myocardium, pericardium, heart valves, conduction system, as well as coronary arteries. However, it remains asymptomatic for a long time, which leads to delayed diagnosis and poor prognosis. Accurate and early detection of cardiac abnormalities may warrant a better outcome in SSc. Recent advances in cardiac magnetic resonance imaging (CMR) improved the non-invasive evaluation of heart morphology and function. CMR can accurately identify both left and right ventricle dysfunction, which has a significant clinical and prognosis impact on SSc patients. In terms of myocardial structural alterations, CMR has remarkable diagnosis accuracy in identifying the presence and extent of myocardial fibrosis. When it comes to pulmonary arterial hypertension assessment, emerging data endorse the usefulness of CMR for the non-invasive quantification of it. Two-dimensional and time-resolved three-dimensional phase-contrast velocity-encoded CMR has become promising techniques for the assessment of pulmonary artery flow and stiffness measurements. Furthermore, CMR provides valuable prognostic information, both at the time of diagnosis and during follow-up in SSc patients with pulmonary arterial hypertension. The purpose of this review is to provide an overview of the latest findings in advanced cardiovascular imaging in patients with SSc.

Impact of inhaled treprostinil on risk stratification with noninvasive parameters: a post hoc analysis of the TRIUMPH and BEAT studies.

The 2015 European Society of Cardiology/European Respiratory Society treatment guidelines recommend frequent risk assessment in pulmonary arterial hypertension utilizing risk variables. Our objectives were: (1) to investigate the impact of inhaled treprostinil on risk stratification using the French noninvasive approach and REVEAL 2.0, and (2) to analyze the prognostic utility of both risk stratification methods in the predominantly New York Heart Association/World Health Organization functional class III/IV cohorts of TRIUMPH and BEAT. A post hoc analysis was performed to assess risk at baseline and follow-up at Week 12 in the TRIUMPH cohort (n = 148) and at Week 16, 21, and 30 in the inhaled treprostinil naïve placebo BEAT cohort (n = 73). Overall survival, clinical worsening-free survival, and pulmonary arterial hypertension-related hospitalization-free survival were all assessed in the pooled TRIUMPH and inhaled treprostinil naïve placebo BEAT cohorts based on risk group/strata at Week 12/16 follow-up. Inhaled treprostinil improved REVEAL 2.0 risk stratum (OR: 2.38, 95% CI: 1.09–5.19, p = 0.0298) and REVEAL 2.0 score (p = 0.0008) compared to placebo in the TRIUMPH cohort at Week 12. REVEAL 2.0 risk stratum and the number of low-risk criteria by the French approach improved at Weeks 16, 21, and 30 in the inhaled treprostinil naïve placebo BEAT cohort. Combining cohorts, REVEAL 2.0 risk stratification at follow-up was prognostic for clinical worsening-free, pulmonary arterial hypertension hospitalization-free, and overall survival, whereas the number of low-risk criteria was not. These post-hoc pooled analyses suggest inhaled treprostinil improves risk status and indicates that the REVEAL 2.0 calculator may be more suitable than the French noninvasive method for evaluating short-term clinical change in the New York Heart Association/World Health Organization functional class III/IV population.