Prognosis Of Pulmonary Arterial Hypertension Research Articles

Tricuspid regurgitation in pulmonary arterial hypertension: a right ventricular volumetric and functional analysis.

The consequences of tricuspid regurgitation (TR) for right ventricular (RV) function and prognosis in pulmonary arterial hypertension (PAH) are poorly described and effects of tricuspid valve repair on the RV are difficult to predict. In 92 PAH patients with available cardiac magnetic resonance (CMR) studies, TR volume was calculated as the difference between RV stroke volume and forward stroke volume, i.e. pulmonary artery (PA) stroke volume. Survival was estimated from the time of the CMR scan to cardiopulmonary death or lung transplantation. In a subgroup, pressure-volume loop analysis including two-parallel elastances was applied to evaluate effective elastances, including net afterload (effective arterial elastance (E a)), forward afterload (effective pulmonary arterial elastance (E pa)) and backward afterload (effective tricuspid regurgitant elastance (E TR)). The effects of tricuspid valve repair were simulated using the online software package Harvi. 26% of PAH patients had a TR volume ≥30 mL. Greater TR volume was associated with increased N-terminal pro-brain natriuretic peptide (p=0.018), mean right atrial pressure (p<0.001) and RV end-systolic and -diastolic volume (both p<0.001). TR volume ≥30 mL was associated with a poor event-free survival (p=0.008). In comparison to E a, E pa correlated better with indices of RV dysfunction. Lower end-systolic elastance (E es) (p=0.002) and E TR (p=0.030), higher E pa (p=0.001) and reduced E es/E pa (p<0.001) were found in patients with a greater TR volume. Simulations predicted that tricuspid valve repair increases RV myocardial oxygen consumption in PAH patients with severe TR and low E es unless aggressive volume reduction is accomplished. In PAH, TR has prognostic significance and is associated with low RV contractility and RV-PA uncoupling. However, haemodynamic simulations showed detrimental consequences of tricuspid valve repair in PAH patients with low RV contractility.

(18)F-fluorodeoxyglucose uptake by positron emission tomography in patients with IPAH and CTEPH.

Pulmonary arterial hypertension (PAH) is driven by pathologies associated with increased metabolism such as pulmonary revascularization, vasoconstriction and smooth muscle cell proliferation in pulmonary artery wall. 18-fluorodeoxyglucose positron emission tomography (18FDG-PET) is an imaging technique sensitive to glucose metabolism and might be considered as a non-invasive method for diagnosis due to significant role of inflammation in idiopathic pulmonary artery hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH). The present study aimed to investigate the role of PET/CT imaging of patients with IPAH and CTEPH as an alternative diagnosis method. Demographic characteristics, FDG uptake in lungs, pulmonary artery and right ventricle (RV) of 17 patients (10 IPAH, 7 CTEPH), and 30 controls were evaluated. PET scanning, 6-min walk test, pro-BNP level, right heart catheterization of patients were performed both at the onsert and after 6-month PAH specific treatment. IPAH and CTEPH patients had significantly higher left lung FDG (p = 0.006), right lung FDG (p = 0.004), right atrial (RA) FDG (p < 0.001) and RV FDG (p < 0.001) uptakes than controls. Positive correlation was detected between the RV FDG uptake and the mean pulmonary artery pressure (mPAP) (r = 0.7, p = 0.012) and between the RA FDG uptake and the right atrial pressure (RAP) (r = 0.5, p = 0.02). Increased RV FDG and RA FDG uptakes predicts the presence of pulmonary hypertension and correlates with mPAP and RAP, respectively, which are important indicators in the prognosis of PAH. Further studies are required whether FDG PET imaging can be used to diagnose or predict the prognosis of pulmonary hypertension.

Pulmonary hypertension and metabolic disorders

This review presents current data regarding the relationship between hyperuricemia, obesity, diabetes mellitus, lipid disorders and pulmonary arterial hypertension (PAH), chronic thromboembolic pulmonary hypertension (CTEPH). Hyperuricemia is associated with a higher risk of developing of PAH, worse prognosis of PAH and greater severity of the patient's condition. Obesity leads to the development of pro-inflammatory and vasoconstrictor effects, hypoxia, which contributes to the progression of PH, however, the survival rate of patients with PH and overweight or obesity is higher than with normal or reduced body weight. Diabetes mellitus and concomitant insulin resistance are associated with a high risk of hospitalization for right ventricular heart failure and mortality. The presence of PAH is associated with lower values of total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, and probably high-density lipoprotein cholesterol (HDL-C). At the same time, higher levels of LDL-С and HDL-С in PAH and CTEPH determine a better prognosis of the disease.All metabolic disorders considered have common mechanisms of influence on PH. Further study of their pathogenetic basis will make it possible to develop unified approaches to methods of their correction in patients with various types of pulmonary hypertension.

The significance of dynamic monitoring plasma TMAO level in pulmonary arterial hypertension - a cohort study.

Gut microbiota assumes an essential role in the development and progression of pulmonary arterial hypertension (PAH). Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite, is correlated with the prognosis of patients with PAH. However, the correlation between changes in TMAO (ΔTMAO) and the prognosis of PAH remains elusive. To investigate the association between ΔTMAO and prognosis of PAH, and explore whether dynamic assessment of TMAO level was superior to measurement at a single time point in predicting prognosis. Single-center cohort study. Consecutive patients diagnosed with PAH and had at least two TMAO measurements taken from May 2019 to June 2020 were eligible. The outcome events of this study were defined as adverse clinical events. A total of 117 patients with PAH who had two TMAO measurements and follow-up were included in this study. Patients with ΔTMAO ⩾1.082 μmol/L had over four times increased risk of adverse clinical events than their counterparts after adjusting for confounders [hazard ratio (HR) 4.050, 95% confidence interval (CI): 1.468-11.174; p = 0.007]. Patients with constant high TMAO levels at both time points had the highest risk of adverse clinical events compared with patients with constant low TMAO levels (HR 3.717, 95% CI: 1.627-8.492; p = 0.002). ΔTMAO was also associated with changes in parameters reflecting PAH severity (p < 0.05). Changes in TMAO were independently correlated with prognosis in patients with PAH, irrespective of baseline level of TMAO. ΔTMAO also correlated with alteration in disease severity. Repeated assessment of TMAO level contributes to better identification of patients with increased risk of adverse clinical events.

Diagnostic Value of Serum Galectin-3 Binding Protein Level in Patients with Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) still lacks effective biomarkers to assist in its diagnosis and prognosis. Galectin-3 binding protein (Gal-3BP) plays a role in immune and inflammatory diseases. This study aimed to evaluate Gal-3BP as a prognostic and predictive factor in patients with PAH. From January 2017 to December 2019, we enrolled 167 consecutive PAH patients and 58 healthy controls. Right heart catheterization (RHC) was used to diagnose PAH. Serum Gal-3BP levels were measured by high-sensitivity human enzyme-linked immunosorbent assay (ELISA). Serum Gal-3BP levels in the PAH group were significantly higher compared with the control group (4.87±2.09 vs 2.22±0.86 μg/mL, p<0.001). Gal-3BP level was correlated with several hemodynamic parameters obtained from RHC (p<0.001). Multivariate linear regression analysis showed that Gal-3BP was a risk factor for PAH (odds ratio (OR)=2.947, 95% CI: 1.821-4.767, p<0.001). The optimal cut-off value of serum Gal-3BP level for predicting PAH was 2.89 μg/mL (area under the curve (AUC)=0.860, 95 % CI: 0.811-0.910, p<0.001). Kaplan-Meier analysis showed that Gal-3BP levels above the median (4.87 μg/mL) were associated with an increased risk of death in patients with PAH (hazard ratio (HR)=8.868, 95 % CI: 3.631-21.65, p<0.0001). Cox multivariate risk regression analysis showed that Gal-3BP was a risk factor for death in PAH patients (HR=2.779, 95 % CI: 1.823-4.237, p<0.001). Serum Gal-3BP levels were increased in patients with PAH, and levels of Gal-3BP were associated with the severity of PAH. Gal-3BP might have predictive value for the diagnosis and prognosis of PAH.

Risk Stratification and Prognosis of Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

Risk Stratification and Prognosis of Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

Impact of Epicardial Adipose Tissue on Right Cardiac Function and Prognosis in Pulmonary Arterial Hypertension

Although epicardial adipose tissue (EAT) is linked to effects on survival in left-sided heart failure, the association between EAT and right-sided heart failure caused by pulmonary arterial hypertension (PAH) remains unknown. What are the potential impacts of EAT volume (EATV) on right ventricular function, biomarkers of myocardial injury, and long-term prognosis in patients with PAH? A total of 135 age- and BMI-matched patients with PAH and 49 control participants were included in this study. EATV was quantified by using cardiac magnetic resonance and was related to clinical correlates, N-terminal pro-brain natriuretic peptide, and cardiac function. Levels of EATV associated with the risk of clinical worsening were evaluated on a continuous scale (restricted cubic splines) and by previously defined centile categories with Cox proportional hazards regression models and Kaplan-Meier survival estimates. Compared with the control participants, patients with PAH had a lower EATV (ln [EATV], 3.2 ± 0.8mL vs3.5 ± 0.7mL; P= .034). The association of EATV with right ventricular end-diastolic volume (Pnonlinear= .001), right ventricular end-diastolic volume index (P< .001), right ventricular cardiac output (P= .003), N-terminal pro-brain natriuretic peptide (P= .030), and the risk of clinical worsening (P= .014) was U shaped. Compared with individuals with middle-level EATV, multivariable-adjusted hazard ratio for clinical worsening was 6.0 (95%CI, 1.3-27.8) for the individuals with low-level EATV and 6.8 (95%CI, 1.5-30.2) for high-level EATV in patients with PAH. Patients with PAH had a decreased EATV compared with control participants. EATV exhibited a U-shaped association with right ventricular function and biomarkers of myocardial injury in patients with PAH. Low and high levels of EATV might reduce long-term event-free survival in patients with PAH. Chinese Clinical Trial Registry; No. ChiCTR2100049804; www.chictr.org.cn.

Sleep-disordered breathing patterns and prognosis in pulmonary arterial hypertension: A cluster analysis of nocturnal cardiorespiratory signals

BackgroundSleep-disordered breathing (SDB) is common among pulmonary arterial hypertension (PAH) patients and has been associated with unfavorable outcomes. This study aims to cluster overnight cardiorespiratory signals to investigate PAH phenotypes and examining their prognostic implications. MethodsIn this retrospective cohort study, we recruited consecutive PAH patients who underwent right heart catheterization and nocturnal cardiorespiratory polygraphy to evaluate SDB. Cluster analysis was employed to classify patients based on their SDB patterns. Cox regression analysis and Kaplan-Meier curves were utilized to assess the association between cluster membership and clinical outcomes. Logistic regression was used to identify risk factors associated with the cluster at higher risk of adverse outcomes. ResultsThe study comprised 386 PAH patients, with a mean age of 44.7 ± 17.0 years, of which 46.6 % were male. Three distinct clusters of PAH patients were identified: Cluster 1 (N = 182) presented with minimal SDB, Cluster 2 (N = 125) displayed obstructive sleep apnea (OSA) without significant hypoxemia, and Cluster 3 (N = 79) exhibited predominantly severe hypoxemic burden along with comorbid OSA. Notably, patients in Cluster 3 had an independent association with an increased risk of clinical worsening (hazard ratio 1.96, 95 % confidence interval [CI] 1.08–3.56, P = 0.027) compared to those in Clusters 1, even after adjusting for common confounders. The rate of clinical worsening for PAH-related events and mortality was higher in Cluster 3 than in Clusters 1 and 2 (26.6 % vs. 12.6 % and 19.2 %, respectively, log-rank P = 0.024). Moreover, the left ventricular mass index was identified as an independent risk factor for Cluster 3 (odds ratios 1.01, 95 % CI 1.00–1.02, P = 0.004). ConclusionsPatients with PAH who have nocturnal hypoxemia and OSA had worse clinical outcomes compared to those with only minimal SDB. Tailored management strategies that address both PAH and nocturnal hypoxemia may be effective in improving clinical outcomes.

Effects of inhaled seralutinib on right ventricular-pulmonary arterial (RV-PA) coupling and right heart function in pulmonary arterial hypertension (PAH)

Abstract Background Impaired RV-PA coupling portends a poor prognosis in PAH, and right ventricular free wall strain/systolic pulmonary artery pressure (RVFWS/sPAP) has been reported as a measure of RV-PA coupling. Furthermore, increased RVFWS and right atrial area (RAA), as well as decreased pulmonary artery compliance (PAC) are associated with increased mortality risk in PAH. Seralutinib is a novel, small molecule kinase inhibitor that targets PDGFR, CSF1R, and c-KIT administered via dry powder inhaler. TORREY, a phase 2, double-blind, randomised, placebo-controlled study of inhaled seralutinib in patients with PAH (NCT04456998) met its primary endpoint, demonstrating a significant reduction in pulmonary vascular resistance (PVR) from baseline (BL) to Week 24 compared to placebo. In addition, seralutinib significantly decreased NT-proBNP. Purpose To test the hypothesis that seralutinib would improve RVFWS/sPAP and other measures of right heart function after 24 weeks of treatment compared to placebo in the TORREY study. Methods Eighty-six patients with WHO Group 1 PH (Functional Class II, III), ages ≥18 years, pulmonary vascular resistance ≥400 dyne*s/cm5, and on stable PAH standard of care therapy (the majority of whom were on double and triple therapy with approved PAH medications) were enrolled. Right heart catheterisation (RHC) and full echocardiography were performed at BL and Week 24 and at BL, Week 12, and Week 24, respectively; both were analysed in a blinded central laboratory. To calculate RVFWS/sPAP, the pulmonary artery systolic pressure from RHC was used. PAC was calculated from RHC data with the formula (SV/(PAS-PAD)). Statistical analysis was performed using ANCOVA. Results At Week 24, the change in RVFWS/sPAP was lower in the seralutinib group compared to placebo (Table). The changes in RVFWS and RAA were lower in the seralutinib group vs placebo at Week 12 and Week 24 (Table). Change in NT-proBNP correlated with change in RAA (r = 0.43). At Week 24, change in PAC was greater in the seralutinib group (-0.02 ± 0.085 placebo, 0.19 ± 0.089 seralutinib; LSMD 0.22 (0.104) p = 0.04). There was no effect of seralutinib on left ventricular ejection fraction. Conclusion Treatment with seralutinib was associated with a significant reduction of RVFWS/sPAP. In addition, significant differences in RVFWS itself, RAA, and PAC were observed. These treatment effects support improved RV-PA coupling and right heart function. In conjunction with concordant reductions in PVR and NT-proBNP, these data suggest potential favourable effects of seralutinib in PAH. Seralutinib is in clinical development as a potential new treatment option for patients with PAH.

Impact of reduced apolipoprotein A-I levels on pulmonary arterial hypertension

ObjectiveThe significance of apolipoprotein A-I (ApoA-I) is the anti-inflammatory functional component of high-density lipoprotein, which needs to be further studied in relation to pulmonary arterial hypertension (PAH). This study aimed to identify the predictive value of ApoA-1 on the risk and prognosis of PAH, as well as the underlying anti-inflammatory mechanism. MethodsProteomic analysis was conducted on lung tissue from 6 PAH patients and 4 lung donors. Prediction of risk and mortality risk factors associated with PAH in 343 patients used logistic analysis and Cox regression analysis, respectively. The protective function of ApoA-I was assessed in human pulmonary arterial endothelial cells (HPAEC), while its anti-inflammatory function was evaluated in THP-1 macrophages. ResultsIn the lung tissues of patients with PAH, 168 differentially expressed proteins were associated with lipid metabolism according to GO and KEGG enrichment analysis. A protein-protein interaction network identified ApoA-I as a key protein associated with PAH. Lower ApoA-I levels were independent risk factors for PAH and displayed a stronger predictive value for PAH mortality. Plasma interleukin 6 (IL-6) levels were positively correlated with risk stratification and were higher in PAH patients with lower ApoA-I levels. ApoA-I was downregulated in the lung tissues of monocrotaline (MCT) -induced rats. ApoA-I could reduce the IL-6-induced pro-proliferative and pro-migratory abilities of HPAEC and inhibit the secretion of IL-6 from macrophages, which is compromised under hypoxic conditions. ConclusionOur study identified the significance of ApoA-I as a biomarker for predicting the survival outcome of PAH patients, which might relate to its altered anti-inflammatory properties.

Relationship between CONUT score and mortality in patients with pulmonary arterial hypertension

Abstract&#x0D; Purpose: Data about the association of malnutrition with prognosis in pulmonary arterial hypertension (PAH) is limited. This study aims to evaluate the relationship of Controlling Nutritional Status (CONUT) score with long-term mortality in PAH.&#x0D; Materials and methods: All consecutive patients newly diagnosed with PAH between 2013 and 2020 were evaluated. CONUT score at diagnosis was calculated through total lymphocyte, albumin and total cholesterol levels. Primary outcome was long-term all-cause mortality. Patients were followed up for 62 (31.3-91.5) months.&#x0D; Results: 92 patients (mean age=43.915.7 years, 65.2% women) were included. 37% of the patients had any degree of malnutrition according to CONUT score (2). Patients without malnutrition were significantly more in the low-risk categories of risk stratification tools (44.8% vs 17.6% according to ESC/ERS guideline, p=0.03; 70.7% vs 35.3% and 70.7% vs 32.4% according to REVEAL 2.0 and REVEAL Lite 2, p

Evaluation effect of COMPERA 2.0 risk assessment model on prognosis of Chinese patients with pulmonary arterial hypertension

Objectives: To clarify the evaluation effect of COMPERA 2.0 risk assessment model on prognosis of pulmonary arterial hypertension (PAH) in China. Methods: Patients with newly diagnosed PAH admitted in Fuwai hospital between April 2019 and March 2022 were enrolled retrospectively and divided in low, intermediate-low, intermediate-high and high strata by scores of COMPERA 2.0 risk assessment model. All the patients were followed up by clinic or telephone. The primary endpoint was defined as a composite of all-cause mortality, exacerbated heart failure and aggravated symptoms. Kaplan-Meier analysis and log-rank trend test were used to determine the risk of endpoints among the 4 groups. Multivariate Cox proportional hazards regression were used to analyze the association between COMPERA 2.0 scores and prognosis in patients with PAH. Results: A total of 951 patients with PAH were enrolled in this study. The age [M (Q1, Q3)] of the patients was 35 (28, 47) years, of which 706 cases (74.2%) were females. A total of 328 cases (34.5%) were assigned in low strata, 264 cases (27.8%) in intermediate-low strata, 193 cases (20.3%) in intermediate-high strata, and 166 cases (17.5%) in high strata. During the duration [M (Q1, Q3)] of follow-up after discharge of 1.8 (1.0, 2.8) years, the primary endpoint was occurred in 12.8% (42/328), 21.2% (56/264), 28.5% (55/193) and 42.8% (71/166) of low, intermediate-low, intermediate-high and high strata, respectively. The rates of primary endpoint were significantly increased with strata rising (P<0.001). Multivariate Cox proportional hazards regression showed that COMPERA 2.0 risk scores were associated with the primary endpoints in PAH patients (HR=1.801, 95%CI: 1.254-2.588, P=0.001) after adjusting confounders. Conclusion: COMPERA 2.0 risk assessment model is a simple and effective tool for evaluating the prognosis of newly diagnosed PAH patients in China.

Insights into the management of pulmonary arterial hypertension patients in Spain

Introduction and objectivesAccurate risk stratification is pivotal to tailor therapy according to the prognosis of pulmonary arterial hypertension (PAH) patients to positively impact the course of the disease. We conducted a nationwide study to assess how the current European Society of Cardiology/European Respiratory Society guidelines for risk assessment and management of PAH patients are followed in real-world practice in Spain. MethodsHospital-based physicians answered an online questionnaire describing their yearly caseload of PAH patients and their management of virtual cases scenarios for Word Health Organization functional class (FC) II–III PAH patients. ResultsThe main tests requested for a regular risk assessment were echocardiography, 6-minute walk test, measurement of brain natriuretic peptide/N-terminal pro-B-type natriuretic peptide plasma levels and right heart catheterization. The main treatment prescribed was an oral double-combination therapy with an endothelin receptor antagonist (ERA) and a phosphodiesterase type 5 inhibitor (PDE5i) or guanylate cyclase stimulator. Around 20% of the clinicians would also add the selective prostacyclin-receptor agonist (selexipag) to ERA and PDE5i as initial therapy for FC III patients, and nearly all clinicians (99%) would add a prostacyclin pathway agent to FC III PAH patients presenting multiple new intermediate-risk parameters despite a 6-month dual therapy with ERA and PDE5i. ConclusionsThe main decisive factor for the management of PAH patients in Spanish hospitals is their functional class and intermediate-risk parameters. Selexipag was more frequently prescribed than parenteral prostacyclin-analogs in triple-combination therapy for FC II–III PAH patients presenting low-risk and intermediate-risk parameters.

The heart of the matter: Right heart imaging indicators for treatment escalation in pulmonary arterial hypertension.

Right heart (RH) structure and function are major determinants of symptoms and prognosis in pulmonary arterial hypertension (PAH). RH imaging provides detailed information, but evidence and guidelines on the use of RH imaging in treatment decisions are limited. We conducted a Delphi study to gather expert opinion on the role of RH imaging in decision-making for treatment escalation in PAH. A panel of 17 physicians with expertise in PAH and RH imaging used three surveys in a modified Delphi process to reach consensus on the role of RH imaging in PAH. Survey 1 used open-ended questions to gather information. Survey 2 contained Likert scale and other questions intended to identify consensus on topics identified in Survey 1. Survey 3 contained Likert scale questions derived from Survey 2 and summary information on the results of Survey 2. The Delphi panel reached consensus that RH imaging is likely to improve the current risk stratification algorithms and help differentiate risk levels in patients at intermediate risk. Tricuspid annular plane systolic excursion, right ventricular fractional area change, right atrial area, tricuspid regurgitation, inferior venae cavae diameter, and pericardial effusion should be part of routine echocardiography in PAH. Cardiac magnetic resonance imaging is valuable but limited by cost and access. A pattern of abnormal RH imaging results should prompt consideration of hemodynamic evaluation and possible treatment escalation. RH imaging is an important tool for decisions about treatment escalation in PAH, but systematically collected evidence is needed to clarify its role.

Evaluation of the European Society of Cardiology/European Respiratory Society derived three- and four-strata risk stratification models in pulmonary arterial hypertension: introducing an internet-based risk stratification calculator.

Estimation of prognosis in pulmonary arterial hypertension (PAH) has been influenced by that various risk stratification models use different numbers of prognostic parameters, as well as the lack of a comprehensive and time-saving risk assessment calculator. We therefore evaluated the various European Society of Cardiology (ESC)-/European Respiratory Society (ERS)-based three- and four-strata risk stratification models and established a comprehensive internet-based calculator to facilitate risk assessment. Between 1 January 2000 and 26 July 2021, 773 clinical assessments on 169 incident PAH patients were evaluated at diagnosis and follow-ups. Risk scores were calculated using the original Swedish Pulmonary Arterial Hypertension Registry (SPAHR)/Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) three-strata model, the updated SPAHR three-strata model with divided intermediate risk, and the simplified three-parameter COMPERA 2.0 four-strata model. The original SPAHR/COMPERA and the updated SPAHR models were tested for both 3-6 and 7-11 available parameters, respectively. Prognostic accuracy [area under the receiver operating characteristic (ROC) curve (AUC)] and Uno's cumulative/time-dependent C-statistics (uAUC) were calculated for 1-, 3-, and 5-year mortality. At baseline, both the original SPAHR/COMPERA and the updated SPAHR models, using up to six parameters, provided the highest accuracy (uAUC = 0.73 for both models) in predicting 1-, 3-, and 5-year mortality. At follow-ups, the updated SPAHR model with divided intermediate risk (7-11 parameters) provided the highest accuracy for 1-, 3-, and 5-year mortality (uAUC = 0.90), followed by the original SPAHR/COMPERA model (7-11 parameters) (uAUC = 0.88) and the COMPERA 2.0 model (uAUC = 0.85). The present study facilitates risk assessment in PAH by introducing a comprehensive internet-based risk score calculator (https://www.svefph.se/risk-stratification). At baseline, utilizing the original or the updated SPAHR models using up to six parameters was favourable, the latter model additionally offering sub-characterization of the intermediate risk group. Our findings support the 2022 ESC/ERS pulmonary hypertension guidelines' strategy for risk stratification suggesting the utilization of a three-strata model at baseline and a simplified four-strata model at follow-ups. Our findings furthermore support the utility of the updated SPAHR model with divided intermediate risk, when a more comprehensive assessment is needed at follow-ups, complementing the three-parameter COMPERA 2.0 model. Larger multi-centre studies are encouraged to validate the utility of the updated SPAHR model. By introducing an internet-based risk score calculator (https://www.svefph.se/risk-stratification), risk assessment is facilitated. Our results support the 2022 ESC/ERS pulmonary hypertension guidelines' risk stratification strategy, additionally suggesting the updated SPAHR three-strata model with divided intermediate risk, as a promising complement to the new simplified three-parameter COMPERA 2.0 four-strata strategy, when a more comprehensive overview is needed.

Multi-Task Learning for Pulmonary Arterial Hypertension Prognosis Prediction Via Memory Drift and Prior Prompt Learning on 3D Chest CT.

Pulmonary arterial hypertension (PAH) prognosis prediction on 3D non-contrast CT images is one of the most important tasks for PAH treatment. It will help clinicians stratify patients into different groups for early diagnosis and timely intervention via automatically extracting the potential biomarkers of PAH to predict mortality. However, it is still a task of great challenges due to the large volume and low-contrast regions of interest in 3D chest CT images. In this paper, we propose the first multi-task learning-based PAH prognosis prediction framework, P 2-Net, which effectively optimizes the model and powerfully represents task-dependent features via our Memory Drift (MD) and Prior Prompt Learning (PPL) strategies. 1) Our MD maintains a large memory bank to provide a dense sampling of the deep biomarkers' distribution. Therefore, although the batch size is very small caused by our large volume, a reliable (negative log partial) likelihood loss is still able to be calculated on a representative probability distribution for robust optimization. 2) Our PPL simultaneously learns an additional manual biomarkers prediction task to embed clinical prior knowledge into our deep prognosis prediction task in hidden and explicit ways. Therefore, it will prompt the prediction of deep biomarkers and improve the perception of task-dependent features in our low-contrast regions. Our P 2-Net achieves a high prognostic correlation of the prediction and great generalization with the highest 70.19% C-index and 2.14 HR. Extensive experiments with promising results on our PAH prognosis prediction reveal powerful prognosis performance and great clinical significance in PAH treatment. All of our code will be made publicly available online Opened source: https://github.com/YutingHe-list/P2-Net.

Differential effect of basal vitamin D status in monocrotaline induced pulmonary arterial hypertension in normal and vitamin D deficient rats: Possible involvement of eNOS/TGF-β/α-SMA signaling pathways

Vitamin D deficiency is common and linked to poor prognosis in pulmonary arterial hypertension (PAH). We investigated the differential effect of basal vitamin D levels in monocrotaline (MCT) induced PAH in normal and vitamin D deficient (VDD) rats. Rats were fed a VDD diet and exposed to filtered fluorescent light to deplete vitamin D. Normal rats were pretreated with vitamin D 100 IU/d and treated with vitamin D 100 and 200 IU/d, while VDD rats received vitamin D 100 IU/d. Vitamin D receptor (VDR) silencing was done in human umbilical vein endothelial cells (HUVECs) using VDR siRNA. Calcitriol (50 nM/mL) was added to human pulmonary artery smooth muscle cells (HPASMCs) and HUVECs before and after the exposure to TGF-β (10 ng/mL). Vitamin D 100 IU/d pretreatment in normal rats up-regulated the expression of eNOS and inhibited endothelial to mesenchymal transition significantly and maximally. Vitamin D 100 IU/d treatment in VDD rats was comparable to vitamin D 200 IU/d treated normal rats. These effects were significantly attenuated by L-NAME (20 mg/kg), a potent eNOS inhibitor. Exposure to TGF- β significantly reduced the expression of eNOS and increased the mesenchymal marker expression in normal and VDR-silenced HUVECs and HPASMCs, which were averted by treatment and maximally inhibited by pretreatment with calcitriol (50 nM). To conclude, this study provided novel evidence suggesting the beneficial role of higher basal vitamin D levels, which are inversely linked with PAH severity.

Does arterial oxygenation during exercise add prognostic value in pulmonary arterial hypertension?

BackgroundThe 6-min walking distance (6MWD) is often used to assess prognosis in pulmonary arterial hypertension (PAH) patients. Whether or not changes in arterial oxygen saturation (SpO2) during exercise add prognostic value to the 6MWD in these patients is unclear. The objective of this study was to investigate if SpO2 changes during exercise adds prognostic value to the 6MWD in PAH patients. MethodsAmbispective study that includes 137 patients with PAH: 38 idiopathic/heritable (i/h PAH), 42 with connective tissue disease (CTD-PAH), 34 with porto-pulmonary hypertension (PoPH), 21 with HIV-associated PAH and 2 with pulmonary venous occlusive disease (PVOD). Patients were characterized and, treated according to international recommendations, and were followed-up for 5 years. To integrate SpO2 changes during exercise, we calculated the desaturation distance ratio (DDR) either in its original form (from a maximal theoretical value of 100%) or the actual resting SpO2 value of the patient (new DDR) as well as the distance saturation product (DSP). Results(1) during follow-up, 40 patients died (29.2%); (2) results confirmed the prognostic value of the 6MWD (AUC 0.913 [IQR 0.868–0.958]; p < 0.0001), original DDR (AUC 0.923 [0.881–0.966]; p < 0.001), New DDR (AUC 0.917 [0.872–0.961], p < 0.001), and DSP (AUC 0.914 [0.869–0.959], p < 0.001); and, (3) neither the original or new DDR or DSP added significant prognostic value to 6MWD in these patients. ConclusionsConsideration of three different composite indices of arterial oxygenation changes during exercise does not add prognostic value to that of the 6MWD in patients with PAH.

Abstract 13542: Associations of Pulmonary Artery Stiffness With Mortality in Pulmonary Arterial Hypertension

Introduction: Pulsatility, the relative area change of the pulmonary artery (PA) during the cardiac cycle has been associated with impaired prognosis in pulmonary arterial hypertension (PAH), but other measurements of stiffness are not well explored. Hypothesis: Multiple indices of PA stiffness derived from cardiac magnetic resonance (CMR) and right heart catheterization (RHC) predict outcome in PAH Methods: Retrospective chart review on 108 patients with PAH who had a clinically indicated CMR and RHC within 90 days, and for the primary endpoint of all-cause mortality. From CMR and RHC data, PA areas and indexes of stiffness (pulsatility, compliance, capacitance, distensibility, elastic modulus, and the pressure-independent stiffness index beta) were measured. Data was analyzed using Cox-proportional hazards models. Results: We included 108 patients with average age of 51 (+/- 13) years, 79% female with a mean PA pressure of 46 +/-12 mmHg, and a mean right ventricular ejection fraction (RVEF) of 38 +/-14%. After a median follow-up of 6 years, 58 (54%) patients had died. Most indices of increased stiffness were associated with higher mortality after adjusting for age, sex, diuretic use, mean PA pressure and RVEF ( Table ). Conclusions: Among patients with PAH, most measurements of PA stiffness strongly correlated with mortality.

Upregulation of miR-335-5p Contributes to Right Ventricular Remodeling via Calumenin in Pulmonary Arterial Hypertension.

Right ventricular (RV) failure determines the prognosis in pulmonary arterial hypertension (PAH), but the underlying mechanism is still unclear. Growing evidence has shown that microRNAs participate in RV remodeling. This study is undertaken to explore the role of miR-335-5p in regulating RV remodeling induced by PAH. Two PAH models were used in the study, including the monocrotaline rat model and hypoxia/su5416 mouse model. miRNA sequencing and RT-qPCR validation identified that miR-335-5p was elevated in the RV of PAH rats. In vitro, miR-335-5p expression was increased after angiotensin II treatment, and miR-335-5p inhibition relieved angiotensin II-induced cardiomyocyte hypertrophy. The luciferase reporter assay showed that calumenin was a target gene for miR-335-5p. Pretreatment with miR-335-5p inhibitors could rescue calumenin downregulation induced by angiotensin II in H9C2 cells. Moreover, intracellular Ca2+ concentration and apoptosis were increased after angiotensin II treatment, and miR-335-5p inhibition decreased intracellular Ca2+ accumulation and apoptosis. Finally, in vivo miR-335-5p downregulation (antagomir miR-335-5p) attenuated RV remodeling and rescued calumenin downregulation under conditions of hypoxia/su5416 exposure. Our work highlights the role of miR-335-5p and calumenin in RV remodeling and may lead to the development of novel therapeutic strategies for right heart failure.