Pulmonary Arterial Hypertension Subgroups Research Articles

Analysis of prognostic predictors and differences between subgroups of pulmonary arterial hypertension associated with portal hypertension and HIV infection

Abstract Background Pulmonary arterial hypertension (PAH) represents a complication of both portal hypertension (Po-PAH) and HIV infection (HIV-PAH). Due to overlapping risk factors, it is frequent to have an overlap PAH form associated with both portal hypertension and HIV (HIV/Po-PAH). Methods We enrolled 204 patients with Po-PAH (128), HIV-PAH (41) and HIV/Po-PAH (35), with the aim of comparing the characteristics and identifying the prognostic determinants. At baseline, in patients with Po-PAH and HIV/Po-PAH, the severity of liver disease was estimated using the Child-Turcotte-Pugh (CTP) score, MELD score (Model for End-stage Liver Disease); instead, in patients with HIV-PAH and HIV/Po-PAH it was defined whether they received HAART (Highly Active Anti-Retroviral Therapy) and the CD4+ lymphocytes number. Data are expressed as median (interquartile range) and compared with Dunn’s test. Prognostic determinants were identified by univariate and multivariate Cox-regression analysis. Survival was assessed using Kaplan Meier method. Results HIV-infected patients [40 (37-43) years] and HIV/Po-PAH [44 (39-48) years] are younger than Po-PAH patients [53 (44-60) years]; the exercise capacity assessed by the 6-minute walking test of patients with HIV/Po-PAH [516 (432-571) m] was superior to both patients with Po-PAH [426 (366-504) m] and HIV-PAH [448 (370-510) m], presumably justified by the demographic and haemodynamic differences between these groups. In fact, patients with concomitant portal hypertension (Po-PAH and HIV/Po-PAH) have a better haemodynamic profile than patients with HIV-PAH, specifically, lower pulmonary vascular resistance [6.2 (4.9-8.8) and 7.0 (5.5-11.2) WU vs 8.9 (7.5-12.2) WU] and higher cardiac index [3.1 (2.6-3.8) and 3.0 (2.7-3.7) l/min/m2 vs 2.6 (2.2-2.9) l/min/m2] and mixed venous oxygen saturation [70 (65-75) and 67 (62-71) % vs 61 (55-66)%] values. Despite these differences, the survival of the three groups of patients was not statistically different (5-year survival of patients with Po-PAH was 41%; of patients with HIV/Po-PAH was 46%; and of patients with HIV-PAH was 51%; log-rank test p-value= 0.059) and the prognostic factors that emerge at the multivariate analysis are only parameters associated with the underlying disease. In particular, the parameters independently associated with prognosis are, in patients with Po-PAH, only the CTP score [HR 1.665 (CI 1.153-2.403), p= 0.007]; in patients with HIV-PAH only the treatment with HAART [HR 0.283 (CI 0.119-0.675), p= 0.004]; in patients with HIV/Po-PAH both MELD-Na+ [HR 1.224 (CI 1.064-1.408), p= 0.005] and trans-hepatic venous gradient [HR 1.125 (CI 1.026-1.235), p= 0.013]. Conclusions In patients with Po-PAH, HIV-PAH, and HIV/Po-PAH adequately treated with PAH medications, the prognosis seems to be related to the underlying disease. This may explain why their survival is not statistically different despite significant demographic, exercise and hemodynamic differences.

Abstract 14112: Reproductive Risk Factors and Pulmonary Arterial Hypertension in Women

Introduction: Pulmonary arterial hypertension (PAH) is a devastating disease that affects women more often than men. The female predominance has increased over time; recent U.S. cohorts demonstrate a female:male ratio of nearly 4:1. The role of women-specific risk, such as reproductive exposures, is poorly understood in the pathophysiology of PAH. Hypothesis/Goals: We hypothesize that reproductive exposures influence the development and/or severity of PAH in women. We sought to investigate the role of reproductive factors and contribution of exogenous estrogen exposures to PAH onset and severity. Methods: Using reproductive history/exposure questionnaires from 390 women with PAH, enrolled in both the PAH Biobank and United States Pulmonary Hypertension Scientific Registry, we conducted linear regression analyses to assess the association between individual disease severity variables, as well as REVEAL Lite 2.0 scores, and patient reported reproductive variables as the predictors (Table 1). We adjusted for potential confounders including age, race, BMI, and PAH sub-group (idiopathic, heritable, or associated). Results: We found that younger menopause age, less than or equal to 40 years old, associates with a lower cardiac index (CI) at diagnosis [β -0.57, p 0.02]. The association persisted when controlling for use of hormone replacement therapy (HRT). There was a trend toward lower CI in those with menopause age of 41 to 50 years old, but not statistically significant [p 0.10]. Ever use of HRT was associated with a higher pulmonary vascular resistance [β 1.6, p 0.05] and lower CI [β -0.28, p 0.01] at diagnosis. Conclusion: Premature menopause (age less than 40 years) and ever use of HRT associate with worse hemodynamics at diagnosis in women with PAH, including lower cardiac index. Further investigations into reproductive exposures may offer an opportunity for more comprehensive risk factor screening and modification by physicians treating PAH patients.

Long-Term Survival of Patients with Connective Tissue Disease-Associated Pulmonary Arterial Hypertension: A Single-Center Cohort.

Pulmonary arterial hypertension (PAH) is a rare but severe complication of connective tissue disease (CTD). CTD-associated PAH (CTD-PAH) is the most common subgroup of PAH in East Asia. We prospectively collected 41 patients with CTD-PAH and followed them for a mean period of 43 ± 36 months. The long-term survival rates of the CTD-PAH patients at 1, 2, 3 and 5 years were 90%, 80%, 77%, and 60%, respectively. The non-survivors had more dilated main pulmonary arteries, higher pulmonary artery pressure and pulmonary vascular resistance (PVR). PAH-specific therapy resulted in improvements in functional class, 6-minute walk distance, serum uric acid, right ventricular function and PVR. Increased C-reactive protein during follow-up, indicating inflammatory processes, was also crucial for the management of CTD-PAH. Therefore targeting both PAH and inflammation is important in this specific subgroup of PAH. The results of this study may help develop treatment strategies for CTD-PAH patients.

Pulmonary artery compliance in different forms of pulmonary hypertension

ObjectivePulmonary artery compliance (PAC), estimated as stroke volume (SV) divided by pulmonary artery pulse pressure (PP), may be a predictor of survival in pulmonary arterial hypertension (PAH). Resistance–compliance (RC) time,...

Characteristics of exercise intolerance in different subgroups of pulmonary arterial hypertension associated with congenital heart disease

BackgroundExercise intolerance is a major manifestation of pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD). We aimed to investigate the characteristics of exercise intolerance in different subgroups of PAH-CHD. MethodsWe retrospectively enrolled 171 adult patients with PAH-CHD and 30 age and sex-matched healthy subjects and performed cardiopulmonary exercise testing. Gas exchange parameters, including peak oxygen uptake (peak V̇o2), anaerobic threshold, and the slope of ventilatory equivalent for carbon dioxide (V̇e/V̇co2 slope), were recorded. ResultsThe median age of patients at enrollment was 27.8 years, and 131 (76.6%) were female. Peak V̇o2 was reduced in patients compared to healthy controls (median, 14.8 ml/kg/min versus 26.9 ml/kg/min, p < 0.001). Of all 171 patients, 60 (35.1%) had Eisenmenger syndrome, 35 (20.5%) had PAH associated with systemic-to-pulmonary shunts (PAH-SP), 39 (22.8%) had PAH with small defects (PAH-SD), and 37 (21.6%) had PAH after cardiac defect correction (PAH-CD). Patients with Eisenmenger syndrome had the lowest peak V̇o2 (p = 0.003) and the highest V̇e/V̇co2 slope (p = 0.012), compared with other patients, representing the worst exercise capacity and ventilatory efficiency. Patients with PAH-SP had the best exercise capacity among the four groups, indicated by the highest peak V̇o2 (p = 0.003) compared with other patients. Peak V̇o2 was negatively correlated with pulmonary vascular resistance (r = −0.411, p < 0.001). ConclusionsExercise capacity was severely reduced in patients with PAH-CHD. Among the four subgroups, patients with Eisenmenger syndrome had the worst exercise capacity and ventilatory efficiency.

A machine learning approach to identifying patients with pulmonary hypertension using real-world electronic health records

BackgroundThis study aimed to develop a machine learning (ML) model to identify patients who are likely to have pulmonary hypertension (PH), using a large patient-level US-based electronic health record (EHR) database. MethodsA gradient boosting model, XGBoost, was developed using data from Optum's US-based de-identified EHR dataset (2007–2019). PH and disease control adult patients were identified using diagnostic, treatment and procedure codes and were randomly split into the training (90%) or test set (10%). Model features included patient demographics, physician visits, diagnoses, procedures, prescriptions, and laboratory test results. SHapley Additive exPlanations values were used to determine feature importance. ResultsWe identified 11,279,478 control and 115,822 PH patients (mean age, respectively: 62 and 68 years, both 53% female). The final model used 165 features, with the most important predictive features including diagnosis of heart failure, shortness of breath and atrial fibrillation. The model predicted PH with an area under the receiver operating characteristic curve (AUROC) of 0.92. AUROC remained above 0.80 for the prediction of PH up to and beyond 18 months before diagnosis. Among the PH patients, we also identified 955 pulmonary arterial hypertension (PAH) and 1432 chronic thromboembolic pulmonary hypertension (CTEPH) patients, and the range of AUROCs obtained for these cohorts was 0.79–0.90 and 0.87–0.96, respectively. ConclusionsThis model to detect PH based on patients’ EHR records is viable and performs well in subgroups of PAH and CTEPH patients. This approach has the potential to improve patient outcomes by reducing diagnostic delay in PH.

Diversity of hemodynamic types in connective tissue disease associated pulmonary hypertension: more than a subgroup of pulmonary arterial hypertension

ObjectiveConnective tissue disease associated pulmonary hypertension (CTD-PH) is classified as a subgroup of WHO group 1 PH, also called pulmonary arterial hypertension (PAH). However, not all CTD-PH fit hemodynamic definition of PAH. This study investigates the diversity of hemodynamic types of CTD-PH, their differences in clinical characteristics and outcomes.MethodWe performed a retrospective cohort study. CTD-PH patients were enrolled and divided into WHO group1 PH, WHO group 2 PH and hyperdynamic PH (mPAP > 20 mmHg, PVR < 3WU, PAWP < 15 mmHg) according to hemodynamics obtained by right heart catheterization. Patients with severe lung diseases, heart failure with reduced ejection fraction, pulmonary embolism, and hepatic cirrhosis were excluded. Baseline characteristics, autoantibodies, cardiac function, echocardiogram parameters, hemodynamics and survival rates were compared.ResultA total of 202 CTD-PH patients were included, 138 in WHO group 1 PH, 33 in WHO group 2 PH and 31 in hyperdynamic PH. We found hyperdynamic PH is less severe, presenting lower NT-proBNP level, better WHO function class, lower mPAP and PVR, higher cardiac output, and less cardiac remodeling. Incidence of anti-RNP was significantly lower in patients with elevated PAWP. Short-term survival was worse in WHO group 2 PH, yet 5-year survival rates didn’t differ between groups.ConclusionConsidering diversity in hemodynamic types, CTD-PH is more than a subgroup of PAH. Different types of CTD-PH present different clinical phenotypes and outcome. Phenotyping PH in CTD-PH patients is important.

Incidence and outcomes of pulmonary hypertension in the Ireland

IntroductionPulmonary hypertension (PH) is a progressive disease of the pulmonary vasculature, which is characterised by premature morbidity and mortality. The aim of this study is to define the characteristics of...

Analysis of necroptosis and its association with pyroptosis in organ damage in experimental pulmonary arterial hypertension.

In this study, a role of cell loss due to necroptosis and its linkage with pyroptosis in organ damage under the conditions of pulmonary arterial hypertension (PAH) was examined. Monocrotaline (MCT) was used to induce PAH in Wistar rats, and depending on the severity of the disease progression, they were further divided into two subgroups: MCT group—sacrificed 4 weeks after MCT administration and ptMCT group—prematurely sacrificed due to rapid deterioration in vital functions (on Day 24,11 ± 0,7). The elevation of respiratory rate and right ventricular (RV) hypertrophy were more evident in ptMCT group, while the heart rate and cardiac haemodynamic stress markers were comparably higher in both diseased groups. Detailed immunoblotting analysis revealed that the upregulation of pThr231/Ser232‐RIP3 proceeded into necroptosis execution in the RVs, unlike in the lungs of both PAH stages. The elevated pulmonary pThr231/Ser232‐RIP3 levels in both PAH subgroups were associated rather with GSDMD‐mediated pyroptosis. On the contrary, other inflammasome forms, such as AIM2 and NLRC4, were higher in the RV, unlike in the lungs, of diseased groups. The PAH‐induced increase in the plasma RIP3 levels was more pronounced in ptMCT group, and positively correlated with RV hypertrophy, but not with haemodynamic stress. Taken together, we indicated for the first time that pThr231/Ser232‐RIP3 upregulation resulting in two different necrosis‐like cell death modes might underlie the pathomechanisms of PAH and that the plasma RIP3 might serve as an additional diagnostic and prognostic marker of cardiac injury under these conditions.

Prospective clinical assessment of patients with pulmonary arterial hypertension switched from bosentan to macitentan (POTENT).

Even though pulmonary arterial hypertension (PAH) remains an incurable disease, the combination of PAH‐specific therapies allowed evolving from symptom‐based strategies to others aiming to move patients to low‐risk conditions. Endothelin‐1 (ET‐1) receptor antagonists emerged as specific‐PAH drugs that can be used in combination with other specific therapies. This work aimed to perform a prospective clinical assessment of patients with PAH that switched from bosentan to macitentan (POTENT), due to inadequate response. POTENT is a prospective, open‐label, single‐arm, uncontrolled study including PAH patients from our ongoing SAUDIPH registry. It enrolled 50 PAH patients divided as follows: idiopathic/heritable pulmonary arterial hypertension (I/HPAH); n = 24; PAH associated with congenital heart disease, n = 19; PAH associated with connective tissue diseases, n = 5; and pulmonary veno‐occlusive disease and/or pulmonary capillary haemangiomatosis (PVOD/PCH), n = 2. At baseline, most patients were in World Health Organization Functional Class (WHO FC) II/III (52.0%). After switching to macitentan, patients were more likely to be in WHO FC I/II (78%) and 22% of the overall cohort moved to a lower risk condition, with three low risk stratification parameters. Mean 6‐min walking distance increased about 34 m after 12 months, with a significant mean change over time (12.63 ± 11.69 at month 3 vs. 40.75 ± 12.57 at month 12, p = 0.002). Most haemodynamic parameters decreased over time, with corresponding negative mean changes (p < 0.001). The safety of macitentan was confirmed by the absence of anaemia and liver injury; clinical worsening was observed only in a small group of patients. In general, macitentan might be a valid alternative to bosentan in PAH stable patients on combination therapy with insufficient clinical response, and presenting intermediate and high‐risk parameters. We anticipate that studying this strategy in PAH subgroups would further clarify its potential and limitations.

Metabolomics-based mechanism exploration of pulmonary arterial hypertension pathogenesis: novel lessons from explanted human lungs.

Pulmonary arterial hypertension has led to global health and social problems, but the pathogenic mechanism has not been fully elucidated. Dysregulated metabolism is closely associated with the pathogenesis of pulmonary arterial hypertension. Here, we investigated metabolic profile shifts to reveal the molecular mechanisms underlying pulmonary hypertension. Explanted lung tissues from 13 idiopathic pulmonary arterial hypertension patients, 5 pulmonary arterial hypertension associated with congenital heart disease patients, and 16 controls were collected for untargeted metabolomics analysis with liquid chromatography coupled with tandem mass spectrometry. The KEGG database and MetaboAnalyst 5.0 were used for pathway analysis. A Cox survival analysis model was applied to evaluate the predictive value of metabolites on prognosis. Protein expression levels in human and rat pulmonary arterial hypertension lungs and hypoxia-exposed human pulmonary artery smooth muscle cells were detected by Western blotting to study the molecular mechanisms. Significant differences in metabolites and metabolic pathways were identified among the pulmonary arterial hypertension subgroups and control tissues. The levels of spermine were positively correlated with the patients' cardiac output, and (2e)-2,5-dichloro-4-oxo-2-hexenedioic acid was positively correlated with the patients' serum creatinine levels. Patients with higher thymine levels had a better prognosis. Moreover, seven differential metabolites were associated with the AKT pathway. AKT pathway inactivation was confirmed in human and rat pulmonary hypertensive lungs and pulmonary artery smooth muscle cells exposed to hypoxia. Our findings provide the first metabolomics evidence for pulmonary arterial hypertension pathogenesis in human lungs and may contribute to the improvement in therapeutic strategies.

Genetic Counseling and Testing for Pulmonary Arterial Hypertension in the United States

Genetic Counseling and Testing for Pulmonary Arterial Hypertension in the United States

Standardizing registry data to the OMOP Common Data Model: experience from three pulmonary hypertension databases

BackgroundThe Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) can be used to transform observational health data to a common format. CDM transformation allows for analysis across disparate databases for the generation of new, real-word evidence, which is especially important in rare disease where data are limited. Pulmonary hypertension (PH) is a progressive, life-threatening disease, with rare subgroups such as pulmonary arterial hypertension (PAH), for which generating real-world evidence is challenging. Our objective is to document the process and outcomes of transforming registry data in PH to the OMOP CDM, and highlight challenges and our potential solutions.MethodsThree observational studies were transformed from the Clinical Data Interchange Standards Consortium study data tabulation model (SDTM) to OMOP CDM format. OPUS was a prospective, multi-centre registry (2014–2020) and OrPHeUS was a retrospective, multi-centre chart review (2013–2017); both enrolled patients newly treated with macitentan in the US. EXPOSURE is a prospective, multi-centre cohort study (2017–ongoing) of patients newly treated with selexipag or any PAH-specific therapy in Europe and Canada. OMOP CDM version 5.3.1 with recent OMOP CDM vocabulary was used. Imputation rules were defined and applied for missing dates to avoid exclusion of data. Custom target concepts were introduced when existing concepts did not provide sufficient granularity.ResultsOf the 6622 patients in the three registry studies, records were mapped for 6457. Custom target concepts were introduced for PAH subgroups (by combining SNOMED concepts or creating custom concepts) and World Health Organization functional class. Per the OMOP CDM convention, records about the absence of an event, or the lack of information, were not mapped. Excluding these non-event records, 4% (OPUS), 2% (OrPHeUS) and 1% (EXPOSURE) of records were not mapped.ConclusionsSDTM data from three registries were transformed to the OMOP CDM with limited exclusion of data and deviation from the SDTM database content. Future researchers can apply our strategy and methods in different disease areas, with tailoring as necessary. Mapping registry data to the OMOP CDM facilitates more efficient collaborations between researchers and establishment of federated data networks, which is an unmet need in rare diseases.

Plasma markers in pulmonary hypertension subgroups correlate with patient survival

BackgroundRecent studies have provided evidence for an important contribution of the immune system in the pathophysiology of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). In this report, we investigated whether the inflammatory profile of pulmonary hypertension patients changes over time and correlates with patient WHO subgroups or survival.Methods50 PAH patients (16 idiopathic (I)PAH, 24 Connective Tissue Disease (CTD)-PAH and 10 Congenital Heart Disease (CHD)-PAH), 37 CTEPH patients and 18 healthy controls (HCs) were included in the study. Plasma inflammatory markers at baseline and after 1-year follow-up were measured using ELISAs. Subsequently, correlations with hemodynamic parameters and survival were explored and data sets were subjected to unbiased multivariate analyses.ResultsAt diagnosis, we found that plasma levels of interleukin-6 (IL-6) and the chemokines (C-X3-C) motif legend CXCL9 and CXCL13 in CTD-PAH patients were significantly increased, compared with HCs. In idiopathic PAH patients the levels of tumor growth factor-β (TGFβ), IL-10 and CXCL9 were elevated, compared with HCs. The increased CXCL9 and IL-8 concentrations in CETPH patients correlated significantly with decreased survival, suggesting that CXCL9 and IL-8 may be prognostic markers. After one year of treatment, IL-10, CXCL13 and TGFβ levels changed significantly in the PAH subgroups and CTEPH patients. Unbiased multivariate analysis revealed clustering of PH patients based on inflammatory mediators and clinical parameters, but did not separate the WHO subgroups. Importantly, these multivariate analyses separated patients with < 3 years and > 3 years survival, in particular when inflammatory mediators were combined with clinical parameters.DiscussionOur study revealed elevated plasma levels of inflammatory mediators in different PAH subgroups and CTEPH at baseline and at 1-year follow-up, whereby CXCL9 and IL-8 may prove to be prognostic markers for CTEPH patients. While this study is exploratory and hypothesis generating, our data indicate an important role for IL-8 and CXCL9 in CHD and CTEPH patients considering the increased plasma levels and the observed correlation with survival.ConclusionIn conclusion, our studies identified an inflammatory signature that clustered PH patients into WHO classification-independent subgroups that correlated with patient survival.

Respiratory and peripheral muscle involvement in patients with pulmonary arterial hypertension due to congenital heart diseases.

Skeletal and respiratory muscle dysfunction has been previously described in patients with other etiologic subgroups of pulmonary arterial hypertension (PAH) but has never been investigated in patients with PAH due to congenital heart diseases (CHD). This study aims to show the involvement of skeletal and respiratory muscles in these patients. This cross-sectional study included patients with PAH due to CHD and healthy controls. Patients' demographic properties, six-minute walk tests; shoulder abduction, handgrip, knee extension, and ankle dorsiflexion muscle strength, maximum inspiratory (MIP) and expiratory pressures (MEP) were measured. Deltoid, flexor digitorum superficialis, and profundus, tibialis anterior and rectus femoris muscles were visualized with ultrasonography and their cross-sectional areas (CSA) were also measured in both groups. 12 patients and 12 controls were included. Mean MIP was 104.22±32.57 cm H2O for healthy participants while 61.33±29.74 cm H2O for patients (p<0.001). For mean MEP, it was 100.08±26.05 cm H2O in healthy participants and 69.75±39.79 cmH2O in controls (p=0.004). When the strength of skeletal muscles was compared, there were significant differences between the groups in all measurements except for bilateral grip strength. In the correlation analysis, MIP and MEP values showed no significant correlations with clinical parameters. They showed significant moderate correlations with skeletal muscle strength. When CSAs of the muscles were compared, there were significant differences in all measurements except for left FDS and FDP and bilateral rectus femoris. This study showed that in patients with pulmonary arterial hypertension due to CHD, respiratory muscle strength is significantly worse than healthy participants. Patients had also significantly worse skeletal muscle strength except for grip strength.

Pulmonary pressure-to-longitudinal strain ratio by echocardiography: a rapid surrogate to magnetic resonance for right ventricular failure assessment

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): United Christian Hospital Ruttonjee and Tang Siu Kin Hospitals Background Better risk stratification in pulmonary hypertension (PH) by echocardiography (echo) to detect ventricular vascular uncoupling may act as gate-keeper for downstream management, such as MRI and expensive therapies. Studies showed modest correlation found between RV peak global longitudinal strain (RVGLS), which is afterload dependent, and right ventricular ejection fraction (RVEF) Purpose To test the accuracy and optimal cut-off of echo derived mean PA pressure-to-RVGLS ratio against MRI detected severe RV dysfunction (defined as RVEF&amp;lt; 35%), RV dilatation (defined as RVEDVi &amp;gt;87ml), and correlate native T1-values (nT1) Method Strain analyses by echo and volumetric assessment by 1.5 tesla MRI were performed in all patients. Contoured MRI short axis images provided RVEF. In a subgroup of pulmonary arterial hypertension (PAH), right heart catheterization and MRI non-contrast native T1 mapping were performed (Figure 1). Using previous study data, to identify a difference of 1.8 pressure-to-strain ratio between mild and severe PH with a variance of 2.2 , power of 80% and a significance level of 0.05, a total of 11 participants per group were needed Result Thirty-one PH patients (13 female, age 60 ± 14y, 13 had PAH) were recruited prospectively. Strong correlation was demonstrated between the mean PA pressure-to-RVGLS ratio to MRI derived RVEF (r = 0.80, p &amp;lt; 0.01), and to catheterization derived pulmonary vascular resistance and indexed cardiac output (r = -0.80, p= 0.001; r= -0.75, p = 0.003 respectively). The cut-off value of -2.5 had best accuracy in ROC analyses (Table 1) In PAH patients, this ratio correlated with global nT1 at basal short-axis level (r= -0.91, p = 0.004), but not at the mid short-axis level. Their basal posterior interventricular insertion regions had significantly higher nT1 than those of age-matched normal controls at the same region on the same scanner (1256 ± 217 ms vs. 932 ± 25 ms, p = 0.04) Conclusion In terms of detection of severe right ventricular dysfunction by echocardiography, mean PA pressure-to-RVGLS ratio performed better than RVGLS alone, and a ratio cutoff of -2.5 predicts MRI determined ventricular vascular uncoupling in pulmonary hypertension Table 1 Echo detect MRI AUC standard error 95% CI sens (%) spec (%) p Mean PA pressure -to-RVGLS ratio RVEF &amp;lt; 35% 0.86 0.073 0.71-1.00 72 83 0.007 RVEDVi &amp;gt; 87ml 0.81 0.081 0.65-0.97 83 70 0.004 RVGLS RVEF &amp;lt; 35% 0.76 0.100 0.57-0.96 60 83 0.048 RVEDVi &amp;gt; 87ml 0.73 0.090 0.55-0.91 67 70 0.032 PA pulmonary artery; RVGLS: RV global longitudinal strain; RVEDVi: indexed RV end-diastolic volume Abstract Figure 1

Could we suspect pulmonary veno-oclussive disease with a cardiopulmonary exercise test?

Abstract Background Cardiopulmonary exercise test (CPET) provides information about the pathophysiology of the exercise limitation. CPET parameters in pulmonary arterial hypertension (PAH) exhibit distinctive features, such as low peak oxygen uptake (pVO2), low end tidal carbon dioxide tension (PetCO2) and high ventilation-carbon dioxide slope (VE/VCO2).Pulmonary veno-oclussive disease (PVOD) is a PAH subgroup with particular underlying physiology, difficult diagnosis and poor prognosis. Purpose We hypothesized that different CPET patterns could be identified in PAH subgroups, and this may contribute to their diagnosis workup. Methods CPETs performed on the following PAH subgroups between September 2019 and January 2020 were prospectively included: Idiopathic PAH (IPAH), Heritable PAH (HPAH), and PAH responders to calcium channel blockers (CCB-R). Due to its low prevalence and its clinical relevance, CPET data on PVOD patients was retrospectively included. Results 57 CPET were included: 20 IPAH (35%); 13 HPAH (22.8%); 9 CCB-R (15.8%),15 PVOD (26.3%). All patients presented impaired functional capacity with reduced peakVO2 and increased VE/VCO2). Remarkably, PVOD patients,in spite of a younger age, exhibit the worst functional capacity and ventilatory efficiency even showing downward PetCO2 kinetics. CCB-R group achieved the highest peakVO2 and had better ventilatory parameters.(Table 1) Conclusion CPET is a useful tool to classify patients by PAH subgroups. Very low PetCO2 at rest and a downward PetCO2 kinetic strongly suggest PVOD, which has significant implications on treatment. Funding Acknowledgement Type of funding source: None

The reveal, reveal 2.0, compera and fphn risk scores in predciting the pah mortality: a single-centre study

Abstract Aims Several risk prediction models have been developed for risk assessment at the time of diagnosis and during follow-up in patients (pts) with pulmonary arterial hypertension (PAH). In this single-centre study we aimed to compare baseline REVEAL, REVEAL 2.0, COMPERA and FPHN risk scores in predicting the mortality in pts with PAH. Methods Study group comprised of 504 pts (age 54.4±18.9 years, female 64.4%) with PAH out of the overall 852 pts with pulmonary hypertension enrolled fourteen year period. Subgroups of PAH were as follows; IPAH (39%), CHD-PAH (51%), CTD-PAH (7.7%) and other PAH (3.3%). Functional-class (FC), six-minute-walking-distance (6MWD), pericardial effusion (PE), right atrial area (RAA), tricuspid-annular-planary-systolic-excursion (TAPSE) and systolic annular velocity (St), Echo and Catheter pulmonary artery mean presures (PAMP) and N-terminal-pro brain natriuretic-peptide (NT-proBNP) measures were evaluated at baseline and periodical control examinations with 6-months apart. Baseline assessments for REVEAL, REVEAL 2.0, COMPERA and FPHN risk scores were performed in all pts. Results In baseline assessment mean FC and 6MWD were 3 (3–4 IQR), and 230±100 m, repectively. Mean PAMP was 51.5±26 mm Hg, and pulmonary vascular resistance was 8.8±6.5 Wood units. Mono, dual and triple combination therapies were noted in 42%, 40%, and 18% of pts. Median follow-up time was (1470 (275–4840 IQR)) and overall all-cause mortality was 32.1%. Using the Cox proportional hazard model, likelihood ratio (LR) of scores and p values were as follows; REVEAL: 95.09 (p&amp;lt;0.001), REVEAL-2: 122.16 (p&amp;lt;0.001), COMPERA: 22.73 (p&amp;lt;0.001) and FPHN: 1.63 (p=0.210). Adding the TAPSE on REVEAL 2.0 score did not increase the LR of REVEAL 2.0. When comparing the different combinations including REVEAL 2.0, with likelihood ratio test, the LR of REVEAL 2.0 plus TAPSE vs REVEAL 2.0 was 7.32 (p=0.12), Conclusions In this single-centre study, REVEAL 2.0 as compared to REVEAL, COMPERA and FPHN models provided the highest prediction for mortality, and adding the TAPSE on the REVEAL 2.0 scoring offered no additional benefit for risk assessment. Funding Acknowledgement Type of funding source: None

Prognostic role of comorbidities in patients with pulmonary arterial hypertension

Abstract Background Epidemiology of pulmonary arterial hypertension (PAH) is changing and the age at diagnosis and the prevalence of comorbidities are increasing but their prognostic relevance is substantially undefined. Purpose To evaluate the prognostic value of comorbidities in patients with PAH and in the different clinical subgroups. Methods All patients with PAH referred to a single centre underwent baseline right heart catheterization, brain natriuretic peptide (BNP) plasma levels, 6-min walking distance (6MWD), WHO functional class and anamnestic comorbidities evaluation. Cox regression model was used for analysis (p-value &amp;lt;0.1 was considered for inclusion in multivariate analysis). Results 1311 patients were included [age 51 years; aetiology: 522 idiopathic/heritable/drug-induced (I/H/D)-PAH, 258 connective tissue disease (CTD)-associated PAH, 242 congenital heart disease (CHD)-associated PAH, 196 portal hypertension/HIV (PoHIV)-associated PAH and 93 pulmonary veno-occlusive disease (PVOD)]. 5% of patients have no comorbidities. At multivariate analysis comorbidities independently associated with prognosis are: systemic hypertension in I/H/D [HR 0.616, p=0.030], mean systemic blood pressure in CTD [HR 0.980, p=0.002] and PVOD [HR 0.962, p=0.006], dyslipidemia in CTD [HR 0.447, p=0.001] and PoHIV [HR 0.201, p=0.026], estimated glomerular filtration rate in PoHIV [HR 1.000, p&amp;lt;0.001] and body mass index (BMI) [HR 0.966, p=0.069] in CTD. In CHD comorbidities are not independent determinants of prognosis. Other variables independently predictive of a worse prognosis are: advanced age in all PAH subgroups except PVOD; male gender in I/H/D; reduced 6MWD in I/H/D, CTD and PVOD; high BNP in I/H/D, CHD and PVOD; low cardiac index in CTD, high right atrial pressure in I/H/D and low mixed venous oxygen saturation in CHD. Conclusion The age at PAH diagnosis and the prevalence of comorbidities are increasing but their prognostic role seems of poor relevance as we found a protective role of these variables: high systemic blood pressure (maybe indicative of a better haemodynamic stability) in I/H/D, CTD and PVOD; dyslipidemia and high BMI (maybe indicative of a better nutritional status and a less severe autoimmune disease) in CTD; dyslipidemia and a high glomerular filtration rate (both indicative of a less severe liver disease) in PoHIV. Funding Acknowledgement Type of funding source: None

SWITCHING TO RIOCIGUAT IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION NOT AT TREATMENT GOAL WITH PHOSPHODIESTERASE TYPE-5 INHIBITORS: SUBGROUP ANALYSIS RESULTS OF THE REPLACE STUDY

SWITCHING TO RIOCIGUAT IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION NOT AT TREATMENT GOAL WITH PHOSPHODIESTERASE TYPE-5 INHIBITORS: SUBGROUP ANALYSIS RESULTS OF THE REPLACE STUDY