Inflammation and Obesity Correlate in Pulmonary Hypertension but Associate with Diverging Outcomes.

Rationale & Objectives: Inflammation is associated with all types of Pulmonary Hypertension (PH) both as a known cause and/or a putative confounder. The most common marker of inflammation, C-reactive protein (CRP), has not been widely studied in PH. This study set out to clarify if CRP informed clinical endotyping and outcomes.

Seralutinib for the Treatment of Pulmonary Arterial Hypertension in Adults: TORREY Open-Label Extension Study.

Introduction: Seralutinib is an inhaled tyrosine kinase inhibitor targeting platelet-derived growth factor receptor (PDGFR) α/β, colony stimulating factor 1 receptor (CSF1R), and mast/stem cell growth factor receptor kit (c-KIT) kinases. TORREY, a phase 2, double-blind, randomized, placebo-controlled study of seralutinib in pulmonary arterial hypertension (PAH), met its primary endpoint, demonstrating a significant reduction in pulmonary vascular resistance (PVR) over placebo after 24 weeks (NCT04456998; EudraCT 2019-002669-37). We present results (as of December 5, 2024) from an open-label extension (OLE) study evaluating long-term safety, tolerability, and efficacy of seralutinib in adults with PAH (NCT04816604).

Association of the Right Ventricle Cardiac Power Index with Glucose Metabolism and Prognosis in Pulmonary Arterial Hypertension Patients-PET/MRI Study.

: In pulmonary arterial hypertension (PAH), there is still a need for new prognostic markers to precisely identify patients before clinical deterioration. We investigated the right ventricle cardiac power index (RV CPI) as a tool to assess RV function. We also hypothesized that hemodynamic changes occurring in PAH assessed with the RV CPI are related with cardiac metabolism alterations in PET imaging, which affects prognosis.

Lysosomal dysfunction and inflammatory sterol metabolism in pulmonary arterial hypertension.

Vascular inflammation regulates endothelial pathophenotypes, particularly in pulmonary arterial hypertension (PAH). Dysregulated lysosomal activity and cholesterol metabolism activate pathogenic inflammation, but their relevance to PAH is unclear. Nuclear receptor coactivator 7 () deficiency in endothelium produced an oxysterol and bile acid signature through lysosomal dysregulation, promoting endothelial pathophenotypes.

PPARγ/ETV2 axis regulates endothelial-to-mesenchymal transition in pulmonary hypertension.

Endothelial-to-mesenchymal transition (EndoMT) plays an important role in pulmonary hypertension (PH) but the molecular mechanisms regulating EndoMT remain to be defined. We demonstrate that the axis of the transcription factors PPARγ (Peroxisome Proliferator-Activated Receptor gamma) and ETV2 (ETS variant 2) play important roles in the pathogenesis of PH. Decreased levels of the expression of PPARγ and ETV2 along with reduced endothelial and increased EndoMT markers are consistently observed in lungs and pulmonary artery endothelial cells (PAECs) of idiopathic pulmonary arterial hypertension patients, in hypoxia-exposed mouse lungs, human PAECs, and in induced-EndoMT cells.

Gaps in evidence in the treatment of prevalent patients with pulmonary arterial hypertension at intermediate risk: An expert consensus.

Despite the innovations introduced in the 2022 European Society of Cardiology/European Respiratory Society Guidelines on Pulmonary Hypertension, risk discrimination and management of pulmonary arterial hypertension (PAH) patients at intermediate risk still represents a grey zone. Additionally, clinical evidence derived from currently available studies is limited. This expert panel survey intends to aid physicians in choosing the best therapeutic strategy for patients at intermediate risk despite ongoing oral therapy.

Changes in REVEAL Lite 2 risk status are associated with long-term outcomes in patients with pulmonary arterial hypertension: A post-hoc analysis of the GRIPHON study.

Background: Mortality risk assessment informs clinical management of pulmonary arterial hypertension (PAH). The Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2 is a simplified risk calculator discriminating 1-year mortality risk.

Methods: This post-hoc analysis of the phase 3 GRIPHON study assessed changes in REVEAL Lite 2 risk score with selexipag versus placebo and whether changes were prognostic or predictive of time to first morbidity/mortality (M/M) event.

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

Background: 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.

Research Question: Can a multiple blood biomarker model of PAH, using previously described biomarkers, improve risk discrimination over current models?

Study Design And Methods: Using a multiplex enzyme-linked immunosorbent assay, we measured N-terminal pro-B-type natriuretic peptide (NT-proBNP), soluble suppressor of tumorigenicity, IL-6, endostatin, galectin 3, hepatoma derived growth factor, and insulin-like growth factor binding proteins (IGFBP1-7) in training (n = 1,623), test (n = 696), and validation (n = 237) cohorts.

Right ventricular phenotyping in incident patients with idiopathic pulmonary arterial hypertension.

Background: Right ventricular (RV) imaging has not a definite role in risk stratification of pulmonary arterial hypertension (PAH) patients. We tested the hypothesis that echocardiography-derived phenotypes, depicting different degrees of RV remodeling and dysfunction, may provide additional prognostic information to current risk stratification tools.

Methods: Consecutive incident PAH patients aged ≥18 years, diagnosed between January 2005 and December 2021, underwent clinical assessment, right heart catheterization, standard echocardiography.

Application of REVEAL Lite 2 and COMPERA 2.0 risk scores to patients with pulmonary arterial hypertension switching to riociguat in the REPLACE study.

In Riociguat rEplacing PDE5i therapy evaLuated Against Continued PDE5i thErapy (REPLACE) (NCT02891850), improvements in risk status were observed in patients with pulmonary arterial hypertension (PAH) at intermediate risk switching to riociguat versus continuing phosphodiesterase-5 inhibitors (PDE5i). This post hoc study applied the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2 and Comparative Prospective Registry of Newly Initiated Therapies for Pulmonary (COMPERA) 2.0 risk-assessment tools to REPLACE to investigate the impact of baseline risk status on clinical improvement.

Seralutinib in adults with pulmonary arterial hypertension (TORREY): a randomised, double-blind, placebo-controlled phase 2 trial.

Background: Morbidity and mortality in pulmonary arterial hypertension (PAH) remain high. Activation of platelet-derived growth factor receptor, colony stimulating factor 1 receptor, and mast or stem cell growth factor receptor kinases stimulates inflammatory, proliferative, and fibrotic pathways driving pulmonary vascular remodelling in PAH. Seralutinib, an inhaled kinase inhibitor, targets these pathways.

The nitric oxide-soluble guanylate cyclase-cGMP pathway in pulmonary hypertension: from PDE5 to soluble guanylate cyclase.

The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway plays a key role in the pathogenesis of pulmonary hypertension (PH). Targeted treatments include phosphodiesterase type 5 inhibitors (PDE5i) and sGC stimulators. The sGC stimulator riociguat is approved for the treatment of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH).

Do Patients With Low-Risk Pulmonary Arterial Hypertension Really Benefit From Upfront Combination Therapy?: Insight From the AMBITION Trial.

Background: Based on results of the Ambrisentan and Tadalafil in Patients with Pulmonary Arterial Hypertension (AMBITION) trial, upfront combination therapy is recommended for treatment-naive patients with low-risk pulmonary arterial hypertension (PAH). However, conflicting data exist whether adopting this treatment strategy in this risk group is beneficial or well tolerated.

Research Question: Do patients with low-risk PAH really benefit from upfront combination therapy?

Study Design And Methods: Using the data from the original AMBITION trial, patients with PAH were classified as low, intermediate, or high risk using the Registry to Evaluate Early and Long-term PAH Disease Management 2.

Treatment effects of pulmonary artery denervation for pulmonary arterial hypertension stratified by REVEAL risk score: Results from PADN-CFDA trial.

Background: The differential treatment effect of pulmonary artery denervation (PADN) in pulmonary arterial hypertension (PAH) patients with different risk burdens remains unclear. This study aimed to determine the effectiveness of PADN in low vs intermediate-high-risk PAH patients.

Methods: In total, 128 patients with treatment naive PAH included in the PADN-CFDA trial were categorized into low-risk and intermediate-high-risk patients.

European Society of Cardiology quality indicators for the care and outcomes of adults with pulmonary arterial hypertension. Developed in collaboration with the Heart Failure Association of the European Society of Cardiology.

Aims: To develop a suite of quality indicators (QIs) for the evaluation of the care and outcomes for adults with pulmonary arterial hypertension (PAH).

Methods And Results: We followed the European Society of Cardiology (ESC) methodology for the development of QIs. This included (i) the identification of key domains of care for the management of PAH, (ii) the proposal of candidate QIs following systematic review of the literature, and (iii) the selection of a set of QIs using a modified Delphi method.

Pulmonary artery compliance in different forms of pulmonary hypertension.

Objective: Pulmonary 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, the product of PAC and pulmonary vascular resistance, is reported to be a physiological constant. We investigated if differences in PAC and RC time exist between pulmonary hypertension (PH) subgroups and examined whether PAC is an independent predictor of transplant-free survival in PAH.

Safety and efficacy of RT234 vardenafil inhalation powder on exercise parameters in pulmonary arterial hypertension: phase II, dose-escalation study design.

Background: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by high mean pulmonary arterial pressure (≥ 20 mmHg) and remodeling of the vascular arteries. Approved therapies improve symptoms and delay clinical worsening in the long term, but they do not relieve acute exertional symptoms. RT234, a drug/device combination (Respira Therapeutics, Palo Alto, CA, USA) that delivers the phosphodiesterase 5 inhibitor vardenafil to the lungs via inhalation, has been shown to reduce pulmonary vascular resistance in patients with PAH.