Management and outcomes in pulmonary arterial hypertension patients with sepsis.

Background: Sepsis is a common cause of death in patients with pulmonary arterial hypertension (PAH). Treatment requires careful fluid management and hemodynamic support. This study compares patients with or without PAH presenting with sepsis with a focus on initial fluid resuscitation.

Association Between Thrombus Histopathology and Hemodynamic Outcomes Among Patients With Chronic Thromboembolic Pulmonary Hypertension Undergoing Pulmonary Endarterectomy.

Background: Pulmonary endarterectomy (PEA) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH). Although most have normalization of pulmonary artery (PA) pressures, development of residual pulmonary hypertension (RPH) is challenging to predict.

Research Question: Among patients with CTEPH undergoing PEA, is there a relationship between specimen histopathology and postoperative hemodynamics?

Study Design And Methods: In this single-center retrospective cohort study, patients with CTEPH who underwent PEA were classified by thrombus chronicity: organized (chronic), organizing (subacute), or mixed (combined organizing and organized).

Efficacy and safety of selexipag in patients with inoperable or persistent/recurrent CTEPH (SELECT randomised trial).

Background: SELECT was the first global randomised controlled trial of selexipag with standard of care in patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension.

Methods: SELECT was a multicentre, randomised, double-blind, placebo-controlled, parallel-group, group-sequential, phase 3 study (ClinicalTrials.gov: NCT03689244).

Macitentan and Tadalafil Combination Therapy in Incident and Prevalent Pulmonary Arterial Hypertension: Real-World Evidence from the OPUS/OrPHeUS Studies.

Introduction: Historically, patients recently (≤ 6 months) diagnosed with pulmonary arterial hypertension (PAH; incident) have had poorer survival than those with a longer (> 6 months) time from PAH diagnosis (prevalent). Despite guideline recommendations for initial combination therapy for most patients with PAH, many are initiated and maintained on monotherapy. Real-world evidence to evaluate the benefit of early combination treatment in newly-diagnosed patients is lacking.

Pulmonary hypertension associated with lung diseases.

Pulmonary hypertension (PH) associated with chronic lung disease (CLD) is both common and underrecognised. The presence of PH in the setting of lung disease has been consistently shown to be associated with worse outcomes. Recent epidemiological studies have advanced understanding of the heterogeneity of this patient population and shown that defining both the specific type of CLD as well as the severity of PH ( deeper phenotyping) is necessary to inform natural history and prognosis.

Integrative Multiomics in the Lung Reveals a Protective Role of Asporin in Pulmonary Arterial Hypertension.

Background: Integrative multiomics can elucidate pulmonary arterial hypertension (PAH) pathobiology, but procuring human PAH lung samples is rare.

Methods: We leveraged transcriptomic profiling and deep phenotyping of the largest multicenter PAH lung biobank to date (96 disease and 52 control) by integration with clinicopathologic data, genome-wide association studies, Bayesian regulatory networks, single-cell transcriptomics, and pharmacotranscriptomics.

Results: We identified 2 potentially protective gene network modules associated with vascular cells, and we validated , coding for asporin, as a key hub gene that is upregulated as a compensatory response to counteract PAH.

Dissecting the lung transcriptome of pulmonary fibrosis-associated pulmonary hypertension.

Integrative multiomics can help elucidate the pathophysiology of pulmonary fibrosis (PF)-associated pulmonary hypertension (PH) (PF-PH). Weighted gene coexpression network analysis (WGCNA) was performed on a transcriptomic dataset of explanted lung tissue from 116 patients with PF. Patients were stratified by pulmonary vascular resistance (PVR), and differential gene expression analysis was conducted.

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.

Atrial Arrhythmias in Patients With Pulmonary Hypertension.

Topic Importance: Atrial arrhythmias (AA) are common in patients with pulmonary hypertension (PH) and contribute to morbidity and mortality. Given the growing PH population, understanding the pathophysiology, clinical impact, and management of AA in PH is important.

Review Findings: AA occurs in PH with a 5-year incidence of 10% to 25%.

Macitentan in Pulmonary Arterial Hypertension Associated with Connective Tissue Disease (CTD-PAH): Real-World Evidence from the Combined OPUS/OrPHeUS Dataset.

Introduction: Data on real-world clinical practice and outcomes of patients with pulmonary arterial hypertension associated with connective tissue disease (CTD-PAH) are scarce. The OPUS/OrPHeUS studies enrolled patients newly initiating macitentan, including those with CTD-PAH. This analysis describes patient characteristics, treatment patterns, outcomes, and safety profiles of patients with CTD-PAH newly initiating macitentan in the US using the OPUS/OrPHeUS combined dataset.

Modelling costs of interventional pulmonary embolism treatment: implications of US trends for a European healthcare system.

Aims: Catheter-directed treatment (CDT) of acute pulmonary embolism (PE) is entering a growth phase in Europe following a steady increase in the USA in the past decade, but the potential economic impact on European healthcare systems remains unknown.

Methods And Results: We built two statistical models for the monthly trend of proportion of CDT among patients with severe (intermediate- or high-risk) PE in the USA. The conservative model was based on admission data from the National Inpatient Sample (NIS) 2016-20 and the model reflecting increasing access to advanced treatment from the PERT™ national quality assurance database registry 2018-21.

Comparison of cardiac magnetic resonance imaging, functional and haemodynamic variables in pulmonary arterial hypertension: insights from REPAIR.

Background: Measures that can detect large treatment effects are important for monitoring therapeutic effectiveness. The 2022 European Society of Cardiology/European Respiratory Society guidelines highlight the importance of imaging in monitoring disease status and treatment response in pulmonary arterial hypertension (PAH). Are the standardised treatment effect sizes (STES) of cardiac magnetic resonance imaging (cMRI) comparable with functional and haemodynamic variables?

Methods: REPAIR (ClinicalTrials.

Effect of Macitentan in Pulmonary Arterial Hypertension and the Relationship Between Echocardiography and cMRI Variables: REPAIR Echocardiography Sub-study Results.

Introduction: The aim of this sub-study was to evaluate the relationship between echocardiography (echo) and cardiac magnetic resonance imaging (cMRI) variables and to utilize echo to assess the effect of macitentan on right ventricle (RV) structure and function.

Methods: REPAIR (NCT02310672) was a prospective, multicenter, single-arm, open-label, 52-week, phase 4 study in pulmonary arterial hypertension (PAH) patients, which investigated the effect of macitentan 10 mg as monotherapy, or in combination with a phosphodiesterase 5 inhibitor, on RV structure, function, and hemodynamics using cMRI and right heart catheterization. In this sub-study, patients were also assessed by echo at screening and at weeks 26 and/or 52.

Safety of Macitentan for the Treatment of Portopulmonary Hypertension: Real-World Evidence from the Combined OPUS/OrPHeUS Studies.

Introduction: Portopulmonary hypertension (PoPH) carries a worse prognosis than other forms of pulmonary arterial hypertension (PAH). Data regarding use of PAH-specific therapies in patients with PoPH are sparse as they are usually excluded from clinical trials. This analysis describes patient characteristics, treatment patterns, outcomes, and safety profiles in patients with PoPH newly initiating macitentan in the USA using the OPUS/OrPHeUS combined dataset.

The prevalence of pulmonary hypertension after successful tuberculosis treatment in a community sample of adult patients.

There are an estimated 155 million survivors of tuberculosis (TB). Clinical experience suggests that post tuberculosis lung disease (PTLD) is an important cause of Group 3 pulmonary hypertension (PH). However, TB is not listed as a cause of PH in most guidelines.

Early selexipag initiation and long-term outcomes: insights from randomised controlled trials in pulmonary arterial hypertension.

Further understanding of when to initiate therapies in pulmonary arterial hypertension (PAH) is important to improve long-term outcomes. analyses of GRIPHON (NCT01106014) and exploratory analyses of TRITON (NCT02558231) suggested benefit of early selexipag initiation on long-term outcomes, despite no additional benefit initial double combination on haemodynamic and functional parameters in TRITON. analyses investigated the effect of early selexipag initiation on disease progression and survival in a large, pooled PAH cohort.

Perfusion imaging heterogeneity during NO inhalation distinguishes pulmonary arterial hypertension (PAH) from healthy subjects and has potential as an imaging biomarker.

Background: Without aggressive treatment, pulmonary arterial hypertension (PAH) has a 5-year mortality of approximately 40%. A patient's response to vasodilators at diagnosis impacts the therapeutic options and prognosis. We hypothesized that analyzing perfusion images acquired before and during vasodilation could identify characteristic differences between PAH and control subjects.

Pregnancy and Pulmonary Hypertension: From Preconception and Risk Stratification Through Pregnancy and Postpartum.

Pulmonary hypertension is one of the highest risk medical conditions in pregnancy and carries significant maternal morbidity and mortality as well as neonatal morbidity. Diagnosis is commonly delayed due to the nonspecific nature of early symptoms. Disease progression can lead to right ventricular failure, which carries mortality rates as high as 25% to 56%.

Safety of macitentan for the treatment of pulmonary hypertension: Real-world experience from the OPsumit® USers Registry (OPUS) and OPsumit® Historical USers cohort (OrPHeUS).

Macitentan is an oral endothelin receptor antagonist for the management of pulmonary arterial hypertension (PAH). The OPsumit® USers Registry (OPUS) and the OPsumit® Historical USers cohort (OrPHeUS) medical chart review provide real-world data for patients newly initiating macitentan. This study aims to describe the characteristics, safety profile, and clinical outcomes of PAH patients newly treated with macitentan in the combined OPUS/OrPHeUS data set.

Using a knowledge translation program to facilitate guideline- and evidence-based patient management: the PAH-QuERI Extension Program.

The Pulmonary Arterial Hypertension-Quality Enhancement Research Initiative Extension Program was designed to support physicians' adherence to pulmonary arterial hypertension (PAH) guidelines. Guidelines were followed in >95% of patients with functional class (FC) II/III, but for only 28.6% of FC IV patients (Month 36).