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.

Digital Inclusion in a Scottish National Pulmonary Hypertension Population.

To evaluate current digital inclusion in the Scottish pulmonary hypertension population, a paper questionnaire was offered to the entirety of patients with pulmonary arterial hypertension in Scotland. The Scottish Index of Multiple Deprivation was used to stratify patients into deprivation deciles. 464 patients returned questionnaires (86%).

Radiological abnormalities persist following COVID-19 and correlate with impaired health-related quality of life: a prospective cohort study of hospitalised patients.

Background: The radiological trajectory of post-COVID-19 is uncertain. We present a prospective, observational, multicentre cohort study using multimodality imaging to describe the pulmonary sequelae of patients hospitalised with COVID-19, predictors of persistent abnormal radiology and implications on health status.

Methods: In survivors of COVID-19, we performed convalescent CT pulmonary angiogram and high-resolution CT imaging as part of the CISCO-19 study (ClinicalTrials.

Pulmonary Hypertension: Intensification and Personalization of Combination Rx (PHoenix): A phase IV randomized trial for the evaluation of dose-response and clinical efficacy of riociguat and selexipag using implanted technologies.

Approved therapies for the treatment of patients with pulmonary arterial hypertension (PAH) mediate pulmonary vascular vasodilatation by targeting distinct biological pathways. International guidelines recommend that patients with an inadequate response to dual therapy with a phosphodiesterase type-5 inhibitor (PDE5i) and endothelin receptor antagonist (ERA), are recommended to either intensify oral therapy by adding a selective prostacyclin receptor (IP) agonist (selexipag), or switching from PDE5i to a soluble guanylate-cyclase stimulator (sGCS; riociguat). The clinical equipoise between these therapeutic choices provides the opportunity for evaluation of individualized therapeutic effects.

Socioeconomic deprivation and illness trajectory in the Scottish population after COVID-19 hospitalization.

Background: The associations between deprivation and illness trajectory after hospitalisation for coronavirus disease-19 (COVID-19) are uncertain.

Methods: A prospective, multicentre cohort study was conducted on post-COVID-19 patients, enrolled either in-hospital or shortly post-discharge. Two evaluations were carried out: an initial assessment and a follow-up at 28-60 days post-discharge.

Blood DNA methylation profiling identifies cathepsin Z dysregulation in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterised by pulmonary vascular remodelling causing premature death from right heart failure. Established DNA variants influence PAH risk, but susceptibility from epigenetic changes is unknown. We addressed this through epigenome-wide association study (EWAS), testing 865,848 CpG sites for association with PAH in 429 individuals with PAH and 1226 controls.

Remote exercise testing in pulmonary hypertension (PHRET).

Remote exercise tests for patients with pulmonary hypertension (PH) would improve the telemedicine strategies in this disease. The PHRET study assessed the validity and feasibility of four remote exercise tests performed by PH patients at home. Participants undergoing diagnostic assessment for PH were included.

The MRC Dyspnoea Scale and mortality risk prediction in pulmonary arterial hypertension: A retrospective longitudinal cohort study.

Risk stratification models in pulmonary arterial hypertension (PAH) rely on World Health Organisation Functional Class (WHO FC). A high proportion of patients are classified as WHO FC III, a heterogenous group which limits the stratification abilities of risk models. The Medical Research Council (MRC) Dyspnoea Scale may allow a more precise assessment of functional status and improve current risk models.

Adjudicated myocarditis and multisystem illness trajectory in healthcare workers post-COVID-19.

Background: We investigated the associations of healthcare worker status with multisystem illness trajectory in hospitalised post-COVID-19 individuals.

Methods And Results: One hundred and sixty-eight patients were evaluated 28-60 days after the last episode of hospital care. Thirty-six (21%) were healthcare workers.

Towards telemedicine in pulmonary hypertension: Assessing the feasibility of remote quality of life and exercise capacity assessment.

Patients with pulmonary hypertension (PH) are happy to perform simple exercise capacity tests at home and believe this is feasible. A proportion of patients are able to use an electronic form to complete quality of life questionnaires. These findings are being used to build a telemedicine strategy for PH patients.

Predicting Group II pulmonary hypertension: diagnostic accuracy of the H2FPEF and OPTICS scores in Scotland.

Objective: Group II pulmonary hypertension (PH) can be challenging to distinguish from Group I PH without proceeding to right heart catheterisation (RHC). The diagnostic accuracy of the H2FPEF and OPTICS scores was investigated in Scotland.

Methods: Patients were included in the study if they were referred to the Scottish Pulmonary Vascular Unit between 2016 and 2020 and subsequently diagnosed with Group II PH or Group I PH which was either idiopathic, heritable or pulmonary veno-occlusive disease.

Autoimmunity Is a Significant Feature of Idiopathic Pulmonary Arterial Hypertension.

Autoimmunity is believed to play a role in idiopathic pulmonary arterial hypertension (IPAH). It is not clear whether this is causative or a bystander of disease and if it carries any prognostic or treatment significance. To study autoimmunity in IPAH using a large cross-sectional cohort.

The right ventricle under pressure: Anatomy and imaging in sickness and health.

The right ventricle (RV) is an important structure which serves a multitude of vital physiological functions in health. For many years, the left ventricle has dominated the focus of understanding in both biology and pathophysiology and the RV was felt to be more of a passive structure which rarely had an effect on disease states. However, it is increasingly recognised that the RV is essential to the homoeostasis of normal physiology and disturbances in RV structure and function have a substantial effect on patient outcomes.

Randomised controlled trial of intravenous nafamostat mesylate in COVID pneumonitis: Phase 1b/2a experimental study to investigate safety, Pharmacokinetics and Pharmacodynamics.

Background: Many repurposed drugs have progressed rapidly to Phase 2 and 3 trials in COVID19 without characterisation of Pharmacokinetics /Pharmacodynamics including safety data. One such drug is nafamostat mesylate.

Methods: We present the findings of a phase Ib/IIa open label, platform randomised controlled trial of intravenous nafamostat in hospitalised patients with confirmed COVID-19 pneumonitis.

Using the Plasma Proteome for Risk Stratifying Patients with Pulmonary Arterial Hypertension.

NT-proBNP (N-terminal pro-brain natriuretic peptide), a biomarker of cardiac origin, is used to risk stratify patients with pulmonary arterial hypertension (PAH). Its limitations include poor sensitivity to early vascular pathology. Other biomarkers of vascular or systemic origin may also be useful in the management of PAH.

Clinical and radiological characteristics of acute pulmonary embolus in relation to 28-day and 6-month mortality.

Background: Patients with acute pulmonary embolism (PE) exhibit a wide spectrum of clinical and laboratory features when presenting to hospital and pathophysiologic mechanisms differentiating low-risk and high-risk PE are poorly understood.

Objectives: To investigate the prognostic value of clinical, laboratory and radiological information that is available within routine tests undertaken for patients with acute PE.

Methods: Electronic patient records (EPR) of patients who underwent Computed Tomography Pulmonary Angiogram (CTPA) scan for the investigation of acute PE during 6-month period (01.

Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood.

Idiopathic pulmonary arterial hypertension (IPAH) is a rare but fatal disease diagnosed by right heart catheterisation and the exclusion of other forms of pulmonary arterial hypertension, producing a heterogeneous population with varied treatment response. Here we show unsupervised machine learning identification of three major patient subgroups that account for 92% of the cohort, each with unique whole blood transcriptomic and clinical feature signatures. These subgroups are associated with poor, moderate, and good prognosis.

Positioning imatinib for pulmonary arterial hypertension: A phase I/II design comprising dose finding and single-arm efficacy.

Pulmonary arterial hypertension is an unmet clinical need. Imatinib, a tyrosine kinase inhibitor, 200 to 400 mg daily reduces pulmonary artery pressure and increases functional capacity in this patient group, but is generally poorly tolerated at the higher dose. We have designed an open-label, single-arm clinical study to investigate whether there is a tolerated dose of imatinib that can be better targeted to patients who will benefit.

Thromboembolic Risk in Hospitalized and Nonhospitalized COVID-19 Patients: A Self-Controlled Case Series Analysis of a Nationwide Cohort.

Objective: To assess the associations between coronavirus disease 2019 (COVID-19) infection and thromboembolism including myocardial infarction (MI), ischemic stroke, deep vein thrombosis (DVT), and pulmonary embolism (PE).

Patients And Methods: A self-controlled case-series study was conducted covering the whole of Scotland's general population. The study population comprised individuals with confirmed (positive test) COVID-19 and at least one thromboembolic event between March 2018 and October 2020.

Mendelian randomisation and experimental medicine approaches to interleukin-6 as a drug target in pulmonary arterial hypertension.

Background: Inflammation and dysregulated immunity are important in the development of pulmonary arterial hypertension (PAH). Compelling preclinical data supports the therapeutic blockade of interleukin-6 (IL-6) signalling.

Methods: We conducted a phase 2 open-label study of intravenous tocilizumab (8 mg·kg) over 6 months in patients with group 1 PAH.

Impairment of skeletal muscle oxygen extraction and cardiac output are matched in precapillary pulmonary hypertension.

https://bit.ly/3hQUY8m.