Circulating markers of inflammation and angiogenesis and clinical outcomes across subtypes of pulmonary arterial hypertension.

BACKGROUND: Subtypes of pulmonary arterial hypertension (PAH) differ in both fundamental disease features and clinical outcomes. Angiogenesis and inflammation represent disease features that may differ across subtypes and are of special interest in connective tissue disease-associated PAH (CTD-PAH). We compared inflammatory and angiogenic biomarker profiles across different etiologies of PAH and related them to clinical outcomes. METHODS: Participants with idiopathic PAH, CTD-PAH, toxin-associated PAH (tox-PAH), or congenital heart disease-associated PAH (CHD-PAH) were enrolled into a prospective observational cohort. Baseline serum concentrations of 33 biomarkers were related to 3-year mortality, echocardiogram, REVEAL score, and 6-minute walk distance (6MWD). Findings were validated using plasma proteomic data from the UK PAH Cohort Study. RESULTS: One hundred twelve patients were enrolled: 45 idiopathic, 27 CTD-PAH, 20 tox-PAH, and 20 CHD-PAH. Angiogenic and inflammatory biomarkers were distinctly elevated within the CTD-PAH cohort. Six biomarkers were associated with mortality within the entire PAH cohort: interleukin-6 (IL-6, HR:1.6, 95% CI:1.18-2.18), soluble fms-like tyrosine kinase 1 (sFlt-1, HR:1.35, 95% CI:1.02-1.80), placental growth factor (PlGF, HR:1.55, 95% CI:1.07-2.25), interferon gamma-induced protein 10 (IP-10, HR:1.44, 95% CI:1.04-1.99), tumor necrosis factor-beta (TNF-ß, HR:1.81, 95% CI:1.11-2.95), and NT-proBNP (HR:2.19, 95% CI:1.52-3.14). Only IL-6 and NT-proBNP remained significant after controlling for multiple comparisons. IL-6, IP-10, and sFlt-1 significantly associated with mortality in CTD-PAH, but not non-CTD-PAH subgroups. In the UK cohort, IP-10, PlGF, TNF-ß, and NT-proBNP significantly associated with 5-year survival. CONCLUSION: Levels of angiogenic and inflammatory biomarkers are elevated in CTD-PAH, compared with other etiologies of PAH, and may correlate with clinical outcomes including mortality.

Thyroid-stimulating hormone and mortality in pulmonary arterial hypertension.

INTRODUCTION: Pulmonary arterial hypertension (PAH) remains a serious and life-threatening illness. Thyroid dysfunction is relatively understudied in individuals with PAH but is known to affect cardiac function and vascular tone in other diseases. The aim of this observational study was to evaluate the association between thyroid-stimulating hormone (TSH), mortal and non-mortal outcomes in individuals with PAH. METHODS: The Seattle Right Ventricle Translational Science (Servetus) Study is an observational cohort that enrolled participants with PAH between 2014 and 2016 and then followed them for 3 years. TSH was measured irrespective of a clinical suspicion of thyroid disease for all participants in the cohort. Linear regression was used to estimate the relationships between TSH and right ventricular basal diameter, tricuspid annular plane systolic excursion and 6-minute walk distance. Logistic regression was used to estimate the relationship with New York Heart Association Functional Class, and Cox proportional hazards were used to estimate the relationship with mortality. Staged models included unadjusted models and models accounting for age, sex at birth and aetiology of pulmonary hypertension with or without further adjustment for N-terminal-pro hormone brain natriuretic peptide. RESULTS: Among 112 participants with PAH, TSH was strongly associated with mortality irrespective of adjustment. There was no clear consistent association between TSH and other markers of severity in a cohort with PAH. DISCUSSION: This report reinforces the important observation that TSH is associated with survival in patients with PAH, and future study of thyroid dysfunction as a potential remediable contributor to mortality in PAH is warranted.

Pulmonary Arterial Hypertension Emergency Complications and Evaluation: Practical Guide for the Advanced Practice Registered Nurses in the Emergency Department.

Pulmonary hypertension (PH) complicates common diseases and can lead to worsening symptoms and increased mortality. A specific group of PH, pulmonary arterial hypertension (PAH), World Health Organization Group 1, may present to the emergency department (ED). We review common ED presentations of patients with PAH such as cardiac arrest/sudden death, right ventricular failure, syncope, hypoxemic respiratory failure, arrhythmias, hemoptysis, pulmonary embolism, chest pain/left main compression syndrome, infection, and considerations for PAH medication administration. We include a case study to illustrate a real example with a positive outcome, and an algorithm for evaluating and triaging patients with PAH in the ED. The ability to recognize, triage, and communicate changes in PAH disease status in a multidisciplinary team approach between the patient, family, specialty pharmacy, and specialized health care providers such as the PH team, is essential for ED providers who are evaluating and treating patients with PAH.