Autoantibodies in hospitalised patients with COVID-19.

Objectives: CD209L and its homologous protein CD209 act as alternative entry receptors for the SARS-CoV-2 virus and are highly expressed in the virally targeted tissues. We tested for the presence and clinical features of autoantibodies targeting these receptors and compared these with autoantibodies known to be associated with COVID-19.

Methods: Using banked samples ( = 118) from Johns Hopkins patients hospitalised with COVID-19, we defined autoantibodies against CD209 and CD209L by enzyme-linked immunosorbent assay (ELISA).

Defining Echocardiographic Degrees of Right Heart Size and Function in Pulmonary Vascular Disease from the PVDOMICS Study.

Background: Defining qualitative grades of echocardiographic metrics of right heart chamber size and function is critical for screening, clinical assessment, and measurement of therapeutic response in individuals with pulmonary vascular disease (PVD). In a population enriched for PVD, we sought to establish qualitative grades and prognostic value of right heart chamber size and function.

Methods: We investigated 1053 study participants in the Redefining Pulmonary Hypertension through PVD Phenomics program (PVDOMICS) to determine clinical and echocardiographic differences associated with increasing pulmonary vascular resistance (PVR) severity.

Alterations in Mitochondrial Function in Pulmonary Vascular Diseases.

Alterations of mitochondrial bioenergetics and arginine metabolism are universally present and mechanistically linked to pulmonary arterial hypertension (PAH), but there is little knowledge of arginine metabolism and mitochondrial functions across the different pulmonary hypertension (PH) groups. We hypothesize that abnormalities in mitochondrial functions are present across all PH groups and associated with clinical phenotypes. We test the hypothesis in PH patients and healthy controls from the Pulmonary Vascular Disease Phenomics Program cohort, who had comprehensive clinical phenotyping and follow-up for at least 4 years for death or transplant status.

Association of Male Sex With Worse Right Ventricular Function and Survival in Pulmonary Hypertension in the Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics Cohort.

Background: Sex-based differences are important in the development and progression of pulmonary arterial hypertension. However, it is not established whether these differences are generalizable to all forms of pulmonary hypertension (PH).

Research Question: What are the sex-based differences in right ventricle (RV) function and transplant-free survival in patients with PH from the Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics (PVDOMICS) cohort?

Study Design And Methods: Patients with PH enrolled in the PVDOMICS cohort study underwent right heart catheterization, cardiac MRI, and echocardiography.

Hemodynamic markers independent of pulmonary capillary wedge pressure can discriminate between pre and postcapillary exercise-induced pulmonary hypertension.

The discrimination between pre and postcapillary exercise-induced pulmonary hypertension relies on accurate measurement of pulmonary capillary wedge pressure, which can be unreliable. We found that exercise pulmonary artery compliance and right atrial pressure (AUC 0.88, 0.

Single-cell transcriptomics reveal diverging pathobiology and opportunities for precision targeting in scleroderma-associated versus idiopathic pulmonary arterial hypertension.

Introduction: Pulmonary arterial hypertension (PAH) involves progressive cellular and molecular change within the pulmonary vasculature, leading to increased vascular resistance. Current therapies targeting nitric oxide (NO), endothelin, and prostacyclin pathways yield variable treatment responses. Patients with systemic sclerosis-associated PAH (SSc-PAH) often experience worse outcomes than those with idiopathic PAH (IPAH).

Clinical Implications of Pretest Probability of HFpEF on Outcomes in Precapillary Pulmonary Hypertension.

Background: Patients with group 1 pulmonary hypertension (PH) and risk factors for heart failure with preserved ejection fraction (HFpEF) demonstrate worse response to pulmonary vasodilator therapy. The mechanisms and optimal diagnostic approach to identify such patients remain unclear.

Objectives: The purpose of this study was to compare exercise capacity, cardiac function, and hemodynamic responses to provocative maneuvers among patients with group 1 PH based upon pretest probability of HFpEF.

Prognostic Value of Echocardiographic Coupling Metrics in Systemic Sclerosis-Associated Pulmonary Vascular Disease.

Background: Ineffective right ventricular (RV) adaptation to increasing pulmonary arterial (PA) afterload in pulmonary vascular disease (PVD) significantly contributes to morbidity and mortality. Pulmonary vascular disease in systemic sclerosis (SSc) arises through various mechanisms, yet detecting abnormal contractile response remains challenging. Here we examine whether echocardiographic RV-PA coupling metrics correlate with invasive pressure-volume (PV) loops, enhancing the prediction of adverse clinical outcomes in SSc-PVD patients.

MK-5475, an inhaled soluble guanylate cyclase stimulator, for treatment of pulmonary arterial hypertension: the INSIGNIA-PAH study.

Background: MK-5475 is an investigational inhaled soluble guanylate cyclase stimulator hypothesised to avoid most side-effects of systemic vasodilation.

Methods: The phase 2 INSIGNIA-PAH (NCT04732221) trial randomised adults with pulmonary arterial hypertension (PAH) on stable background therapy 1:1:1:1 to once-daily dosing with placebo, MK-5475 32 µg, 100 µg or 380 µg dry powder inhalation for 12 weeks.

Objectives: The objectives were to evaluate pulmonary vascular resistance (PVR; primary), 6-min walk distance (6MWD; secondary), additional selected haemodynamic parameters, and safety and tolerability in participants with PAH.

Pathophysiology of the right ventricle and its pulmonary vascular interaction.

The right ventricle and its stress response is perhaps the most important arbiter of survival in patients with pulmonary hypertension of many causes. The physiology of the cardiopulmonary unit and definition of right heart failure proposed in the 2018 World Symposium on Pulmonary Hypertension have proven useful constructs in subsequent years. Here, we review updated knowledge of basic mechanisms that drive right ventricular function in health and disease, and which may be useful for therapeutic intervention in the future.

Phosphodiesterase 5 Inhibitor Treatment Is Associated With Improved Survival in Pulmonary Hypertension Associated With COPD in the Pulmonary Vascular Research Institute GoDeep Meta-Registry.

Background: Patients with COPD frequently demonstrate pulmonary hypertension (PH). Severe PH in patients with COPD, identified by pulmonary vascular resistance (PVR) of > 5 Wood units (WU), is closely linked to impaired transplant-free survival. The impact of PH-targeting pharmacotherapy in this context remains unclear.

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.

Early predictive values of clinical assessments for ARDS mortality: a machine-learning approach.

Acute respiratory distress syndrome (ARDS) is a devastating critical care syndrome with significant morbidity and mortality. The objective of this study was to evaluate the predictive values of dynamic clinical indices by developing machine-learning (ML) models for early and accurate clinical assessment of the disease prognosis of ARDS. We conducted a retrospective observational study by applying dynamic clinical data collected in the ARDSNet FACTT Trial (n = 1000) to ML-based algorithms for predicting mortality.

Non-invasive prediction of pulmonary vascular disease-related exercise intolerance and survival in non-group 1 pulmonary hypertension.

Aims: The clinical utility of pulmonary hypertension (PH) risk scores in non-group 1 PH with pulmonary vascular disease (PVD) remains unresolved.

Methods And Results: We utilized the prospective multicenter PVDOMICS cohort with group 2, 3, 4 or 5 PH-related PVD and calculated group 1 PH risk scores (REVEAL 2.0, REVEAL Lite 2, French registry score and COMPERA 2).

Collagen 18A1/Endostatin Expression in the Progression of Right Ventricular Remodeling and Dysfunction in Pulmonary Arterial Hypertension.

Numerous studies have demonstrated that endostatin (ES), a potent angiostatic peptide derived from collagen type XVIII α 1 chain and encoded by , is elevated in pulmonary arterial hypertension (PAH). It is important to note that elevated ES has consistently been associated with altered hemodynamics, poor functional status, and adverse outcomes in adult and pediatric PAH. This study used serum samples from patients with Group I PAH and plasma and tissue samples derived from the Sugen/hypoxia rat pulmonary hypertension model to define associations between /ES and disease development, including hemodynamics, right ventricle (RV) remodeling, and RV dysfunction.

Resistin predicts disease severity and survival in patients with pulmonary arterial hypertension.

Background: Abnormal remodeling of distal pulmonary arteries in patients with pulmonary arterial hypertension (PAH) leads to progressively increased pulmonary vascular resistance, followed by right ventricular hypertrophy and failure. Despite considerable advancements in PAH treatment prognosis remains poor. We aim to evaluate the potential for using the cytokine resistin as a genetic and biological marker for disease severity and survival in a large cohort of patients with PAH.

Poor cardiac output reserve in pulmonary arterial hypertension is associated with right ventricular stiffness and impaired interventricular dependence.

Background: Pulmonary arterial hypertension (PAH) is characterised by poor exercise tolerance. The contribution of right ventricular (RV) diastolic function to the augmentation of cardiac output during exercise is not known. This study leverages pressure-volume (-) loop analysis to characterise the impact of RV diastology on poor flow augmentation during exercise in PAH.

Pulmonary hypertension across the spectrum of left heart and lung disease.

Aims: Patients with pulmonary hypertension (PH) are grouped based upon clinical and haemodynamic characteristics. Groups 2 (G2, left heart disease [LHD]) and 3 (G3, lung disease or hypoxaemia) are most common. Many patients display overlapping characteristics of heart and lung disease (G2-3), but this group is not well-characterized.

Preacinar Arterial Dilation Mediates Outcomes of Quantitative Interstitial Abnormalities in the COPDGene Study.

Quantitative interstitial abnormalities (QIAs) are a computed tomography (CT) measure of early parenchymal lung disease associated with worse clinical outcomes, including exercise capacity and symptoms. The presence of pulmonary vasculopathy in QIAs and its role in the QIA-outcome relationship is unknown. To quantify radiographic pulmonary vasculopathy in QIAs and determine whether this vasculopathy mediates the QIA-outcome relationship.

Sildenafil Versus Placebo for Early Pulmonary Vascular Disease in Scleroderma (SEPVADIS): protocol for a randomized controlled trial.

Background: Pulmonary hypertension (PH) is a leading cause of death in patients with systemic sclerosis (SSc). An important component of SSc patient management is early detection and treatment of PH. Recently the threshold for the diagnosis of PH has been lowered to a mean pulmonary artery pressure (mPAP) threshold of > 20 mmHg on right heart catheterization (RHC).

Health-Related Quality of Life Across the Spectrum of Pulmonary Hypertension.

Background: Health-related quality of life (HRQOL) is frequently impaired in pulmonary arterial hypertension. However, little is known about HRQOL in other forms of pulmonary hypertension (PH).

Research Question: Does HRQOL vary across groups of the World Symposium on Pulmonary Hypertension (WSPH) classification system?

Study Design And Methods: This cross-sectional study included patients with PH from the Pulmonary Vascular Disease Phenomics (PVDOMICS) cohort study.

Germline and Somatic Mutations in DNA Methyltransferase 3A Predispose to Pulmonary Arterial Hypertension (PAH) in Humans and Mice: .

Background: Mutations are found in 10-20% of idiopathic PAH (IPAH) patients, but none are consistently identified in connective tissue disease-associated PAH (APAH), which accounts for ∼45% of PAH cases. mutations, a cause of clonal hematopoiesis of indeterminant potential (CHIP), predispose to an inflammatory type of PAH. We now examine mutations in another CHIP gene, , in PAH.