Epicardial Adipose Tissue Is an Independent Risk Factor for Mortality in Pulmonary Arterial Hypertension.

Background: Increased epicardial adipose tissue (EAT) has adverse effects in cardiovascular diseases, independent of body mass index (BMI). Estrogen levels may impact EAT accumulation. Little is known about the predictors and potential impact of EAT in PAH.

Novel Liver Injury Phenotypes and Outcomes in Clinical Trial Participants with Pulmonary Hypertension.

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) cause right ventricular dysfunction, which can impact other solid organs. However, the profiles and consequences of hepatic injury resulting from PAH and CTEPH have not been well studied. We aimed to identify underlying patterns of liver injury in a cohort of patients with PAH and CTEPH enrolled in 15 randomized clinical trials conducted between 1998 and 2014.

Pulmonary Hypertension and Anastrozole (PHANTOM): A Randomized, Double-Blind, Placebo-Controlled Trial.

Inhibition of aromatase with anastrozole reduces pulmonary hypertension in experimental models. We aimed to determine whether anastrozole improved the 6-minute-walk distance (6MWD) at 6 months in pulmonary arterial hypertension (PAH). We performed a randomized, double-blind, placebo-controlled phase II clinical trial of anastrozole in subjects with PAH at seven centers.

Pulmonary arterial hypertension treatment: an individual participant data network meta-analysis.

Background And Aims: Effective therapies that target three main signalling pathways are approved to treat pulmonary arterial hypertension (PAH). However, there are few large patient-level studies that compare the effectiveness of these pathways. The aim of this analysis was to compare the effectiveness of the treatment pathways in PAH and to assess treatment heterogeneity.

Electrocardiographic Abnormalities and Their Association with Outcomes in Randomized Clinical Trials of Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease with manifestations including right atrial enlargement, right ventricular dysfunction, dilation, and hypertrophy. Electrocardiography (ECG) is a noninvasive, inexpensive test that is routinely performed in clinical settings. Prior studies have described separate abnormal findings in the electrocardiograms of patients with PAH.

Novel Liver Injury Phenotypes and Outcomes in Pulmonary Arterial Hypertension.

Background: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are disorders of the pulmonary vasculature that cause right ventricular dysfunction. Systemic consequences of right ventricular dysfunction include damage to other solid organs, such as the liver. However, the profiles and consequences of hepatic injury due to PAH and CTEPH have not been well-studied.

Heterogeneity of treatment effects by risk in pulmonary arterial hypertension.

Background: It is currently unknown if disease severity modifies response to therapy in pulmonary arterial hypertension (PAH). We aimed to explore if disease severity, as defined by established risk-prediction algorithms, modified response to therapy in randomised clinical trials in PAH.

Methods: We performed a meta-analysis using individual participant data from 18 randomised clinical trials of therapy for PAH submitted to the United States Food and Drug Administration to determine if predicted risk of 1-year mortality at randomisation modified the treatment effect on three outcomes: change in 6-min walk distance (6MWD), clinical worsening at 12 weeks and time to clinical worsening.

CT imaging determinants of persistent hypoxemia in acute intermediate-risk pulmonary embolism.

The factors associated with persistent hypoxemia after pulmonary embolus (PE) are not well understood. Predicting the need for oxygen post discharge at the time of diagnosis using available CT imaging will enable better discharge planning. To examine the relationship between CT derived imaging markers (automated computation of arterial small vessel fraction, pulmonary artery diameter to aortic diameter ratio (PA:A), right to left ventricular diameter ratio (RV:LV) and new oxygen requirement at the time of discharge in patients diagnosed with acute intermediate-risk PE.

Minimal Clinically Important Difference in the 6-minute-walk Distance for Patients with Pulmonary Arterial Hypertension.

The 6-minute-walk distance (6MWD) is an important clinical and research metric in pulmonary arterial hypertension (PAH); however, there is no consensus about what minimal change in 6MWD is clinically significant. We aimed to determine the minimal clinically important difference in the 6MWD. We performed a meta-analysis using individual participant data from eight randomized clinical trials of therapy for PAH submitted to the U.

Baseline Sex Differences in Pulmonary Arterial Hypertension Randomized Clinical Trials.

Sex-based differences in pulmonary arterial hypertension (PAH) are known, but the contribution to disease measures is understudied. We examined whether sex was associated with baseline 6-minute-walk distance (6MWD), hemodynamics, and functional class. We conducted a secondary analysis of participant-level data from randomized clinical trials of investigational PAH therapies conducted between 1998 and 2014 and provided by the U.

BMI and Treatment Response in Patients With Pulmonary Arterial Hypertension: A Meta-analysis.

Background: Obesity is increasingly prevalent in pulmonary arterial hypertension (PAH) but is associated with improved survival, creating an "obesity paradox" in PAH. It is unknown if the improved outcomes could be attributable to obese patients deriving a greater benefit from PAH therapies.

Research Question: Does BMI modify treatment effectiveness in PAH?

Study Design And Methods: Using individual participant data, a meta-analysis was conducted of phase III, randomized, placebo-controlled trials of treatments for PAH submitted for approval to the U.

Secular and Regional Trends among Pulmonary Arterial Hypertension Clinical Trial Participants.

The population of patients with pulmonary arterial hypertension (PAH) has evolved over time from predominantly young White women to an older, more racially diverse and obese population. Whether these changes are reflected in clinical trials is not known. To determine secular and regional trends among PAH trial participants.

Health-related quality of life and hospitalizations in chronic thromboembolic pulmonary hypertension versus idiopathic pulmonary arterial hypertension: an analysis from the Pulmonary Hypertension Association Registry (PHAR).

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, morbid, potentially curable subtype of pulmonary hypertension that negatively impacts health-related quality of life (HRQoL). Little is known about differences in HRQoL and hospitalization between CTEPH patients and idiopathic pulmonary arterial hypertension (IPAH) patients. Using multivariable linear regression and mixed effects models, we examined differences in HRQoL assessed by emPHasis-10 (E10) and SF-12 between CTEPH and IPAH patients in the Pulmonary Hypertension Association Registry, a prospective multicenter cohort of patients newly evaluated at a Pulmonary Hypertension Care Center.

Loss of Pulmonary Vascular Volume as a Predictor of Right Ventricular Dysfunction and Mortality in Acute Pulmonary Embolism.

Background: In acute pulmonary embolism, chest computed tomography angiography derived metrics, such as the right ventricle (RV): left ventricle ratio are routinely used for risk stratification. Paucity of intraparenchymal blood vessels has previously been described, but their association with clinical biomarkers and outcomes has not been studied. We sought to determine if small vascular volumes measured on computed tomography scans were associated with an abnormal RV on echocardiography and mortality.

Diagnosis of Deep Venous Thrombosis and Pulmonary Embolism: New Imaging Tools and Modalities.

Imaging continues to be the modality of choice for the diagnosis of venous thromboembolic disease, particularly when incorporated into diagnostic algorithms. Improvement in imaging techniques as well as new imaging modalities and processing methods have improved diagnostic accuracy and additionally are being leveraged in prognostication and decision making for choice of intervention. In this article, we review the role of imaging in diagnosis and prognostication of venous thromboembolism.

Ventricular Geometry From Non-contrast Non-ECG-gated CT Scans: An Imaging Marker of Cardiopulmonary Disease in Smokers.

Rationale And Objectives: Imaging-based assessment of cardiovascular structure and function provides clinically relevant information in smokers. Non-cardiac-gated thoracic computed tomographic (CT) scanning is increasingly leveraged for clinical care and lung cancer screening. We sought to determine if more comprehensive measures of ventricular geometry could be obtained from CT using an atlas-based surface model of the heart.

Enrichment of selective miRNAs in exosomes and delivery of exosomal miRNAs in vitro and in vivo.

Exosomes are nanovesicles secreted by cells and contain various molecules including protein, lipid, and DNA/RNA. They are crucial mediators of the intercellular communication and serve as promising vehicles for drug delivery and gene therapy. Recently, accumulating evidence suggests that microRNAs (miRNAs) may serve as new and potentially powerful targets for therapeutic interventions against various human diseases.

Extracellular Vesicles Facilitate the Intercellular Communications in the Pathogenesis of Lung Injury.

Extracellular vesicles (EVs) are a group of heterogeneous, nano-sized structures surrounded by lipid bilayer membranes that are released by cells. Depending on their size and mechanisms of formation, EVs are often referred to as exosomes, microvesicles (MVs) and apoptotic bodies (AB). EVs are evolutionally conserved vesicles that mediate intercellular communications and cross-talk, via transferring proteins, lipids and nucleic acids.

Arterial and Venous Pulmonary Vascular Morphology and Their Relationship to Findings in Cardiac Magnetic Resonance Imaging in Smokers.

Objective: Prior work has described the relationship between pulmonary vascular pruning on computed tomography (CT) scans and metrics of right-sided heart dysfunction in smokers. In this analysis, we sought to look at pruning on a lobar level, as well as examine the effect of the arterial and venous circulation on this association.

Methods: Automated vessel segmentation applied to noncontrast CT scans from the COPDGene Study in 24 subjects with cardiac magnetic resonance imaging scans was used to create a blood volume distribution profile.