Marked activation of endothelium, platelets, and leukocytes occurs in VTE, and VTE, or the accompanying inflammatory process, involves the release of EMP and formation of EMP-monocyte conjugates and PLC. These findings support prior studies suggesting that release of EMP and their binding to monocytes are key events in thrombogenesis. Our findings also support the concept that the formation of PLC regulates leukocyte activation and participates in linking thrombosis with inflammation.

Most patients with PAH in our cohort died of their disease; however, right ventricular failure or sudden death was the sole cause of death in less than half of patients.

Rationale: High-density lipoprotein cholesterol (HDL-C) promotes healthy vascular function, and it is decreased in insulin resistance. Insulin resistance predisposes to pulmonary vascular disease. Objectives: We hypothesized that HDL-C is associated with clinical outcomes in pulmonary arterial hypertension (PAH). Methods: Plasma HDL-C concentrations were measured in 69 patients with PAH (age, 46.7 6 12.9 yr; female, 90%) and 229 control subjects (age, 57 6 13 yr; female, 48%). Clinical outcomes of interest included hospitalization for PAH, lung transplantation, and all-cause mortality. Survival and time to clinical worsening curves were derived by the Kaplan-Meier method. Cox regression modeling of outcome versus HDL-C with individual covariate adjustments was performed. Measurement and Main Results: HDL-C was low in subjects with PAH compared with control subjects (median, interquartile range: PAH: 36, 29-40 mg/dl; control subjects: 49, 40-60 mg/dl; P , 0.001). An HDL-C level of 35 mg/dl discriminated survivors from nonsurvivors, with a sensitivity of 100% and specificity of 60%. After a median follow-up of 592 days, high HDL-C was associated with decreased mortality (hazard ratio for every 5-mg/dl increase in HDL-C, 0.643; 95% confidence interval, 0.504-0.822; P 5 0.001) and less clinical worsening (hazard ratio for every 5-mg/dl increase in HDL-C, 0.798; 95% confidence interval, 0.663-0.960; P 5 0.02). HDL-C remained a significant predictor of survival after adjusting for cardiovascular risk factors, C-reactive protein, indices of insulin resistance, and severity of PAH (all P , 0.05). Conclusions: Low plasma HDL-C is associated with higher mortality and clinical worsening in PAH. This association does not appear to be explained by underlying cardiovascular risk factors, insulin resistance, or the severity of PAH.

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Background We provide the first multicenter analysis of patients cared for by eight Pulmonary Embolism Response Teams (PERTs) in the United States (US); describing the frequency of team activation, patient characteristics, pulmonary embolism (PE) severity, treatments delivered, and outcomes. Methods We enrolled patients from the National PERT Consortium™ multicenter registry with a PERT activation between 18 October 2016 and 17 October 2017. Data are presented combined and by PERT institution. Differences between institutions were analyzed using chi-squared test or Fisher's exact test for categorical variables, and ANOVA or Kruskal-Wallis test for continuous variables, with a two-sided P value < 0.05 considered statistically significant. Results There were 475 unique PERT activations across the Consortium, with acute PE confirmed in 416 (88%). The number of activations at each institution ranged from 3 to 13 activations/month/1000 beds with the majority originating from the emergency department (281/475; 59.3%). The largest percentage of patients were at intermediate–low (141/416, 34%) and intermediate–high (146/416, 35%) risk of early mortality, while fewer were at high-risk (51/416, 12%) and low-risk (78/416, 19%). The distribution of risk groups varied significantly between institutions ( P = 0.002). Anticoagulation alone was the most common therapy, delivered to 289/416 (70%) patients with confirmed PE. The proportion of patients receiving any advanced therapy varied between institutions ( P = 0.0003), ranging from 16% to 46%. The 30-day mortality was 16% (53/338), ranging from 9% to 44%. Conclusions The frequency of team activation, PE severity, treatments delivered, and 30-day mortality varies between US PERTs. Further research should investigate the sources of this variability.

Background:Little is known about the association between left ventricular (LV) diastolic dysfunction and outcomes in patients with idiopathic or heritable pulmonary arterial hypertension (PAH). Our rationale was to investigate the prevalence of LV diastolic dysfunction, and its association with disease severity and outcomes, in patients with idiopathic or heritable PAH. Methods: Using the Cleveland Clinic Pulmonary Hypertension Registry, we identifi ed subjects with heritable or idiopathic PAH who underwent Doppler echocardiography and right-sided heart catheterization. Echocardiographic diastolic parameters were assessed in each patient. Results: A total of 61 patients met the inclusion criteria (idiopathic 85%, heritable 15%). The age at the time of echocardiography was 48.3 Ϯ 18 years, 84% of the subjects were women, and 48% were on PAH-targeted therapies. Normal LV diastolic function, impaired relaxation, and pseudonormalization were seen in 10%, 88%, and 2% of the patients, respectively. Peak early diastolic (peak E) velocity was directly associated with LV end-diastolic volume and cardiac index and inversely associated with the degree of right ventricular dilation, right atrial pressure, and pulmonary vascular resistance. Peak E velocity was associated with mortality adjusted for age and sex (hazard ratio [HR], 1.5; 95% CI, 1.1-2 per 10 cm/s decrease; P 5 .015) and age, sex, 6-min walk distance, and cardiac output (HR, 1.8; 95% CI, 1.2-2.9 per 10 cm/s decrease; P 5 .01). Conclusions: LV diastolic dysfunction of the impaired relaxation type is observed in the majority of patients with advanced idiopathic or heritable PAH. A decrease in transmitral fl ow peak E velocity is associated with worse hemodynamics and outcome. CHEST 2012; 141(6):1457-1465Abbreviations: A 5 late diastolic; D 5 anterograde diastolic; E 5 early diastolic; HR 5 hazard ratio; LA 5 left atrial; LV 5 left ventricular; NYHA 5 New York Heart Association; PAH 5 pulmonary arterial hypertension; PAOP 5 pulmonary artery occlusion pressure; PAP 5 pulmonary artery pressure; PVR 5 pulmonary vascular resistance; RA 5 right atrial; RHC 5 right-sided heart catheterization; RV 5 right ventricular; S 5 systolic

Pulmonary hypertension (PH) is a frequently under recognized complication of myelofibrosis (MF). The pathophysiology of PH in MF is unknown and no definitive therapies have been established. We studied 15 patients with MF-associated PH and compared their echocardiographic and PH relevant biomarkers (nitric oxide (NO), N-terminal pro-hormone of brain natriuretic peptide (NT-pro BNP), von Willebrand antigen (vWB), ristocetin-cofactor activity (RCA) and uric acid (UA)) pre- and post-ruxolitinib treatment. Ruxolitinib decreased the plasma levels of NT-pro BNP (73%; P=0.043), UA (60%), vWB (86%) and RCA (73%; P=0.036). Improvements in echocardiographic findings were also seen in 66% of patients (P=0.022). Furthermore, marked increase in NO compared with baseline (69.75 vs 40.1 picomolar (pM); P=0.001) was observed post-ruxolitinib therapy, whereas no changes were noted with conventional therapies. Treatment with ruxolitinib also resulted in the reduction of key cytokines (tumor necrosis factor alpha, interleukin-4 (IL-4), IL-6 and IL-8) and induction of interferon-gamma. Animal studies further supported the role of ruxolitinib in the induction of NO levels. In conclusion, aberrant Janus kinase (JAK)-signal transducer and activator of transcription signaling in MF may mediate PH through dysregulation of NO and cytokine levels, which can be restored by therapy with JAK inhibitors suggesting that inhibition of this pathway is a novel target for the management of patients with PH.