Acute Pulmonary Embolism and Immunity in Animal Models.

Venous thromboembolism, encompassing acute pulmonary embolism (APE) and deep vein thrombosis (DVT), is a potentially fatal disease with complex pathophysiology. Traditionally, the Virchow triad provided a framework for understanding the pathogenic contributors to thrombus formation, which include endothelial dysfunction, alterations in blood flow and blood hypercoagulability. In the last years, it has become apparent that immunity plays a central role in thrombosis, interacting with classical prothrombotic mechanisms, oxidative stress and vascular factors. Thrombosis amplifies inflammation, and exaggerated inflammatory processes can trigger thrombosis mainly due to the activation of leukocytes, platelets, and endothelial cells. APE-related endothelium injury is a major trigger for immune system activation. Endothelium is also a key component mediating inflammatory reaction and it is relevant to maintain vascular permeability. Exaggerated right ventricular wall stress and overload, with coexisting systemic hypotension and hypoxemia, result in myocardial injury and necrosis. Hypoxia, tissue factor activation and cytokine storm are engaged in the thrombo-inflammatory processes. Thrombus development is characterized by inflammatory state vascular wall caused mainly by an early extravasation of leukocytes and intense selectins and cytokines production. Nevertheless, immunity of DVT is well described, little is known about potential chemokine and cellular differences between thrombus that develops in the vein and thrombus that detaches and lodges in the pulmonary circulation being a cause of APE. There is a paucity of data considering inflammatory state in the pulmonary artery wall during an acute episode of pulmonary embolism. The main aim of this review is to summarize the knowledge of immunity in acute phase of pulmonary embolism in experimental models.

The Vulnerable Elders Survey-13 scale is superior to the simplified Pulmonary Embolism Score Index in predicting 3-month postdischarge mortality in elderly survivors of acute pulmonary embolism.

INTRODUCTION: Acute pulmonary embolism (APE) is the most serious manifestation of venous thromboembolism. The simplified Pulmonary Embolism Severity Index (sPESI) is employed for prediction of 30-day mortality in APE. The Vulnerable Elders Survey (VES-13) is used to identify participants at a risk of health impairment. OBJECTIVES: We aimed to compare the VES-13 and sPESI scales for prediction of 3-month mortality inelderly patients hospitalized for APE. PATIENTS AND METHODS: All patients with APE were managed according to the European Society of Cardiology (ESC) guidelines and followed up for at least 3 months after discharge. Clinical evaluation of all patients involved the Charlson Comorbidity Index (CCI) and biochemical tests. The patients with VES-13 score equal to or above 3 (VES-13≥3) were evaluated with comprehensive geriatric assessment (CGA). RESULTS: A total of 164 patients met the inclusion criteria. There were significantly fewer men in the VES-13≥3 than the VES-13<3 group (34% vs 54.5%; P <0.01). The patients in the VES-13≥3 group had lower median (interquartile range [IQR]) body mass index and higher sPESI score than those in the VES-13<3 group (25.6 [21.8-28.4] kg/m2 vs 28 [25.3-31] kg/m2; P = 0.001 and 2 [1-2] points vs 1 [0-1] point; P <0.001, respectively). There were no differences in APE severity according to the ESC stratification and CCI. Logistic regression analysis identified the VES-13 score as a significant independent risk factor for 3-month mortality. CONCLUSIONS: The VES-13 score is a better tool than sPESI for predicting 3-month mortality. Geriatric survivors of APE characterized with VES-13≥3 points should be closely monitored after discharge. The Norton Scale Score in a combination with the VES-13 may be useful in predicting 3-month mortality among numerous tests used in the CGA.

Th17/Treg imbalance in patients with primary hyperaldosteronism and resistant hypertension.

INTRODUCTION: Inflammation plays a pivotal role in blood pressure regulation. Data on experimental models of hypertension and hypertensive patients reflect the imbalance between T regulatory (Treg) and Th17 effector cells (Th17). OBJECTIVES: The aim of this study was to quantify peripheral blood Treg lymphocytes and Th17 subsets in individuals with primary hyperaldosteronism (PHA) and resistant hypertension (RHT) presenting with elevated blood pressure levels and augmented cardiovascular risk when compared with normotensive controls (CTRL). PATIENTS AND METHODS: Twenty CTRL participants, 21 patients with PHA, and 20 patients with RHT were enrolled. Plasma renin and angiotensin II, serum aldosterone concentration, ambulatory blood pressure monitoring (ABPM), echocardiography, clinical data, and phenotype of peripheral blood cells were assessed. RESULTS: There were no statistically significant differences in terms of age and sex between the groups. Similar systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels in ABPM were observed in individuals with PHA and RHT. PHA patients had lower angiotensin II and 4­fold higher aldosterone concentrations than CTRL patients. Both, PHA and RHT were associated with cardiac hypertrophy and coronary artery disease. RHT patients presented a significantly higher CD4+IL­17A+ T cell number when compared with PHA and CTRL ones. The number of CD4+CD25+FOXP3+ T cells did not differ between patients with secondary hypertension and normotensive controls. Finally, positive correlations between the data on 24 h SBP and the content of CD4+IL­17A+ and CD4+CD25+FOXP3+ in the PHA were found. CONCLUSIONS: Elevated 24 h SBP in PHA was associated with the increased numbers of CD4+IL­17 and CD4+CD25+FOXP3+ T cells.

Acidic urine as a novel risk factor for diuretic resistance and worse in­hospital prognosis in patients with acute heart failure.

Introduction: Loop diuretic resistance (LDR) is a risk factor for poor prognosis in patients with acute heart failure (AHF). Acidic urine (pH <⁠6) might be associated with diminished effect of diuretics and worse in-hospital course in this patient population. Objectives: The aim of the study was to assess the influence of acidic urine on in-hospital prognosis and diuretic efficacy in patients with AHF. Patients and methods: This was a retrospective analysis of hospitalizations due to AHF in patients with ejection fraction of 50% or less. Analyzed end points were: in-hospital death and composite end point (death, myocardial infarction, stroke, unplanned revascularization, or catecholamine infusion). Diuretic efficacy was assessed as diuresis per intravenous furosemide dose equivalent. Receiver operating characteristic curve analysis for in-hospital death was used to set a cutoff value for diuretic resistance. Logistic regression analysis was used to select independent risk factors for the occurrence of in-hospital death, composite end point, and LDR. Results: A total of 373 hospitalizations (300 patients) were analyzed. Urine pH of less than 6 on admission was present in 158 cases (42.1%). In-hospital mortality was 7.5% in cases with nonacidic urine as compared with 15% of those with acidic urine (P = 0.03). Composite end point occurred in 10% of patients with nonacidic urine as compared with 31% of those with acidic urine (P <⁠0.001). Acidic urine was found to be an independent risk factor for the composite end point. The threshold for LDR was set at 691.45 ml of diuresis/40 mg of intravenous furosemide. Low urine pH was found to be an independent risk factor for LDR. Conclusions: Low urine pH might be a useful marker identifying patients at high risk for LDR and adverse in-hospital outcome.