Antithrombotic therapy in ventricular assist device (VAD) management : from ancient beliefs to updated evidence : a narrative review

Platelets play a key role in the pathogenesis of ventricular assist device (VAD) thrombosis; therefore, antiplatelet drugs are essential, both in the acute phase and in the long-term follow-up in VAD management. Aspirin is the most used agent and still remains the first-choice drug for lifelong administration after VAD implantation. Anticoagulant drugs are usually recommended, but with a wide range of efficacy targets. Dual antiplatelet therapy, targeting more than one pathway of platelet activation, has been used for patients developing a thrombotic event, despite an increased risk of bleeding complications. Although different strategies have been attempted, bleeding and thrombotic events remain frequent and there are no uniform strategies adopted for pharmacological management in the short and mid- or long-term follow up. The aim of this article is to provide an overview of the evidence from randomized clinical trials and observational studies with a focus on the pathophysiologic mechanisms underlying bleeding and thrombosis in VAD patients and the best antithrombotic regimens available

Persistent left ventricular dysfunction after acute lymphocytic myocarditis: Frequency and predictors.

BACKGROUND: Persistent left ventricular (LV) systolic dysfunction in patients with acute lymphocytic myocarditis (LM) is widely unexplored. OBJECTIVES: To assess the frequency and predictors of persistent LV dysfunction in patients with LM and reduced LVEF at admission. METHODS AND RESULTS: We retrospectively evaluated 89 consecutive patients with histologically-proven acute myocarditis enrolled at three Italian referral hospitals. A subgroup of 48 patients with LM, baseline systolic impairment and an available echocardiographic assessment at 12 months (6-18) from discharge constituted the study population. The primary study end-point was persistent LV dysfunction, defined as LVEF <50% at 1-year, and was observed in 27/48 patients (56.3%). Higher LV end-diastolic diameter at admission (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.04-1.43, p = 0.002), non-fulminant presentation (OR 8.46, 95% CI 1.28-55.75, p = 0.013) and presence of a poor lymphocytic infiltrate (OR 12.40, 95% CI 1.23-124.97, p = 0.010) emerged as independent predictors of persistent LV dysfunction at multivariate analysis (area under the curve 0.91, 95% CI 0.82-0.99). Pre-discharge LVEF was lower in patients with persistent LV dysfunction compared to the others (32%±8 vs. 53%±8, p <0.001), and this single variable showed the best accuracy in predicting the study end-point (area under the curve 0.95, 95% CI 0.89-1.00). CONCLUSIONS: More than half of patients presenting with acute LM and LVEF <50% who survive the acute phase show persistent LV dysfunction after 1-year from hospital discharge. Features of subacute inflammatory process and of established myocardial damage at initial hospitalization emerged as predictors of this end-point

Impact of blood glucose variability on carotid artery intima media thickness and distensibility in type 1 diabetes mellitus

Aims. Diabetes mellitus is characterized by structural and functional alterations of the large- and medium-size arteries. Whether blood glucose variability, i.e. the glycemic oscillations occurring during the 24-h period, represents a risk factor for vascular alterations additional to and independent on HbA1c in type 1 diabetes mellitus is still undefined. The present study was carried out with the aim at investigating the impact of different measures of blood glucose variability on arterial structure and function. We studied 17 non-complicated type 1 diabetic patients (11 males, six females) with an age of 40.8 ± 7.6 years (mean ± SD). In each patient, 24-h glucose profile was obtained by continuous glucose monitoring system and glucose variability was expressed as mean ± SD of 24-h blood glucose levels, mean amplitude of glycemic excursions and postprandial hyperglycemic spikes. Arterial structure and function was measured as carotid IMT and stiffness. Major findings. The different approaches to assessing blood glucose variability well correlated between and with HbA1c. Carotid IMT and stiffness showed significant correlations with age, blood pressure, heart rate and daily insulin intake but a non- significant correlation with blood glucose variability. Principal conclusion. Thus, in type 1 diabetes mellitus, measures of glycemic variability are useful in predicting both actual and long-lasting glycemic control. In absence of diabetes-related complications and of any intima-media thickness alterations, the major predictors of arterial distensibility are represented by traditional risk factors beside glycemic 24-h control. © 2013 Scandinavian Foundation for Cardiovascular Researc

Prediction of QTc length as function of BMI: A clinical tool to establish arrhythmias risk in obesity

Aims. Among the electrocardiographic alterations used for stratifying the cardiovascular risk of life threatening arrhythmias (LFA) and sudden death (SD) there is the increment of the corrected QT(QTc). This increment is usually observable in obese patients (OP). Therefore, a study has been planned to investigate the possibility to predict QTc values in OP simply by detecting the best fitting regression method that represents the relationship between QTc and Body Mass Index (BMI). Materials and Methods. The study has been carried on 144 individuals classified as a function of their BMI in normoponderal subjects (NPS, No. 24; F/M=15/9; BMI=21.8 +/- 1.7 kg/m(2)), Class IOP (No. 24; F/M=17/7; BMI=32.5 +/- 1.1 kg/m(2)); Class II OP (No. 24; F/M=17/7; BMI=37.7 +/- 1.5 kg/m(2));. Class IIIa (No. 24, F/M=15/9; BMI=44.4 +/- 27 kg/m(2)), Class IIIb (No. 24; F/M=14/10; BMI 54.3 +/- 2.7 kg/m(2)); Class IIIc (No. 24; F/M=14/10; BMI=63.3 +/- 4.5 kg/m(2)). Both linear and non-linear fitting modes have been tested. Results. While the BMI progressively increases in classified OP, the QTc shows an intergroup difference that is not only not constant but also declining in Class IIIc obesity. The optimal regressive model was found to be the following fourth order degree polynomial: QTc=317,15+(7,47xBMI)+(-0,28*BMI2)+(0,005xBMI(3))+(-0,00003xBMI(4)). Conclusion. By entering the BMI of a given OP into the above-cited formula, the QTc can be easily predicted and compared to that of NPS. Importantly, to have the possibility for a pre-electrocardiographic estimation of QTc allows all the medical and paramedical personnel, involved in the multidisciplinary treatment of obesity, to immediately establish the cardiovascular risk in the OP under observation. Clin Ter 2011; 162(6):e155-15

8C.04: possible role of arterial function in cancer treatment targeting vascular endothelial growth factor receptor oncologic response

In the last two decades new drugs that oppose the effects of vascular endothelial growth factor receptor (VEGFR), and thus angiogenesis, have considerably improved treatment of solid tumors. These anti-VEGFR drugs, however, are burdened by several side effects, particularly relevant on heart and vessels. Aim of this study was to analyze the changes in cardiovascular structure and function associated with use of anti-VEGFR drugs

Occurrence of Legionella in showers at recreational facilities

Critical environments, including water systems in recreational settings, represent an important source of Legionella pneumophila infection in humans. In order to assess the potential risk for legionellosis, we analyzed Legionella contamination of water distribution systems in 36 recreational facilities equipped with swimming pools. One hundred and sixty water samples were analyzed from shower heads or taps located in locker rooms or in bathrooms. By culture method and polymerase chain reaction, 41/160 samples were positive for Legionella from 12/36 recreational centers. Hotels (57.1%) and sports centers (41.2%) were the most contaminated. L. pneumophila serotypes 2-14 (25/41) were more frequently found than serotype 1 (10/41). Samples at temperature ≥30 °C were more frequently positive than samples at temperature 10 CFU/mL. Maintenance, good hygiene practices, interventions on the hydraulic system and regular controls must be implemented to minimize exposure to L. pneumophila infection risk

Recombinant LCAT (Lecithin:Cholesterol Acyltransferase) Rescues Defective HDL (High-Density Lipoprotein)-Mediated Endothelial Protection in Acute Coronary Syndrome

Objective- Aim of this study was to evaluate changes in LCAT (lecithin:cholesterol acyltransferase) concentration and activity in patients with an acute coronary syndrome, to investigate if these changes are related to the compromised capacity of HDL (high-density lipoprotein) to promote endothelial nitric oxide (NO) production, and to assess if rhLCAT (recombinant human LCAT) can rescue the defective vasoprotective HDL function. Approach and Results- Thirty ST-segment-elevation myocardial infarction (STEMI) patients were enrolled, and plasma was collected at hospital admission, 48 and 72 hours thereafter, at hospital discharge, and at 30-day follow-up. Plasma LCAT concentration and activity were measured and related to the capacity of HDL to promote NO production in cultured endothelial cells. In vitro studies were performed in which STEMI patients' plasma was added with rhLCAT and HDL vasoprotective activity assessed by measuring NO production in endothelial cells. The plasma concentration of the LCAT enzyme significantly decreases during STEMI with a parallel significant reduction in LCAT activity. HDL isolated from STEMI patients progressively lose the capacity to promote NO production by endothelial cells, and the reduction is related to decreased LCAT concentration. In vitro incubation of STEMI patients' plasma with rhLCAT restores HDL ability to promote endothelial NO production, possibly related to significant modification in HDL phospholipid classes. Conclusions- Impairment of cholesterol esterification may be a major factor in the HDL dysfunction observed during acute coronary syndrome. rhLCAT is able to restore HDL-mediated NO production in vitro, suggesting LCAT as potential therapeutic target for restoring HDL functionality in acute coronary syndrome

Pulse wave velocity and depression in hypertensive patients

Objective: Abnormal large artery function plays an important role in the pathogenesis of cardiovascular (CV) diseases. Prior studies have suggested that the principal determinants of arterial stiffening are age, Blood Pressure (BP) and others CV risk factors such as dyslipidemia and diabetes. However, scanty data are available on the role of psychological factors on arterial stiffness. Previous work have shown that arterial stiffness was associated with depression in the elderly and in healthy adolescents, but no study has focused on the role of depression and other psychological variables in hypertensive patients. The aim of the current cross-sectional study was to evaluate the association between depression, anxiety, perceived stress, Type A personality, and Type D personality and Pulse Wave Velocity (PWV) in a cohort of hypertensive patients, using baseline examination data of the TIPICO project. Design and method: A total of 259 outpatients (ages 18–80 years) followed by the Hypertension Unit of S. Gerardo Hospital (Monza, Italy) affected by essential hypertension were recruited. Aortic stiffness was evaluated by PWV between the carotid and the femoral artery of the same side with the patient in the supine position. Moreover, anamnestic data, clinical BP, and laboratory data were evaluated. Patients were asked to complete a battery of psychological questionnaires under the guidance of a psychologist. The associations between psychological variables and PWV was explored using multivariate stepwise linear regression analysis and regression coeffi cients (b) were given per 1-point increment. Results: The mean age was 55.9 ± 10.1years, SBP and DBP were 135.6 ± 17.7 and 82.5 ± 9.1mmHg and PWV was 8.6 ± 2.1m/s. The results from the multivariate stepwise linear regression analysis showed that age (beta = 0.284, p < 0.001), pulse pressure (beta = 0.369, p < 0.001), dyslipidemia (beta = 0.130, p = 0.012), family history of CV disease (beta = -0.123, p = 0.017), and depression (beta = 0.126, P = 0.014) were signifi cantly and independently associated with PWV. Conclusions: The current study shows that, among psychological factors, higher levels of depression is related to higher PWV, while anxiety, perceived stress, Type A personality, and Type D personality are not associated with arterial stiffness. Depression assessment and target intervention to reduce it are recommended in hypertensive patients