BACKGROUND: The first few months after admission are the most vulnerable period in patients with acute decompensated heart failure (ADHF). METHODS AND RESULTS: We assessed the association of the updated ADHF/N-terminal pro-B-type natriuretic peptide (NT-proBNP) risk score with 90-day and in-hospital mortality in 701 patients admitted with advanced ADHF, defined as severe symptoms of worsening HF, severely depressed left ventricular ejection fraction, and the need for i.v. diuretic and/or inotropic drugs. A total of 15.7% of the patients died within 90 days of admission and 5.2% underwent ventricular assist device (VAD) implantation or urgent heart transplantation (UHT). The C-statistic of the ADHF/NT-proBNP risk score for 90-day mortality was 0.810 (95% CI: 0.769-0.852). Predicted and observed mortality rates were in close agreement. When the composite outcome of death/VAD/UHT at 90 days was considered, the C-statistic decreased to 0.741. During hospitalization, 7.6% of the patients died. The C-statistic for in-hospital mortality was 0.815 (95% CI: 0.761-0.868) and Hosmer-Lemeshow χ(2)=3.71 (P=0.716). The updated ADHF/NT-proBNP risk score outperformed the Acute Decompensated Heart Failure National Registry, the Organized Program to Initiate Lifesaving Treatment in Patients Hospitalized for Heart Failure, and the American Heart Association Get with the Guidelines Program predictive models. CONCLUSIONS: Updated ADHF/NT-proBNP risk score is a valuable tool for predicting short-term mortality in severe ADHF, outperforming existing inpatient predictive models.

Vitamin D deficiency is a condition that affects a high percentage of individuals of all ages. Considerable attention has been paid recently to the possible role of deficiency of this vitamin in the development of several chronic diseases, including cardiovascular and metabolic diseases. In particular, vitamin D deficiency is associated with an increase in conditions such as obesity, insulin-resistance, hypertension, diabetes, and an increased risk of death from these pathologies. There is also a significant correlation with mortality for major cardiovascular events such as heart failure, myocardial infarction, sudden cardiac death, stroke, atrial fibrillation, and peripheral vascular disease. The pathophysiological mechanisms of these correlations are yet to be determined, but hyperactivity of the renin-angiotensin-aldosterone system seems to play a leading role. The role of therapy with vitamin D supplements in improving cardiovascular outcome in patients with low levels of vitamin D remains to be determined.

Abstract BACKGROUND: Alterations of glucose metabolism represent well known risk factors for the atherosclerotic process and then for cardiovascular disease. OBJECTIVE: to investigate the association between fasting glucose and early signs of atherosclerosis, by means of carotid intima-media thickness (c-IMT) in a population of apparently healthy overweight/obese subjects. In addition, we evaluated the possible existence of a glycemic threshold above which the risk of atherosclerosis significantly increases. METHODS: 179 overweight/obese (mean BMI: 32 ± 5 kg/m2) subjects, 44 men, aged 40 ± 12.4 years, were enrolled in the study. Blood glucose, insulin, total cholesterol, high and low density lipoprotein cholesterol and triglycerides were detected in all subjects. The Homeostasis Model Assessment of insulin resistance index (HOMA-IR) was also obtained. All subjects underwent carotid echo color Doppler ultrasound to identify c-IMT. RESULTS: In our population of obese/overweight subjects with insulin resistance (HOMA-IR=3.4 ± 2), c-IMT was positively related to male gender (r = 0.23, P<0.01), age (r = 0.53, P<0.001), waist circumference (r = 0.15, P=0.04), systolic and diastolic blood pressure (r=0.27, P<0.001 and r=0.24, P<0.001 respectively), fasting glucose (r=0.29, P<0.001), triglycerides (r= 0.16 P=0.03), total and low density lipoprotein cholesterol levels (r=0.25 P<0.001 and r=0.21, P<0.01 respectively). Only male gender and fasting glycaemia were associated to c-IMT (P<0.01 and P< 0.001, respectively) at Conclusion: Blood glucose represented an independent predictor of atherosclerosis in our study population. Moreover, this seemed to be able to favor c-IMT progression for values greater than 90 mg/dl.

To evaluate the role of bioelectrical impedance vector analysis (BIVA) and brain natriuretic peptide (BNP) in detecting peripheral congestion in heart failure (HF). Background BIVA/BNP are biomarkers for congestion in acute (ADHF) and chronic HF. Methods 487 ADHF and 413 chronic HF patients underwent BIVA and BNP tests. Results BIVA was more accurate than BNP in detecting peripheral congestion both in ADHF (AUC 0.88 vs 0.57 respectively; p < 0.001) and chronic HF patients (AUC 0.89 vs 0.68, respectively; p < 0.001). In ADHF patients, the optimal BNP cut-off for discriminating presence or absence of edema was >870 pg/mL (PPV = 48% and NPV = 58%) whereas in chronic HF it was >216 pg/mL (PPV = 18% and NPV = 95%). The BIVA detected edema when the vector fell into the lower pole of 75th percentile tolerance ellipse (PPV = 84% and NPV = 78%) in ADHF, the lower pole of 50% (PPV = 68% and NPV = 95%) in chronic HF. Conclusions In HF patients, BIVA is an easy, fast technique to assess peripheral congestion, and is even more accurate than BNP.

Aortic diseases include a wide range of pathological conditions: aortic aneurysms, pseudoaneurysms, acute aortic syndromes, atherosclerotic and inflammatory conditions, genetic diseases and congenital anomalies. Acute aortic syndromes have acute onset and may be life-threatening. They include aortic dissection, intramural haematoma, penetrating aortic ulcer and traumatic aortic injury. Pain is the common denominator to all acute aortic syndromes. Pain occurs regardless of age, gender and other associated clinical conditions. In this review, we deal with the main findings in the clinical setting and the most recent indications for diagnostic imaging, which are aimed to start an appropriate treatment and improve the short- and long-term prognosis of these patients. © The Author(s) 2016.

The aim of our study was to analyze morphological and functional aspects of cerebral veins by means of ecocolor-Doppler in young (i.e., ≤ 30 years old) and older (i.e., >30 years old) patients suffering from multiple sclerosis. 552 multiple sclerosis patients were evaluated by means of a dedicated Echo-Color-Doppler support (MyLab Vinco echocolor Doppler System, Esaote), in both supine and sitting positions. 458 (83%) showed alterations in their morphological and functional structures of cerebral veins and were divided in two different groups: 1) ≤ 30 (110 patients) and 2) >30 years old (348 patients). Young patients showed a statistically significant higher number of both hemodynamically (44% vs. 35%, p<0.01) and non-hemodynamically (51% vs. 45%, p<0.05) significant stenosis in the internal jugular veins as compared to older patients. A lower percentage of young patients showed blocked outflow in the cervical veins (50% vs. 65%, p<0.01) as compared to older ones. Patients >30 years old outlined a significantly higher disability degree (Expanded Disability Status Scale score: 5 vs. 3, p<0.01) as well as higher disease duration (12 vs. 5 months, p<0.01) than younger. No differences could be outlined about multiple sclerosis clinical form of the disease. It was evidenced that young and adult groups are different kind of patients, the former showing much more cerebral veins stenosis and blocked flow in internal jugular veins and vertebral veins than the latter. Duration of disease could explain such differences: the higher the diseases duration, the higher the degree of vascular alterations and, therefore, the disability degree. This could be due to the complex venous hemodynamic impairments induced by alterations in vascular walls: the blocked or difficult blood flow through stenosis could increase the hydrostatic pressure in the skull and this could induce damages to cerebral cells leading to the genesis of more advanced morphological abnormalities. Furthermore, the vessels' alterations could impair venous endothelial functions which could turn in a possible alteration of the controls of cerebral vein return which could worsen the cerebral vascular outflow. It may be possible that early clinical, pharmacological and/or invasive vascular interventions could exert a possible role in the natural history of multiple sclerosis. Nevertheless, further trials are needed in order to confirm such considerations.

Aims: Brugada syndrome (BrS) is an inherited channelopathy that can be characterized by mild right ventricular (RV) abnormalities that are not detectable with conventional echocardiography. The aim of this study was to evaluate the presence of RV abnormalities in BrS patients when compared with controls and a group of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) using two-dimensional (2D) strain analysis. Methods and results: We enrolled 25 BrS, 15 ARVD/C patients, and 25 controls. Right and left ventricular dimension and systo-diastolic function were evaluated by conventional echocardiography. Longitudinal systolic strain (sS) peak, systolic and early diastolic strain rate of lateral RV segments were evaluated by 2D speckle tracking analysis. Left ventricle global and segmental strain measures were also evaluated. A reduced basal or mid-RV lateral sS were the parameters mostly associated with both BrS and ARVD/C. In BrS patients the minimum sS observed in these segments was significantly lower than that of controls (-28.9±3.2% vs. -32.3±3.2%, P: 0.002) but significantly greater than that evaluated in ARVD/C patients (-24.6 ±6.7%, P < 0.001 both vs. BrS and controls). No differences were found between the BrS and the control group when left ventricular strain measures were analysed. Conclusion: By 2D strain technique it is possible to observe mild abnormalities in RV systolic and diastolic function of BrS patients that are less pronounced than those observed in ARVD/C patients. These results help to better define the phenotypic characteristics of BrS patients and represent the basis for future studies aimed at testing their clinical usefulness in BrS patients.

The manuscript describes the case of a 23 year-old woman, with acute myopericarditis associated with food poisoning without other cardiovascular disease. The patient had a history of hypothyroidism, treated with levothyroxine 75 μg/d, however she was clinically and biochemically euthyroid. We present a discussion of this rare association, followed by clinical presentation and treatment. This case report underlines the importance of considering possible cardiac complications when treating patients with food poisoning.

Severe acute arterial hypertension is usually defined as ‘hypertensive crisis’, although ‘hypertensive emergencies’ or ‘hypertensive urgencies’, as suggested by the Joint National Committee and the European Society of Hypertension, have completely different diagnostic and therapeutic approaches. The prevalence and demographics of hypertensive emergencies and urgencies have changed over the last four decades, but hypertensive emergencies and urgencies are still associated with significant morbidity and mortality. Different scientific societies have repeatedly produced upto- date guidelines; however, the treatment of hypertensive emergencies and urgencies is still inappropriate, with potential clinical implications. This review focuses on hypertensive emergencies and urgencies management and treatment, as suggested by recent data.

Background. Although individual patient outcomes are highly variable, coronary artery anomalies may be associated with sudden cardiac death or acute coronary syndrome. Methods. We report 5 cases of anomalous origin of coronary arteries: a single coronary artery originating from the right sinus of Valsalva, a case of isolated anomalous right coronary artery originating separately from the left sinus of Valsalva, a case of right coronary artery originating between the right and left sinus of Valsalva, a case of anomalous left circumflex artery originating from the right sinus of Valsalva, and a case of anomalous left anterior descending coronary artery originating from the right sinus of Valsalva. Results. Although in one case the right coronary artery runned between the aorta and the right pulmonary artery, no significant alterations due to coronary artery compression or atheromatous lesions at the anomalous coronary ostia were observed. In all reported cases, symptoms were different as a result of cardiovascular comorbidities. All coronary anomalies were identified at coronary angiography, which was performed for other indications. Conclusions. The identification of a clear correlation between symptoms and coronary artery anomalies seems challenging in clinical practice. However, it is crucial to confirm or rule out the presence of coronary compression caused by the anomalous origin of coronary arteries.

AIM: To evaluate the influence of selected maternal and neonatal characteristics on aorta walls in term, appropriately grown-for-gestational age newborns. METHODS: Age, parity, previous abortions, weight, height, body mass index before and after delivery, smoking, and history of hypertension, of diabetes, of cardiovascular diseases, and of dyslipidemia were all assessed in seventy mothers. They delivered 34 males and 36 females healthy term newborns who underwent ultrasound evaluation of the anteroposterior infrarenal abdominal aorta diameter (APAO), biochemical profile (glucose, insulin, total cholesterol, HDL and LDL cholesterol, triglycerides, fibrinogen, and D-dimers homeostasis model assessment [HOMAIR]index), and biometric parameters. RESULTS: APAO was related to newborn length (r = +0.36; P = 0.001), head circumference (r = +0.37; P = 0.001), gestational age (r = +0.40, P = 0.0005), HOMA index (r = +0.24; P = 0.04), and D-dimers (r = +0.33, P = 0.004). Smoke influenced APAO values (odds ratio: 1.80; confidence interval 95%: 1.05-3.30), as well as diabetes during pregnancy (r = +0.42, P = 0.0002). Maternal height influenced neonatal APAO (r = +0.47, P = 0.00003). Multiple regression analysis outlined neonatal D-dimers as still significantly related to neonatal APAO values. CONCLUSIONS: Many maternal and neonatal characteristics could influence aorta structures. Neonatal D-dimers are independently related to APAO.

Objective: The first goal of our study was to investigate major determinants of aortic stiffness in postmenopausal women using an echocardiographic method to calculate global pulse wave velocity (PWVg) rather than the less accurate carotid-femoral pulse wave velocity (PWVc). The second goal was to relate PWVg to the absolute risk of major cardiovascular (CV) events estimated by CV risk factors. Patients and methods: Two hundred forty-four consecutive women who presented to our heart station were screened. One hundred twenty-two were postmenopausal, either natural or surgical, whereas 122 were premenopausal. The mean age of the patients was 54 ± 13 years. Individuals were categorized as current smokers, former smokers, or nonsmokers and hypertensive or not. Hypercholesterolemia and diabetes mellitus were defined. Aortic stiffness was assessed by PWVg measured with pulsed Doppler, the interval between the beginning of QRS complex and the foot of the systolic upstroke in the Doppler spectral envelope was calculated at the aortic valve site and at the right common femoral artery. PWVg was calculated between the aortic valve and right common femoral artery by dividing the straight line distance between the two by the transit time. Results: There was a highly significant statistical difference (P < 0.0012) in PWVg between menstruating women and postmenopausal women. Similarly, this difference in PWVg was also noted among the menstruating population (P < 0.0014) when comparing normotensive women and hypertensive women. In postmenopausal women, PWVg was 6.8 m/sec in normotensive women and 7.56 m/sec in hypertensive women (P < 0.007). Conclusion: PWVg was increased in postmenopausal women compared with menstruating women. Systemic hypertension has an independent, but additive effect on aortic stiffness assessed by PWVg. Our study supports the usefulness of the assessment of aortic stiffness as a marker of CV disease and to identify subjects at risk at an early age

Thromboembolic events, principally stroke, represent among the leading causes of morbidity and mortality of subjects with atrial fibrillation, with an incidence about 5 times higher compared to healthy subjects. Chronic kidney disease, frequently associated with atrial fibrillation, determines itself a further increase of thromboembolic events, bleeding and mortality. In addition, the presence of renal failure complicates the pharmacological management of these patients, mainly due to the side effects of antiarrhythmic and anticoagulant drugs with renal excretion, due to their accumulation. Apixaban is a new oral anticoagulant characterized by good bioavailability and renal elimination accounting for only 25%, showing a safety profile and effectiveness in patients with renal impairment, who very often are under-treated or inadequately treated during atrial fibrillation. In this manuscript, we reviewed the data available in the literature regarding the use of apixaban in the management of non-valvular atrial fibrillation in patients with renal failure, in order to clarify an often-debated topic in clinical practice. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Bemiparin is a low molecular weight heparin (LMWH) indicated for the acute treatment of deep vein thrombosis with or without pulmonary embolism, for the prophylaxis of venous thromboembolism in surgical and non-surgical patients and for the prevention of clotting in the extracorporeal circuit during hemodialysis. Due to its excellent pharmacological profile—the second-generation LMWH with the lowest molecular weight, the longest half-life and the highest anti-Factor Xa/anti-Factor IIa activity ratio—it can be safely used in special categories of patients (children, elderly, patients with renal impairment and congestive heart failure). Several studies demonstrated its safety and efficacy, while cost analyses show the economic benefits of bemiparin treatment as compared to other heparins. Recent evidences suggested the application of bemiparin even in the management of diabetic foot ulcers. The aim of this narrative review was to evaluate literature according to results coming from studies involving bemiparin administration in various clinical conditions.

Abstract BACKGROUND: Oat and barley beta-glucans are prebiotic fibers known for their cholesterol-lowering activity, but their action on the human gut microbiota metabolism is still under research. Although the induction of short-chain fatty acids (SCFA) following their ingestion has previously been reported, no study has investigated their effects on proteolytic uremic toxins p-cresyl sulfate (pCS) and indoxyl sulfate (IS) levels, while others have failed to demonstrate an effect on the endothelial function measured through flow-mediated dilation (FMD). OBJECTIVE: The aim of our study was to evaluate whether a nutritional intervention with a functional pasta enriched with beta-glucans could promote a saccharolytic shift on the gut microbial metabolism and improve FMD. METHODS: We carried out a pilot study on 26 healthy volunteers who underwent a 2-month dietary treatment including a daily administration of Granoro "Cuore Mio" pasta enriched with barley beta-glucans (3g/100g). Blood and urine routine parameters, serum pCS/IS and FMD were evaluated before and after the dietary treatment. RESULTS: The nutritional treatment significantly reduced LDL and total cholesterol, as expected. Moreover, following beta-glucans supplementation we observed a reduction of serum pCS levels and an increase of FMD, while IS serum levels remained unchanged. CONCLUSIONS: We demonstrated that a beta-glucans dietary intervention in healthy volunteers correlates with a saccharolytic shift on the gut microbiota metabolism, as suggested by the decrease of pCS and the increase of SCFA, and associates with an improved endothelial reactivity. Our pilot study suggests, in addition to cholesterol, novel pCS-lowering properties of beta-glucans, worthy to be confirmed in large-scale trials and particularly in contexts where the reduction of the microbial-derived uremic toxin pCS is of critical importance, such as in chronic kidney disease.

In recent years, bioresorbable vascular scaffolds (BVS) have been introduced into clinical practice. The main advantage of BVS is that they overcome the problem of the foreign body in the treated artery. BVS, once placed into narrowed coronary vessels, behave like a conventional drug-eluting stent, but a device that disappears over time can preserve the anatomy and physiology of the treated vessel. The progression of stenosis after stenting has been attributed, at least in part, to inflammation around metallic struts, that, however, disappears gradually when using BVS. BVS have proven to be effective and safe as drug-eluting stents; in fact, the rate of adverse cardiovascular events and scaffold thrombosis in patients is low. The aim of this review article is to provide a comprehensive and updated description of the status of the art on BVS, highlighting the current evidence and future perspectives of this technology.

Introduction: Silent ischemia is an asymptomatic form of myocardial ischemia, not associated with angina or anginal equivalent symptoms, which can be demonstrated by changes in ECG, left ventricular function, myocardial perfusion, and metabolism. The aim of this study was to evaluate the prevalence of silent myocardial ischemia in a group of patients with asymptomatic carotid stenosis. Methods: A total of 37 patients with asymptomatic carotid plaques, without chest pain or dyspnea, was investigated. These patients were studied for age, sex, hypertension, diabetes, dyslipidemia, smoking, and family history of cardiac disease, and underwent technetium-99 m sestamibi myocardial stress-rest scintigraphy and echo-color Doppler examination of carotid arteries. Results: A statistically significant relationship (P = 0.023) was shown between positive responders and negative responders to scintigraphy test when both were tested for degree of stenosis. This relationship is surprising in view of the small number of patients in our sample. Individuals who had a positive scintigraphy test had a mean stenosis degree of 35% ± 7% compared with a mean of 44% ± 13% for those with a negative test. Specificity of our detection was 81%, with positive and negative predictive values of 60% and 63%, respectively. Conclusion: The present study confirms that carotid atherosclerosis is associated with coronary atherosclerosis and highlights the importance of screening for ischemic heart disease in patients with asymptomatic carotid plaques, considering eventually plaque morphology (symmetry, composition, eccentricity or concentricity of the plaque, etc) for patient stratification.

Polycystic ovary syndrome (PCOS), or Stein-Leventhal syndrome, is a common endocrine disorder defined by two of the three following features: i) oligoovulation or anovulation, ii) clinical and/or biochemical signs of hyperandrogenism, or iii) polycystic ovaries, once the related endocrinological and gynaecological disorders have been excluded. PCOS does not exclusively involve the reproductive apparatus , it has a complex number of systemic relevancy symptoms. It leads to Metabolic Syndrome, with severe consequences on the cardiovascular apparatus. Many clinical studies have underlined the connection between PCOS and the cardiovascular risk profile of such female patients, due to a lipid/glucose altered metabolism, hypertension, systemic inflammatory condition (assessable by markers such as VES, TNF-alfa, citokines and C-reactive protein (hsPCR) levels), and vascular injuries. Considering the early onset of the disease, PCOS could be considered as a real cardiovascular risk factor which affects the quality of life seriously. The current review aimed to point out the main connections between PCOS and cardiovascular risk factors according to the latest findings coming from literature data analysis, and try to depict the great influences that such a common disease can have on the patients’ health integrity.

Abstract: Fruits and vegetables (typically associated with the Mediterranean diet) are very rich in carotenoids, i.e. fat-soluble pigments really important in human life. Structurally, carotenoids consists of eleven (beta-carotene, zeaxanthin, lycopene) or ten (alpha-carotene, lutein) conjugated double bonds, responsible for their antioxidant capability in agreement with their substituents. Low-Density Lipoprotein (LDL) particles oxidation process is the one of the most important first steps of atherosclerotic disease and, consequentially, the first pathogenetical step of cerebro- and cardiovascular events like myocardial infarction and stroke, which are the first cause of death in industrialized countries. Reactive oxygen species (ROS) also seem to be the target of Carotenoids main action, by scavenging singlet oxygen ( 1 O ) and free radicals. Literature data showed that ROS increase atherosclerotic individual burden. The carotenoids scavenging action could reduce atherosclerosis progression partly due to such a decrease in ROS concentrations. Many studied demonstrated such a 2 reduction by analyzing the relationship between carotenoids and Intima-Media Thickness of common carotid artery wall (CCA-IMT), [a well established marker of atherosclerosis evolution] reduction. Aim of this review is to evaluate actual knowledge about the importance of carotenoids molecules in slowing down the starting and the progression of atherosclerotic plaque, and to consider their implementation in everyone's diet as a tool to obtain a sharp decrease of LDL oxidation and their possible effect on endothelial function.

Aims: Carotid intima-media thickness (IMT) is one of the best non-invasive parameters for evaluating previous vascular lesions and could be used to identify a preclinical stage of the atherosclerotic process. The aim of our research was to develop an epidemiological study of the normal mean values of IMT of the common carotid artery, adjusted for age and sex, in the Italian population. Methods and results: In this multicenter study, a total of 1017 patients (596 males, mean age: 58.5\+13.2 years) were enrolled at four different Italian centers. Inclusion criteria were the absence of cardiovascular risk factors or presence of not more than one. Patients underwent two-dimensional echo-color Doppler scanning of the carotid arteries, adopting a high-definition vascular echographic apparatus and a 11-3 MHz linear electronic probe. The arithmetical mean of the IMT value was calculated. Data obtained from this study show the carotid IMT changes in relation to age and sex. In particular, it grows higher with increasing age, and is always higher in men than in women. Conclusion: In relation to the percentile distribution of the values in the population analyzed, the normal range of m- IMT could be established just on the basis of the patient's age and sex. In this way, the ultrasound scan operator can rely on a simple reference scheme. This will help to refine the use of carotid ultrasound as an excellent tool for detecting asymptomatic carotid alterations and patients at high risk for cerebral and cardiovascular disease.

The aim of this study was to evaluate outcomes and feasibility of carotid artery stenting versus carotid endarterectomy, both procedures performed in the same patient. Forty-five subjects (33 males, 70 ± 7 years) underwent carotid endarterectomy or carotid artery stenting, the counter procedure on the contralateral carotid performed after a variable period. We evaluated the post-procedural percentage of carotid stenosis at 30, 180 days and one-year follow-up, and the occurrence of acute myocardial infarction, New York Heart Association class progression, stroke, death, cardiovascular death, angina, transient ischemic attack and renal failure. Carotid artery stenting treatment reduced the degree of re-stenosis after 180 days equally to carotid endarterectomy procedure (difference: 0.033%, P = 0.285). No statistically significant differences were observed according to the occurrence of acute myocardial infarction and New York Heart Association class progression, revealing odds ratio (OR) equal to 0.182 (P = 0.361) for acute myocardial infarction and 0.303 (P = 0.434) for New York Heart Association class progression. Carotid endarterectomy confirms its efficacy in carotid revascularization, but carotid artery stenting constitutes a good alternative when the procedures are selected based on patient-specific risk factors

Objective: There is a close link between heart failure and endothelial dysfunction. Brachial flow-mediated dilation (FMD) is a validated non-invasive measure of endothelial function. The aim of this study was to investigate the clinical correlates of FMD in patients with chronic heart failure (CHF). Design, setting, patients: Weevaluated 60CHFoutpatients (age 62 ± 14 years; 49 males, NYHA class 2.2 ± 0.7, left ventricular ejection fraction, LVEF, 33 ± 8%) taking conventional medical therapy (ACE-inhibitors and/or ARBs 93%, beta-blockers 95%) and in stable clinical conditions. Main outcome measures: The maximum recovery value of FMD was calculated as the ratio of the change in diameter (maximum-baseline) over the baseline value. Results: As compared with patients with a higher FMD, those with FMD below the median value (4.3%) were more frequently affected by ischemic cardiopathy (50 vs. 23%; p = 0.032) and diabetes mellitus (20 vs. 3%; p = 0.044), had a higher NYHA class (2.5 ± 0.5 vs. 1.9 ± 0.7; p< 0.001) and NT-proBNP (2,690 ± 3,690 vs. 822 ± 1,060; p = 0.001), lower glomerular filtration rate estimated by Cockcroft-Gault (GFRCG: 63 ± 28 vs. 78 ± 25; p = 0.001) and LVEF (29 ± 8 vs. 37 ± 9; p = 0.001), as well as more frequently showing a restrictive pattern (40 vs. 7%; p = 0.002). In a multivariate regression model (R2 = 0.48; p<0.001), FMD remained associated only with the NYHA class (p = 0.039) and diabetes mellitus (p = 0.024). Conclusions: This study demonstrates that a better functional status and absence of diabetes mellitus are associated to higher FMD regardless of the etiology of the cardiac disease.

Objectives; Nitrate-stimulated head-up tilt testing (HUT) is currently recommended to confirm the diagnosis of vasovagal syncope in subjects with syncope of unknown origin. Given the few data currently available, the aim of this study was to assess correlations between nitrateinduced HUT outcomes and the clinical characteristics of patients. Methods; Two hundred and thirty consecutive, otherwise healthy subjects with a history of recurrent unexplained syncope underwent HUT. After 10 min supine rest, they were tilted to 70°, and the test was potentiated by the administration of 300 μg of nitroglycerin after 20 min. Results Out of 178 subjects who underwent nitroglycerin administration during HUT, 95 fainted. At univariate Cox regression analysis, a reduced probability of VVS occurrence after nitrates was associated with greater systolic blood pressure and body mass index values, to male gender and smoking. At multivariate Cox regression analysis, only male gender (HR - 0.61; P - 0.039) and smoking (HR - 0.18; P - 0.001) remained significantly associated with HUT outcomes during the pharmacological phase of the test. Interpretation; Smokers and males are less likely to faint after nitrate administration during HUT than non-smokers and females. Further studies should clarify the possibility of improving the diagnostic power of HUT in these patients.

Takotsubo cardiomyopathy (TTC) is characterized by transient systolic ventricular dysfunction. It is supposed to be caused by a cathecolaminergic wave which leads to myocardial stunning through a massive action on beta2-adrenoreceptor. Moreover, beta2-receptor hyperactivity negatively influences endothelial function. It can be detected by brachial flow mediated dilation (b-FMD) which assesses endothelium regulated vasomotility. The study aim is to analyze the b-FMD variability during hospitalization in 50 patients admitted with TTC. In addition, we investigated a possible correlation between b-FMD at admission and both length of hospital stay (LOHS) and troponin I peak. We detected b-FMD by measuring the hypoxic induced vasoreactivity through assessing brachial artery dilation after 5 min of iatrogenic ischemia obtained by inflating a sphygmomanometer cuff. Artery diameter modifications were assessed by high-resolution ultrasound, and a dedicated software calculated accurately the percentage of dilation after ischemia by comparing it to the basal. These values were measured at admission and on discharge. The obtained values were compared for each patient to explore their variability during hospitalization. Moreover, the correlation between the b-FMD at admission and both the troponin I peak and the LOHS was investigated. There was a statistical significant difference between mean FMD measured at admission and at discharge (respectively 1.54 ± 0.34 and 8.92 ± 2.48%; p < 0.001). Moreover, we found a significant negative correlation between troponin I peak and FMD values at admission (r = - 0.7645; p < 0.001) and a significant inverse correlation between FMD at admission and LOHS (r = - 0.7543; p < 0.001). There is a significant improvement of b-FMD during hospitalization in patients admitted for Tako-Tsubo Cardiomyopathy. Moreover, for the first time, a direct correlation among b-FMD, troponin I peak and LOHS has been detected.

Obstructive Sleep Apnea (OSA) is a sleep-related breathing disorder associated with the development of cardiovascular diseases and atherosclerosis. Systemic inflammation plays an important role in the development of cardiovascular complications in OSA patients. The aim of the study was to evaluate the relationship between carotid intima-media thickness (cIMT) and inflammatory markers plasma levels in OSA patients. We enrolled 80 OSA patients and 40 controls matched for age and body mass index (BMI). The presence and severity of sleep apnea was determined by in-laboratory portable monitoring (PM). Demographic data, blood pressure, heart rate, and cIMT were measured. High-sensitive C-Reactive Protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α and pentraxin (PTX)-3 serum concentrations were detected. cIMT was higher in OSA patients than controls (0.89 ± 0.13 mm vs. 0.65 ± 0.1 mm, p < 0.01). Moderate-severe OSA patients (0.95 ± 0.09 mm) had significantly increased cIMT than mild OSA (0.76 ± 0.1 mm; p < 0.01) and control (0.65 ± 0.1 mm; p < 0.01). hsCRP, IL-6, TNF-α, and PTX-3 in patients with OSA (1.67 ± 0.66 mg/L, 2.86 ± 1.39 pg/mL, 20.09 ± 5.39 pg/mL, 2.1 ± 0.59 ng/mL, respectively) were significantly higher than in controls (1.08 ± 0.53 mg/L, p < 0.01; 1.5 ± 0.67 pg/mL, p < 0.01; 12.53 ± 3.48 pg/mL, p < 0.01; 1.45 ± 0.41 ng/mL, p < 0.01, respectively). Carotid IMT was significantly correlated to CRP (r = 0.44; p < 0.01), IL-6 (r = 0.42; p < 0.01), TNF-α (r = 0.53; p < 0.01), and PTX-3 (r = 0.49; p < 0.01). OSA patients showed increased cIMT, CRP, IL-6, TNF-α, and PTX-3 levels. Inflammatory markers levels are correlated to cIMT in OSA patients.

Abstract Cardiovascular disease related to atherosclerosis represents nowadays the largest cause of morbidity and mortality in developed countries. Due to inflammatory nature of atherosclerosis, several studies had been conducted in order to search for substances with anti-inflammatory activity on arterial walls, able to exert beneficial roles on health. Researches investigated the role of dietary carotenoids supplementation on cardiovascular disease, due to their free radicals scavenger properties and their skills in improving low-density lipoprotein cholesterol resistance to oxidation. Nevertheless, literature data are conflicting: although some studies found a positive relationship between carotenoids supplementation and cardiovascular risk reduction, others did not find any positive effects or even prooxidant actions. This paper aimed at defining the role of carotenoids supplementation on cardiovascular risk profile by reviewing literature data, paying attention to those carotenoids more present in our diet ( β -carotene, α -carotene, β -cryptoxanthin, lycopene, lutein, zeaxanthin, and astaxanthin).

Abstract BACKGROUND AND AIM: To establish, using echocardiography, color-flow Doppler and tissue doppler imaging (TDI), physiological values of systolic/diastolic indexes in healthy term/pre-term newborns, and to identify how different degrees of maturity influence morpho-functional cardiac alterations during the transitional period. STUDY DESIGN AND SUBJECTS: 33 term newborns (M = 19, F = 14; gestational ages: 37th-41st week), and 20 pre-term infants (M = 11, F = 9; gestational ages: 31st-36th week) admitted to our department were studied. All infants underwent to clinical and Doppler ultrasound evaluations, carried out by the third to fourth day. Investigations included: M-mode echocardiography, color-flow Doppler and TDI. OUTCOME MEASURES AND RESULTS: Term and preterm neonates differed for: interventricular septum and left systolic/diastolic ventricle diameters (p<0.01 and <0.05 respectively); left ventricle posterior wall in systole (p<0.01); shortening and ejection fraction (p<0.05). Color-flow Doppler parameters on the tricuspid (peak E, peak A, ratio E/A; p<0.05) and on the mitral (peak E and E/A ratio; p<0.01) significantly differed between the two groups. Significant differences were also present for basal left ventricular lateral wall and right ventricular lateral wall in the Ew (p<0.01 and <0.05 respectively), Sw peak (p<0.01 and <0.05 respectively), and Ew/Aw (p<0.05). The isovolumetric relax time and the E/Ew measured on the medial mitral annulus also demonstrated significant differences (p<0.01) between the two groups. CONCLUSIONS: TDI is feasible in preterm neonates and enables assessment of myocardial velocities. With increasing gestational age, higher myocardial velocities and lower E/E' Πratios were found. TDI addition to standard neonatal echocardiography may provide further important information about cardiac function.

Abstract BACKGROUND: The study aim was to test the accuracy (intra and interobserver variability), sensitivity, and specificity of a simplified noninvasive ultrasound methodology for mapping superficial and deep veins of the lower limbs. METHODS: 62 consecutive patients, aged 62 ± 11 years, were enrolled. All underwent US-examinations, performed by two different investigators, of both legs, four anatomical parts, and 17 veins, to assess the interobserver variability of evaluation of superficial and deep veins of the lower limbs. RESULTS: Overall the agreement between the second versus the first operator was very high in detecting reflux (sensitivity 97.9, specificity 99.7, accuracy 99.5; P = 0.80 at McNemar test). The higher CEAP classification stages were significantly associated with reflux (odds ratio: 1.778, 95% confidence interval: 1.552-2.038; P < 0.001) as well as with thrombosis (odds ratio: 2.765, 95% confidence interval: 1.741-4.389; P < 0.001). Thus, our findings show a strict association between the symptoms of venous disorders and ultrasound evaluation results for thrombosis or reflux. CONCLUSION: This study demonstrated that our venous mapping protocol is a reliable method showing a very low interobserver variability, which makes it accurate and reproducible for the assessment of the morphofunctional status of the lower limb veins.

Neonatal sepsis still represents an important cause of mortality and morbidity among infants. According to the onset, we can distinguish “early onset sepsis” when microbiological cultures positive for external pathogens come from newborns during the first 7 days of life (maternal intrapartum transmission); “late onset sepsis” when microbiological cultures positive for external pathogens come from newborns after the first 7 days from delivery (postnatal acquisition). In this review we synthesize the incidence, risk factors, clinical manifestations, and methods of diagnosis and treatment of each type of neonatal infection, in order to better define such a pathological condition which is of great importance in common clinical practice. Copyright ª 2015, Taiwan Pediatric Association.

Neonatal sepsis still represents an important cause of mortality and morbidity among infants. According to the onset, we can distinguish “early onset sepsis” when microbiological cultures positive for external pathogens come from newborns during the first 7 days of life (maternal intrapartum transmission); “late onset sepsis” when microbiological cultures positive for external pathogens come from newborns after the first 7 days from delivery (postnatal acquisition). In this review we synthesize the incidence, risk factors, clinical manifestations, and methods of diagnosis and treatment of each type of neonatal infection, in order to better define such a pathological condition which is of great importance in common clinical practice. Copyright ª 2015, Taiwan Pediatric Association.

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BACKGROUND: Peripheral arterial disease (PAD) is almost invariably associated with a generalized atherosclerotic involvement of the arterial tree and endothelial dysfunction. Previous short-term studies showed improvement of vascular reactivity and walking capacity in PAD patients by measures aimed at restoring nitric oxide (NO) production. NO is also known to prevent the progression of atherosclerosis. We wished to assess whether the prolonged administration of an NO-donating agent (NCX 4016) improves the functional capacity of PAD patients and affects the progression of atherosclerosis as assessed by carotid intima-media thickness (IMT). METHODS: This prospective, double-blind, placebo-controlled study enrolled 442 patients with stable intermittent claudication who were randomized to NCX 4016 (800 mg, twice daily) or its placebo for 6 months. The primary study outcome was the absolute claudication distance on a constant treadmill test (10% incline, 3 km/h). The main secondary end point was the change of the mean far-wall right common carotid artery IMT. RESULTS: The increase of absolute claudication distance at 6 months compared with baseline was 126±140 meters in the placebo-treated group and 117±137 meters in the NCX 4016-treated group, with no significant differences. Carotid IMT increased in the placebo-treated group (+0.01±0.01 mm; P=.55) and decreased in the NCX 4016-treated group (-0.03±0.01 mm; P=.0306). Other secondary end points did not differ between the two treatments. CONCLUSIONS: Long-term NO donation does not improve the claudication distance but does reduce progression of atherosclerosis in patients with PAD. Further studies aimed at assessing whether long-term NO donation may prevent ischemic cardiovascular events are warranted. Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved

AIM: Although the underlined mechanisms are still unknown, metabolic/coagulation alterations related to childhood obesity can induce vascular impairments. The aim of this study was to investigate the relationship between metabolic/coagulation parameters and endothelial function/vascular morphology in overweight/obese children. METHODS: Thirty-five obese/overweight children (22 pre-pubertal, mean age: 9.52±3.35 years) were enrolled. Body mass index (BMI), homeostasis model assessment index (HOMAIR), metabolic and coagulation parameters, [adiponectin, fibrinogen, high molecular weight adiponectin (HMW), endothelin-1, and vonWillebrand factor antigen] ultrasound early markers of atherosclerosis [flow-mediated dilatation (FMD), common carotid intima-media thickness (C-IMT), and anteroposterior diameter of infra-renal abdominal aorta (APAO)] were assessed. RESULTS: APAO was related to anthropometric (age: r=0.520, p=0.001; height: r=0.679, p＜0.001; weight: r=0.548, p=0.001; BMI: r=0.607, p＜0.001; SBP: r=0.377, p=0.026) and metabolic (HOMAIR: r=0.357, p=0.035; HMW: r=－0.355, p=0.036) parameters. Age, height, and systolic blood pressure were positively related to increased C-IMT (r=0.352, p=0.038; r=0.356, p=0.036; r=0.346, p=0.042, respectively). FMD was not related to any clinical and biochemical characteristics of the pediatric population. Age, HOMAIR, fasting glucose levels, and HMW were independent predictors for APAO increase. Each unit decrease in HMW concentrations (1 μg/ml) induced a 0.065 mm increase in APAO. CONCLUSION: High molecular weight adiponectin is related to cardiovascular risk in overweight/obese children.

Background. Hepatitis C virus (HCV) infection can exert proatherogenic activities due to its direct action on vessel walls and/or via the chronic inflammatory process involving the liver. Aims. To clarify the role of HCV in atherosclerosis development in monoinfected HCV patients at different degrees of liver fibrosis and with no risk factors for coronary artery disease. Methods. Forty-five patients were included. Clinical, serological, and anthropometric parameters, liver fibrosis (transient liver elastometry (fibroscan) and aspartate aminotransferase to platelet ratio index (APRI)), carotid intima-media thickness (c-IMT), and brachial artery flow-mediated vasodilatation (FMD) were assessed. Patients were divided into 3 tertiles according to fibroscan values. Results. Patients in the third tertile (fibroscan value >11.5 KPa) showed FMD values were significantly lower than second and first tertiles ( versus , ). FMD values were inversely related to liver elastomeric values. c-IMT values were normal. The risk for endothelial dysfunction development in the third tertile () was 6.9 higher than the first tertile. A fibroscan value >11.5 KPa had a positive predictive power equal to 79% for endothelial dysfunction. Conclusions. HCV advanced liver fibrosis promotes atherosclerosis by inducing endothelial dysfunction independently of common cardiovascular risk factors.

BACKGROUND: Endothelial dysfunction has been already reported in inflammatory bowel diseases (IBD). However, case series so far examined were rather heterogeneous as for disease severity and subsets investigated. OBJECTIVE: We evaluated endothelial dysfunction by brachial artery flow-mediated vasodilatation (FMD), and subclinical atherosclerosis by assessment of common carotid intima-media thickness (CCA-IMT) in a cohort of patients with Crohn's disease (CD) or Ulcerative colitis (UC) in active phase compared to healthy control subjects. METHODS: Forty-nine patients (mean age 41±16years), 25 with CD and 23 with UC, and forty controls (mean age 45±15years) were enrolled. Diagnosis was based on the standard clinical, endoscopic and histological criteria. Disease activity was assessed by Crohn's Disease Activity Index or Disease Activity Index. All patients, were under medical treatment as appropriate. RESULTS: FMD values were lower in IBD patients than controls (6.1±3.0 vs 8.2±3.4. p=0.003); no difference was seen between UC/CD groups (5.9±3.5 vs 6.3±2.6, p=0.67). No changes in statistical differences occurred after adjustment for age, gender, body mass index and family history of cardiovascular disease. Finally, no differences in IMT values were seen between IBD patients and controls. Disease duration and medical treatment did not affect endothelial function. CONCLUSIONS: Our study showed a lower FMD in IBD patients. Inflammation and immune response could explain endothelial dysfunction, which is the earliest stage of atherosclerotic process. IBD patients in active phase might therefore be at higher risk for atherosclerosis progression.

OBJECTIVE: To evaluate cardiovascular risk factors and pre-clinical atherosclerosis in subjects affected by Idiopathic Sudden Sensorineural Hearing Loss (ISSHL). METHODS: In this study, 29 ISSHL patients and 29 healthy controls were evaluated. All of the patients underwent a complete audiovestibular and clinical evaluation. Carotid intima-media thickness (C-IMT) and flow-mediated dilation (FMD) of the brachial artery were assessed as early markers of atherosclerosis. RESULTS: Our results showed that FMD was significantly lower in the ISSHL patients than in the controls (5.6 ± 1.6% vs. 7.7 ± 3.7%, p < 0.01). Moreover, the total cholesterol and low density lipoprotein cholesterol were significantly higher in the ISSHL patients than in the controls (p < 0.05). The two groups did not differ with regards to C-IMT and other cardiovascular risk factors. Vestibular involvement was shown to be associated with lower FMD values (4.1 ± 1.7% vs. 5.8 ± 1.5%, p < 0.05). No relationship was found between C-IMT and vestibular involvement. Finally, multiple logistic regression highlighted the finding that only FMD values seemed to predispose individuals to developing ISSHL (p = 0.03, OR: 1.4). CONCLUSIONS: ISSHL seemed to be associated with vascular endothelial dysfunction and an increased cardiovascular risk, which supports the hypothesis of a vascular aetiology for this disease

Objective: To assess the effect of olive oil, non fried fish and nuts on endothelial function in overweight/obese patients. Methods: 47 overweight/obese patients (24 men, mean age 54 ± 11 years) fed healthy diet (HD) defined according to the Nureta- PREDIMED study for 3 months; after this 3 months of HD, the patients were blindly divided into 4 groups: Controls (24: HD), Group A (8: HD+olive oil), Group B (8: HD+not-fried fish), Group C (7: HD+nuts). These four groups were also followed-up for further 15 months. All patients were evaluated at baseline, at 3 and 18 months for glucose and lipid profile, anthropometric measures and brachial artery Flow-Mediated Dilatation (FMD). Results: HD alone significantly increased FMD at 3 and 18 months follow-up as compared to baseline. Olive oil or not-fried fish or nuts significantly increased FMD as compared to HD at 18 months follow-up. Waist circumference, body mass index significantly decreased after 3 and 18 months; lipid parameters at 18 months improved in all groups as compared to baseline. Fasting glycemia did not change after 18 months (baseline: 101 ± 19 mg/dl vs 18 months: 98 ± 12 mg/dl; p=ns). Conclusions: HD is able to improve endothelial function after a short (3 months) period and olive oil, not fried fish and nuts adding seem to increase such an improvement at a longer (18 months) period. Thus, HD and some of its components can improve cardiovascular risk profile of individuals.

We read with great interest the article of Dr. Blomster H and colleagues entitled:“Endothelial function is well preserved in obese patients with mild obstructive sleep apnea”[1]. In the manuscript, the authors clearly show that mild obstructive sleep apnea (OSA) does not correlate with endothelial dysfunction, measured by brachial artery flow-mediated dilatation (FMD), assuming that in mild OSA, endothelial function is still preserved. The data are very interesting, although the authors did not analyze the time of onset of symptoms, as well as ...

Chronic kidney disease and its worsening are recurring conditions in chronic heart failure (CHF) which are independently associated with poor patient outcome. The heart and kidney share many pathophysiological mechanisms which can determine dysfunction in each organ. Cardiorenal syndrome is the condition in which these two organs negatively affect each other, therefore an accurate evaluation of renal function in the clinical setting of CHF is essential. This review aims to revise the parameters currently used to evaluate renal dysfunction in CHF with particular reference to the usefulness and the limitations of biomarkers in evaluating glomerular dysfunction and tubular damage. Moreover, it is reported the possible utility of renal arterial resistance index (a parameter associated with abnormalities in renal vascular bed) for a better assesment of kidney disfunction.

Abstract Background The aim of this study was to evaluate the effect of exercise training on cardiac function in heart failure (HF) patients recently suffering from acute decompensation. Radionuclide ambulatory ventricular function monitoring (VEST) was used to detect variations in cardiac hemodynamics during training period. Methods This was a monocentric, randomized, controlled trial. We enrolled 72 HF patients [left ventricle ejection fraction (LVEF) < 40%] within two weeks after acute cardiogenic pulmonary edema: 40 in the elderly group, 32 in the middle-aged group. Trained patients underwent a specific four-weeks exercise program (closed-chain resistive activities and abdominal exercises) which was supervised by a therapist in agreement with patients' characteristics. Catecholamines at rest, echocardiography, right-heart catheterization, and bicycle ergometer were performed. VEST was performed at the end of the 4 weeks-training in all patients in order to assess patients' cardiac hemodynamics [LVEF, cardiac output (CO), stroke volume]. Results Exercise training significantly improved exercise duration, peak oxygen consumption, and ventilatory threshold both in elderly and middle-aged patients (p < 0.0001) after the 4-week controlled training. Despite age (F = 35.086, p < 0.0001; F = 16.967, p < 0.0001; F = 42.574, p = 0.03, respectively), training reliably influence previous cardiopulmonary parameters (F = 29.402, F = 16.421, F = 26.80, p < 0.0001, respectively). Norepinephrine and epinephrine were significantly reduced in both trained groups. Peak LVEF (37.3 ± 4.7% vs 34 ± 6.2%, p = 0.002), peak stroke volume (43.3 ± 3.9% vs 37.5 ± 4.3%, p = 0.001), and peak CO (63.4 ± 6.1% vs 48.2 ± 4.7%, p < 0.0001) increased in middle-aged patients after 4-week training. Conclusions Exercise training improves cardiac performance indexes and pulmonary function in both middle-aged and elderly HF patients early after an acute episode of cardiac decompensation.

PURPOSE: Project Leonardo represented a feasibility study to evaluate the impact of a disease and care management (D&CM) model and of the introduction of "care manager" nurses, trained in this specialized role, into the primary health care system. PATIENTS AND METHODS: Thirty care managers were placed into the offices of 83 general practitioners and family physicians in the Apulia Region of Italy with the purpose of creating a strong cooperative and collaborative "team" consisting of physicians, care managers, specialists, and patients. The central aim of the health team collaboration was to empower 1,160 patients living with cardiovascular disease (CVD), diabetes, heart failure, and/or at risk of cardiovascular disease (CVD risk) to take a more active role in their health. With the support of dedicated software for data collection and care management decision making, Project Leonardo implemented guidelines and recommendations for each condition aimed to improve patient health outcomes and promote appropriate resource utilization. RESULTS: Results show that Leonardo was feasible and highly effective in increasing patient health knowledge, self-management skills, and readiness to make changes in health behaviors. Patient skill-building and ongoing monitoring by the health care team of diagnostic tests and services as well as treatment paths helped promote confidence and enhance safety of chronic patient management at home. CONCLUSION: Physicians, care managers, and patients showed unanimous agreement regarding the positive impact on patient health and self-management, and attributed the outcomes to the strong "partnership" between the care manager and the patient and the collaboration between the physician and the care manager. Future studies should consider the possibility of incorporating a patient empowerment model which considers the patient as the most important member of the health team and care managers as key health care collaborators able to enhance and support services to patients provided by physicians in the primary health care system.

Statin treatment represents the gold standard in the reduction of low-density lipoprotein cholesterol and cardiovascular risk. Although statin therapy is generally well tolerated, some patients fail to achieve the target level of low-density lipoprotein cholesterol or discontinue the treatment for the occurrence of adverse events. In recent years new lipid-modifying agents have been studied to overcome these limitations and to reduce low-density lipoprotein cholesterol plasma levels. Alirocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9, thereby preventing its interaction with low density lipoprotein receptors. Several trials have been conducted in the last few years to evaluate long-term effects of this new molecule on low-density lipoprotein cholesterol levels and cardiovascular risk.

Statins are recommended as first-line therapy for patients with hypercholesterolaemia. A sizable proportion of patients, however, does not reach therapeutic goals, is statin intolerant, or, despite optimal statin therapy, is at high risk of ischaemic events. Proprotein convertase subtilisin/ kexin type 9 (PCSK9) plays a major role in lipid metabolism and several comorbidities. Monoclonal antibodies targeting PCSK9 are a new lipid-lowering approach with the potential to improve clinical outcomes in patients with dyslipidaemia. In this review, we discuss current experimental and clinical evidence of the role of PCSK9 and its inhibition on lipid metabolism and several pathologic conditions with a focus on clinical outcomes. A state-of-the-art analysis of current clinical evidence and future directions on PCSK9 and its inhibition is provided.

Myocarditis is an inflammatory disease of myocardium, associated with nonischemic necrosis and degeneration of myocytes. Although the clinical course is rapid, myocarditis can lead to dilated cardiomyopathy with chambers dilatation and ventricular dysfunction. The pathophysiology of myocarditis in humans is not completely understood. There are several etiological agents implicated, mainly viral agents. The clinical presentation is extremely various, with nonspecific systemic symptoms until sudden death. The great variability of symptoms makes the diagnosis, therefore, extremely difficult. We report the case of a 40-year-old woman who developed, after childbirth, hyperthermia associated with neck and left arm pain; initially treated with acetaminophen, without any benefit, the young woman, after few days, died suddenly. The autopsy documented the presence of edematous lungs and enlarged and congested liver. The microbiological tests performed 4 days after death were negative. The heart was normal in shape and volume; a section of the left ventricle wall showed subendocardial discromic areas histologically characterized by multifocal perivascular and interstitial inflammatory infiltrates. These infiltrates consisted mainly of neutrophils with eosinophil component associated with myocyte necrosis and hemorrhagic interstitial infiltration.

Background: Galectin-3 (Gal-3) is a novel biomarker reflecting inflammation status and fibrosis involving worsening of both cardiac and renal functions. Objectives: The aim of this study was to evaluate the relationship between Gal-3 serum levels and microalbuminuria in a group of chronic heart failure (CHF) outpatients. Patients and Methods: We enrolled CHF outpatients having stable clinical conditions and receiving conventional therapy. All patients underwent clinical evaluation, routine chemistry analysis, echocardiography, and evaluation of the urinary albumin/creatinine ratio (UACR). Results: Among the patients enrolled, 61 had microalbuminuria (UACR, 30-299) and 133 normoalbuminuria (UACR, < 30). Patients with normoalbuminuria showed significantly higher levels of Gal-3 than those without (19.9 ± 8.8 vs. 14.6 ± 5.5 ng/mL). The stepwise regression analysis indicated that Gal-3 was the first determinant of microalbuminuria (odds ratio [OR]: 1.08; 95% confidence interval [CI]: 1.02 - 1.14, P = 0.012), followed by diabetes (OR 2.14; 95% CI: 1.00 - 4.57; P = 0.049) and high central venous pressure (OR 2.80; 95% CI: 1.04 - 7.58; P= 0.042). Conclusions: Our findings indicate an independent association between Gal-3 levels and microalbuminuria, an early marker of altered renal function. This suggests the possible role of Gal-3 in the progression of cardiorenal syndrome in CHF outpatients.

Hyperpolarization and Cyclic Nucleotide (HCN) -gated channels represent the molecular correlates of the "funny" pacemaker current (I(f)), a current activated by hyperpolarization and considered able to influence the sinus node function in generating cardiac impulses. HCN channels are a family of six transmembrane domain, single pore-loop, hyperpolarization activated, non-selective cation channels. This channel family comprises four members: HCN1-4, but there is a general agreement to consider HCN4 as the main isoform able to control heart rate. This review aims to summarize advanced insights into the structure, function and cellular regulation of HCN channels in order to better understand the role of such channels in regulating heart rate and heart function in normal and pathological conditions. Therefore, we evaluated the possible therapeutic application of the selective HCN channels blockers in heart rate control.

Hereditary hemochromatosis (HH), a common autosomal recessive disease, is characterized by excessive iron overload/toxicity in multiple organs (joints, liver, heart, pancreas, pituitary, adrenals and skin). Symptoms and signs depend upon the location of the excess iron deposition. Dilated cardiomyopathy is a typical complication of HH. Juvenile haemochromatosis is a rare disorder of iron metabolism with clinical manifestations before 30 years of age. Two common mutations of the haemochromatosis associated gene (HFE), cys282tyr (C282Y) and his63asp (H63D), have been implicated in the HH. These genes also appear to be modulators in cardiovascular disease. In fact the HFE gene defects are related to idiopathic dilated cardiomyopathy (IDCM) in some patients, even though the results of genotype analyses were conflicting. In this case report we investigate a 21 year-old male patient affected by juvenile haemochromatosis associated with heterozygosity for the H63D mutation with an idiopathic dilated cardiomyopathy.

Objective. Our study investigates major common cardiovascular risk factors relation with aortic stiffness on 269 postmenopausal women by global pulse wave velocity (PWVg), useful to relate PWVg to risk of major cardiovascular events. Patients and Methods. Women were categorized as hypertensive (H), hypercholesterolemic (C), or diabetic (D). Aortic stiffness was assessed by PWVg measured with pulsed Doppler, at the left ventricular outflow tract (LVOT) and at the right common femoral artery. Results. All population mean PWVg was 8.2 m/s. 85 (26.5%) women were H; mean PWVg was 7.9 m/s. HC women were 118 (36.7%), with mean PWVg 8.3 m/s. HD women were 30 (9.5%), with mean PWVg 7.8 m/s. HDC women were 36 (11.2%), with mean PWVg 9.3 m/s. 52 (16.1%) menstruate women without risk factor were control group (CG), with mean PWVg 6.5 m/s. Highly significant was the statistical difference in PWVg between HDC women and each other group: versus CG; versus H; versus HC, and versus HD. No difference in PWG was observed comparing the other groups. There was difference for age among all groups, except for CG, made by younger women. Conclusion. PWVg was highly increased in postmenopausal women affected by hypertension, diabetes, and hypercholesterolemia all at once. Hypertension is the major determinant for PWVg. The only addition of diabetes or hypercholesterolemia did not increase significantly PWVg. Our study supports the usefulness of the assessment of aortic stiffness as a marker of cardiovascular disease.

Spontaneous coronary artery dissection (SCAD) is a separation of the coronary wall layers, not related to trauma, medical procedures or atherosclerosis. The dissection causes the blood entry in the vascular wall with the consequent formation of a false lumen and intramural hematoma (IMH). Two pathogenetic mechanisms have been proposed to explain SCAD: a “primary” rupture of coronary endothelium or the rupture of the “vasa vasorum”. Clinical presentation and severity of manifestations are variable, ranging from complete absence of symptoms to acute coronary syndrome (ACS), cardiogenic shock, cardiac arrest or sudden cardiac death. Despite coronary angiography is the first-line examination, by supplying two-dimensional images of the lumen, it does not always allow an incontrovertible diagnosis of SCAD. New intravascular imaging techniques, such as optical coherence tomography (OCT) and intravascular ultrasound (IVUS), have been recently introduced and may be extremely helpful in assessing the coronary wall integrity, thus improving coronary angiography diagnostic accuracy. Because of the lack of large randomized trials comparing different strategies, the optimal treatment of SCAD is still controversial. The first-line approach is conservative and based on medical therapy. Nevertheless, in particular situations an invasive approach is necessary. In the last years, several new strategies have improved the way to perform percutaneous coronary interventions (PCI), such as new generation drug eluting stents (DES), bio-resorbable scaffolds (BRS), sirolimus self-expandable stent (SES), drug eluting balloons (DEB), and cutting balloon. Cardiac artery bypass graft (CABG) is an even more invasive method to restore coronary flow and should be considered in urgent/emergent settings when PCI is not feasible or has failed. Cause the therapeutic approach of SCAD can be substantially different from that of atherosclerotic coronary artery disease, an accurate diagnosis is crucial to set up the best treatment strategy.

Hypertensive Cardiomyopathy diagnosis includes different clinical conditions, on asymptomatic patients, assessed by LV changes in geometry, mass and function, i.e. concentric remodeling, concentric or eccentric hypertrophy and filling impairment or early stage of diastolic dysfunction. Often LA is involved and increases its volume and undergoes to geometrical remodeling. Sometimes it occurs clinical heart failure, the patients became symptomatic, with either a preserved or a reduced LVEF. There is considerable variability in the progression from hypertension to Hypertensive Cardiomyopathy, according to differences in the pressure or volume load and to underlying neurohormonal status; but these differences in LV geometry probably are influenced on genetic basis too. A better comprehension of the mechanisms underlying the development of Hypertensive Cardiomyopathy on hypertensive patients will help to prevent among them the onset of cardiovascular events.

Abstract BACKGROUND: Idarucizumab, a humanized monoclonal antibody fragment acting as specific antidote for dabigatran, is approved for reversing the dabigatran-associated possible bleeding from critical sites or bleeding persisting despite local post-procedure haemostasis, moreover it can also be applied to reverse the dabigatran anticoagulant activity in emergency surgery or in other invasive procedure at high risk of bleeding. OBJECTIVE: In this manuscript, we discuss idarucizumab in light of the available literature data by conducting extensive research in the PubMed, EMBASE and Cochrane Library on the topic, using as Mesh terms idarucizumab, dabigatran and their combinations, and focusing on high impact investigations. RESULTS: Several studies have demonstrated the capacity of idarucizumab to reverse laboratory measures of dabigatran-associated coagulopathy, however the efficacy and safety in real world patients is still not very clear because of the scarcity of available data and should be assessed with an extensive post market surveillance. CONCLUSION: The introduction of idarucizumab as dabigatran antidote in clinical practice represents a useful tool for clinicians. The possibility to rapidly restore the anticoagulation activity of dabigatran makes simpler and more manageable its use. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

AIM: to evaluate the influence of cerebral venous drainage on the pathogenesis of idiopathic sudden sensorineural hearing loss (ISSHL) and Ménière syndrome (MD). METHODS: we enrolled 59 consecutive patients (32 males, mean age 53.05+15.37 years): 40 ISSHL and 19 MD. All underwent physical examination, biochemical evaluation (glycemic and lipid profile, viral serology, C reactive protein, etc), audiometric (tonal, vocal, vestibular evoked myogenic potentials and auditory brainstem response test) and impedentiometric examination. The pure tone average (PTA) was calculated for the following frequencies: 250, 500, 1000, 2000, 3000, 4000, 8000. An echo-color Doppler evaluation of the venous cerebral veins, internal jugular (IJV) and vertebral veins (VV) at supine and 90° position was performed. RESULTS: no morphological alterations were found both in patients and controls. There were no signs of stenosis, blocked flow, membranes, etc. We found lower minimum, mean and maximum velocities in distal IJVs (p=0.019; p=0.013; p=0.022; respectively) and left VVs (p=0.027; p=0.008; p=0.001; respectively) in supine (0°) position in both MD and ISSHL patients as compared to controls. The same was for orthostatic position (90°). We found negative correlations between the velocities in extracranial veins and PTA values: therefore, the worst the audiometric performance of the subjects, the lower the velocities in the venous cerebral drainage. CONCLUSIONS: ISSHL and MD patients showed altered venous flow in IJVs and VVs as compared to controls, independently from posture. This different behavior of venous tone control can influence the ear performance and may have a role in the pathogenesis of both diseases. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Obstructive sleep apnea syndrome (OSAS) in children can induce endothelial dysfunction, a well-known early marker of atherosclerosis. The study aimed to evaluate a link among endothelial function (measured by flow-mediated vasodilation (FMD)), obesity (evaluated by body mass index (BMI)), and sleep disordered breathing (SDB), assessed with apnoea/hypopnoea index (AHI), in a paediatric population. We demonstrated that our little OSAS patients showed an impaired endothelial function as compared to controls. In particular, the higher the AHI, the worst the FMD values and thus the endothelial function. Although the population sample is small, this study demonstrated that OSAS could impair endothelial function and worsen cardiovascular risk profile since childhood.

Abstract BACKGROUND: Implantable cardioverter-defibrillators (ICDs) have a role in preventing cardiac arrest in patients at risk for life-threatening ventricular arrhythmias. PURPOSE: To compare ICD therapy with conventional care for the primary prevention of death of various causes in adults with ischemic or nonischemic cardiomyopathy. DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, and EMBASE databases, as well as several Web sites, from 1 April 1976 through 31 March 2017. STUDY SELECTION: Randomized controlled trials, published in any language, comparing ICD therapy with conventional care and reporting mortality outcomes (all-cause, sudden, any cardiac, or noncardiac) in the primary prevention setting. DATA EXTRACTION: 2 independent investigators extracted study data and assessed risk of bias. DATA SYNTHESIS: Included were 11 trials involving 8716 patients: 4 (1781 patients) addressed nonischemic cardiomyopathy, 6 (4414 patients) ischemic cardiomyopathy, and 1 (2521 patients) both types of cardiomyopathy. Mean follow-up was 3.2 years. An overall reduction in all-cause mortality, from 28.26% with conventional care to 21.37% with ICD therapy (hazard ratio [HR], 0.81 [95% CI, 0.70 to 0.94]; P = 0.043), was found. The magnitude of reduction was similar in the cohorts with nonischemic (HR, 0.81 [CI, 0.72 to 0.91]) and ischemic (HR, 0.82 [CI, 0.63 to 1.06]) disease, although the latter estimate did not reach statistical significance. The rate of sudden death fell from 12.15% with conventional care to 4.39% with ICD therapy (HR, 0.41 [CI, 0.30 to 0.56]), with a similar magnitude of reduction in patients with ischemic (HR, 0.39 [CI, 0.23 to 0.68]) and those with nonischemic disease (HR, 0.44 [CI, 0.17 to 1.12]). Noncardiac and any cardiac deaths did not differ significantly by treatment. LIMITATION: Heterogeneous timing of ICD placement; heterogeneous pharmacologic and resynchronization co-interventions; trials conducted in different eras; adverse events and complications not reviewed. CONCLUSION: Overall, primary prevention with ICD therapy versus conventional care reduced the incidence of sudden and all-cause death. PRIMARY FUNDING SOURCE: None.

Background: It has been demonstrated that hypothyroidism can lead to significant hemodynamic alterations favoring the onset of chronic heart failure (CHF) as well as its progression. Furthermore, amiodarone, an iodinecontaining antiarhythmic drug frequently used in CHF patients, is often the cause of primary hypothyroidism. Aim of the Study: To define the prevalence and incidence of hypothyroidism in a group of CHF outpatients in stable clinical conditions, with particular reference to the role of amiodarone therapy. Results: Among the 422 enrolled patients (326 males, aged 65±12 years), 51 (12%) had a previous diagnosis of hypothyroidism while 21 (5%) were newly diagnosed at the enrolment. Then, the overall prevalence of hypothyroidism at the first evaluation was 17% and, as expected, it was significantly higher in females than males (33% vs 13%; p<0.001). During follow-up (median 28 months) hypothyroidism occurred in further 19 patients (incidence rate: 26/1000/year) and it was mainly attributable to amiodarone therapy. Considering all together the hypothyroid patients, either those affected by thyroid failure at the enrolment than those developing hypothyroidism during the follow-up, levothyroxine therapy was continued or started in 69% of them; however, normal serum TSH values were obtained only in 76% of treated cases (mean levothyroxine dose: 69±44 mcg/day). In any case, in the group of patients affected by hypothyroidism a significantly greater occurrence of heart failure progression was observed. Conclusions: Hypothyroidism, especially the subclinical form, frequently occurs in patients affected by CHF receiving amiodarone therapy. Given the unfavorable impact of hypothyroidism on the progression and prognosis of CHF, and the opportunity to adequately manage thyroid failure by means of levothyroxine replacement therapy without the need to withdraw amiodarone, we recommend regular testing of thyroid function in CHF patients, in particular in those submitted to amiodarone therapy, in order to early diagnose a condition of hypothyroidism and titrate substitutive treatment.

Diabetic foot is a common complication in diabetes mellitus course, able to increase the overall morbidity/mortality risk of such a disease. The aim was to investigate the outcomes, the incidence of clinical events, the number of recurrent ulcers in patients with diabetic foot during 1 year follow-up after angioplasty (PTA) revascularization. From January 2007 to August 2009, 103 diabetic patients with diabetic foot undergoing revascularization of a lower limb by PTA were recruited. At 1 year follow-up we assessed: "major" (death, stroke, Myocardial Infaction (MI) and "minor" (Deep Vein Thrombosis (DVT), renal failure, restenosis) events incidence; recurrent ulcers incidence; the predictive elements of all these events. At 1 year follow-up, "major"/"minor" events incidence was 15% (deaths:5, stroke: 1, MI: 9%) and 34% (renal failure: 11, DVT: 9, restenosis: 14%), respectively. Obesity, high low density level-cholesterol levels and distal arterial lesions (at posterior tibial artery in particular) were statistically significantly associated with major events (p<0.05); only obesity resulted statistically associated with minors (p = 0.043). High levels of C-reactive protein had a statistically significant relationship with the recurrence of ulcers (p = 0.006) while distal arterial obstructions showed a trend toward significance. To improve diabetic foot mortality and morbidity rate, our study underlines the importance of a prompt diagnosis and appropriate revascularization treatment. Other studies are needed to ascertain these. © 2012 Asian Network for Scientific Information.

Background: Obstructive Sleep Apnea Syndrome (OSAS) is a common airways disease recognized as an independent cardiovascular risk factor. It is often associated with obesity, diabetes and dyslipidemia. Its pathophysiological consequences (hypoxia, hypercapnia, micro-arousals, sympathetic hyperactivity, oxidative stress, systemic inflammation and hyper-coagulability) are implicated in the development of hypertension, endothelial dysfunction and higher intima-media thickness (IMT) values, all elements known to lead to atherosclerosis. The study aim was to demonstrate a relationship between OSAS duration and IMT values and to confirm how OSAS severity could influence IMT (a marker of atherosclerosis). Methods: We enrolled 156 patients (125 men, mean age: 60 ± 12 years) affected by OSAS of different severity: 111 (71%) were in CPAP therapy; some of the population were also affected by hypertension [102 (65%)], dyslipidemia [52 (33%)] and diabetes [38 (24%)]. Patients underwent evaluation of carotid artery IMT and answered a questionnaire investigating the time of onset (confirmed by a person aware of the patient's previous sleeping habits) and the duration of the disease. Results: We found a statistically significant higher IMT value in patients with longer-lasting disease (OSAS duration in IMT < 0.9 mm: 120 (60-192) months versus OSAS duration in IMT ≥ 0.9 mm: 200 (120-310) months; p < 0.001). OSAS severity is positively related to IMT values. We found a positive relationship between IMT and OSAS duration [r = 0.34; p < 0.001] and between AHI and IMT [r = 0.51; p < 0.001]. Conclusions: Our study shows that the duration of OSAS and its severity are important factor related with higher values of IMT and hence with a higher risk of atherosclerosis.

Elevated heart rate could negatively influence cardiovascular risk in the general population. It can induce and promote the atherosclerotic process by means of several mechanisms involving endothelial shear stress and biochemical activities. Furthermore, elevated heart rate can directly increase heart ischemic conditions because of its skill in unbalancing demand/supply of oxygen and decreasing the diastolic period. Thus, many pharmacological treatments have been proposed in order to reduce heart rate and ameliorate the cardiovascular risk profile of individuals, especially those suffering from coronary artery diseases (CAD) and chronic heart failure (CHF). Ivabradine is the first pure heart rate reductive drug approved and currently used in humans, created in order to selectively reduce sinus node function and to overcome the many side effects of similar pharmacological tools (ie, β-blockers or calcium channel antagonists). The aim of our review is to evaluate the role and the safety of this molecule on CAD and CHF therapeutic strategies.

Lo scopo di questa indagine è quello di analizzare i tempi di attesa durante il percorso diagnostico-terapeutico dei pazienti con by-pass aorto-coronarico, al fine di calcolare il lasso di tempo effettivo che intercorre tra la valutazione clinica del paziente e l'intervento chirurgico, secondo il programma nazionale italiano per la gestione della lista d'attesa 2010-2012 che introduce specifici standard di riferimento in ordine all’efficacia dei tempi di intervento. In particolare, le Regioni italiane devono garantire che la fase diagnostica venga completata entro 30 giorni per il 90% dei pazienti, e lo stesso vale per la fase terapeutica. Inoltre, è necessario individuare il momento esatto dal quale comincia la lista d'attesa fino alla fine della fase diagnostica e il tempo trascorso tra la prenotazione del ricovero e l’effettivo ricovero in ospedale, durante il quale i pazienti vengono sottoposti all’intervento chirurgico

Abstract INTRODUCTION: Coronary artery disease (CAD) is quite common among diabetic patients, our study goal is to detect the prevalence of left ventricular (LV) adverse changes in geometry, mass and diastolic function on diabetic, but not hypertensive patients, with coronary artery disease(CAD) and LV ejection fraction(LVEF)>45%, actually unknown, because of current guidelines that do not include echocardiographic assessment for follow up of diabetic patients. PATIENTS AND METHODS: 665 consecutive diabetic patients (443 females, mean age 66±9years), performed a complete echocardiographic assessment according to current ASE echo-guidelines: diastolic dysfunction (DD), eccentric hypertrophy (EH), concentric hypertrophy (CH) and concentric remodeling (CR) of LV were reported. CAD was assessed only by reports of bypass surgery, angioplasty or patients hospitalized for acute myocardial infarction. RESULTS: 218 patients (32.8%) presented LV changes: LVDD 49 (7.4%), LVEH 68 (10.2%), LVDD and EH 46 (6.9%), LVDD and CH 36 (5.4%), LVDD and CR 19 (2.9%). 447 (67.2%) had no LV changes. 81 (12.1%) patients with CAD, presented: LVDD 17 (21%), LVEH 32 (39.5%), LVDD and EH 9 (11.1%), LVDD and CH 7 (8.6%), LVDD and CR 8 (9.9%), 8 (9.9%) had no LV adverse changes. There were among CAD patients, a significantly higher prevalence of LVDD (p<0.02), LV eccentric hypertrophy (EH) (p<0.05), DD and LVEH (p<0.04), DD and LV concentric hypertrophy(CH) (p<0.03) and DD and LV concentric remodeling (p<0.02), when compared with those patients without CAD. CONCLUSION: CAD is related to all different patterns of LV adverse changes in mass, geometry and diastolic function, with a significantly higher prevalence in our population of diabetic patients with normal systolic function. These changes however remain unrecognized until they undergo to a conventional echocardiographic assessment. We support this tool need to be included into future guidelines concerning follow-up of diabetic patients.

The assessment of left ventricular (LV) diastolic function should be an integral part of a routine examination of hypertensive patient; indeed when LV diastolic function is impaired, it is possible to have heart failure even with preserved LV ejection fraction. Left ventricular diastolic dysfunction (LVDD) occurs frequently and is associated to heart disease. Doppler echocardiography is the best tool for early LVDD diagnosis. Hypertension affects LV relaxation and when left ventricular hypertrophy (LVH) occurs, it decreases compliance too, so it is important to calculate Doppler echocardiography parameters, for diastolic function evaluation, in all hypertensive patients. The purpose of our review was to discuss about the strong relationship between LVDD and hypertension, and their relationship with LV systolic function. Furthermore, we aimed to assess the relationship between the arterial stiffness and LV structure and function in hypertensive patients.

The aim of this study was to evaluate the role of macrophages and mast cells and of microvascular density in atherosclerotic plaques collected from 63 consecutive symptomatic and asymptomatic patients undergoing carotid endarterectomy for carotid disease. Results have shown no statistically significant differences between the two groups as concerns: (i) the degree of stenosis; (ii) the extention of the lipidic core; (iii) the thickness of the fibrous cup; (iv) the inflammatory infiltrate; (v) the degree of calcification; (vi) the intraplaque hemorrhage. Otherwise, statistically significant difference was found in microvascular density, in the number of CD68-positive macrophages and tryptase-positive mast cells in plaques from symptomatic patients, as compared to asymptomatic patients. Overall, this study indicate that although advanced symptomatic and asymptomatic carotid plaques present similar histomorphological characteristics, the degree of macrophage and mast cell infiltration and differences in microvascular density could help to discriminate between symptomatic and asymptomatic patients.

AIMS: The aim of this study was to evaluate isometric muscle contraction (handgrip) changes on key elements of cardiac afterload, before and after raloxifene administration in postmenopausal women. METHODS/RESULTS: 12 postmenopausal and 12 fertile women were studied. Postmenopausal women underwent raloxifene administration (60 mg/day for 30 days). We evaluated vascular reactivity in superficial palmar arterial arch during handgrip in postmenopausal women before and after (M+R) drug administration, and in controls. Blood flow was higher after raloxifene administration (p<0.05). Mean arterial pressure (MAP)/mean arterial flow (Fmed) and arterial pulse pressure (APP)/systolic maximum arterial flow (Fmax syst) were lower after raloxifene administration (p<0.001). Systolic blood pressure (SBP)/R-R ratio was higher in postmenopausal women than in the controls and M+R (p<0.01). End-handgrip systolic and diastolic blood pressure were higher in patients before raloxifene administration than in controls (p<0.001); diastolic and mean arterial pressure reduced after raloxifene administration (p<0.001). End-effort APP/Fmax syst-ratio before treatment was higher than baseline (p<0.05). Controls and no-treated patients showed a MAP/Fmed ratio at end-handgrip higher than M+R group and rest (p<0.05). Handgrip reduced R-R interval and increased SBP/R-R ratio were shown in all groups (p<0.05). CONCLUSIONS: Raloxifene reduced the vascular effects of isometric muscle contraction by modulating the vasomotor tone of peripheral vessels in relation to exercise.

Venous echo-color-Doppler (ECD) showed that chronic cerebrospinal venous insufficiency (CCSVI) syndrome is related to multiple sclerosis (MS). Study aims were to assess interobserver variability in ultrasound evaluation of MS patients and to relate echo-markers to MS clinical symptoms and the disability degree. 277 MS patients (117 men, mean age 43.05+10.04 years) admitted to the Neurology Department of Bari University General Hospital, underwent clinical, Expanded Disability Status Scale (EDSS) evaluation, and a cerebro-venous system ECD evaluation. Two operators reevaluated 32 patients to calculate interobserver variability. McNemar test confirmed the procedure reproducibility between two operators (p=ns). Septa/membranes correlated with deep cerebral veins reflux [right: 16% absence vs. 58% presence, p < 0.0001; left: 26% vs. 50%, p < 0.0001]; their absence in Primary Progressive (PP) MS form [right: 11% vs. 2%, p < 0.001; left: 12% vs. 2%, p < 0.001]. Internal jugular veins (IJVs) reflux absence was in Relapsing-remitting (RR) form [right: 60% vs. 74%, p=0.036; left: 56% vs. 85%, p < 0.0001] like hemodynamically significant stenosis [right: 57% vs. 69%, p=0.033; left: 49% vs. 73%, p < 0.001] not present in PP [right: 11% vs. 2%, p < 0.001; left: 10% vs. 3%, p=0.009]. A supine IJVs blocked flow was related to the EDSS class [right: 4.8±1.5 vs. 5.4±1.4, p=0.006; left: 4.7±1.6 vs. 5.5±1.2, p < 0.0001]; its absence was linked to RR [right: 60% vs. 76%, p=0.016; left: 58% vs. 79%, p < 0.001]. ECD has an important value in MS patients with IJV anomalies detection and a good interobserver procedure reproducibility. MS is associated with CCSVI, although further studies are needed

Venous echo-color-Doppler (ECD) showed that chronic cerebrospinal venous insufficiency (CCSVI) syndrome is related to multiple sclerosis (MS). Study aims were to assess interobserver variability in ultrasound evaluation of MS patients and to relate echo-markers to MS clinical symptoms and disability degree. 277 MS patients (117 men, mean age 43.05±10.04 years) admitted to the Neurology Department of Bari University General Hospital, underwent to clinical, Expanded Disability Status Scale (EDSS) evaluation, and to a cerebro-venous system ECD evaluation. Two operators re-evaluate 32 patients to calculate interobserver variability. McNemar test confirmed the procedure reproducibility between two operators (p=ns). Septa/membranes correlated with deep cerebral veins reflux [right: absence 16% vs 58% presence, p<0.0001; left: 26% vs 50%, p<0.0001]; their absence to Primary Progressive (PP) MS form [right: 11% vs 2%, p<0.001; left: 12% vs 2%, p<0.001]. Internal jugular veins (IJVs) reflux absence was in Relapsing-remitting (RR) form [right: 60% vs 74%, p=0.036; left: 56% vs 85%, p<0.0001] like hemodinamically significant stenosis [right: 57% vs 69%, p=0.033; left: 49% vs 73%, p<0.001] not present in PP [right: 11% vs 2%, p<0.001; left: 10% vs 3%, p=0.009]. A supine IJVs blocked flow was related to EDSS class [right: 4.8±1.5 vs 5.4±1.4, p=0.006; left: 4.7±1.6 vs 5.5±1.2, p<0.0001]; its absence was linked to RR [right: 60% vs 76%, p=0.016; left: 58% vs 79%, p<0.001]. ECD has an important value in MS patients with IJV anomalies detection and a good interobserver procedure reproducibility. MS is associated to CCSVI, although further studies are needed

BACKGROUND: The relevance of the temporal relationship between unipolar (UEGM) and bipolar electrograms (BEGM) in determining the site of origin (SOO) of focal arrhythmias has been largely demonstrated. OBJECTIVE: We sought to demonstrate that also a negative concordance in the initial forces of these EGMs, is helpful in predicting the SOO of premature ventricular contractions (PVCs). METHODS: Mapping and radiofrequency (RF) ablation were performed in 41 patients with symptomatic PVCs in absence of structural heart disease. Simultaneous recordings of minimally filtered (0.5-500 Hz) UEGM and filtered BEGM (30-500 Hz) were analyzed at 247 mapping sites, where RF was attempted. EGMs of 63 mechanically-induced PVCs were separately analyzed as a validation group. All ablation sites had a QS pattern in the UEGM. Acute PVCs suppression was defined as complete disappearance of ventricular ectopic beats after a 60 sec pulse of RF. RESULTS: RF ablation obtained PVC suppression (RF+) in 33 sites (33/247, 13,3%). Negative concordance pattern (NCP) during the initial 20 ms of both UEGM and BEGM was observed in 31/33 (94%) RF+ sites compared to 10/214 RF- sites, p < 0,0001. The NCP criterion demonstrated to be an additional powerful predictor of acute RF success with sensitivity, specificity, positive and negative predictive values of 94%, 95%, 76%, 99% respectively. Similarly to RF+ sites, the NCP was observed in 60/63 sites (95,2%) in the mechanical PVCs group. CONCLUSIONS: A NCP in both UEGM and BEGM may be helpful as an additional criterion to localize the SOO of focal ventricular arrhythmias.

Despite advances in neonatal intensive care and the improvements in surveillance, prevention and vaccination programs, neonatal meningitis still represents an important cause of morbidity and mortality in infants, with the highest mortality in the newborn population.

According to the American Heart Association (AHA) , primitive dilated cardiomyopathy (PDCM) is a "progressive dilation of the left or both ventricles and a depressed contractility in absence of abnormal load conditions ". It evolves in progressive heart-failure. The term &quot;cardiogenic dementia&quot; expresses the intimate connection between heart diseases and cognitive functions. The association between PDCM and the neuropsychological functions is unclear: the main pathophysiological hypotheses are cerebral hypoperfusion and cardiogenic emboli. The aim of this study is to evaluate the impact that the PDCM has on neuropsychological decline and to detect early echocardiographic markers of cognitive impairment. We enrolled 235 patients: 168 suffering from PDCM as sample group and 67 suffering from hypertensive dilated cardiomyopathy (HTCM) as control group. They underwent a cardiology examination and a neuropsychological assessment . A p &lt;0.05 was considered significant. The two groups showed no differences in risk factors, demographic and cardiovascular parameters (except for dimensions of aortic root, left atrium and ventricle which appeared greater in PDCM and left ventricle ejection fraction that appeared lower in PDCM). Among administered neuropsychological tests, only the Stroop Test (which explores executive and attentive functions) appeared significantly lower in PDCM (p = 0.029). Moreover left ventricle end-diastolic diameter was inversely related to the Stroop Test Score (r= -0.32). PDCM doesn't appear to be at the basis of a generalized cognitive and neuropsychological decline. Only the executive functions seem impaired in PDCM. Left ventricle dilation seems to be associated to attentive and executive functions decline.

Abstract BACKGROUND: The aim of this study was to investigate neutrophil activation and its role in long pentraxin-3 (PTX3) release and oxidative stress generation during haemodialysis (HD) and to correlate neutrophil PTX3 and oxidant expression with endothelial dysfunction. METHODS: Forty-seven uraemic patients on stable HD, 12 healthy subjects and 15 patients with congestive heart failure (New York Heart Association classes III and IV) were enrolled. Neutrophil PTX3 protein expression was evaluated by confocal microscopy. l-selectin expression, intracellular PTX3 localization and reactive oxygen species (ROS) generation in human neutrophils were measured by flow cytometry. NADPH-dependent superoxide generation was investigated by chemiluminescence. PTX3 plasma concentrations were measured by ELISA. Endothelial dysfunction was studied by flow-mediated dilation (FMD). RESULTS: The low baseline levels of FMD significantly improved after HD, but worsened by 24 h. A significant up-regulation of PTX3 protein expression, localized within secondary granules, was detected in neutrophils isolated at 30 and 240 min of HD, along with an increase in l-selectin expression. The up-regulation in intracellular PTX3 in neutrophils was associated with a significant increase in PTX3 plasma concentrations at 240 min. HD increased ROS production and NADPH oxidase activity in neutrophils. In a univariate analysis, pre-treatment with FMD was inversely correlated with PTX3 expression and ROS generation in neutrophils. In a multivariate analysis, both circulating pre-HD PTX3 and intracellular ROS generation by neutrophils were independent predictors of abnormal FMD. CONCLUSIONS: Neutrophil overexpression of PTX3 is associated with ROS overproduction and endothelial dysfunction and may represent an emerging marker of vascular damage progression in HD patients. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

The study aim was to evaluate the acute hemodynamic effects of intranasal 17-beta-estradiol on ophthalmic arterial circulation in postmenopausal women. METHODS: Twenty-one healthy women in natural menopause for at least 6 months (mean age: 53.2± 2.9 years) were investigated. Each patient received 300 µg intranasal 17-beta-estradiol. We evaluated the heart rate, systolic and diastolic blood pressure, ophthalmic artery velocity at systolic and diastolic peak and its flow curve integral (FCI) before and 30, 60 and 180 minutes after the administration of the drug. RESULTS: At all time points, the ophthalmic artery FCI showed statistically significant variations (p<0.001) of velocity (cm/sec) compared to T0 (speed recorded at baseline before drug administration). Moreover, systolic blood pressure, diastolic blood pressure and heart rate did not significantly differ each other after drug administration. CONCLUSIONS: Administration of a single dose of intranasal 17-beta-estradiol to healthy postmenopausal women increases ophthalmic artery perfusion.

Mitral regurgitation (MR) is the most prevalent valvular heart disease (VHD) and represents an important cause of heart failure. Medical therapy has a limited role in improving symptoms and does not hinder the progression of valvular disease. Surgery is the treatment of choice for severe symptomatic MR; valve repair is currently the preferred surgical approach because it reduces peri-operative mortality and ensures a good medium- to long-term survival outcome. Nevertheless, a non-negligible proportion of patients with indications for surgical correction are considered to be at prohibitive perioperative risk, mainly because of old age and multiple comorbidities. The introduction of percutaneous interventions to clinical practice has changed the natural history of this population. Percutaneous edge-to-edge transcatheter mitral valve repair (Mitraclip®, Abbott Vascular, Menlo Park, CA) is a state-of-the-art therapy for approaching MR in patients with a high surgical risk. Despite having been only recently introduced, this transvenous transfemoral percutaneous intervention has already been performed in more than 40,000 subjects worldwide, with reassuring post-operative results in terms of safety, feasibility, mortality and morbidity. Since Mitraclip® is considered to be minimally invasive, it is currently indicated in "frail" patients with severe comorbidities. We provide a critical review of the literature to clarify current indications, procedural details, patient selection criteria, and future perspectives for this innovative technique.

Congenital third-degree (complete) atrioventricular block requires pacemaker implantation where prenatal hydrops, low ventricular rate (&lt;45 bpm) non-response to inotropes, and/or left ventricular dysfunction is present. A permanent pacemaker was implanted in a 1200g 9 day old preterm: the smallest newborn successfully subjected to this procedure, according to literature.

Abstract Scientific advances in cardiovascular research during the last decades have afforded effective pharmacological treatment to those surviving their first acute myocardial infarction. This secondary prevention treatment, based upon the combined administration of statins, aspirin, beta-blockers and renin-angiotensin blockers, might avert great part of the relapses contributing substantially to the overall incidence of acute coronary syndromes in the general population. However, a treatment gap separates evidence-based recommendations from their daily clinical application, a condition frequently explored even in the Italian medical setting. However, a general overview of the problem is missing insofar, a contribution that might eventually help to improve the status of secondary coronary prevention in our national environment.

Although the survival rate for preterm subjects has improved considerably, due to the progress in the field of perinatal medicine, preterm birth is frequently the cause underlying a series of notorious complications: morphological, neurological, ophthalmological, and renal alterations. In addition, it has recently been demonstrated how low gestational age and reduced foetal growth contribute towards an increased cardiovascular risk in preterm neonates. In fact, cardiovascular mortality is higher among former preterm adults than those born at term. This condition is referred to as cardiovascular perinatal programming. In the light of the above, an early, constant, and prolonged cardiological follow-up programme should be implemented in former preterm individuals. The aim of this paper was to perform a comprehensive literature review about two new emerging conditions predisposing to an increased cardiovascular risk: prematurity and low weight at birth.

Several studies examined the possibility that idiopathic pulmonary hypertension is related to thyroid autoimmune diseases. The aim of our study was to highlight the possible correlations between the pulmonary hypertension and Hashimoto's thyroiditis (HT). A total of 93 patients were enrolled, 70 suffering from HT in euthyroidism state and 23 controls. All underwent anthropometric [weight (Kg); height (m); Body Mass Index (Kg/m2): waist circumference (cm)] and biochemical [fasting blood glucose (mg/dl), TSH (µUI/mL), FT3 (pg/ml), FT4 (pg/ml), total, HDL and LDL-cholesterol (mg/dl), triglycerides (mg/dl)] evaluations. All patients underwent two-dimensional trans-thoracic echocardiographic evaluations in order to measure systolic (sPAP) and the end-diastolic pressure of the pulmonary artery (dPAP). There were no differences between the two populations regarding anthropometric and biochemical parameters. Patients with HT had higher sPAP values than controls (Hashimoto: 20.06 ± 6.56 mmHg vs controls: 19.96 ± 8.58 mmHg, p = 0.044). Patients with HT had lower dPAP values than controls (2.51 ± 0.90 mmHg vs. controls 3.17 ± 1.58 mmHg, p &lt; 0.0001), and there was a statistically significant difference in the left ventricle ejection fraction between the two groups (60.57 ± 1.60 % in patients with HT vs. 61.04 ± 2.03 % in controls, p = 0.037). The multivariate regression analysis did not confirm such results. We demonstrated that patients with HT did not show relevant pulmonary hypertension when compared to healthy controls.

The influence of thyroid hormones on cardiovascular system is well established. Thyroid diseases can effectively enhance the alteration on cardiovascular system by influencing chronotropic and inotropic actions of the heart; altering the strength and the speed of contraction, the speed of relaxation, the duration of the potential of action, and the duration of the refractory period and atrio-ventricular conduction time; modulating circulation and peripheral vascular beds. One of the more intriguing insights in the connection between thyroid diseases and cardiovascular alterations is related to the evaluation of the influence of thyroid hormones on pulmonary vascular beds. Literature reported several studies regarding the association between both hypothyroidism and hyperthyroidism and the occurrence of increased vascular pulmonary arterial pressure. Nevertheless, the pathogenetic mechanisms able to explain such relationship are not fully understood. Many doubts still persist in the comprehension of the mechanisms of pulmonary hypertension in thyroid diseases. The aim of this review was to provide possible explanation about the possible interaction between pulmonary vascular beds and thyroid function in order to evaluate the possibility of novel perspectives in the general management of patients suffering from thyroid and cardiovascular diseases.

Objective: The study aim was to compare C3 levels with the common carotid artery intima-media thickness (CCAIMT) in subjects of both genders, with a wide range of BMI, independently of age, gender, and abdominal obesity. Method: 140 euthyroid, mainly overweight/obese subjects (age 18-30 years) were examined. BMI, waist circumference, blood pressure, fasting insulin, glucose, lipids, C3 and C-reactive protein serum concentrations, and insulin resistance degree (estimated by homeostasis model assessment for insulin resistance (HOMAIR)) were measured. Results: CCA-IMT was positively (p < 0.001) correlated with BMI, waist circumference, systolic and diastolic blood pressures, HOMAIR, and insulin, CRP, and C3 serum levels. The multiple linear regression analysis showed that only male gender and waist circumference maintained an independent relation with the CCA-IMT. Conclusion: This study suggests that central fat accumulation and male gender independently increase the thickness of the arterial wall, whereas inflammation and inflammatory markers do not have an independent effect on this parameter.

Abstract Background and aims: The Mediterranean Diet (MedD) is considered a very healthy diet useful in the prevention of cardiovascular disease. The present study aims to evaluate adherence to MedD in unselected premenopausal women and its relation with ankle-brachial index (ABI), an index of preclinical atherosclerosis. Methods and results: A group of 425 patients (age range 45e54 years) was investigated. They were enrolled only if they were asymptomatic for cardiovascular disease. Nutritional parameters were assessed by a self-administered food frequency validated questionnaire (116 items) completed by an interviewer administered 24 h diet recall. They all underwent ABI measurement. The mean MedD Score was 32.2 6.1 (Q1eQ3 range 26e37) comparing with data from Italian population (46 8.3) was significantly lower. Intake of food categories sources of antioxidants was higher in patients with a greater adherence to Med D and was mainly related to fruit and vegetables. Patients were categorized in quartile according to MedD Score and we evaluate the distribution of ABI index within quartile. 31.4% of women in Q1 (lower adherence to MedD) had an ABI lower than 0.9 compared to 18.3% of women in Q4 (higher adherence to MedD): p < 0.01. Obesity was more frequent in Q1 compared to Q4 and in women with lower ABI. Conclusions: Women with a low MedD Score were more obese and showed instrumental sign of preclinical peripheral atherosclerosis. MedD rich in antioxidants from fruit, vegetables and nuts influenced the development of atherosclerosis and was associated with a lower incidence of asymptomatic atherosclerosis.

Background: The obstructive sleep apnoea syndrome (OSAS) is a common airways disease which often involves cardiovascular structures, causing vessel inflammation as well as hypoxia, induced by difficulties in the passage of air through the upper airways. Aim of our research is to evaluate the effects of Continuous Positive Airway Pressure (CPAP) on the syndrome itself and the patients cardiovascular risk profile, practically adopting Flow-Mediated Vasodilation (FMD) technique to evaluate endothelial function. Methods and results: We enrolled 63 patients (49 males and 14 female, mean age: 54 ± 10 years) subdivided into four groups: high cardiovascular risk factors, no CPAP therapy, CPAP therapy started less- and more than 3 months before. The patients underwent FMD of the brachial artery using a high resolution ultrasonograph connected to an image analysis system. The maximum recovery value was calculated as the ratio (maximum-baseline) of the change in diameter over the baseline value. Data obtained from this study demonstrate the significant reversibility of FMD in patients treated for more than 3 months with CPAP therapy (Group 4). Conclusions: Our study shows the importance of administering CPAP therapy for more than 3 months in patients suffering from OSAS to improve EF to a level equal to high cardiovascular risk subjects probably due to a recovery from the systemic hypoxia. Besides, our work points out the importance of FMD as a clinical tool able to point out any improvement or regression after therapies.

Abstract AIM OF THE STUDY: To evaluate whether right ventriculo-arterial coupling obtained by the estimation of the two-dimensional right ventricular (RV) longitudinal strain and of the pulmonary arterial systolic pressure (PASP) could improve prognostic stratification of chronic heart failure (CHF) outpatients. METHODS: CHF outpatients in a stable clinical condition and in conventional therapy were enrolled. The global RV longitudinal strain (RV-GLS) and the strain of the RV free wall (RV-fwLS) were evaluated. PASP was estimated on the basis of tricuspid regurgitation velocity and the estimated central venous pressure. Both RV-GLS and RV-fwLS were then indexed for PASP. RESULTS: Of the 315 patients evaluated, 69 died during follow-up. Both RV-GLS/PASP and RV-fwLS/PASP were significantly associated with an increased risk of death at univariate (HR: 0.43; 95%CI: 0.34-0.56; p<0.001 and HR: 0.44; 95% CI: 0.34-0.57; p<0.001, respectively) and multivariate analysis (HR: 0.66; 95% CI: 0.49-0.89; p: 0.008 and HR: 0.65; 95% CI: 0.49-0.85; p: 0.002, respectively) after correction for age, NYHA class, mean arterial pressure, left ventricular ejection fraction, natremia, glomerular filtration rate and NT-proBNP. CONCLUSIONS: Indexing RV function, assessed by speckle-tracking analysis, with an estimation of pulmonary systolic arterial pressure provides a parameter of ventricular arterial coupling that is independently associated with an increased risk of mortality. Copyright © 2017 Elsevier B.V. All rights reserved.

Rosuvastatin is a fully synthetic statin wich acts by interfering with the endogenous synthesis of cholesterol through competitively inhibiting the 3-hydroxy-3-methylglutaryl coenzyme A reductase, a liver enzyme responsible of the rate-limiting step in cholesterol synthesis. When compared to other molecules of the same class, it shows high efficacy in the improvement of lipid profile, and, thanks to its non-cholesterol-lowering actions (anti-inflammatory, antioxidant and antithrombotic), represents a crucial tool for cardiovascular primary and secondary prevention. Moreover, recent data highlight rosuvastatin beneficial effects in several other fields. In this manuscript we analyzed literature sources in order to better define rosuvastatin features and discuss some critical issues. Copyright © 2016 Elsevier Ltd. All rights reserved.

Abstract BACKGROUND AND OBJECTIVES: The new oral anticoagulants (NOACs) are used for the prevention of thromboembolic complications in patients with non-valvular atrial fibrillation (AF) and those at risk of deep venous thrombosis. Their rapid onset of action and predictable pharmacokinetic and pharmacodynamic profiles make them the optimal alternative to warfarin in the treatment of these two categories of patients. Unfortunately, however, NOACs cannot be used in patients with valvular AF or valvular cardiac prostheses. Although mechanical valves are effectively a contraindication to NOAC use due to several pathophysiological mechanisms that promote the use of warfarin rather than NOACs, few data exist regarding the use of such new pharmacological compounds on patients with cardiac biological valves or those who have undergone mitral repair or tubular aortic graft implantation. METHODS: Our case series involved 27 patients [mean age 70 ± 10 years; mean CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥75 years (doubled), Diabetes mellitus, Stroke/transient ischemic attack (doubled), Vascular disease, Age 65-74 years, Sex category): 6 ± 1.4; and mean HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile international normalized ratios, Elderly, Drugs or alcohol): 4 ± 1] with AF and biological prostheses, repaired mitral valves, or tubular aortic graft who were treated with the factor Xa inhibitor rivaroxaban due to inefficacy or adverse effects of warfarin. RESULTS: The mean left ventricular ejection fraction was 48 ± 9 %, the left atrial diameter was 46.5 ± 7 mm, and the estimated glomerular filtration rate was 45 ± 21 mL/min/1.73 m2. The mean duration of treatment was 15 ± 2 months. No relevant complications or recurrent thromboembolic events occurred. Three patients had recurrent nose bleeding and two had hematuria that led to reduction of the rivaroxaban dose by the treating physician to 15 mg once a day after 4 months of therapy. No further bleeding episode was recorded after escalating the dose. CONCLUSIONS: Rivaroxaban is a valuable treatment option for patients with biological prostheses, repaired mitral valves, or a tubular aortic graft in order to prevent thromboembolic complications.

AIMS: Osteoprotegerin (OPG) plays a key role in atherosclerosis progression and plaque destabilization. We investigated the relationship between intima-media thickness of the common carotid artery (CCA-IMT; an early marker of atherosclerosis) and OPG levels in patients with acute coronary syndrome (ACS) and chronic coronary artery disease (CAD). METHODS: We studied 133 consecutive patients, mean age 65 ± 9 years, referred to our department for coronary angiography. They were evaluated for cardiovascular risk factors, OPG levels and CCA-IMT and accordingly divided in two subgroups: ACS and chronic CAD. RESULTS: Except for age, the two groups were similar according to conventional cardiovascular risk factors. The chronic CAD group showed a CCA-IMT lower than the ACS group (0.86 ± 0.15 vs. 0.94 ± 0.22 mm, P = 0.027); there were no differences regarding the extension of coronary atherosclerosis on angiograms. The OPG levels were higher in chronic CAD patients than in ACS patients (5.36 ± 3.06 vs. 3.85 ± 2.96 pmol/l, P = 0.004). Moreover, the CCA-IMT was significantly correlated with the age of the patients (r = 0.5; P &lt; 0.001). OPG values were not related either to age or to the CCA-IMT. At analysis of covariance, when adjusting the groups for age, the comparison of the two groups lost statistical significance for CCA-IMT (P = 0.41), whereas the OPG values remained significant after the correction (P = 0.001). CONCLUSION: OPG levels are higher in chronic CAD patients. CCA-IMT confirmed its importance in predicting CAD, showing significantly higher values in the patients in the ACS group as compared with those in the chronic CAD group.

INTRODUCTION: Previous studies support the fact that extracorporeal shockwave (SW) induces angiogenesis and improves symptoms in patients affected by limb ischemia. The aim of this study was to evaluate the effects of SW therapy in patients with peripheral artery disease (PAD). METHODS: Twenty-two patients were enrolled in this study and were randomly assigned into two groups: SW treatment (12 patients, 67 ± 9 years) and control (10 patients, 68 ± 12 years). The inclusion criteria were the following: age over 40 years, PAD diagnosis, optimal medical therapy, and ankle-brachial index less than 0.9. SW therapy was administered using the Minilith® SL1 litotriptor with an ultrasound guide able to detect the target area using a B-mode technique and a 7.5 MHz convex probe emitting 2,000 impulses with an energy flux density of 0.03 mJ/mm(2). RESULTS: The variation in the degree of stenosis before and after treatment was statistically significant between the groups (-9% ± -10% vs. 0% ± 0%; P = 0.001). In addition, a significantly higher number of treated patients than controls showed a reduction in the Fontaine stage (12 [63%] vs. 0 [0%]; P &lt; 0.001). This result was confirmed by analyzing the difference in patients' pain-free walking distance before and after SW therapy (76 ± 46 m vs. 0 ± 0 m for treated patients vs. controls; P &lt; 0.001) and the difference in pain severity (measured on a pain scale; -1.4 ± 0.5 in the treated patients vs. -0.2 ± 0.4 in the controls; P &lt; 0.001). CONCLUSION: On the basis of these results the authors hypothesized a direct effect of SW on the ultrastructural composition of the vessel walls, inducing a reduction in artery stenosis. These data support the application of SW therapy as a new medical tool to improve the natural clinical course of PAD

Speckle tracking analysis: a new tool for left atrial function analysis in systemic hypertension: an overview.

Abstract Primary cardiac tumors are a rare entity whose incidence in the general population ranges from 0.0017% to 0.28%. Myxomas represent nearly half of all primary benign cardiac tumors and they prevalently affect female patients. Embolic manifestation is rare with a reported incidence of 0.06%.We present the case of a 30-year-old male patient with acute anterolateral infarction caused by total occlusion of the left anterior descending artery as a consequence of a left atrial myxoma embolization. Urgent surgical resection of the mass didn't avoid early recurrence of atrial myxoma, whose second presentation was again myocardial infarction.This case alerts physicians to "unusual" myocardial infarction patients, when atherosclerotic pathogenesis appears unlikely. In these cases early echocardiographic evaluation should be mandatory and atrial myxoma should be considered among the possible causes. Complete surgical resection is the only effective therapeutic option to improve prognosis; the chance of tumor recurrence should dictate careful research for additional myxomas during surgery and stricter follow-up planning.

Pregnancy may predispose to paroxysmal supraventricular tachycardia (SVT), in sub- jects with or without identifiable heart disease. Many physiological conditions such as autonomic nervous system changes, altered systemic hemodynamics, etc. can contrib- ute to the onset of arrhythmias during pregnancy. Some cases reported the occur- rence of arrhythmias in relation to systemic fluid variations. We report the case of a pregnant woman who experienced SVT due to fluid depletion, detected by bioimped- ance vector analysis (BIVA), which was successfully treated by water repletion under tight BIVA monitoring. Emergency physicians can overcome dangerous drug adminis- tration by considering historical examination and using fast and reproducible tech- niques such as BIVA.

Abstract BACKGROUND: Heart failure with reduced ejection fraction caused by ischemic heart disease is associated with increased morbidity and mortality. It remains unclear whether revascularization by either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) carries benefits or risks in this group of stable patients compared with medical treatment. METHODS AND RESULTS: We performed a meta-analysis of available studies comparing different methods of revascularization (PCI or CABG) against each other or medical treatment in patients with coronary artery disease and left ventricular ejection fraction ≤40%. The primary outcome was all-cause mortality; myocardial infarction, revascularization, and stroke were also analyzed. Twenty-one studies involving a total of 16 191 patients were included. Compared with medical treatment, there was a significant mortality reduction with CABG (hazard ratio, 0.66; 95% confidence interval, 0.61-0.72; P<0.001) and PCI (hazard ratio, 0.73; 95% confidence interval, 0.62-0.85; P<0.001). When compared with PCI, CABG still showed a survival benefit (hazard ratio, 0.82; 95% confidence interval, 0.75-0.90; P<0.001). CONCLUSIONS: The present meta-analysis indicates that revascularization strategies are superior to medical treatment in improving survival in patients with ischemic heart disease and reduced ejection fraction. Between the 2 revascularization strategies, CABG seems more favorable compared with PCI in this particular clinical setting. © 2017 American Heart Association, Inc.

Purpose: According to the literature, estradiol has a direct vasodilator action by means of endothelium-derived relaxing factor synthesis. The present study aims to evaluate the acute hemodynamic effects of intranasal 17-β-estradiol on cerebral and lower limb arterial circulation in postmenopausal women. METHODS: Sixteen healthy women in natural menopause (mean age: 54 ± 3 years) were investigated for at least 6 months, each receiving 300 µg of intranasal 17-β-estradiol. We evaluated the heart rate, systolic/diastolic blood pressure, peak systolic velocity, end-diastolic velocity, and velocity-time integral (VTI) at the level of internal carotid and posterior tibial arteries, before and after 30, 60, and 180 minutes of drug administration. RESULTS: After intranasal 17-β-estradiol administration, the internal carotid artery VTI showed statistically significant (P < .05) variations at all the time intervals after administration of the drug (30, 60, and 180 minutes) when compared with "time zero" (T0, ie, the speed recorded at baseline before drug administration). No significant variation was found at the posterior tibial artery. The systolic/diastolic blood pressure and heart rate did not significantly differ before and after drug administration. CONCLUSIONS: The administration of a single intranasal dose of 17-β-estradiol in healthy postmenopausal women increased cerebral perfusions, whereas the effect on peripheral circulation was much more limited.

Atherosclerosis and its complications are the most important causes of death all over the world, especially in Western countries. Diet habits, modern stress life, smoking, sedentary way of life and an involvement of genetic pattern of individuals lead to a sure degeneration of quality of life increasing the risk of atherosclerosis development. For this reason, the main purpose of actual medicine is to identify all the markers that could allow the physicians to evaluate the first moments of the development of this dangerous pathological process. The aim is to reduce the speed of its evolution, trying to delay indefinitely the risk coming from the morphological alterations of the vessels. 'Endothelium function' could allow physicians to detect the first moment of the natural history of atherosclerosis process. Its impairment is the first step in the degeneration of vascular structures. Many methods [flow-mediated vasodilatation (FMD); antero-posterior abdominal aorta diameter (APAO); intima-media thickness of the common carotid artery (CCA-IMT); arterial stiffness; and so on] try to evaluate its function, but many limitations come from general population characteristics. A standardization of the methods should take into account individuals' peculiarities. Two elements, not modifiable, should be taken into account for vascular evaluation: age and sex. The aim of this review is to outline the linkage among age, sex and instrumental evaluation of patients considered for a noninvasive assessment of their cardiovascular risk profile.

Cardiovascular diseases are the leading cause of death worldwide: among them, coronary artery disease and arrhythmias represent the most frequent pathological conditions. Similarly, the gastrointestinal disorders, that is, gastroesophageal reflux and inflammatory bowel diseases, have a high incidence in the general population.Several pieces of evidence have documented a link between cardiac and gastrointestinal disorders as they often share similar risk factors and symptoms. Furthermore, both can simultaneously occur in the same patient, thus creating problems in the correct clinical diagnosis.It is well known that gastrointestinal disorders may present with chest pain and mimic angina pectoris. In contrast, they can also unmask heart disease, such as in the case of the angina-linked ischemia.The aim of this review was to elucidate the mechanisms underlying the relationship between cardiac and gastrointestinal diseases to better understand the causal or casual character of such a linkage.

Aim. The purpose of this study was to investigate the feasibility of contrast-enhanced ultrasound (CEUS) in the evaluation of renal artery stenosis as compared with traditional techniques: echo color Doppler (ECD) investigation and selective angiography .CEUS is a technique based on the injection of an intravascular biocompatible tracer, namely an intravenous contrast galactose microparticle suspension containing microbubbles (Levovist), that has a similar rheology to that of red blood cells, allowing quantification of renal tissue perfusion. Methods. A population of 120 hypertensive patients (82 men, mean age 55) with a systolic abdominal murmur and/or a diagnosis of poly-districtual atherosclerosis was studied by ECD and CEUS (Levovist). Selective angiography was performed in patients with renal artery stenosis demonstrated by one of the two ultrasonographic techniques. Results. Forty of the 120 patients in the study population showed renal artery stenosis at one of the two ultrasound techniques: ECD identified renal artery stenosis in 33 cases and CEUS in 38. Instead, selective angiography had detected renal artery stenosis in 38 patients, the same with renal artery stenosis diagnosed by CEUS. Thus, CEUS sensitivity, specificity and accuracy were similar to those of angiography while six false negatives and two false positives were obtained with ECD. Conclusion. Our results suggest that this renal CEUS is a promising, new, non-invasive method for screening patients with suspected renal artery stenosis. This technique appears to be superior to traditional ECD flow imaging for diagnosing renal artery stenosis and so may be an important aid in cardiovascular diagnostics.

Abstract BACKGROUND: the literature shows that a healthy diet, rich in fruits and vegetables, has positive effects on overall cardiovascular risk, protecting against atherosclerosis. DESIGN: a cross sectional study in a population of apparently healthy young-adult men with the aim of investigating dietary determinants of early atherosclerosis, assessed by measuring carotid intima-media thickness (cIMT) and flow-mediated dilation (FMD) of the brachial artery. METHODS: 615 males (mean age ± SD: 40.8±9.8 years) without overt atherosclerosis were evaluated. Dietary intake was quantified by the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire. Intake of antioxidants was expressed in relation to total caloric intake. RESULTS: Neither absolute, recommended daily allowance or weight-related values of nutritional intake variables were associated with cIMT. Vitamin E to total calories intake (odds ratio, OR=0.08, 95%CI=0.03-0.89) was inversely associated with impaired FMD. Non-nutritional correlates of FMD &amp;lt;10% were: age (OR=1.02, 95%CI=1.0-1.05) and waist circumference (OR=1.03, 95%CI=1.0-1.06), and those of cIMT &amp;gt;0.8 mm were age (OR=1.10, 95%CI=1.05-1.15), pack-years (OR=1.02, 95%CI=1.0-1.04), C-reactive protein (OR=1.17, 95%CI=1.04-1.33) and total cholesterol (OR=1.01, 95%CI=1.0-1.02). Conclusions Differences in the factors correlating with cIMT &amp;gt;0.8 mm and FMD &amp;lt;10% might have implications for cardiovascular risk reduction. A lower antioxidant to caloric intake ratio might be a risk factor for impaired FMD.

In this paper we propose the Electronic Multimedia Health Fascicle (EMHF), a truly new software system for the very large number of available electronic health records. It allows the physician to see at a glance the patient's clinical biometric measurements and biologic parameters, so as to be able to link any alarming physical status to his recent medical history. Web based, accessible from any mobile device, and easy to use by both physicians and patients, the system facilitates patient-medical interaction. Using the system can also promote better adherence to medical guidelines by the physicians and to medical prescriptions and advice by the patients.

Background: Left ventricular diastolic dysfunction (LVDD) associated with left ventricular hypertrophy (LVH) has been reported to play a major role in cardiovascular heart failure. Although, right ventricular diastolic dysfunction (RVDD) in patients with LVH was known to be clinically relevant, no systematic study had been performed regarding this relationship between left ventricular (LV) geometry associated with LVH and RVDD. The goal of this study was to evaluate an association between RVDD; LVDD, LVH and LV altered geometry for early diagnosis of heart failure. Methods and Results: Out of 426 patients, 396 patients (93%) were found to have both RVDD and LVDD. In this cohort, LV concentric geometry (LVCG) was identified in 138 patients (32.3%). RVDD and LVDD were diagnosed by measurement of E/A and tissue doppler imaging (E’/A’) for mitral and tricuspid valves. The mean value of mitral E/A in the LVCG group was lower than that of controls; 0.63±0.03 vs. 1.44±0.03, p<0.02. Mitral E’/A’ was also lower in LVCG than that of controls; 0.60±0.02 vs. 1.36±0.03, p<0.01. Similarly, E/A of Tricuspid valve in patients with LVCG was found to be lower than E/A of Tricuspid valve of controls; 0.52±0.07 vs. 0.69±0.02, p<0.001 and E’/A’ of tricuspid valve was lower than that of controls; 0.44±0.02 vs. 0.63±0.06, p<0.05. Conclusions: This study demonstrated that simple doppler trans-valvular inflow parameters and tissue doppler imaging may identify patients with biventricular diastolic dysfunction. This finding was more often observed in patients with LV concentric geometry, a pattern associated with an increased risk of cardiovascular events.

Abstract AIMS: The renal arterial resistance index (RRI) is a measure of renal blood flow obtained by Doppler ultrasonography, which has been demonstrated to reflect both vascular and parenchymal renal abnormalities. The aim of the study was to evaluate clinical correlates and the prognostic relevance of RRI in a group of patients affected by chronic heart failure (CHF). METHODS AND RESULTS: We enrolled 250 CHF outpatients in a stable clinical condition and receiving conventional therapy. Peak systolic velocity and end-diastolic velocity of a segmental renal artery were obtained by pulsed Doppler flow. Then the RRI was calculated. Standard renal function assessment was obtained by the measurement of creatinine serum levels and the estimation of the glomerular filtration rate (GFR). During follow-up (21.4 ± 11.3 months), 41 patients experienced heart failure progression (hospitalization and/or heart transplantation and/or death due to worsening heart failure). Considered as a continuous variable, RRI was associated with events at univariate [hazard ratio (HR) 1.14; 95% confidence interval (CI) 1.09-1.19; P < 0.001] as well as at multivariate Cox regression analysis (HR 1.08; 95% CI 1.02-1.13; P = 0.004) after correction for independent predictors of the reference model. When the RRI was added to the reference model including GFR, a significant improvement of reclassification according to both category-free net reclassification improvement (NRI, 47%; 95% CI 13-80%; P = 0.006) and integrated discrimination improvement (IDI, 0.034; 95% CI 0.006-0.061; P = 0.016) was observed. CONCLUSIONS: Quantification of arterial renal perfusion provides a new parameter that independently predicts CHF patient outcome, thus strengthening its possible role in current clinical practice in order to better characterize renal function and stratify patients' prognosis

AIMS: The renal arterial resistance index (RRI) is a measure of renal blood flow obtained by Doppler ultrasonography, which has been demonstrated to reflect both vascular and parenchymal renal abnormalities. The aim of the study was to evaluate clinical correlates and the prognostic relevance of RRI in a group of patients affected by chronic heart failure (CHF). METHODS AND RESULTS: We enrolled 250 CHF outpatients in a stable clinical condition and receiving conventional therapy. Peak systolic velocity and end-diastolic velocity of a segmental renal artery were obtained by pulsed Doppler flow. Then the RRI was calculated. Standard renal function assessment was obtained by the measurement of creatinine serum levels and the estimation of the glomerular filtration rate (GFR). During follow-up (21.4 ± 11.3 months), 41 patients experienced heart failure progression (hospitalization and/or heart transplantation and/or death due to worsening heart failure). Considered as a continuous variable, RRI was associated with events at univariate [hazard ratio (HR) 1.14; 95% confidence interval (CI) 1.09-1.19; P < 0.001] as well as at multivariate Cox regression analysis (HR 1.08; 95% CI 1.02-1.13; P = 0.004) after correction for independent predictors of the reference model. When the RRI was added to the reference model including GFR, a significant improvement of reclassification according to both category-free net reclassification improvement (NRI, 47%; 95% CI 13-80%; P = 0.006) and integrated discrimination improvement (IDI, 0.034; 95% CI 0.006-0.061; P = 0.016) was observed. CONCLUSIONS: Quantification of arterial renal perfusion provides a new parameter that independently predicts CHF patient outcome, thus strengthening its possible role in current clinical practice in order to better characterize renal function and stratify patients' prognosis.

Dietary omega-3 polyunsaturated fatty acids (ω-3 PUFAs) benefits are not clearly defined in childhood although already well-defined in adults. Recent studies demonstrated their positive effects on bronchial asthma, neuropsychiatric disorders and cognitive brain function in childhood. Furthermore, it has been demonstrated a relationship between the increased incidence of childhood obesity and the role of ω-3 PUFAs in reducing the metabolic and vascular alterations induced by the fat accumulation since young age. Such relationship could be more important in prevention future cardiovascular events. In facts, ω-3 PUFAs could improve endothelial function and structure since childhood. By considering endothelial dysfunction as a well-known early marker of atherosclerosis, its amelioration since first years of individuals life will certainly reduce the cardiovascular risk profile in adulthood. Nevertheless, their use is limited by several factors: the lacking of studies in children and the awful taste of the products enriched with ω-3 PUFAs, although several patents had been managed in order to overcome such defects and develop the use of these molecules. This paper is a literature studies and patents analysis aiming at exploring key issues regarding ω-3 PUFAs administration in childhood in order to take into account the opportunity of their routinely use in everyday life since early moments of life. Nevertheless, it is well-established that further studies are needed to endorse the promising results outlined by literature analysis.

Abstract BACKGROUND: Cardiovascular and renal disease are nowadays among the leading cause of morbidity and mortality in Western Countries. Low birth weight has been recently considered a key factor in determining cardiovascular disease and long term renal disease in adulthood. METHODS: In our study we analyzed, through echocardiography, eco color Doppler of carotid arteries, ultrasound of abdominal aorta and kidneys, morphological characteristics of cardiovascular and renal system, in a in a group of children born preterm with very low birth weight, (birth weight<1500 grams) and in a group of children, age and sex matched, born at term with weight appropriate for gestational age. 15 children born very low birth weight preterm (cases), aged from 3 to 5 years, and 15, age and sex matched children, born appropriate for gestational age at term (controls) were enrolled in the study. RESULTS: The two groups were homogeneous for interventricular septum diameter, left ventricular end-systolic diameter, left atrial diameter, and ejection fraction. Left ventricular end diastolic diameter was higher in case compared to controls (p=0.04), while aortic diameter root smaller (p=0.005). E and A waves peak velocities and E/A ratio resulted lower in cases compared to controls (p=0.02, p<0.001and p <0.001, respectively). Tei index, S, e' and a' waves velocities were similar in the two groups, while E/e' ratio was higher in cases (p=0.046). Intima-media thickness and antero-posterior diameter of abdominal aorta values did not differ in cases versus controls. Longitudinal diameters of both kidneys were reduced in cases compared to controls (p <0.05). CONCLUSIONS: Although limited by the small sample size, our study highlighted an increased size of the left ventricle and altered left ventricular diastolic function in children born very low birth weight preterm, but no long term consequences on systolic performance and vascular structure have been found. The finding of smaller kidneys in ex-preterm very low birth weight children could explain their higher susceptibility to develop renal disease in adulthood.

Background: The reports of ultrasound evaluation of lower limb veins are difficult to understand by general practitioners (GPs) and physicians who are not specialized. We developed software for a three-dimensional (3D) electronic report of venous hemodynamic mapping (MEVeC®) in order to represent lower limb venous vasculature in a 3D way. The aim of the study is to compare the novel 3D report with the standard report. Methods: Thirty subjects (medical students and GPs) evaluated a standard report and a novel 3D report of the lower limb veins of a prespecified patient. The cases were randomly and blindly taken from an archive of 100 cases. GPs and students answered a questionnaire made up of 13 questions that were structured in order to investigate the readability and comprehension of the two reports. A score ranging from 0 to 10 (0= not understandable; 10= full comprehension) was attributed to each report for each question according to the readability of the venous scheme proposed. Results: The scores from each question of the questionnaire were compared. The 3D report (MEVeC®) obtained higher scores than those from the evaluation of the standard report (P<0.0001). Each question revealed the superiority of the 3D report (MEVeC®) as compared with the standard report of the ultrasound evaluation of lower limbs. When dividing the scores according to percentiles, the 3D report (MEVeC®) still continued to show more readability than the standard report in a statistically significant way (P<0.0001). Conclusion: The new 3D report (MEVeC®) concerning ultrasound evaluation of lower limb veins is more reproducible than the standard report when evaluated by medical physicians not specialized in the evaluation of the vein tree of lower limbs.

Apixaban is a new oral anticoagulant (NOACs: Novel Oral Anticoagulant), as like dabigatran, rivaroxaban, edoxaban. All of them are prescribed to patients with non valvular atrial fibrillation or venous thromboembolism, to replace warfarin, because of the lower probability of bleedings, however they can cause bleedings by themselves. Bleeding is an adverse event in patients taking anticoagulants. It is associated with a significant increase of morbidity and risk of death. However, these drugs should be used only for the time when anticoagulation is strictly required, especially when used for preventing deep vein thrombosis. Prolonged use increases the risk of bleeding. In the ARISTOTLE Trial Apixaban, compared with warfarin, was associated with a lower rate of intracranial hemorrhages and less adverse consequences following extracranial hemorrhage. Many physicians still have limited experience with new oral anticoagulants and about bleeding risks managment. We reviewed the available literature on extracranial and intracranial bleeding concerning apixaban.

A great debate in literature exists nowadays on the role of uric acid as a marker of cardiovascular and metabolic organ damage or a risk factor for cardiovascular and metabolic disease.

Background: Small-for-gestational-age (SGA) children have increased cardiovascular risk, but the mediating factors are poorly understood. We hypothesized that birth size could affect the cardiovascular system since childhood in the absence of other risk factors. We investigated endothelial and myocardial function in SGA children with regular catch-up growth. Methods and Results: Biochemical markers, blood pressure, flow-mediated vasodilation (FMD), common carotid intima-media thickness (cIMT), anteroposterior diameter of the infrarenal abdominal aorta (APAO) and echocardiographic parameters of left and right ventricular (LV and RV) function were studied in 27 SGA and 25 appropriate-forgestational-age (AGA) subjects. SGA subjects had a higher homeostasis model assessment index than controls (2.61±1.27 vs. 1.56±0.40, P=0.01), higher cIMT (0.51±0.04mm vs. 0.45±0.07mm, P=0.007) and APAO (1.31±1.35cm vs. 1.30±0.16cm, P=0.005), and lower FMD (10.11±4.17% vs. 12.34±4.28, P=0.04) than controls. On echocardiography SGA had higher Tei index both at LV and RV than controls (P=0.001). Reduced RV systolic function was also observed in SGA subjects. Conclusions: SGA subjects had vascular morphological and function abnormalities compared with AGA, which increase their cardiovascular risk profile. Furthermore, a subtle cardiac alteration in both RV and LV functions was seen in SGA patients compared with AGA.

The present review is addressed to analyse the complex interplay between left ventricle and arterial tree in hypertension. The different methodological approaches to the analysis of ventricular vascular coupling in the time and frequency domain are discussed. Moreover, the role of hypertension-related changes of arterial structure and function (stiffness and wave reflection) on arterial load and how ventricular-vascular coupling modulates the process of left ventricular adaptation to hypertension are analysed.The different interplay between vascular bed and left ventricle emerges as the pathophysiological basis for the development of the multiple patterns of ventricular structural adaptation in hypertension and provides a pathway for the interpretation of systolic and diastolic functional abnormalities observed in hypertensive patients. Targeting the therapeutic approach to improve ventricular-vascular coupling may have relevant impact on reversing left ventricular hypertrophy and improving systolic and diastolic dysfunction.