Multicentric Atrial Strain COmparison between Two Different Modalities: MASCOT HIT Study.

Two methods are currently available for left atrial (LA) strain measurement by speckle tracking echocardiography, with two different reference timings for starting the analysis: QRS (QRS-LASr) and P wave (P-LASr). The aim of MASCOT HIT study was to define which of the two was more reproducible, more feasible, and less time consuming. In 26 expert centers, LA strain was analyzed by two different echocardiographers (young vs senior) in a blinded fashion. The study population included: healthy subjects, patients with arterial hypertension or aortic stenosis (LA pressure overload, group 2) and patients with mitral regurgitation or heart failure (LA volume-pressure overload, group 3). Difference between the inter-correlation coefficient (ICC) by the two echocardiographers using the two techniques, feasibility and analysis time of both methods were analyzed. A total of 938 subjects were included: 309 controls, 333 patients in group 2, and 296 patients in group 3. The ICC was comparable between QRS-LASr (0.93) and P-LASr (0.90). The young echocardiographers calculated QRS-LASr in 90% of cases, the expert ones in 95%. The feasibility of P-LASr was 85% by young echocardiographers and 88% by senior ones. QRS-LASr young median time was 110 s (interquartile range, IR, 78-149) vs senior 110 s (IR 78-155); for P-LASr, 120 s (IR 80-165) and 120 s (IR 90-161), respectively. LA strain was feasible in the majority of patients with similar reproducibility for both methods. QRS complex guaranteed a slightly higher feasibility and a lower time wasting compared to the use of P wave as the reference.

The analysis of left atrial function predicts the severity of functional impairment in chronic heart failure: The FLASH multicenter study.

BACKGROUND: Heart failure (HF) patients present with a variety of symptoms at different stages of the disease, but the underlying pathophysiology still is unclear. Left atrial (LA) function might be tightly related to changes in patients' symptoms, more than morphological and anatomic heart features, measurable by ultrasound imaging technique. This study sought to investigate the correlation between LA function, assessed by Speckle Tracking Echocardiography (STE) and Quality of Life (QoL), assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ), in patients with chronic HF. METHODS: Clinically stable HF outpatients (n = 369) were enrolled from 7 different international centres and underwent echocardiographic studies. Patients >75 years old and with atrial fibrillation were excluded. LA strain during reservoir phase (LASr) by STE was measured in all subjects by averaging the 6 atrial segments. LA size was assessed using biplane volume and 4-chamber area acquisition. RESULTS: LASr strongly correlated with both MLHFQ total score (r = -0.87; p < 0.0001). Less significant correlations between MLHFQ and either LA volume or left ventricular global longitudinal strain (LV-GLS) were found (r = 0.28; p = 0.05 and r = 0.30; p = 0.01, respectively). No significant correlation was found between MLHFQ score, LVEF (r = -0.15; p = ns), E/E' ratio (r = 0.19; p = ns), and E/A ratio (r = 0.20; p = ns). Among all echocardiographic parameters analyzed, LASr presented the highest diagnostic accuracy (AUC = 0.74) in predicting a poor QoL (>45), when compared with LV-GLS (AUC = 0.61), LA volume (AUC = 0.54) and E/e' ratio (AUC = 0.51). CONCLUSIONS: In patients with HF, irrespective of etiology, LA function strongly correlates with patients' QoL.

The effect of surgical versus transcatheter aortic valve replacement on endothelial function. An observational study.

BACKGROUND: The effects of surgical aortic valve replacement versus transcatheter aortic valve replacement on endothelial function are unknown. We investigated the effects of surgical and transcatheter aortic valve replacement on early and 90-day endothelial function measured by brachial flow mediated dilation and apoptotic rate in the human umbilical vein endothelial cells in patients with significant aortic stenosis, intermediate risk of surgery, and no coronary artery disease. METHODS: We conducted a prospective observational case control single-blind study at a single tertiary center. Endothelial function was measured at baseline, early post-procedure (4 days), and follow-up (90 days). A blood pressure cuff was used to elicit reactive hyperemia for measuring brachial wall shear stress and flow mediated dilation. The apoptosis rate was observed in the human umbilical vein endothelial cells after 48-h incubation with 20% serum from patients. The rate of apoptosis was assessed by determining the number of annexin V and propidium iodide positive cells by flow cytometry. RESULTS: Early post-procedure flow dilation was significant lower in the surgical group (p < 0.003). At follow-up, both groups showed incremental increases in flow mediated dilation. Surgical group apoptotic rate did not significantly change, while transcatheter apoptotic rate steadily decreased, suggesting a trend toward improved endothelial function. CONCLUSIONS: The data suggest that conventional surgical aortic valve replacement may be associated with an early and transient decrease in endothelial function, likely due to the use of cardio-pulmonary bypass.

Left atrial, ventricular and atrio-ventricular strain in patients with subclinical heart dysfunction.

Arterial hypertension (AH) and diabetes mellitus (DM) are the most common causes of heart deterioration because of their high prevalence in the population. The aim of this study was to evaluate peak left atrial (LA), longitudinal strain (PALS), left ventricular (LV), longitudinal  strain (LS) and global atrial-ventricular strain (GAVS), by speckle-tracking echocardiography (STE), in asymptomatic patients with AH or/and DM and normal LA, LV size and ejection fraction (EF), to analyze their capability to detect early subclinical dysfunction. We enrolled 162 patients affected by AH and/or DM with normal indexed LA volume, LV end-diastolic diameter and a LVEF > 52% (females) or > 54% (males) (60 hypertensives, 52 diabetics and 50 both) and 60 healthy controls. All subjects underwent standard and advanced STE. PALS, LS and GAVS were measured. GAVS was calculated as the algebraic sum of absolute PALS and LS values in four- and two-chambers views. LS, although with lower values in hypertensives, diabetics and both, did not show significant differences between groups. PALS and GAVS were significantly reduced in AH (31.9 ± 10.3% and 49.7 ± 11.2%, respectively) and DM (26.2 ± 7.1% and 42.6 ± 9.8%) compared to controls, and even more if the two coexisted (20.4 ± 6.5% and 37.1 ± 8.4%). PALS had the highest statistical significance and was able to identify subclinical damage independently from LS value. PALS was reduced in patients with AH and/or DM without alteration of standard echo indexes. The value of PALS was independent from LS and was sufficient to identify heart dysfunction in an earlier stage.

To Bleed or Not to Bleed: That is the Question. The Side Effects of Apixaban.

Apixaban is a new oral anticoagulant (NOACs: Novel Oral Anticoagulant), like dabigatran, rivaroxaban, and 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 bleeding, however they can cause bleeding 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 risk managment. We reviewed the available literature on extracranial and intracranial bleeding concerning apixaban.

Evaluation of body composition with bioimpedence. A comparison between athletic and non-athletic children.

PURPOSE: Conventional Bioelectrical Impedance Analysis (BIA) or Bioelectrical Impedance Vector Analysis (BIVA) can provide direct evaluations of body composition. The purpose of this study was to evaluate lean and fat mass (FM), and hydration of children involved in daily competitive sports. METHODS: 190 non-athletic [8.2-10.5 years] and 29 competitive children [8.0-10.5 years] were enrolled. They were evaluated: at baseline (t0), 6 months (t1) and one year (t2). Anthropometric, BIA and BIVA, lean and FM, and hydration evaluations were performed. RESULTS: Resistance (R/h) and reactance (Xc/h) were lower at t0 in competitive individuals when compared to controls. Xc/h (+3.28) significantly increases in competitive when compared to non-competitive individuals (+0.66, p for difference: 0.011), while phase angle (PA) was lower at t0 (5.72 vs. 6.17, p < .001) and after 6 months (p = .001). Total body water adjusted for height (TBW/h) significantly increased only in non-athletes (+0.50 ± 0.13, p < .001) between t0 and t1. At t1, extracellular water (ECW) significantly decreased (p = .026) in the two groups: -0.45 ± 0.19% in non-competitive, -1.63 ± 0.49% in competitive subjects, while intracellular water (ICW) increased. At one-year follow-up (t2), there were no statistically significant differences in R/h, Xc/h and PA in competitive individuals when compared to baseline and t1. Furthermore, we observed at t2 that hours/week of training, age, male gender and body mass index can influence FFM/h and FM/h in both competitive and non-competitive subjects. In particular, a direct correlation was for hours/week and FFM/h, inverse for hours/week and FM/h. CONCLUSIONS: Body mass index does not allow evaluating differences in lean body mass and FM between athletes and non-athletes. BIA and BIVA can give more reliable details about body composition differences in competitive adolescents and non-competitive, outlining a progressive decline in ECW and increase in ICW without affecting TBW composition of athletes.

Survival Benefits of Invasive Versus Conservative Strategies in Heart Failure in Patients With Reduced Ejection Fraction and Coronary Artery Disease: A Meta-Analysis.

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.

Evaluation of endothelial function and cardiovascular risk in non-obese patients with slight degree of obstructive sleep apnea syndrome.

Recently, it has been clearly described an independent relationship between obstructive sleep apnea syndrome (OSAS) and cardiovascular risk, with underlying mechanisms also including endothelial dysfunction. We enrolled 32 consecutive non-obese patients (mean age of 39.5±11.5 years), of which 16 with mild OSAS and 16 snoring without OSAS. Mild OSAS is defined by an AHI index between 5 and 15. We have investigated if whether there was a relationship between mild OSAS, endothelial function and carotid intima-media thickness (C-IMT). The population was divided into two groups: Group 1 (16 simple snorer patients with an average age of 39.4±12.1 years) and Group 2 (16 subjects with mild OSAS with an average age of 39.6±11.2 years). Each group underwent cardiovascular investigation including measurement of flow-mediated dilation (FMD) of the brachial artery and C-IMT. Both groups comprised non-obese subjects. Patients with mild OSAS had serum total cholesterol values statistically significantly higher than simple snores patients (178.6±24.9 vs 159.2±25.3; p=0.038). OSAS patients had also a trend towards higher values of maximum C-IMT compared to simple snorer patients (0.70±0.15 vs 0.65±0.16), although below the level of significance. Between the two groups, no difference was found for FMD values. The present results on mild OSAS strengthen the importance of a diagnosis of OSAS as soon as possible, in order to encourage all primary prevention interventions to correct risk factors responsible for disease progression and the occurrence of cardiovascular diseases, not excluding the use of therapies of non-invasive ventilation even in the early stages of the disease.

From proprotein convertase subtilisin/kexin type 9 to its inhibition: state-of-the-art and clinical implications.

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.

ST2L Transmembrane Receptor Expression: An Immunochemical Study on Endarterectomy Samples.

BACKGROUND: ST2 (suppression of tumorigenity) has been described as a receptor for the interleukin-33, a member of the IL-1 family of cytokines. It is associated to coronary artery disease, all-causes mortality and cardiovascular mortality. AIMS: The present study was designed to assess the immunohistochemical expression of the ST2 receptor (ST2L/Il-1R) in atherosclerotic plaques of formalin fixed paraffin-embedded internal carotid arteries of patients with and without cerebro-vascular symptoms. METHODS AND RESULTS: The study involved 41 cases (23 asymptomatic and 18 symptomatic). All the clinical and morphological parameters examined were uniformly distributed between the two groups, with a mild predominance of degree of calcification in asymptomatic cases (p = 0.01). ST2L expression was found to be more evident as a membrane pattern in macrophages when observing carotid atherosclerotic plaques of symptomatic patients, rather than in asymptomatic patients' plaques (77.7% vs 39.1%; p = 0.015), and its expression was particularly remarkable in VI type plaque (AHA). Significantly, ST2L was marked by the endothelium of neoangiogenetic vessels on the shoulder region of the plaque, but not (apart from a few cases) in the endothelium covering the residual lumen of the vessel. CONCLUSIONS: The ST2L immunohistochemical expression was for the first time investigated in a large number of human carotid atherosclerotic plaques, as for its pattern of distribution in the different plaque cell populations. Furthermore, ST2L was particularly remarkable on macrophages, as a membrane pattern, of symptomatic patients' plaque. Considering our data, we hypothesize that ST2L/IL33 axis could drive the mechanism of plaque development and eventually rupture.

Pulmonary hypertension in thyroid diseases.

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.

Rosuvastatin: Beyond the cholesterol-lowering effect.

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.

Echocardiographic findings and plasma endothelin-1 levels in obese patients with and without obstructive sleep apnea.

OBJECTIVE: Obstructive sleep apnea (OSA) and obesity are increasingly prevalent worldwide. Both promote endothelial dysfunction contributing to systemic and pulmonary hypertension over time. Endothelin-1 (ET-1) plays a pivotal role in the development of pulmonary hypertension (PH). The aim of the present study was to assess the association between plasma ET-1 and echocardiographic findings in obese individuals with and without OSA, as well as in non-obese patients with OSA. METHODS: Ninety-seven subjects (56 males) were enrolled in the study. All subjects underwent the following tests: venous endothelin-1 levels, pulmonary function testing, and arterial blood gas analysis. All patients except controls underwent transthoracic echocardiography and portable testing for sleep-disordered breathing. RESULTS: Plasma ET-1 levels were significantly higher in obese patients, both with and without OSA (respectively, n = 30 (mean value, 268.06 ± 49.56 pg/ml) and n = 32 (mean value, 263.12 ± 65.26 pg/ml)), compared with non-obese patients with OSA or to healthy controls (respectively, n = 20 (mean value, 149.8 ± 23.09 pg/ml) and n = 15 (mean value, 152.3 ± 27.64 pg/ml); p < 0.0001). Pulmonary artery pressure (PAPs) in obese patients with OSA were significantly higher than in obese patients without OSA (p < 0.0001), while there was no statistical difference between PAPs of obese patients without OSA, compared with the group of non-obese OSA patients. Plasma ET-1 levels significantly correlated with systolic PAPs in obese patients both with and without OSA (respectively, n = 30, r = 0.385, p = 0.03567; n = 32, r = 0.3497, p = 0.0497). CONCLUSIONS: Our study suggests that endothelin levels are more strongly associated with weight than the presence of sleep-disordered breathing, but pulmonary artery hypertension is associated with both weight and OSA.

Bioresorbable vascular scaffolds: design, clinical trials, and current applications.

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.

Focus on alirocumab: A PCSK9 antibody to treat hypercholesterolemia.

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.

Endothelial dysfunction correlates with liver fibrosis in chronic HCV infection.

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 (4.7 ± 1.7% versus 7.1 ± 2.8%, p = 0.03). FMD values were inversely related to liver elastomeric values. c-IMT values were normal. The risk for endothelial dysfunction development in the third tertile (p = 0.02) 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.

[Vitamin D deficiency and cardiovascular diseases]. / Deficit di vitamina D e malattie cardiovascolari.

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.

Inflammatory bowel disease, liver diseases and endothelial function: is there a linkage?

Atherosclerosis is a systemic inflammatory disease able to deeply worsen the outcome of patients because of its serious clinical consequences. The complex inflammatory background underlining such a disease makes atherosclerosis linked to several systemic inflammatory conditions able to impair endothelial function and morphology. Inflammatory bowel diseases are a group of gastrointestinal diseases including Crohn's disease and ulcerative colitis, that is, syndromes characterized by changes in mucosal immunity and gastrointestinal physiology, which could negatively influence the vascular endothelial function and structure. Hepatitis (i.e. inflammatory diseases of the liver mainly due to viral infections) and nonalcoholic fatty liver disease could be aligned to inflammatory bowel disease in such an induction of atherosclerosis disease.Many studies tried to point out the relationship between bowel and liver inflammatory diseases and early vascular changes, considered the first step for atherosclerosis development.The aim of such a narrative review is to explain the relationship between inflammatory bowel disease, hepatitis and nonalcoholic fatty liver disease and their role in increasing cardiovascular risk profile due to early impairment in vascular function and morphology.