Aspirin in Primary Prevention: Looking for Those Who Enjoy It.

Based on a wealth of evidence, aspirin is one of the cornerstones of secondary prevention of cardiovascular disease. However, despite several studies showing efficacy also in primary prevention, an unopposed excess risk of bleeding leading to a very thin safety margin is evident in subjects without a clear acute cardiovascular event. Overall, the variability in recommendations from different scientific societies for aspirin use in primary prevention is a classic example of failure of simple risk stratification models based on competing risks (atherothrombosis vs. bleeding), perceived to be opposed but intertwined at the pathophysiological level. Notably, cardiovascular risk is dynamic in nature and cannot be accurately captured by scores, which do not always consider risk enhancers. Furthermore, the widespread use of other potent medications in primary prevention, such as lipid-lowering and anti-hypertensive drugs, might be reducing the benefit of aspirin in recent trials. Some authors, drawing from specific pathophysiological data, have suggested that specific subgroups might benefit more from aspirin. This includes patients with diabetes and those with obesity; sex-based differences are considered as well. Moreover, molecular analysis of platelet reactivity has been proposed. A beneficial effect of aspirin has also been demonstrated for the prevention of cancer, especially colorectal. This review explores evidence and controversies concerning the use of aspirin in primary prevention, considering new perspectives in order to provide a comprehensive individualized approach.

Speckle-tracking echocardiography: state of art and its applications.

Echocardiographic evaluation of left ventricular ejection fraction (LVEF) provides important information regarding both myocardial function and prognosis. This parameter presents various limitations and does not allow early detection of myocardial dysfunction. LVEF may be related to hemodynamic load, geometric assumptions, to image quality, and it does not reflect myocardial contractility. It has been hypothesized that speckle tracking echocardiography (STE) may allow overcoming such limits. STE through the measurement of strain and strain rate, which detect myocardial deformation, allows earlier identification of myocardial dysfunction in different settings both in presence of systolic and diastolic dysfunction, helps to predict left ventricular remodeling after acute myocardial infarction (AMI), and helps to decide the timing of surgery in asymptomatic severe valvular heart disease which is still a problematic issue. Increasingly interest regards the role of STE for the assessment of cardiomyopathies, myocarditis, and pulmonary hypertension. STE may be applied to the evaluation of systolic and diastolic dysfunction. STE is useful in all conditions in which cardiac dysfunction is not still overt, but a subclinical involvement is undoubtedly present such as in presence of cardiovascular risk factors and in cardio-oncology at earlier stages. It has been confirmed its role in predicting left ventricular remodeling after AMI which represents an important prognostic datum and in deciding the timing of surgery in asymptomatic valvular diseases. STE is an important tool to detect myocardial impairment even at earlier stages. 3DSTE and layer-specific strain represent promising fields of clinical application of STE.

[Bileaflet mechanical valve dysfunction related to fibrous pannus: the role of cine-fluoroscopy]. / Disfunzione di protesi valvolare meccanica bileaflet da panno fibroso: non dimenticare la cine-fluoroscopia!

We report the case of a 72-year-old female patient admitted for worsening heart failure. The patient had undergone aortic valve replacement with a mechanical prosthesis 28 years before and since then she had several acute heart failure episodes, with a progressive increase in transprosthetic gradients, without identifying a specific cause.We describe the diagnostic tools used to reach a diagnosis, with particular emphasis on the use of cine-fluoroscopy that allowed to make the decisively diagnosis of prosthetic valve dysfunction, subsequently confirmed by cardiac computed tomography (CT). By cine-fluoroscopy, a widespread, easy, low-cost, and safe tool (no need for medium contrast and low radiation dose), it is possible to precisely define the function of the valve leaflets and measure their opening and closing angles, comparing them to the specific reference angles. To make the correct diagnosis we also performed a cardiac CT demonstrating a sub-aortic fibrous pannus. However, although cardiac CT is highly accurate for the identification of valve leaflet neoformations and abnormalities and for the discrimination between thrombotic formations and fibrous pannus, it is burdened by high costs, use of contrast medium, and limited available dedicated devices.

Coagulative Disorders in Critically Ill COVID-19 Patients with Acute Distress Respiratory Syndrome: A Critical Review.

In critically ill patients with acute respiratory distress syndrome (ARDS) coronavirus disease 2019 (COVID-19), a high incidence of thromboembolic and hemorrhagic events is reported. COVID-19 may lead to impairment of the coagulation cascade, with an imbalance in platelet function and the regulatory mechanisms of coagulation and fibrinolysis. Clinical manifestations vary from a rise in laboratory markers and subclinical microthrombi to thromboembolic events, bleeding, and disseminated intravascular coagulation. After an inflammatory trigger, the mechanism for activation of the coagulation cascade in COVID-19 is the tissue factor pathway, which causes endotoxin and tumor necrosis factor-mediated production of interleukins and platelet activation. The consequent massive infiltration of activated platelets may be responsible for inflammatory infiltrates in the endothelial space, as well as thrombocytopenia. The variety of clinical presentations of the coagulopathy confronts the clinician with the difficult questions of whether and how to provide optimal supportive care. In addition to coagulation tests, advanced laboratory tests such as protein C, protein S, antithrombin, tissue factor pathway inhibitors, D-dimers, activated factor Xa, and quantification of specific coagulation factors can be useful, as can thromboelastography or thromboelastometry. Treatment should be tailored, focusing on the estimated risk of bleeding and thrombosis. The aim of this review is to explore the pathophysiology and clinical evidence of coagulation disorders in severe ARDS-related COVID-19 patients.

Brugada syndrome and syncope: A systematic review.

INTRODUCTION: Distinguishing syncope due to malignant arrhythmias from an incidental benign form in Brugada syndrome (BrS) is often difficult. Through systematic literature review, we evaluated the role of syncope in predicting subsequent malignant arrhythmias in BrS. METHODS: A comprehensive literature search was performed on PubMed (MeSH search terms "Brugada syndrome" and "syncope"). Overall, 9 studies for a total of 1347 patients were included. Patients were stratified as affected by suspected arrhythmic syncope (SAS), undefined syncope (US) or neurally-mediated syncope (NMS). RESULTS: Overall, 15.7% of the 279 patients with SAS had malignant arrhythmic events during a mean follow-up of 67 months, corresponding to 2.8 events per 100/person year. At the same time, 7% of the 527 patients affected by US had malignant arrhythmias during a mean follow-up of 39 months, corresponding 2.2 events per 100/person year. Conversely, 0.7% of 541 patients with NMS had malignant arrhythmic events at follow-up, corresponding to 0.13 events per 100/person year (p = .0001 NMS versus SAS and US pooled). CONCLUSION: In BrS population, the risk of arrhythmic events in the follow-up may be stratified according to the clinical evaluation. The "relatively" low predictive value of the clinical diagnosis of SAS warrants for a more accurate multi-parametric assessment, to restrict the number of candidates for implantable cardioverter-defibrillator therapy.

Stress cardiomyopathy (tako-tsubo) triggered by nervous system diseases: a systematic review of the reported cases.

BACKGROUND: It is not clarified whether the transient, regional left ventricular dysfunction (TRLVD) associated with several neurological disorders shares the same pathophysiology with the classical tako-tsubo cardiomyopathy occurring without overt neurological disease, and whether it is appropriate to include these patients in a single stress cardiomyopathy (SCM) condition. METHODS: In February 2012, we systematically explored major electronic medical information sources to identify cases of TRLVD triggered by neurological disorders. RESULTS: The 81 selected papers reported a total of 124 patients, suffering from neurological disorders, in whom TRLVD occurred: 117 with central nervous system diseases, 6 with peripheral nervous system diseases and 1 with both systems involved. Most patients were females (n=102), mean age was 63 ± 15 years, and the majority presented with an apex-involving pattern. The most common disease described was subarachnoid hemorrhage (n=52), followed by stroke/transient ischemic attack (n=24), and seizures (n=18). TRLVD in neurological patients was often associated with need of inotropic support, orotracheal intubation, cerebrovascular spasm and delayed surgery. CONCLUSIONS: TRLVD is a complication of neurological diseases, in particular in female patients in post-menopausal phase. The predilection for neurological damage at or close to the insular cortex highlights the pivotal role of sympathetic over-activation. Many other similarities with tako-tsubo support the inclusion in a single SCM category.

Serum levels of γ-glutamyltransferase and progression of coronary atherosclerosis.

BACKGROUND: Progression of coronary atherosclerosis (ATS) has clinical implications. Serum levels of γ-glutamyltransferase (GGT), a marker of oxidative stress, predict the risk of cardiovascular events. However, the role of GGT levels in the progression of coronary ATS has never been established. MATERIALS AND METHODS: Consecutive patients undergoing two coronary angiographies (CAs) separated by at least 6 months were prospectively enrolled between May 2008 and June 2010. All patients were discharged on statins after the first CA. The severity and extent of coronary ATS were graded according to Bogaty's score, and the variation (Δ) in stenosis score and extent index between follow-up (S2 and E2) and basal values (S1 and E1) were calculated. Predictors of ΔS2-1 and ΔE2-1 were assessed among clinical and laboratory data, including GGT levels, analyzed as Δ between follow-up and basal values (ΔGGT2-1). RESULTS: We enrolled 100 consecutive patients (age 64±11 years, 68% men). Compliance with statin therapy was 100%. At multiple regression analysis, ΔGGT2-1 was the only independent predictor of ΔS2-1 (B=0.18, SE=0.07, P=0.05), with Δlow-density lipoprotein-cholesterol2-1 levels being of borderline statistical significance (P=0.07). On multiple regression analysis, ΔGGT2-1 was the only independent predictor of ΔE2-1 (B=0.32; SE=0.11; P=0.04), with active smoking habit and Δfibrinogen2-1 levels being of borderline statistical significance (P=0.08 and 0.06, respectively). CONCLUSION: ΔGGT2-1 is associated with angiographic coronary ATS progression in patients with ischemic heart disease on statin treatment, suggesting that oxidative stress may be another therapeutic target for preventing ATS progression beyond that of lipid-lowering therapies.

Inflammatory biomarkers and coronary heart disease: from bench to bedside and back.

Inflammation plays a pivotal role in all stages of atherosclerosis from endothelial dysfunction and plaque formation to plaque destabilization and disruption. Inflammatory biomarkers, originally studied to better understand the pathophysiology of atherosclerosis, have generated increasing interest among clinicians, because of their utility in the challenging problems of diagnosis and risk assessment of patients with suspected or proved coronary heart disease. Moreover, in fascinating perspective, they could be used as therapeutic target, counteracting initiation, progression, and development of complications of atherosclerosis. In this review, we will provide an overview of the more promising inflammatory biomarkers, focusing on their utility and limitations in the clinical setting.

Cystatin C is associated with an increased coronary atherosclerotic burden and a stable plaque phenotype in patients with ischemic heart disease and normal glomerular filtration rate.

OBJECTIVE: Cystatin C (Cys-C) is an accurate marker of renal function. Recent studies have shown that serum Cys-C levels predict the risk of cardiovascular events. The causes of this association, however, are largely unknown. METHODS AND RESULTS: Seventy consecutive patients (age 62+/-12, male sex 87%) undergoing coronary angiography because of typical chest pain and found to have coronary artery disease were included in the present study. Patients with abnormal creatinine-derived glomerular filtration rate (<90ml/min/1.73m(2)) were excluded in order to avoid the well-known effect of overt renal insufficiency on coronary atherosclerosis. Coronary angiography was evaluated by two expert angiographers who assessed disease severity and extent according to the Sullivan's score and lesion morphology. In all patients, Cys-C and C-Reactive Protein (CRP) serum levels were measured on admission. Multivariable analysis was performed to assess independent predictors of angiographic measures. Diabetes was the only predictor of disease severity (p=0.005), while male sex (p=0.03), hypercholesterolemia (p=0.04), diabetes (p<0.0001) and Cys-C (p<0.0001) were independent predictors of disease extent. Independent predictors of smooth lesions were diabetes (p<0.001) and Cys-C (p=0.005). No correlation was found between Cys-C and CRP serum levels (p=0.6). CONCLUSION: Cys-C is associated with coronary atherosclerosis extent and a smooth lesion morphology. The long-term prognostic role of Cys-C might be accounted for by a greater atherosclerotic burden, a necessary substrate for plaque destabilization.