Beyond its role in hemostasis, von Willebrand factor (VWF) is an emerging mediator of vascular inflammation. Recent studies highlight the involvement of VWF and its regulator, ADAMTS13, in mechanisms that underlie vascular inflammation and immunothrombosis, like leukocyte rolling, adhesion, and extravasation; vascular permeability; ischemia/reperfusion injury; complements activation; and NETosis. The VWF/ADAMTS13 axis is implicated in the pathogenesis of atherosclerosis, promoting plaque formation and inflammation through macrophage and neutrophil recruitment in inflamed lesions. Moreover, VWF and ADAMTS13 have been recently proposed as prognostic biomarkers in cardiovascular, metabolic, and inflammatory diseases, such as diabetes, stroke, myocardial infarction, and sepsis. All these features make VWF an attractive therapeutic target in thromboinflammation. Several lines of research have recently investigated “tailor-made” inhibitors of VWF. Results from animal models and clinical studies support the potent anti-inflammatory and antithrombotic effect of VWF antagonism, providing reassuring data on its safety profile. This review describes the role of VWF in vascular inflammation “from bench to bedside” and provides an updated overview of the drugs that can directly interfere with the VWF/ADAMTS13 axis.

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IntroductIonThe European Society of Cardiology (ESC) definition for sudden death (SD) is a nontraumatic, unexpected fatal event occurring within 1 h of the onset of symptoms in an apparently healthy control. If death is not witnessed, the definition applies when the victim was in good health 24 h before the event. [1] Cardiovascular (CV) diseases are responsible for approximately 17 million deaths every year in the world and about 25% of which are sudden cardiac death (SCD). [2] A SD may be defined as a SCD when a congenital, or acquired, potentially fatal cardiac condition was known to be present during life, or autopsy has identified a cardiac or vascular anomaly as the probable cause of the event, or no obvious extra cardiac causes have been identified by postmortem examination, and therefore, an arrhythmic event is a likely cause of death. [1] In last years, the number of sport practitioners has increased by many times. The benefits of sport practice in improving CV health are unquestionable, but an increase in CV events has also been demonstrated during its practice. Therefore, the absolute number of people at risk of SCD during exercise is also increasing. [3] SCD of an athlete is a rare, but tragic event, which devastates families, institutions, the community, and sports medicine team. It is widely publicized by the media with significant social implications, conveying the idea that such an event can be preventable.Sport activity might play a trigger role of cardiac arrest in athletes with structural or electrical heart abnormalities, generating malignant arrhythmias, as ventricular fibrillation. The culprit diseases are often clinically silent and unlikely to be suspected or identified on the basis of spontaneous symptoms. [4] Preparticipation screening (PPS) protocol proposed by the ESC focuses on three points: family and personal history, physical examination, and 12-lead electrocardiogram (ECG), showing Echocardiography is a noninvasive imaging technique useful to provide clinical data regarding physiological adaptations of athlete's heart. Echocardiographic characteristics may be helpful for the clinicians to identify structural cardiac disease, responsible of sudden death during sport activities. The application of echocardiography in preparticipation screening might be essential: it shows high sensitivity and specificity for identification of structural cardiac disease and it is the first-line imagining technique for primary prevention of SCD in athletes. Moreover, new echocardiographic techniques distinguish extreme sport cardiac remodeling from beginning state of cardiomyopathy, as hypertrophic or dilated cardiomyopathy and arrhythmogenic right ventricle dysplasia. The aim of this paper is to review the scientific literature and the clinical knowledge about athlete's heart and main structural heart disease and to describe the rule of echocardiography in primary prevention of SCD in athletes.

Aims  To obtain the normal range for 2D echocardiographic (2DE) measurements of left ventricular (LV) layer-specific strain from a large group of healthy volunteers of both genders over a wide range of ages. Methods and results  A total of 287 (109 men, mean age: 46 ± 14 years) healthy subjects were enrolled at 22 collaborating institutions of the EACVI Normal Reference Ranges for Echocardiography (NORRE) study. Layer-specific strain was analysed from the apical two-, three-, and four-chamber views using 2DE software. The lowest values of layer-specific strain calculated as ±1.96 standard deviations from the mean were −15.0% in men and −15.6% in women for epicardial strain, −16.8% and −17.7% for mid-myocardial strain, and −18.7% and −19.9% for endocardial strain, respectively. Basal-epicardial and mid-myocardial strain decreased with age in women (epicardial; P = 0.008, mid-myocardial; P = 0.003) and correlated with age (epicardial; r = −0.20, P = 0.007, mid-myocardial; r = −0.21, P = 0.006, endocardial; r = −0.23, P = 0.002), whereas apical-epicardial, mid-myocardial strain increased with the age in women (epicardial; P = 0.006, mid-myocardial; P = 0.03) and correlated with age (epicardial; r = 0.16, P = 0.04). End/Epi ratio at the apex was higher than at the middle and basal levels of LV in men (apex; 1.6 ± 0.2, middle; 1.2 ± 0.1, base 1.1 ± 0.1) and women (apex; 1.6 ± 0.1, middle; 1.1 ± 0.1, base 1.2 ± 0.1). Conclusion  The NORRE study provides useful 2DE reference ranges for novel indices of layer-specific strain.

Anabolic-androgenic steroids (AAS) are used by power athletes to improve performance. However, the real effects of the chronic consumption of AAS on cardiovascular structures are subjects of intense debate. To detect by speckle tracking echocardiography (STE) underlying left atrial (LA) dysfunction in athletes abusing AAS and assess possible correlation between LA myocardial function and exercise capacity during cardiopulmonary stress test. 65 top-level competitive bodybuilders were selected (45 males), including 35 athletes misusing AAS for at least 5 years (users), 30 anabolic-free bodybuilders (non-users), compared to 40 age- and sex-matched healthy sedentary controls. Standard Doppler echocardiography, STE analysis and bicycle ergometric test were performed to assess LA myocardial function and exercise capacity. Athletes showed increased left ventricular (LV) mass index, wall thickness and stroke volume compared with controls, whereas LV ejection fraction, LV end-diastolic diameter and transmitral Doppler indexes were comparable between the three groups. Conversely, LA volume index, LV and LA strain and LV E/Em were significantly increased in AAS users. By multivariate analyses, LV E/Em (beta = - 0.30, p < 0.01), LA volume index (- 0.42, p < 0.001) and number of weeks of AAS use per year (- 0.54, p < 0.001) emerged as the only independent determinants of LA lateral wall peak STE. In addition, a close association between LA myocardial function and VO peak during cardiopulmonary exercise testing was evidenced (p < 0.001), showing a powerful incremental value with respect to clinical and standard echocardiographic data. STE represents a promising technique to assess LA myocardial function in athletes abusing steroids. AAS users showed a more impaired LA deformation, associated with reduced functional capacity during physical effort.

Objectives To analyze left ventricular (LV) myocardial deformation and contractile reserve (CR) in asymptomatic patients with severe aortic regurgitation (AR) at rest and during exercise, and their correlation with functional capacity. Background The natural history of chronic AR is characterized by a prolonged silent phase before onset of symptoms and overt LV dysfunction. Assessment of LV systolic function and contractile reserve has an important role in the decision‐making of AR asymptomatic patients. Methods Standard echo, lung ultrasound, and LV 2D speckle tracking strain were performed at rest and during exercise in asymptomatic patients with severe AR and in age‐ and sex‐comparable healthy controls. Results 115 AR patients (male sex 58.2%; 52.3 ± 18.3 years) and 55 controls were enrolled. Baseline LV ejection fraction was comparable between the groups. Resting LV global longitudinal strain (GLS) and myocardial work efficiency (MWE) were significantly reduced in AR (GLS‐15.8 ± 2.8 vs −21.4 ± 4.4; P < .001). Patients with AR and CR− showed reduced resting LV GLS and MWE and increased B‐lines. MWE was closely related to peak effort watts, VO2, LV E/e′, and B‐lines, at a multivariable analysis. Both GLS and MWE were strong independent predictors of CR. A resting LV GLS cutoff of −12% differentiated CR+ and CR− (78% sensitivity and 84% specificity). Conclusions The lower resting values of LV GLS and MWE in severe AR asymptomatic patients suggest an early subclinical myocardial damage that seems to be closely associated with lower exercise capacity, greater pulmonary congestion, and blunted LV contractile reserve during stress.

Owing to its ease of application, noninvasive nature, and safety, echocardiography is an essential imaging modality to assess cardiac function in patients affected by ischemic heart disease (IHD). Over the past few decades, we have witnessed a continuous series of evolutions in the ultrasound field that have led to the introduction of innovative echocardiographic modalities which allowed to better understand the morphofunctional abnormalities occurring in cardiovascular diseases. This article offers an overview of some of the newest echocardiographic modalities and their promising application in IHD diagnosis, risk stratification, management, and monitoring after cardiac rehabilitation.

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