Felice Gragnano

The Role of von Willebrand Factor in Vascular Inflammation: From Pathogenesis to Targeted Therapy

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.

von Willebrand Factor and Venous Thromboembolism: Pathogenic Link and Therapeutic Implications

&NA; Venous thromboembolism (VTE) is a frequent cause of disability and mortality worldwide. Von Willebrand factor (VWF) is a major determinant of hemostasis and clot formation, in both arteries and veins. Although VWF is mainly known for its role in arterial thrombosis, several studies suggest a pathogenic role for VWF and its regulator ADAMTS‐13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) in venous thrombosis. Nongenetic and genetic factors, including gene mutations and polymorphisms, aging, hormone status, ABO blood groups, and systemic inflammation, have been involved in the modulation of both VTE predisposition and plasma levels of VWF. In several clinical settings, including inflammatory disease and cancer, VWF and ADAMTS‐13 are currently investigated as possible determinants of vein thrombosis. These data indicate VWF as a potential therapeutic target in the management of VTE. Several studies report unselective antagonism of VWF for drugs used in daily clinical practice, including heparin and statins. Selective inhibition of VWF pathway has recently been tested in animal models of arterial and venous thrombosis as a novel therapeutic strategy to prevent platelet aggregation and thrombosis, promote vein lumen recanalization, and improve vein valve competency with excellent safety profile. In this review, we summarize the role of VWF in VTE, focusing on clinical and potential therapeutic implications.

Letter by Calabrò and Gragnano Regarding Article, “Dual Antiplatelet Therapy Continuation Beyond 1 Year After Drug-Eluting Stents: A Meta-Analysis of Randomized Trials”

We have read with great interest the recent publication by Ferrante et al1 regarding dual antiplatelet therapy (DAPT) continuation beyond 1 year after drug-eluting stents implantation. The authors reported that (1) extended DAPT was associated with a reduction in the risk of myocardial infarction and an increase in the risk of major bleeding; (2) DAPT prolongation had no substantial effect on mortality, stent thrombosis, and stroke; (3) there is an unmet need in patients treated with drug-eluting stents to identify who may benefit most from prolonging DAPT beyond 1 year. This article adds relevant data on this controversial issue, underlying the absence of standardized approach defining optimal DAPT duration in clinical practice. International guidelines2 recommend DAPT (with low-dose aspirin …

Role of dual lipid-lowering therapy in coronary atherosclerosis regression: Evidence from recent studies

Despite recent therapeutic advances, there is an unmet need in cardiovascular disease prevention. Clinical trials and meta-analyses have established that LDL-C lowering, particularly by statin therapy, reduces the progression of coronary atherosclerosis and the risk of coronary events. Insufficient LDL-C reduction and high residual risk in a significant proportion of statin-treated patients signify that additional therapies are required to deliver more effective coronary care. Pharmacological inhibition of cholesterol absorption (with ezetimibe) and PCSK9 activity (with evolocumab or alirocumab) provides potentially useful approaches for the therapeutic modulation of LDL-C metabolism in statin-treated patients. In recent trials, combination strategies involving a statin and non-statin agent (ezetimibe or evolocumab) have been shown to promote coronary atherosclerosis regression and improve cardiovascular outcomes in patients with moderate-to-high cardiovascular risk. This review summarizes recent evidence on the effects of dual lipid-lowering therapy on coronary atherosclerosis.

Von Willebrand Factor as a Novel Player in Valvular Heart Disease: From Bench to Valve Replacement

von Willebrand Factor (vWF) is a well-known mediator of hemostasis and vascular inflammation. Its dynamic modulation in the bloodstream, according to hemodynamic conditions, makes it an appealing biomarker in patients with valvular heart disease (VHD). Recent studies highlight the close connection between vWF and VHD, with possible implications in the pathogenesis of VHD, promoting valve aging and calcification or favoring the development of infective endocarditis. Moreover, vWF has been recently proposed as a new diagnostic and prognostic tool in patients with valve stenosis or regurgitation, showing a strict correlation with severity of valve disease, outcome, and bleeding (Heyde syndrome). A novel role for vWF is also emerging in patients undergoing percutaneous or surgical valve repair/replacement to select and stratify patients, evaluate periprocedural bleeding risk, and detect procedural complications. We also report our single-center experience, suggesting, for the first time, possible clinical implications for vWF in percutaneous mitral valve repair (MitraClip). This review summarizes recent advances in the role of vWF in VHD with an updated overview going from bench to operating room.

Epidemiology and Management of Patients With Acute Coronary Syndromes in Contemporary Real-World Practice: Evolving Trends From the EYESHOT Study to the START-ANTIPLATELET Registry

The epidemiology and management of patients with acute coronary syndromes (ACSs) have evolved. We aimed to describe recent demographics and therapeutic changes in the Italian ACS population. We analyzed data from 2 multicenter consecutive Italian registries (the EYESHOT [EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalised in iTalian cardiac care units] and START-ANTIPLATELET registries) enrolling patients with ACS between December 2013 and June 2016. An overall population of 3756 patients with ACS was enrolled: 2585 in the EYESHOT and 1171 in the START-ANTIPLATELET. Compared with the EYESHOT, patients in the START-ANTIPLATELET registry presented more frequently with ST-segment elevation myocardial infarction and were more often smokers and dyslipidemic (all P < .001) and had atrial fibrillation (P = .018) but were less frequently aged ≥75 years and with a history of major bleeding (all P < .001). Analysis of treatment strategy showed a significant increase in the use of percutaneous coronary intervention, drug-eluting stents, dual antiplatelet therapy, and ticagrelor in the START-ANTIPLATELET (all P < .001), with a substantial decline in the proportion of patients conservatively managed and on clopidogrel at discharge (P < .001). A lower rate of in-hospital events was recorded in the START-ANTIPLATELET compared with the EYESHOT. The START-ANTIPLATELET and EYESHOT registries provide consecutive snapshots in the contemporary management of patients with ACS in Italy, showing important changes in both demographic characteristics and treatment strategies.

Perioperative care of cardiac patient’s candidate for non-cardiac surgery: a critical appraisal of emergent evidence and international guidelines

The perioperative management of a cardiac-patient candidate to non-cardiac surgery (NCS) remains a topic of considerable debate. In recent years, the overall tendency from professional societies has been to delineate how to identify and manage high-risk patients following the best evidence. However, significant concerns persist, especially in the care of intermediate-risk patients (also labeled at “acceptable” risk), who may not fit into the categories of “completely healthy” or “critically ill”, but that might still encounter dramatic (and unexpected) perioperative events. The specific interest and main goal of this expert viewpoint pertains to the care of cardiac patients scheduled for NCS, addressing central questions of real-life clinical care that practicing anesthesiologists and cardiologists face daily, discussing recent American College of Cardiology/American Heart Association (ACC/AHA), European Society of Cardiology/European Society of Anaesthesiology (ESC/ESA), and Canadian Cardiovascular Society (CCS) guidelines. The viewpoint aims to discuss few of the important topics pertaining perioperative assessment and management: type of NCS and perioperative cardiac events, risk prediction including testing, and perioperative management of cardiac therapy. The fact that cardiac adverse events have reduced in number mostly due to better preoperative management and prevention should not prompt a reduction in clinical evaluations. While debate remains pertaining the most appropriate way to evaluate patients for NCS within international societies, a comprehensive approach-evaluation best recognized to assess functional and heart status, should be maintained, keeping into consideration the surgical procedure and global health management.

Letter by Calabrò et al Regarding Article, “Low-Density Lipoprotein Cholesterol Lowering With Evolocumab and Outcomes in Patients With Peripheral Artery Disease: Insights From the FOURIER Trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk)”

We have read with great interest the results recently published by Bonaca et al1 regarding the effectiveness of evolocumab in patients with peripheral artery disease (PAD) from the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). In their analysis, Bonaca et al1 report that evolocumab reduces the risk of major adverse cardiovascular events and major adverse limb events in patients with PAD, suggesting larger absolute risk reductions relative to those without. Moreover, in line with previous data reported in the literature,2, …

Radial vs femoral access for the prevention of acute kidney injury (AKI) after coronary angiography or intervention: A systematic review and meta-analysis

We sought to investigate the impact of radial vs femoral access on the incidence of acute kidney injury (AKI) after coronary angiography or intervention.