De-escalation of antithrombotic treatment after acute coronary syndrome, a new paradigm.

After an acute coronary syndrome (ACS) it is imperative to balance the bleeding vs. the ischemic risk given the similar prognostic impact of the two events. Since the post-discharge bleeding risk is substantially stable over time whereas the ischemic risk accumulates in the first weeks to months, a strategy of de-escalation of antithrombotic treatment, consisting in the reduction of either the duration (i.e., early interruption of one antiplatelet agent) or the intensity (i.e., switching from the more potent P2Y12-inhibitors prasugrel or ticagrelor to clopidogrel) of dual antiplatelet therapy (DAPT), has been proposed. Reducing the intensity of DAPT can be carried out as a default strategy (unguided approach) or based on the results of either platelet function tests or genetic tests (guided approach). Overall, all de-escalation strategies have shown to consistently decrease bleeding events with no apparent increase in ischemic events as compared to 12-month standard-of-care DAPT. Owing however to several limitations and weaknesses of the available evidence, de-escalation strategies are currently not recommended as a routine, but should rather be considered for selected ACS patients, such as those at increased risk of bleeding.

A COVID-19 specific multiparametric and ECG-based score for the prediction of in-hospital mortality: ELCOVID score.

We aimed to develop and validate a COVID-19 specific scoring system, also including some ECG features, to predict all-cause in-hospital mortality at admission. Patients were retrieved from the ELCOVID study (ClinicalTrials.gov identifier: NCT04367129), a prospective, multicenter Italian study enrolling COVID-19 patients between May to September 2020. For the model validation, we randomly selected two-thirds of participants to create a derivation dataset and we used the remaining one-third of participants as the validation set. Over the study period, 1014 hospitalized COVID-19 patients (mean age 74 years, 61% males) met the inclusion criteria and were included in this analysis. During a median follow-up of 12 (IQR 7-22) days, 359 (35%) patients died. Age (HR 2.25 [95%CI 1.72-2.94], p < 0.001), delirium (HR 2.03 [2.14-3.61], p = 0.012), platelets (HR 0.91 [0.83-0.98], p = 0.018), D-dimer level (HR 1.18 [1.01-1.31], p = 0.002), signs of right ventricular strain (RVS) (HR 1.47 [1.02-2.13], p = 0.039) and ECG signs of previous myocardial necrosis (HR 2.28 [1.23-4.21], p = 0.009) were independently associated to in-hospital all-cause mortality. The derived risk-scoring system, namely EL COVID score, showed a moderate discriminatory capacity and good calibration. A cut-off score of ≥ 4 had a sensitivity of 78.4% and 65.2% specificity in predicting all-cause in-hospital mortality. ELCOVID score represents a valid, reliable, sensitive, and inexpensive scoring system that can be used for the prognostication of COVID-19 patients at admission and may allow the earlier identification of patients having a higher mortality risk who may be benefit from more aggressive treatments and closer monitoring.

[Antithrombotic therapy after surgical mitral valve repair: review of the evidence and updated proposals]. / La terapia antitrombotica dopo chirurgia riparativa della valvola mitrale: revisione delle evidenze e suggerimenti aggiornati.

Surgical mitral valve repair (SMVR) is performed with various techniques that involve the implantation of non-biological material, such as the prolene of the suture threads, the polytetrafluoroethylene of the neo-chordae or the prosthetic ring for the remodeling of the valve annulus, whose exposure to the bloodstream is capable of triggering the blood coagulation cascade and consequently the development of thrombotic/thromboembolic events. The indications of the literature on the use of antithrombotic drugs after SMVR are weak and not univocal given the absence of randomized data and the availability of only small observational case series, which are generally contaminated by the lack of homogeneity of the populations examined. Indeed in these studies, patients not only undergoing SMVR, but also transcatheter repair of the mitral valve or surgical implantation of a biological valve prosthesis (not only in the mitral position) are included. In addition, the indication for antithrombotic therapy, and in particular anticoagulation, is often conditioned by the concomitant presence of atrial fibrillation that either preexists or develops postoperatively. In this review, the current evidence regarding antithrombotic therapy in patients undergoing SMVR, both in the presence or absence of atrial fibrillation, is summarized and updated treatment algorithms are proposed.

De-escalation or abbreviation of dual antiplatelet therapy in acute coronary syndromes and percutaneous coronary intervention: a Consensus Statement from an international expert panel on coronary thrombosis.

Conventional dual antiplatelet therapy (DAPT) for patients with acute coronary syndromes undergoing percutaneous coronary intervention comprises aspirin with a potent P2Y purinoceptor 12 (P2Y12) inhibitor (prasugrel or ticagrelor) for 12 months. Although this approach reduces ischaemic risk, patients are exposed to a substantial risk of bleeding. Strategies to reduce bleeding include de-escalation of DAPT intensity (downgrading from potent P2Y12 inhibitor at conventional doses to either clopidogrel or reduced-dose prasugrel) or abbreviation of DAPT duration. Either strategy requires assessment of the ischaemic and bleeding risks of each individual. De-escalation of DAPT intensity can reduce bleeding without increasing ischaemic events and can be guided by platelet function testing or genotyping. Abbreviation of DAPT duration after 1-6 months, followed by monotherapy with aspirin or a P2Y12 inhibitor, reduces bleeding without an increase in ischaemic events in patients at high bleeding risk, particularly those without high ischaemic risk. However, these two strategies have not yet been compared in a head-to-head clinical trial. In this Consensus Statement, we summarize the evidence base for these treatment approaches, provide guidance on the assessment of ischaemic and bleeding risks, and provide consensus statements from an international panel of experts to help clinicians to optimize these DAPT approaches for individual patients to improve outcomes.

Incidence and mortality of infective endocarditis in the last decade: a single center study.

BACKGROUND: Infective endocarditis (IE) is a significant disease characterized by high mortality and complications. The aim of this study was to evaluate the incidence/100 000 inhabitants and the in-hospital mortality/100 000 inhabitants of IE during the last 10 years in the province of Ravenna. METHODS AND RESULTS: We reviewed the public hospitals discharge database from January 2010 to December 2020 using the international classification of disease codification (ICD-9) for IE. We used the Italian national statistical institute (ISTAT) archive to estimate the number of Ravenna inhabitants/year. In 10 years, we identified a total of 407 patients with diagnosis of IE.The incidence of IE increased significantly from 6.29 cases/100 000 inhabitants in 2010 to 19.58 cases/100 000 inhabitants in 2020 ( P  < 0.001). Also, the in-hospital mortality from IE increased over the same number of years, from 1.8 deaths/100 000 inhabitants in 2010 to 4.4 deaths/100 000 inhabitants in 2020 ( P  < 0.001). The mortality rate (%) of IE over the years did not increase ( P = 0.565). Also, over the years there was no difference in the site of infection ( P  = 0.372), irrespective of the valve localization or type, native valve ( P  = 0.347) or prosthetic valve ( P  = 0.145). On logistic regression analysis, age was the only predictor of in-hospital mortality (odds ratio 1.045, 95% confidence interval: 1.015; 1.075, P  = 0.003). CONCLUSIONS: Ravenna-based data on IE showed increased disease incidence but unchanged mortality rate over 10 years of follow-up. Age remains the sole predictor of population-based mortality, irrespective of the nature of the valve, native or substitute, and the organism detected on microbiology.

Use of bempedoic acid for LDL cholesterol lowering and cardiovascular risk reduction: a consensus document from the Italian study group on atherosclerosis, thrombosis and vascular biology.

The clinical benefit of LDL cholesterol (LDL-C) lowering for cardiovascular disease prevention is well documented. This paper from the Italian Study Group on Atherosclerosis, Thrombosis and Vascular Biology summarizes current recommendations for treatment of hypercholesterolemia, barriers to lipid-lowering therapy implementation and tips to overcome them, as well as available evidence on the efficacy and safety of bempedoic acid. We also report an updated therapeutic algorithm for pharmacological LDL-C lowering in view of the introduction of bempedoic acid in clinical practice.

Acute, periprocedural and longterm antithrombotic therapy in older adults: 2022 Update by the ESC Working Group on Thrombosis

The first international guidance on antithrombotic therapy in the elderly came from the European Society of Cardiology Working Group on Thrombosis in 2015. This same group has updated its previous report on antiplatelet and anticoagulant drugs for older patients with acute or chronic coronary syndromes, atrial fibrillation, or undergoing surgery or procedures typical of the elderly (transcatheter aortic valve implantation and left atrial appendage closure). The aim is to provide a succinct but comprehensive tool for readers to understand the bases of antithrombotic therapy in older patients, despite the complexities of comorbidities, comedications and uncertain ischaemic- vs. bleeding-risk balance. Fourteen updated consensus statements integrate recent trial data and other evidence, with a focus on high bleeding risk. Guideline recommendations, when present, are highlighted, as well as gaps in evidence. Key consensus points include efforts to improve medical adherence through deprescribing and polypill use; adoption of universal risk definitions for bleeding, myocardial infarction, stroke and cause-specific death; multiple bleeding-avoidance strategies, ranging from gastroprotection with aspirin use to selection of antithrombotic-drug composition, dosing and duration tailored to multiple variables (setting, history, overall risk, age, weight, renal function, comedications, procedures) that need special consideration when managing older adults.

Left Atrial Remodeling in Response to Aortic Valve Replacement: Pathophysiology and Myocardial Strain Analysis.

Severe aortic stenosis (AS) is the most common valve disease in the elderly and is associated with poor prognosis if treated only medically. AS causes chronic pressure overload, concentric left ventricular (LV) hypertrophy, myocardial stiffness, and diastolic dysfunction. This adverse remodeling also affects the left atrium (LA), which dilates and develops myocardial fibrosis, with a reduction in intrinsic function and a consequent high risk of the development of atrial fibrillation. Speckle-tracking echocardiography is able to detect myocardial dysfunction before other conventional parameters, such as LV ejection fraction, and also predict clinical outcomes. This review aims at describing LV and LA remodeling in AS and before and after aortic valve replacement and the usefulness of myocardial strain analysis in this clinical setting.

Left atrial myocardial intrinsic function remodeling response to repair of primary mitral regurgitation.

Severe mitral regurgitation (MR) is a common valve disease which is associated with high mortality, if only managed medically. MR produces chronic and progressive volume overload with left atrial (LA) and left ventricular (LV) dilatation and dysfunction, atrial fibrillation (AF) and eventually myocardial fibrosis, irrespective of ejection fraction (EF). Surgical correction (mitral valve repair) of MR removes the volume overload, hence unmasks pre-operative LV structure and function disturbances, including reduced EF and global longitudinal and circumferential strain, as well as LA volume and strain. This review aims at describing LA remodeling before and after surgical repair.

Design of the PERSEO Registry on the management of patients treated with oral anticoagulants and coronary stent.

AIM: Percutaneous coronary intervention with stent implantation (PCI-S) in patients requiring chronic oral anticoagulant therapy (OAC) is associated with an increased risk of bleeding and ischemic complications. Different randomized studies showed a significant advantage of a double antithrombotic therapy and superiority of direct oral anticoagulant (DOAC) compared with warfarin, but real-world data are limited. Aim is to evaluate the antithrombotic management and clinical outcome of patients with an indication for OAC who undergo PCI-S in a 'real-world' setting. METHODS: The multicentre prospective observational PERSEO (PERcutaneouS coronary intErventions in patients treated with Oral anticoagulant therapy) Registry (ClinicalTrials.gov Identifier: NCT03392948) has been designed to enrol patients requiring OAC treated by PCI-S in 25 Italian centres. A target of at least 1080 patients will be followed for 1 year and data on thromboembolic and bleeding events and changes in antithrombotic therapy will be registered. The primary end point is a combined measure of efficacy and safety outcome (NACE), including major bleeding events and major adverse cardiac and cerebral events at 1-year follow-up in patients treated with DOAC (and dual or triple antiplatelet therapy) compared with the corresponding strategies with vitamin K antagonists. A secondary prespecified analysis has been defined to evaluate NACE in dual versus triple antithrombotic therapy after hospital discharge at 1-year follow-up. CONCLUSION: The PERSEO Registry will investigate in a 'real world' setting the safety and efficacy of DOAC versus warfarin and dual versus triple antithrombotic therapy in patients with indication for oral anticoagulant therapy who undergo PCI-S.

[Screening for atrial fibrillation in the general population: experience from a cardiovascular risk campaign in the Emilia-Romagna Region]. / Screening della fibrillazione atriale nella popolazione generale: esperienza della campagna educazionale sul rischio cardiovascolare della Regione Emilia-Romagna.

BACKGROUND: Atrial fibrillation (AF) is a major cause of cerebral ischemia, and its early detection may impact on health. Both invasive and non-invasive devices can be used for the diagnosis of AF. The aim of our study was to estimate the prevalence of AF using a single-lead ECG device (MyDiagnostickTM) on an adult, asymptomatic population during a screening campaign. METHODS: A total of 2547 subjects underwent AF screening. RESULTS: The device detected an arrhythmia in 42 subjects (1.65%), and AF was confirmed on 12-lead ECG in 14 (0.55%) of them. The prevalence of confirmed AF increased in subjects over 65 years of age (1.21%) or with a CHA2DS2-VASc score ≥2 in males or ≥3 in females (1.33%). Furthermore, heart failure (odds ratio [OR] 8.62, 95% confidence interval [CI] 1.87-39.6, p=0.006) and diabetes (OR 4.55, 95% CI 1.25-16.5, p=0.021) significantly increased the risk of AF. CONCLUSIONS: During a screening campaign, the diagnosis of AF increases when subjects with a high thromboembolic risk are selected.

Assessment and Mitigation of Bleeding Risk in Atrial Fibrillation and Venous Thromboembolism: Executive Summary of a European and Asia-Pacific Expert Consensus Paper.

While there is a clear clinical benefit of oral anticoagulation in patients with atrial fibrillation (AF) and venous thromboembolism (VTE) in reducing the risks of thromboembolism, major bleeding events (especially intracranial bleeds) may still occur and be devastating. The decision for initiating and continuing anticoagulation is often based on a careful assessment of both thromboembolism and bleeding risk. The more common and validated bleeding risk factors have been used to formulate bleeding risk stratification scores, but thromboembolism and bleeding risk factors often overlap. Also, many factors that increase bleeding risk are transient and modifiable, such as variable international normalized ratio values, surgical procedures, vascular procedures, or drug-drug and food-drug interactions. Bleeding risk is also not a static "one-off" assessment based on baseline factors but is dynamic, being influenced by aging, incident comorbidities, and drug therapies. In this executive summary of a European and Asia-Pacific Expert Consensus Paper, we comprehensively review the published evidence and propose a consensus on bleeding risk assessments in patients with AF and VTE, with a view to summarizing "best practice" when approaching antithrombotic therapy in these patients. We address the epidemiology and size of the problem of bleeding risk in AF and VTE, and review established bleeding risk factors and summarize definitions of bleeding. Patient values and preferences, balancing the risk of bleeding against thromboembolism, are reviewed, and the prognostic implications of bleeding are discussed. We propose consensus statements that may help to define evidence gaps and assist in everyday clinical practice.

ANMCO position paper on antithrombotic treatment of patients with atrial fibrillation undergoing intracoronary stenting and/or acute coronary syndromes.

Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) with or without acute coronary syndromes (ACS) represent a subgroup with a challenging pharmacological management. Indeed, if on the one hand, antithrombotic therapy should reduce the risk related to recurrent ischaemic events and/or stent thrombosis; on the other hand, care must be taken to avoid major bleeding events. In recent years, several trials, which overall included more than 12 000 patients, have been conducted demonstrating the safety of different therapeutic combinations of oral antiplatelet and anticoagulant agents. In the present ANMCO position paper, we propose a decision-making algorithm on antithrombotic strategies based on scientific evidence and expert consensus to be adopted in the periprocedural phase, at the time of hospital discharge, and in the long-term follow-up of patients with AF undergoing PCI with/without ACS.

In-hospital antithrombotic therapy and outcomes of elderly patients on warfarin undergoing percutaneous coronary intervention: Insights from the WAR-STENT registry.

In the patients on warfarin undergoing percutaneous coronary intervention included in the prospective, multicentre, observational WAR-STENT registry, age ≥75 years was associated with a significant increase in in-hospital major bleeding, length of hospitalization, and use of bare-metal stents, with no differences in the peri-procedural management and antithrombotic therapy.

[ANMCO Position paper: Antithrombotic treatment of patients with atrial fibrillation undergoing intracoronary stenting and/or acute coronary syndromes]. / Position paper ANMCO: Trattamento antitrombotico nei pazienti con fibrillazione atriale e sindromi coronariche acute o croniche sottoposti ad angioplastica coronarica con impianto di stent.

Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) with or without acute coronary syndromes (ACS) represent a subgroup with a challenging pharmacological management. Indeed, if on the one hand antithrombotic therapy should reduce the risk related to recurrent ischemic events and/or stent thrombosis, on the other hand care should be taken to avoid major bleeding events. In recent years, several trials, which overall included more than 12 000 patients, have been conducted demonstrating the safety of different therapeutic combinations of oral antiplatelet and anticoagulant agents. In the present ANMCO position paper we propose a decision-making algorithm on antithrombotic strategies based on scientific evidence and expert consensus to be adopted in the periprocedural phase, at the time of hospital discharge and in the long-term follow-up of patients with AF undergoing PCI with/without ACS.

Assessment and mitigation of bleeding risk in atrial fibrillation and venous thromboembolism: A Position Paper from the ESC Working Group on Thrombosis, in collaboration with the European Heart Rhythm Association, the Association for Acute CardioVascular Care and the Asia-Pacific Heart Rhythm Society.

Whilst there is a clear clinical benefit of oral anticoagulation (OAC) in patients with atrial fibrillation (AF) and venous thromboembolism (VTE) in reducing the risks of thromboembolism, major bleeding events (especially intracranial bleeds) may still occur and be devastating. The decision to initiate and continue anticoagulation is often based on a careful assessment of both the thromboembolism and bleeding risk. The more common and validated bleeding risk factors have been used to formulate bleeding risk stratification scores, but thromboembolism and bleeding risk factors often overlap. Also, many factors that increase bleeding risk are transient and modifiable, such as variable international normalized ratio values, surgical procedures, vascular procedures, or drug-drug and food-drug interactions. Bleeding risk is also not a static 'one off' assessment based on baseline factors but is dynamic, being influenced by ageing, incident comorbidities, and drug therapies. In this Consensus Document, we comprehensively review the published evidence and propose a consensus on bleeding risk assessments in patients with AF and VTE, with the view to summarizing 'best practice' when approaching antithrombotic therapy in these patients. We address the epidemiology and size of the problem of bleeding risk in AF and VTE, review established bleeding risk factors, and summarize definitions of bleeding. Patient values and preferences, balancing the risk of bleeding against thromboembolism are reviewed, and the prognostic implications of bleeding are discussed. We propose consensus statements that may help to define evidence gaps and assist in everyday clinical practice.

Appropriate dosing of the individual direct oral anticoagulants in atrial fibrillation: Differences in the questions to be answered.

Direct oral anticoagulants; Apixaban; Dabigatran; Edoxaban; Rivaroxaban.