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.

Management of acute coronary syndromes in older adults.

Older patients are underrepresented in prospective studies and randomized clinical trials of acute coronary syndromes (ACS). Over the last decade, a few specific trials have been conducted in this population, allowing more evidence-based management. Older adults are a heterogeneous, complex, and high-risk group whose management requires a multidimensional clinical approach beyond coronary anatomic variables. This review focuses on available data informing evidence-based interventional and pharmacological approaches for older adults with ACS, including guideline-directed management. Overall, an invasive approach appears to demonstrate a better benefit-risk ratio compared to a conservative one across the ACS spectrum, even considering patients' clinical complexity and multiple comorbidities. Conversely, more powerful strategies of antithrombotic therapy for secondary prevention have been associated with increased bleeding events and no benefit in terms of mortality reduction. An interdisciplinary evaluation with geriatric assessment should always be considered to achieve a holistic approach and optimize any treatment on the basis of the underlying biological vulnerability.

Detection of myocardial fibrosis by speckle-tracking echocardiography: from prediction to clinical applications.

Myocardial fibrosis (MF) represents the underlying pathologic condition of many cardiac disease, leading to cardiac dysfunction and heart failure (HF). Biopsy studies have shown the presence of MF in patients with decompensating HF despite apparently normal cardiac function. In fact, basic indices of left ventricular (LV) function, such as LV ejection fraction (EF), fail to recognize subtle LV dysfunction caused by MF. Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) is currently recognized as the gold standard imaging investigation for the detection of focal and diffuse cardiac chambers MF; however, its use is limited by its availability and the use of contrast agents, while echocardiography remains the first level cardiac imaging technique due to its low cost, portability and high accessibility. Advanced echocardiographic techniques, above all speckle-tracking echocardiography (STE), have demonstrated reliability for early detection of structural myocardial abnormalities and for the prediction of prognosis in acute and chronic HF. Myocardial strain of both ventricles and also left atrium has been shown to correlate with the degree of MF, providing useful prognostic information in several diseases, such as HF, cardiomyopathies and valvular heart disease. This paper aims to provide an overview of the pathophysiology of MF and the clinical application of STE for the prediction of left and right heart chambers MF in HF patients.

Percutaneous artErial closure devices and ultrasound-guided Trans-femoRal puncture ObservatioNal InvestigatiOn: Insights from the PETRONIO registry.

OBJECTIVE: To evaluate the safety of a single and combined use of ultrasound-guided femoral puncture (U) and percutaneous arterial closure devices (P) in femoral artery procedures (FAP) compared to fluoroscopic guidance (F) and manual compression (M) in a large radial-focused interventional centre. BACKGROUND: U and P, taken individually, have improved safety in femoral arterial access procedures compared to traditional techniques. METHODS: All FAP performed between July 2017 and December 2018 in our centre were divided into three phases: (a) control period with F and M mainly performed; (b) phase out period where U and P were introduced; (c) intervention period where a 6-month expertise on the novel techniques was acquired. The overall population was further stratified into subgroups: F/M, U/M, F/P, U/P. The primary study endpoint was in-hospital access site bleeding events (BE) according to the BARC criteria. The secondary endpoint was vascular site complications (VASC). RESULTS: Four hundred eighteen procedures (14%) out of 3025 were performed via FA access during the study period. The overall access-site in-hospital BE were 97 (23%). Decreasing rates of BE (phase 1: n = 46, 29%; phase 2: n = 38, 22% e phase 3: n = 13, 15%; p = 0.027) and VASC were observed during the three periods. BE occurred significantly more often in F/M group (F/M: n = 48; 32%; U/M: n = 12, 16%; F/P: n = 18, 21%; U/P: n = 19, 17%; p = 0.008). F/M subgroup was an independent predictor of BE both in multivariable analysis and propensity score matching analysis. CONCLUSIONS: The introduction of ultrasound-guided femoral puncture and percutaneous arterial closure devices has reduced access site bleedings with a progressive improvement after the first 6 months learning period.

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.

Could the PARIS Risk Scores Be Useful for the Choice of Triple versus Dual Antithrombotic Therapy in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention?

INTRODUCTION: Current guidelines recommend dual antithrombotic therapy (DAT) for the majority of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) and suggest a short course of triple antithrombotic therapy (TAT) for those at very high thrombotic risk (TR) but low bleeding risk (BR). METHODS: We analyze if the PARIS ischemic-hemorrhagic scale could be useful for the choice of antithrombotic strategy in patients with acute coronary syndromes and AF treated with coronary stenting enrolled in the prospective, observational, nationwide MATADOR-PCI study. RESULTS: Among the 588 patients discharged alive, a TAT was prescribed in 381 (64.8%) and DAT in 52 (8.8%) patients. According to the PARIS scoring system, 142 (24.2%) were classified as low, 244 (41.5%) as intermediate, and 292 (34.3%) as high TR. In parallel, 87 (14.8%) were categorized in the low, 260 (44.2%) in the intermediate, and 241 (41.0%) in the high-risk stratum for major bleedings. Crossing the various strata of the two PARIS risk scores, the largest group of patients consisted of those at high TR and BR (n = 130, 22%), followed by those at intermediate risk according to both scores (n = 122, 21%). At discharge, TAT was mainly used in patients at intermediate to high BR, while DAT in those at intermediate to high TR but low BR, according to the PARIS score. CONCLUSION: Our data suggest that some variables associated with increased TR or BR are poorly considered in the daily practice, while the use of PARIS scales could help in the implementation of guidelines' recommendations.

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.

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.

Management of antithrombotic therapy in patients undergoing transcatheter aortic valve implantation: a consensus document of the ESC Working Group on Thrombosis and the European Association of Percutaneous Cardiovascular Interventions (EAPCI), in collaboration with the ESC Council on Valvular Heart Disease.

Transcatheter aortic valve implantation (TAVI) is effective in older patients with symptomatic severe aortic stenosis, while the indication has recently broadened to younger patients at lower risk. Although thromboembolic and bleeding complications after TAVI have decreased over time, such adverse events are still common. The recommendations of the latest 2017 ESC/EACTS Guidelines for the management of valvular heart disease on antithrombotic therapy in patients undergoing TAVI are mostly based on expert opinion. Based on recent studies and randomized controlled trials, this viewpoint document provides updated therapeutic insights in antithrombotic treatment during and after TAVI.

Electrocardiographic features of 431 consecutive, critically ill COVID-19 patients: an insight into the mechanisms of cardiac involvement.

AIMS: Our aim was to describe the electrocardiographic features of critical COVID-19 patients. METHODS AND RESULTS: We carried out a multicentric, cross-sectional, retrospective analysis of 431 consecutive COVID-19 patients hospitalized between 10 March and 14 April 2020 who died or were treated with invasive mechanical ventilation. This project is registered on ClinicalTrials.gov (identifier: NCT04367129). Standard ECG was recorded at hospital admission. ECG was abnormal in 93% of the patients. Atrial fibrillation/flutter was detected in 22% of the patients. ECG signs suggesting acute right ventricular pressure overload (RVPO) were detected in 30% of the patients. In particular, 43 (10%) patients had the S1Q3T3 pattern, 38 (9%) had incomplete right bundle branch block (RBBB), and 49 (11%) had complete RBBB. ECG signs of acute RVPO were not statistically different between patients with (n = 104) or without (n=327) invasive mechanical ventilation during ECG recording (36% vs. 28%, P = 0.10). Non-specific repolarization abnormalities and low QRS voltage in peripheral leads were present in 176 (41%) and 23 (5%), respectively. In four patients showing ST-segment elevation, acute myocardial infarction was confirmed with coronary angiography. No ST-T abnormalities suggestive of acute myocarditis were detected. In the subgroup of 110 patients where high-sensitivity troponin I was available, ECG features were not statistically different when stratified for above or below the 5 times upper reference limit value. CONCLUSIONS: The ECG is abnormal in almost all critically ill COVID-19 patients and shows a large spectrum of abnormalities, with signs of acute RVPO in 30% of the patients. Rapid and simple identification of these cases with ECG at hospital admission can facilitate classification of the patients and provide pathophysiological insights.

2018 Joint European consensus document on the management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous cardiovascular interventions: a joint consensus document of the European Heart Rhythm Association (EHRA), European Society of Cardiology Working Group on Thrombosis, European Association of Percutaneous Cardiovascular Interventions (EAPCI), and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA).

In 2014, a joint consensus document dealing with the management of antithrombotic therapy in atrial fibrillation (AF) patients presenting with acute coronary syndrome (ACS) and/or undergoing percutaneous coronary or valve interventions was published, which represented an effort of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS). Since publication of this document, additional data from observational cohorts, randomized controlled trials, and percutaneous interventions as well as new guidelines have been published. Moreover, new drugs and devices/interventions are also available, with an increasing evidence base. The approach to managing AF has also evolved towards a more integrated or holistic approach. In recognizing these advances since the last consensus document, EHRA, WG Thrombosis, EAPCI, and ACCA, with additional contributions from HRS, APHRS, Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA), proposed a focused update, to include the new data, with the remit of comprehensively reviewing the available evidence and publishing a focused update consensus document on the management of antithrombotic therapy in AF patients presenting with ACS and/or undergoing percutaneous coronary or valve interventions, and providing up-to-date consensus recommendations for use in clinical practice.

Cardiac arrhythmias in the emergency settings of acute coronary syndrome and revascularization: an European Heart Rhythm Association (EHRA) consensus document, endorsed by the European Association of Percutaneous Cardiovascular Interventions (EAPCI), and European Acute Cardiovascular Care Association (ACCA).

Despite major therapeutic advances over the last decades, complex supraventricular and ventricular arrhythmias (VAs), particularly in the emergency setting or during revascularization for acute myocardial infarction (AMI), remain an important clinical problem. Although the incidence of VAs has declined in the hospital phase of acute coronary syndromes (ACS), mainly due to prompt revascularization and optimal medical therapy, still up to 6% patients with ACS develop ventricular tachycardia and/or ventricular fibrillation within the first hours of ACS symptoms. Despite sustained VAs being perceived predictors of worse in-hospital outcomes, specific associations between the type of VAs, arrhythmia timing, applied treatment strategies and long-term prognosis in AMI are vague. Atrial fibrillation (AF) is the most common supraventricular tachyarrhythmia that may be asymptomatic and/or may be associated with rapid haemodynamic deterioration requiring immediate treatment. It is estimated that over 20% AMI patients may have a history of AF, whereas the new-onset arrhythmia may occur in 5% patients with ST elevation myocardial infarction. Importantly, patients who were treated with primary percutaneous coronary intervention for AMI and developed AF have higher rates of adverse events and mortality compared with subjects free of arrhythmia. The scope of this position document is to cover the clinical implications and pharmacological/non-pharmacological management of arrhythmias in emergency presentations and during revascularization. Current evidence for clinical relevance of specific types of VAs complicating AMI in relation to arrhythmia timing has been discussed.

Bleeding Risk Scores and Scales of Frailty for the Prediction of Haemorrhagic Events in Older Adults with Acute Coronary Syndrome: Insights from the FRASER study.

PURPOSE: Hitherto, no study has yielded important information on whether the scales of frailty may improve the ability to discriminate the risk of haemorrhages in older adults admitted to hospital for acute coronary syndrome (ACS). The aim of this study is to investigate whether frailty scales would predict the 1-year occurrence of haemorrhagic events and if they confer a significant incremental prognostic value over the bleeding risk scores. METHODS: The present study involved 346 ACS patients aged ≥ 70 years enrolled in the FRASER study. Seven different scales of frailty and PARIS, PRECISE-DAPT and BleeMACS bleeding risk scores were available for each patient. The outcomes were the 1-year BARC 3-5 and 2 bleeding events. RESULTS: Adherence to antiplatelet treatment at 1, 6 and 12 months was 98%, 87% and 78%, respectively. At 1-year, 14 (4%) and 30 (9%) patients presented BARC 3-5 and 2 bleedings, respectively. Bleeding risk scores and four scales of frailty (namely Short Physical Performance Battery, Columbia, Edmonton and Clinical Frailty Scale) significantly discriminated the occurrence of BARC 3-5 events. The addition of the scales of frailty to bleeding risk scores did not lead to a significant improvement in the ability to predict BARC 3-5 bleedings. Neither the bleeding risk scores nor the scales of frailty predicted BARC 2 bleedings. CONCLUSIONS: Both the bleeding risk scores and the scales of frailty predicted BARC 3-5 haemorrhages. However, integrating the scales of frailty with the bleeding risk scores did not improve their discriminative ability. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov: NCT02386124.

Time in therapeutic range and major adverse outcomes in atrial fibrillation patients undergoing percutaneous coronary intervention: The Atrial Fibrillation Undergoing Coronary Artery Stenting (AFCAS) registry.

BACKGROUND: Combination of oral anticoagulation (OAC) and antiplatelets is used in atrial fibrillation (AF) patients undergoing percutaneous coronary intervention and stent (PCI-S) procedure but is associated with increased bleeding when triple antithrombotic therapy (TAT) is used. Our aim was to analyze the impact of time in therapeutic range (TTR) on outcomes, in patients prescribed with TAT. METHODS: Ancillary analysis from the AFCAS registry in patients assigned to TAT. TTR was calculated with Rosendaal method. Outcomes were analyzed according to TTR tertiles (T1 [≤56.8%] vs. T2 [56.9-93.8%] vs. T3 [≥93.9%]). Major bleeding was the primary outcome. RESULTS: Of 963 patients enrolled, 470(48.8%) were prescribed with TAT at discharge and qualified for this analysis. Median [IQR] TTR was 80.0% [45.3-100%]. After 359 [341-370] days, major bleeding rates were progressively lower with increasing TTR tertiles (T1 vs. T2 vs. T3: 10.3% vs. 4.7% vs. 2.3%, P=.006). Kaplan-Meier analysis demonstrated a progressively lower risk for major bleeding across tertiles (P=.006). Patients in the highest TTR tertile had a non-significant lower risk for major adverse coronary and cerebrovascular events (MACCE) (log-rank: 4.905, P=.086). Cox regression analysis showed that T2 and T3 were inversely associated with major bleeding (hazard ratio [HR]:0.39, P=.050 and HR: 0.21, P=.005). Continuous TTR was inversely associated with major bleeding (HR: 0.98, P<.001). For MACCE, adjusted Cox analysis found a non-significant lower risk for T3 (HR: 0.64, P=.128). CONCLUSIONS: In AF patients undergoing PCI-S prescribed TAT, good quality anticoagulation control (as reflected by TTR) was closely related to bleeding outcomes during follow-up. Despite some suggestive trends for an inverse relationship between TTR and MACCE, no definitive conclusions can be drawn, and further large studies are needed.

Evaluation of the efficacy and safety of dual antiplatelet therapy with or without warfarin in patients with a clinical indication for DAPT and chronic anticoagulation: A meta-analysis of observational studies.

OBJECTIVE: To compare the efficacy and safety of dual antiplatelet therapy (DAPT) and triple therapy (TT, dual antiplatelet plus warfarin) in patients with myocardial infarction (MI) or PCI with stenting (PCI-S) who also require chronic oral anticoagulation. BACKGROUND: Recommendations for the optimal antiplatelet/anticoagulant treatment regimen for patients undergoing PCI-S or MI who also require oral anticoagulation are largely based on evidence from observational studies and expert opinions. METHODS: A systematic search was performed for studies comparing TT vs. DAPT in patients post PCI-S or MI and requiring chronic anticoagulation. Primary outcome was all-cause mortality. Secondary outcomes were ischemic stroke, major bleeding, MI, and stent thrombosis. Pooled relative risks (RR) were calculated using random effects model. RESULTS: A total of 17 studies were included, with 14,921 patients [TT: 5,819(39%) and DAPT: 9,102(61%)] and a mean follow-up of 1.6 years. The majority of patients required oral anticoagulation for atrial fibrillation. Compared to DAPT, patients treated with TT had no significant difference in all-cause mortality [RR: 0.81, 95% confidence interval (CI): 0.61-1.08, P = 0.15], MI [RR 0.74, 95% CI: 0.51-1.06, P = 0.10], and stent thrombosis [RR 0.67, 95% CI: 0.35-1.30, P = 0.24]. Patients treated with TT had significantly increased risk of major bleeding [RR 1.20, 95% CI: 1.03-1.39, P = 0.02], whereas the risk for ischemic stroke was significantly lower [RR 0.59, 95% CI: 0.38-0.92, P = 0.02]. CONCLUSIONS: All-cause mortality appears similar in patients treated with TT or DAPT although TT was associated with higher rates of major bleeding and a lower risk for ischemic stroke. © 2015 Wiley Periodicals, Inc.

New-generation drug-eluting stents reduce stent thrombosis and myocardial infarction: a propensity-score-adjusted analysis from the multicenter REAL registry (REgistro Regionale AngiopLastiche Dell'Emilia-Romagna).

OBJECTIVES: The aim of this study was to compare long-term clinical outcomes in patients treated with new-generation drug-eluting stent (DES) or early-generation DES in a real-world registry. BACKGROUND: New-generation DESs have proved to be more effective and safer than early-generation DES in randomized trials. However, the effects of new-generation DES versus early-generation DES in everyday clinical practice deserve further verification. METHODS: A propensity-score and inverse-probability weighted analysis of 5,332 patients undergoing DES implantation (2,557 new-generation and 2,775 early-generation) between January 1, 2007 and June 30, 2011 was performed, with a median follow-up of 3 years. We assessed the incidence of major adverse cardiovascular events (MACE: all-cause death, nonfatal myocardial infarction [MI], and target vessel revascularization [TVR]), and angiographic stent thrombosis (ST) during follow-up. RESULTS: At 3-years, new-generation DES in comparison with early-generation DES were associated with a reduced risk of MI (5% versus 7.4%, hazard ratio [HR]=0.65, 95% confidence interval [CI]=0.51-0.82, P=0.0004) and angiographic ST (0.5% vs. 1.1%, HR=0.35, 95% CI 0.17-0.72, P=0.004), whereas, the risk of TVR (10.9% vs. 13.5%; HR 0.99, 95% CI 0.84-1.16, P=0.99) and overall MACE was not significantly different (19.2% vs. 22.4%, HR=0.94, 95% CI=0.83-1.07, P=0.35). CONCLUSIONS: Our data from a large all-comers multicenter registry confirm that, in comparison with early-generation DES, the use of new-generation DES is associated with similar efficacy and increased long-term safety, because of a reduced risk of ST and MI.

Effective Treatment of Intermediate-Risk Pulmonary Embolism by Manual Thrombus Aspiration. A Report of Two Cases.

Manual thrombectomy, part of the armamentarium of interventional cardiologists, might also be considered as an effective and safe alternative to manage intermediate/high risk acute PE patients with contraindications to thrombolysis or with acute haemodynamic decompensation. We here describe two cases with intermediate risk pulmonary embolism and severe hypoxaemia where manual thrombectomy with a 10F dedicated catheter was effective and improved clinical and haemodynamic parameters. Currently, there's no clear and effective treatment for these patients, thus we believe that this therapy, as current ESC guidelines suggest, should become a possible alternative to systemic thrombolysis and anticoagulant regimen.