Spontaneous Reperfusion in Patients with Transient ST-Elevation Myocardial Infarction-Prevalence, Importance and Approaches to Management.

Patients with transient ST-elevation myocardial infarction (STEMI) or spontaneous resolution (SpR) of the ST-segment elevation on electrocardiogram could potentially represent a unique group of patients posing a therapeutic management dilemma. In this review, we discuss the potential mechanisms underlying SpR, its relation to clinical outcomes and the proposed management options for patients with transient STEMI with a focus on immediate versus early percutaneous coronary intervention. We performed a structured literature search of PubMed and Cochrane Library databases from inception to December 2020. Studies focused on SpR in patients with acute coronary syndrome were selected. Available data suggest that deferral of angiography and revascularization within 24-48 h in these patients is reasonable and associated with similar or perhaps better outcomes than immediate angiography. Further randomized trials are needed to elucidate the best pharmacological and invasive strategies for this cohort.

Breast cancer and incident cardiovascular events: A systematic analysis at the nationwide level.

BACKGROUND: Breast cancer (BC) is one of the most common cancers worldwide, and the treatments are frequently cardiotoxic. Whether BC is associated with a higher risk of cardiovascular events is a matter of debate. We evaluated the associations among BC and incident cardiovascular events in a contemporary population. METHODS: All female patients discharged from French hospitals in 2013 with at least 5 years of follow-up and without a history of major adverse cardiovascular event (myocardial infarction [MI], heart failure [HF], ischaemic stroke or all-cause death, and MACE-HF, which includes cardiovascular death, MI, ischaemic stroke or HF) or cancer (except BC) were identified. After propensity score matching, patients with BC were matched 1:1 with patients with no BC. Hazard ratios (HRs) for cardiovascular events during follow-up were adjusted on age, sex and smoking status at baseline. RESULTS: 1,795,759 patients were included, among whom 64,480 (4.3%) had history of BC. During a mean follow-up of 5.1 years, matched female patients with BC had a higher risk of all-cause death (HR 3.55, 95% confidence interval [CI]: 3.47-3.64), new-onset HF (HR 1.08, 95% CI 1.04-1.11), major bleeding (HR 1.43, 95% CI 1.36-1.49), MACE-HF (HR 1.07, 95% CI 1.04-1.11) and net adverse clinical events (NACE) including all-cause death, MI, ischaemic stroke, HF or major bleeding (HR 2.53, 95% CI 2.48-2.58) compared with those with no BC. By contrast, risks were not higher for cardiovascular death (HR 0.94, 95% CI 0.88-1.00) and were lower for MI (HR 0.81, 95% CI 0.75-0.88) and ischaemic stroke (HR 0.85, 95% CI 0.79-1.11). CONCLUSIONS: In a large and contemporary analysis of female patients seen in French hospitals, women with history of breast cancer had a higher risk of all-cause mortality, new-onset heart failure and major bleeding compared to a matched cohort of women without breast cancer. In contrast, they have a reduced risk of cardiovascular mortality, MI and stroke.

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.

Analysis of the ESC/EACTS 2020 Atrial Fibrillation Guidelines With Perioperative Implications.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia worldwide, with an individual lifetime risk of approximately 37% in the United States. Broadly defined as a supraventricular tachyarrhythmia with disorganized atrial activation, AF results in an increased risk of stroke, heart failure, valvular heart disease, and impaired quality of life, and confers a significant burden on the health of individuals and society. AF in the perioperative setting is common and a significant source of perioperative morbidity and mortality worldwide. The latest iteration of the European Society of Cardiology AF guidelines published in 2020 provide the clinician a valuable road map for the management of this arrythmia. This expert review will comprehensively analyze the 2020 European Society of Cardiology guidelines and provide perioperative management tools for the clinician.

In patients with AF and a bioprosthetic mitral valve, rivaroxaban was noninferior to warfarin for time to clinical events.

SOURCE CITATION: Guimarães HP, Lopes RD, de Barros E Silva PG, et al. Rivaroxaban in patients with atrial fibrillation and a bioprosthetic mitral valve. N Engl J Med. 2020;383:2117-26. 33196155.

Hypertension and atrial fibrillation: Closing a virtuous circle.

Ying Gue and Gregory Lip discuss the accompanying study by Ana-Catarina Pinho-Gomes and co-workers on blood pressure lowering treatment in patients with atrial fibrillation.

Out-of-hospital cardiac arrest: A systematic review of current risk scores to predict survival.

IMPORTANCE: The arrest and the post-arrest period are an incredibly emotionally traumatic time for family and friends of the affected individual. There is a need to assess prognosis early in the patient pathway to offer objective, realistic and non-emotive information to the next-of-kin regarding the likelihood of survival. OBJECTIVE: To present a systematic review of the clinical risk scores available to assess patients on admission following out-of-hospital cardiac arrest (OHCA) which can predict in-hospital mortality. EVIDENCE REVIEW: A systematic search of online databases Embase, MEDLINE and Cochrane Central Register of Controlled Trials was conducted up until 20th November 2020. FINDINGS: Out of 1,817 initial articles, we identified a total of 28 scoring systems, with 11 of the scores predicting mortality following OHCA included in this review. The majority of the scores included arrest characteristics (initial rhythm and time to return of spontaneous circulation) as prognostic indicators. Out of these, the 3 most clinically-useful scores, namely those which are easy-to-use, comprise of commonly available parameters and measurements, and which have high predictive value are the OHCA, NULL-PLEASE, and rCAST scores, which appear to perform similarly. Of these, the NULL-PLEASE score is the easiest to calculate and has also been externally validated. CONCLUSIONS: Clinicians should be aware of these risk scores, which can be used to provide objective, nonemotive and reproducible information to the next-of-kin on the likely prognosis following OHCA. However, in isolation, these scores should not form the basis for clinical decision-making.

Thrombotic complications in 2928 patients with COVID-19 treated in intensive care: a systematic review.

A prothrombotic state is reported with severe COVID-19 infection, which can manifest in venous and arterial thrombotic events. Coagulopathy is reflective of more severe disease and anticoagulant thromboprophylaxis is recommended in hospitalized patients. However, the prevalence of thrombosis on the intensive care unit (ICU) remains unclear, including whether this is sufficiently addressed by conventional anticoagulant thromboprophylaxis. We aimed to identify the rate of thrombotic complications in ICU-treated patients with COVID-19, to inform recommendations for diagnosis and management. A systematic review was conducted to assess the incidence of thrombotic complications in ICU-treated patients with COVID-19. Observational studies and registries reporting thrombotic complications in ICU-treated patients were included. Information extracted included patient demographics, use of thromboprophylaxis or anticoagulation, method of identifying thrombotic complications, and reported patient outcomes. In 28 studies including 2928 patients, thrombotic complications occurred in 34% of ICU-managed patients, with deep venous thrombosis reported in 16.1% and pulmonary embolism in 12.6% of patients, despite anticoagulant thromboprophylaxis, and were associated with high mortality. Studies adopting systematic screening for venous thrombosis with Duplex ultrasound reported a significantly higher incidence of venous thrombosis compared to those relying on clinical suspicion (56.3% vs. 11.0%, p < 0.001). Despite thromboprophylaxis, there is a very high incidence of thrombotic complications in patients with COVID-19 on the ICU. Systematic screening identifies many thrombotic complications that would be missed by relying on clinical suspicion and should be employed, with consideration given to increased dose anticoagulant thromboprophylaxis, whilst awaiting results of prospective trials of anticoagulation in this cohort.

Fibrinolysis in Platelet Thrombi.

The extent and duration of occlusive thrombus formation following an arterial atherothrombotic plaque disruption may be determined by the effectiveness of endogenous fibrinolysis. The determinants of endogenous fibrinolysis are the subject of much research, and it is now broadly accepted that clot composition as well as the environment in which the thrombus was formed play a significant role. Thrombi with a high platelet content demonstrate significant resistance to fibrinolysis, and this may be attributable to an augmented ability for thrombin generation and the release of fibrinolysis inhibitors, resulting in a fibrin-dense, stable thrombus. Additional platelet activators may augment thrombin generation further, and in the case of coronary stenosis, high shear has been shown to strengthen the attachment of the thrombus to the vessel wall. Neutrophil extracellular traps contribute to fibrinolysis resistance. Additionally, platelet-mediated clot retraction, release of Factor XIII and resultant crosslinking with fibrinolysis inhibitors impart structural stability to the thrombus against dislodgment by flow. Further work is needed in this rapidly evolving field, and efforts to mimic the pathophysiological environment in vitro are essential to further elucidate the mechanism of fibrinolysis resistance and in providing models to assess the effects of pharmacotherapy.

Rationale and design of "Can Very Low Dose Rivaroxaban (VLDR) in addition to dual antiplatelet therapy improve thrombotic status in acute coronary syndrome (VaLiDate-R)" study : A randomised trial modulating endogenous fibrinolysis in patients with acute coronary syndrome.

Impaired endogenous fibrinolysis is novel biomarker that can identify patients with ACS at increased cardiovascular risk. The addition of Very Low Dose Rivaroxaban (VLDR) to dual antiplatelet therapy has been shown to reduce cardiovascular events but at a cost of increased bleeding and is therefore not suitable for all-comers. Targeted additional pharmacotherapy with VLDR to improve endogenous fibrinolysis may improve outcomes in high-risk patients, whilst avoiding unnecessary bleeding in low-risk individuals. The VaLiDate-R study (ClinicalTrials.gov Identifier: NCT03775746, EudraCT: 2018-003299-11) is an investigator-initiated, randomised, open-label, single centre trial comparing the effect of 3 antithrombotic regimens on endogenous fibrinolysis in 150 patients with ACS. Subjects whose screening blood test shows impaired fibrinolytic status (lysis time > 2000s), will be randomised to one of 3 treatment arms in a 1:1:1 ratio: clopidogrel 75 mg daily (Group 1); clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily (Group 2); ticagrelor 90 mg twice daily (Group 3), in addition to aspirin 75 mg daily. Rivaroxaban will be given for 30 days. Fibrinolytic status will be assessed during admission and at 2, 4 and 8 weeks. The primary outcome measure is the change in fibrinolysis time from admission to 4 weeks follow-up, using the Global Thrombosis Test. If VLDR can improve endogenous fibrinolysis in ACS, future large-scale studies would be required to assess whether targeted use of VLDR in patients with ACS and impaired fibrinolysis can translate into improved clinical outcomes, with reduction in major adverse cardiovascular events in this high-risk cohort.

Impaired endogenous fibrinolysis in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention is a predictor of recurrent cardiovascular events: the RISK PPCI study.

Aims: The endogenous fibrinolytic system serves to prevent lasting thrombotic occlusion and infarction following initiation of coronary thrombosis. We aimed to determine whether impaired endogenous fibrinolysis can identify patients with ST-segment elevation myocardial infarction (STEMI) who remain at high cardiovascular risk despite dual antiplatelet therapy (DAPT). Methods and results: A prospective, observational study was conducted in 496 patients presenting with STEMI for primary percutaneous coronary intervention (PPCI). Blood was tested on arrival pre-PPCI, at discharge and at 30 days to assess thrombotic status using the automated point-of-care global thrombosis test and patients followed for 1 year for major adverse cardiovascular events (MACEs). Endogenous fibrinolysis was significantly impaired [baseline lysis time (LT) ≥2500 s] in 14% of patients and was highly predictive of recurrent MACE [hazard ratio (HR) 9.1, 95% confidence interval (CI) 5.29-15.75; P < 0.001], driven by cardiovascular death (HR 18.5, 95% CI 7.69-44.31; P < 0.001) and myocardial infarction (HR 6.2, 95% CI 2.64-14.73; P < 0.001), particularly within 30 days. Fibrinolysis remained strongly predictive of MACE after adjustment for conventional risk factors (HR 8.03, 95% CI 4.28-15.03; P < 0.001). Net reclassification showed that adding impaired fibrinolysis improved the prediction of recurrent MACE by >50% (P < 0.001). Patients with spontaneous ST-segment resolution pre-PPCI had more rapid, effective fibrinolysis [LT 1050 (1004-1125) s vs. 1501 (1239-1997) s, P < 0.001] than those without. Lysis time was not altered by standard of care STEMI treatment including DAPT and was unchanged at 30 days. Conclusion: Endogenous fibrinolysis assessment can identify patients with STEMI who remain at very high cardiovascular risk despite PPCI and DAPT. Further studies are needed to assess whether these patients may benefit from additional, personalized antithrombotic/anticoagulant medication to reduce future cardiovascular risk. Clinical trial registration: http://www.clinicaltrials.gov. Unique identifier: NCT02562690.

MINOCA presenting with STEMI: incidence, aetiology and outcome in a contemporaneous cohort.

Historical data indicate that approximately 10% of acute coronary syndrome patients have no obstructive coronary artery disease (CAD) but contemporary incidence of non-obstructed coronary arteries in ST-segment elevation myocardial infarction (STEMI) is not clear. We aimed both to identify the contemporary incidence of MI without obstructive CAD (MINOCA)-using the ESC definition-and assess clinical outcomes. We assessed consecutive unselected STEMI patients presenting to the cardiac catheterisation laboratory with a view to undergoing primary percutaneous coronary intervention (PPCI). MINOCA was defined according to ESC criteria. Electronic patient records, blood results, angiographic and echocardiographic data were interrogated to determine final diagnosis, as well as 30-day and 1-year mortality rate. Of 2521 patients with full electronic dataset, 2158 (85.6%) underwent PPCI for obstructive CAD (angiographic stenosis > 70%). A further 167 (6.6%) with obstructive CAD were treated medically or surgically. The remaining 196 (7.8%) patients had absence of obstructive CAD at angiography, of whom 167 had no stenosis (< 30%) and 29 had mild coronary atheroma (stenosis > 30% but < 50%). A total of 110 (4.4%) patients met diagnostic criteria for MINOCA. All-cause mortality at 30-days and 1-year were 3.6% and 4.5%, respectively. In our cohort, 1 in 20 patients presenting with STEMI had MINOCA. This is the first description of the relatively high incidence of MINOCA in a STEMI cohort using current ESC definition and diagnostic criteria and could help power future trials in this area. Mortality rate was relatively high in our study and similar to that in large meta-analyses.

Importance of Endogenous Fibrinolysis in Platelet Thrombus Formation.

The processes of thrombosis and coagulation are finely regulated by endogenous fibrinolysis maintaining healthy equilibrium. When the balance is altered in favour of platelet activation and/or coagulation, or if endogenous fibrinolysis becomes less efficient, pathological thrombosis can occur. Arterial thrombosis remains a major cause of morbidity and mortality in the world despite advances in medical therapies. The role endogenous fibrinolysis in the pathogenesis of arterial thrombosis has gained increasing attention in recent years as it presents novel ways to prevent and treat existing diseases. In this review article, we discuss the role of endogenous fibrinolysis in platelet thrombus formation, methods of measurement of fibrinolytic activity, its role in predicting cardiovascular diseases and clinical outcomes and future directions.

Impact of very low dose rivaroxaban in addition to dual antiplatelet therapy on endogenous fibrinolysis in acute coronary syndrome: The VaLiDate-R study.

BACKGROUND: Impaired endogenous fibrinolysis is adverse cardiovascular risk factor in acute coronary syndrome (ACS) patients. Addition of very low dose rivaroxaban (VLDR) to dual antiplatelet therapy (DAPT) reduces cardiovascular events but increases bleeding. OBJECTIVE: We aimed to assess whether addition of VLDR to DAPT can enhance endogenous fibrinolysis. METHODS: In a prospective, open-label trial, we assessed endogenous fibrinolysis in whole blood, in 549 patients with ACS using the Global Thrombosis Test (GTT) and Thromboelastography (TEG). Patients (n = 180) who demonstrated impaired endogenous fibrinolysis (lysis time [LT] >2000s with the GTT) were randomised 1:1:1 to (i) clopidogrel 75 mg daily; (ii) clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily; or (iii) ticagrelor 90 mg twice daily, for 30 days, in addition to aspirin. Fibrinolytic status was assessed at 0, 2, 4 and 8 weeks. The primary outcome was the change in LT from admission to week 4. We also measured thrombotic occlusion time (OT) at high shear, and rivaroxaban level. RESULTS: There was no difference between the groups with respect to LT or clot lysis with TEG, and no change in these parameters compared to baseline during study drug allocation. In the rivaroxaban plus clopidogrel group, OT was prolonged compared to the other groups, although rivaroxaban levels were low, suggesting non-compliance. CONCLUSION: Addition of rivaroxaban 2.5 mg twice daily to DAPT does not affect endogenous fibrinolysis of thrombus formed at either high or low shear. Further studies are needed to determine whether higher doses of rivaroxaban can favourably modulate fibrinolysis. CONDENSED ABSTRACT: Impaired endogenous fibrinolysis is a strong risk factor in ACS. We aimed to assess whether adding very low dose rivaroxaban (VLDR) to DAPT can enhance fibrinolysis. Fibrin and clot lysis were assessed in whole blood. ACS patients with impaired fibrinolysis were randomised 1:1:1 to clopidogrel 75 mg daily; clopidogrel 75 mg plus VLDR; or ticagrelor 90 mg twice daily, in addition to aspirin. At 30-days, there was no difference in lysis time between the groups, nor change from baseline. VLDR does not improve fibrinolysis at high or low shear. Further studies are needed to determine whether alternative antithrombotic regimens can enhance endogenous fibrinolysis.

Ethnic Differences in Thrombotic Profiles of Acute Coronary Syndrome Patients and Relationship to Cardiovascular Outcomes: A Comparison of East Asian and White subjects.

BACKGROUND: East Asians (EAs), compared to white Caucasians (W), have a lower risk of ischemic heart disease and a higher risk of bleeding with antithrombotic medications. The underlying mechanisms are incompletely understood. OBJECTIVES: We sought to compare thrombotic profiles of EA and W patients with myocardial infarction (MI) and relate these to cardiovascular outcomes. METHODS: In a prospective study in the United Kingdom and Korea, blood samples from patients (n = 515) with ST- or non-ST-elevation MI (STEMI and NSTEMI) were assessed using the Global Thrombosis Test, measuring thrombotic occlusion (OT) and endogenous fibrinolysis (lysis time [LT]). Patients were followed for 1 year for major adverse cardiovascular events (MACE) and bleeding. RESULTS: EA patients showed reduced OT (longer OT) compared to W (646 seconds [470-818] vs. 436 seconds [320-580], p < 0.001), with similar LT. In STEMI, OT (588 seconds [440-759] vs. 361 seconds [274-462], p < 0.001) and LT (1,854 seconds [1,389-2,729] vs. 1,338 seconds [1,104-1,788], p < 0.001) were longer in EA than W. In NSTEMI, OT was longer (OT: 734 seconds [541-866] vs. 580 seconds [474-712], p < 0.001) and LT shorter (1519 seconds [1,058-2,508] vs. 1,898 seconds [1,614-2,806], p = 0.004) in EA than W patients. MACE was more frequent in W than EA (6.3 vs. 1.9%, p = 0.014) and bleeding infrequent. While OT was unrelated, LT was a strong independent predictor of MACE event after adjustment for risk factors (hazard ratio: 3.70, 95% confidence interval: 1.43-9.57, p = 0.007), predominantly in W patients, and more so in STEMI than NSTEMI patients. CONCLUSION: EA patients exhibit different global thrombotic profiles to W, associated with a lower rate of cardiovascular events.

Complete revascularization in elderly patients with myocardial infarction-a safe, effective, and necessary strategy?

The FIRE trial compared culprit-only revascularization to physiology-guided complete revascularization strategy in elderly patients presenting with myocardial infarction. The study has shown that it is a safe approach and may confer additional prognostic benefit in patients with NSTEMI.