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Objective: To assess the impact of hyperglycemia in different age-groups of patients with acute myocardial infarction (AMI).Research Design and Methods: A total of 2,027 patients with AMI were categorized into one of five age-groups: <50 years (n = 301), ≥50 and <60 (n = 477), ≥60 and <70 (n = 545), ≥70 and <80 (n = 495), and ≥80 years (n = 209). Hyperglycemia was defined as initial glucose ≥115 mg/dL.Results: The adjusted odds ratios for hyperglycemia predicting hospital mortality in groups 1-5 were, respectively, 7.57 (P = 0.004), 3.21 (P = 0.046), 3.50 (P = 0.003), 3.20 (P < 0.001), and 2.16 (P = 0.021). The adjusted P values for correlation between glucose level (as a continuous variable) and mortality were 0.007, <0.001, 0.043, <0.001, and 0.064. The areas under the ROC curves (AUCs) were 0.785, 0.709, 0.657, 0.648, and 0.613. The AUC in group 1 was significantly higher than those in groups 3-5.Conclusions: The impact of hyperglycemia as a risk factor for hospital mortality in AMI is more pronounced in younger patients. [ABSTRACT FROM AUTHOR]

High-density lipoprotein (HDL) is associated with decreased incidence of cardiovascular events, and its functionality also influences prognosis. Exercise is an important tool to improve prognosis in the post-infarction (MI) population, but the role of exercise on HDL functionality is poorly understood. Sixty-two patients with acute MI were randomized in a supervised exercise program for 12-14 weeks (exercise group-EG) or a control group (CG). The main objective of the study was to analyze the role of exercise on esterified cholesterol (EC) and unesterified cholesterol (UC) transfer to HDL. For the total population, the baseline mean rate of EC transfer to HDL was 2.53 ± 0.83 and at the end of follow-up, it was 2.74 ± 0.64 ( p = 0.03). The figures for UC were, respectively, 4.08 ± 1.2 and 4.4 ± 1.06 ( p = 0.02). The difference (follow-up minus baseline) for EC was 0.15 ± 0.84 for the control group and 0.27 ± 0.69 for the exercise group ( p = 0.53); for UC, the figures were 0.28 ± 1.14 and 0.35 ± 0.96 ( p = 0.80), respectively, for the control and exercise groups. In post-MI patients, 12-14 weeks of supervised exercise did not improve HDL functionality.

Fungal endocarditis following transcatheter aortic valve implantation (TAVI) is a rare and serious complication of this procedure. We describe a case of a 75-year-old patient who developed fungal endocarditis caused by Candida albicans, complicated by an aortic pseudoaneurysm., (© 2024. The Author(s).)

Aims: Cardiogenic shock (CS) and cardiac arrest (CA) are serious complications in ST-elevation myocardial infarction (STEMI) patients, with lack of long-term data according to their timing of occurrence. This study sought to determine the incidence and relationship between the timing of occurrence and prognostic impact of CS and CA complicating STEMI in the long-term follow-up., Methods and Results: We conducted a retrospective analysis of consecutive STEMI patients treated between 2004 and 2017. Patients were divided into four groups based on the occurrence of neither CA nor CS, CA only, CS only, and both CA and CS (CA-CS-, CA+, CS+, and CA+CS+, respectively). Adjusted Cox regression analysis was used to assess the independent association between the CS and CA categories and mortality. A total of 1603 STEMI patients were followed for a median of 3.6 years. CA and CS occurred in the 12.2% and 15.9% of patients, and both impacted long-term mortality [adjusted hazard ratio (HR) = 2.59, 95% confidence interval (CI): 1.53-4.41, P < 0.001; HR = 3.16, 95% CI: 2.21-4.53, P < 0.001, respectively). CA+CS+ occurred in 7.3%, with the strongest association with higher mortality (adjusted HR = 5.36; 95% CI: 3.80-7.55, P < 0.001). Using flexible parametric models with B-splines, the increased mortality was restricted to the first ∼10 months. In addition, overall mortality rates were higher at all timings (all with P < 0.001), except for CA during initial cardiac catheterization ( P < 0.183)., Conclusion: CS and CA complicating patients presenting with STEMI were associated with higher long-term mortality rate, especially in the first 10 months. Both CS+ and CA+ at any timeframe impacted outcomes, except for CA+ during the initial cardiac catheterization, although this will have to be confirmed in larger future studies, given the relatively small number of patients., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Dual antiplatelet therapy (DAPT) provides additional risk reduction of ischemic events compared to aspirin monotherapy, at cost of higher bleeding risk. There are few data comparing new techniques for reducing bleeding after dental extractions in these patients., Purpose: This study investigated the effectiveness of the HemCon Dental Dressing (HDD) compared to oxidized cellulose gauze., Materials and Methods: This randomized study included 60 patients on DAPT who required at least two dental extractions (120 procedures). Each surgical site was randomized to HDD or oxidized regenerated cellulose gauze as the local hemostatic method. Intra-oral bleeding time was measured immediately after the dental extraction and represents our main endpoint for comparison of both hemostatic agents. Prolonged bleeding, platelet reactivity measured by Multiplate Analyser (ADPtest and ASPItest) and tissue healing comparison after 7 days were also investigated., Results: Intra-oral bleeding time was lower in HDD compared with control (2 [2-5] vs. 5 [2-8] minutes, P=0.001). Prolonged postoperative bleeding was observed in 7 cases (11.6%), all of them successfully managed with local sterile gauze pressure. More HDD treated sites presented better healing when compared with control sites [21 (36.8%) vs. 5 (8.8%), P=0.03]. There was poor correlation between platelet reactivity and intra-oral bleeding time., Conclusions: In patients on DAPT, HDD resulted in a lower intra-oral bleeding time compared to oxidized cellulose gauze after dental extractions. Moreover, HDD also seems to improve healing conditions., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Most of the evidence about the impact of the post-acute COVID-19 Syndrome (PACS) reports individual symptoms without correlations with related imaging., Objectives: To evaluate cardiopulmonary symptoms, their predictors and related images in COVID-19 patients discharged from hospital., Methods: Consecutive patients who survived COVID-19 were contacted 90 days after discharge. The Clinic Outcome Team structured a questionnaire evaluating symptoms and clinical status (blinded for hospitalization data). A multivariate analysis was performed to address the course of COVID-19, comorbidities, anxiety, depression, and post-traumatic stress during hospitalization, and cardiac rehabilitation after discharge. The significance level was set at 5%., Results: A total of 480 discharged patients with COVID-19 (age: 59±14 years, 67.5% males) were included; 22.3% required mechanical ventilation. The prevalence of patients with PACS-related cardiopulmonary symptoms (dyspnea, tiredness/fatigue, cough, and chest discomfort) was 16.3%. Several parameters of chest computed tomography and echocardiogram were similar in patients with and without cardiopulmonary symptoms. The multivariate analysis showed that PACS-related cardiopulmonary-symptoms were independently related to female sex (OR 3.023; 95% CI 1.319-6.929), in-hospital deep venous thrombosis (OR 13.689; 95% CI 1.069-175.304), elevated troponin I (OR 1.355; 95% CI 1.048-1.751) and C-reactive protein during hospitalization (OR 1.060; 95% CI 1.023-1.097) and depression (OR 6.110; 95% CI 2.254-16.558)., Conclusion: PACS-related cardiopulmonary symptoms 90 days post-discharge are common and multifactorial. Beyond thrombotic and markers of inflammation/myocardial injury during hospitalization, female sex and depression were independently associated with cardiopulmonary-related PACS. These results highlighted the need for a multifaceted approach targeting susceptible patients.

Few data from Latin American centers on clinical outcomes in coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome who required extracorporeal membrane oxygenation (ECMO) are published. Moreover, clinical and functional status after hospital discharge remains poorly explored in these patients. We evaluated in-hospital outcomes of severe COVID-19 patients who received ECMO support in two Brazilian hospitals. In one-third of the survivors, post-acute COVID-19 syndrome (PACS), quality of life, anxiety, depression, and return to work were evaluated. Eighty-five patients were included and in-hospital mortality was 47%. Age >65 years (HR: 4.8; 95% confidence interval [CI]: 1.4-16.4), diabetes (HR: 6.0; 95% CI: 1.8-19.6), ECMO support duration (HR: 1.08; 95% CI: 1.05-1.12) and dialysis initiated after ECMO (HR: 3.4; 95% CI: 1.1-10.8) were independently associated with higher in-hospital mortality and mechanical ventilation (MV) duration before ECMO was not (HR: 1.18; 95% CI: 0.71-2.09). PACS-related symptoms were reported by two-thirds and half of patients at 30- and 90-days post-discharge, respectively. The median EQ-5D score was 0.85 (0.70-1.00) and 0.77 (0.66-1.00) at 30 and 90 days. Of the 15 responders, all previously working patients, except one, have returned to work at 90 days. In conclusion, in-hospital mortality in a large Latin American cohort was comparable to the Global extracorporeal life support organization registry., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASAIO.)

Aims: Left ventricular ejection fraction (LVEF) ≤ 40% is a well-established risk factor for mortality after acute coronary syndromes (ACS). However, the long-term prognostic impact of mildly reduced ejection fraction (EF) (LVEF 41-49%) after ACS remains less clear., Methods and Results: This was a retrospective study enrolling patients admitted with ACS included in a single-centre databank. LVEF was assessed by echocardiography during index hospitalization. Patients were divided in the following categories according to LVEF: normal (LVEF ≥ 50%), mildly reduced (LVEF 41-49%), and reduced (LVEF ≤ 40%). The endpoint of interest was all-cause death after hospital discharge. A multivariable Cox model was used to adjust for confounders. A total of 3200 patients were included (1952 with normal EF, 375 with mildly reduced EF, and 873 with reduced EF). The estimated cumulative incidence rates of mortality at 10 years for patients with normal, mildly reduced, and reduced EF were 24.8%, 33.5%, and 41.3%, respectively. After adjustments, the presence of reduced EF was associated with higher mortality compared with normal EF [adjusted hazard ratio (HR) 1.64; 95% confidence interval (CI) 1.36-1.96; P < 0.001], as was mildly reduced EF compared with normal EF (adjusted HR 1.33; 95% CI 1.05-1.68; P = 0.019). The presence of reduced EF was not associated with a statistically significantly higher mortality compared with mildly reduced EF (adjusted HR 1.23; 95% CI 0.96-1.57; P = 0.095)., Conclusions: In patients with ACS, mildly reduced EF measured in the acute phase was associated with higher long-term mortality compared with patients with normal EF. These data emphasize the importance of anti-remodelling therapies for ACS patients who have LVEF in the mildly reduced range., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: The management of acute myocardial infarction (AMI) presents several challenges in patients with diabetes, among them the higher rate of recurrent thrombotic events, hyperglycemia and risk of subsequent heart failure (HF). The objective of our study was to evaluate effects of DPP-4 inhibitors (DPP-4i) on platelet reactivity (main objective) and cardiac risk markers., Methods: We performed a single-center double-blind randomized trial. A total of 70 patients with type 2 diabetes (T2DM) with AMI Killip ≤2 on dual-antiplatelet therapy (aspirin plus clopidogrel) were randomized to receive sitagliptin 100 mg or saxagliptin 5 mg daily or matching placebo. Platelet reactivity was assessed at baseline, 4 days (primary endpoint) and 30 days (secondary endpoint) after randomization, using VerifyNow Aspirin™ assay, expressed as aspirin reaction units (ARUs); B-type natriuretic peptide (BNP) in pg/mL was assessed at baseline and 30 days after (secondary endpoint)., Results: Mean age was 62.6 ± 8.8 years, 45 (64.3%) male, and 52 (74.3%) of patients presented with ST-segment elevation MI. For primary endpoint, there were no differences in mean platelet reactivity ( p = 0.51) between the DPP-4i (8.00 {-65.00; 63.00}) and placebo (-14.00 {-77.00; 52.00}) groups, as well in mean BNP levels ( p = 0.14) between DPP-4i (-36.00 {-110.00; 15.00}) and placebo (-13.00 {-50.00; 27.00}). There was no difference between groups in cardiac adverse events., Conclusions: DPP4 inhibitor did not reduce platelet aggregation among patients with type 2 diabetes hospitalized with AMI. Moreover, the use of DPP-4i did not show an increase in BNP levels or in the incidence of cardiac adverse events. These findings suggests that DPP-4i could be an option for management of T2DM patients with acute MI.

Introduction: Clopidogrel has been demonstrated to be effective in improving coronary microcirculation (CM) among patients with ST-elevation myocardial infarction (STEMI) treated with fibrinolytics. Ticagrelor is a more potent adenosine diphosphate (ADP) receptor blocker proven to be superior to clopidogrel among patients with acute coronary syndromes. The present study aimed to compare the effects of ticagrelor and clopidogrel on CM in patients with STEMI treated with fibrinolytics., Methods: The present study prospectively included 48 patients participating in the TREAT trial, which randomly assigned patients with STEMI undergoing fibrinolysis to ticagrelor versus clopidogrel. The primary endpoint of this study was the evaluation of the CM using the global myocardial perfusion score index (global MPSI) obtained by myocardial contrast echocardiography (MCE). Platelet aggregation to ADP was evaluated by Multiplate® and expressed as area under the curve (AUC)., Results: The global MPSI demonstrated no differences between the groups [mean 1.4 (1.2-1.5) in the ticagrelor group and 1.2 (1.2-1.5) in the clopidogrel group (p = 0.41)]. Platelet aggregability was lower in the ticagrelor group (18.1 ± 9.7 AUC), compared to the clopidogrel group (26.1 ± 12.5 AUC, p = 0.01)., Conclusion: We found no improvement in coronary microcirculation with ticagrelor compared to clopidogrel among patients with STEMI treated with fibrinolytics, despite the fact that platelet aggregation to ADP was lower with ticagrelor., Clinical Trials Registration: NCT03104062., (© 2022. The Author(s).)

Introdution: COVID-19 is associated with an increased risk of thrombotic events. However, the contribution of platelet reactivity (PR) to the aetiology of the increased thrombotic risk associated with COVID-19 remains unclear. Our aim was to evaluate PR in stable patients diagnosed with COVID-19 and hospitalized with respiratory symptoms (mainly dyspnoea and dry cough), in comparison with a control group comprised of non-hospitalized healthy controls., Methods: Observational, case control study that included patients with confirmed COVID-19 (COVID-19 group, n = 60) and healthy individuals matched by age and sex (control group, n = 60). Multiplate electrode aggregometry (MEA) tests were used to assess PR with adenosine diphosphate (MEA-ADP, low PR defined as < 53 AUC), arachidonic acid (MEA-ASPI, low PR < 86 AUC) and thrombin receptor-activating peptide 6 (MEA-TRAP, low PR < 97 AUC) in both groups., Results: The rates of low PR with MEA-ADP were 27.5% in the COVID-19 group and 21.7% in the control group (OR = 1.60, p = 0.20); with MEA-ASPI, the rates were, respectively, 37.5% and 22.5% (OR = 3.67, p < 0.001); and with MEA-TRAP, the incidences were 48.5% and 18.8%, respectively (OR = 9.58, p < 0.001). Levels of D-dimer, fibrinogen, and plasminogen activator inhibitor 1 (PAI-1) were higher in the COVID-19 group in comparison with the control group (all p < 0.05). Thromboelastometry was utilized in a subgroup of patients and showed a hypercoagulable state in the COVID-19 group., Conclusion: Patients hospitalized with non-severe COVID-19 had lower PR compared to healthy controls, despite having higher levels of D-dimer, fibrinogen, and PAI-1, and hypercoagulability by thromboelastometry., Trial Registration: ClinicalTrials.gov identifier, NCT04447131., (© 2021. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Background: Dual antiplatelet therapy is recommended for patients with acute coronary syndromes (ACS). Approximately 10% to 15% of these patients will undergo coronary artery bypass graft (CABG) surgery for index events, and current guidelines recommend stopping clopidogrel at least 5 days before CABG. This waiting time has clinical and economic implications., Objectives: This study aimed to evaluate if a platelet reactivity-based strategy is noninferior to standard of care for 24-h post-CABG bleeding., Methods: In this randomized, open label noninferiority trial, 190 patients admitted with ACS with indications for CABG and on aspirin and P2Y 12 receptor inhibitors, were assigned to either control group, P2Y 12 receptor inhibitor withdrawn 5 to 7 days before CABG, or intervention group, daily measurements of platelet reactivity by Multiplate analyzer (Roche Diagnostics GmbH, Vienna, Austria) with CABG planned the next working day after platelet reactivity normalization (pre-defined as ≥46 aggregation units)., Results: Within the first 24 h of CABG, the median chest tube drainage was 350 ml (interquartile range [IQR]: 250 to 475 ml) and 350 ml (IQR: 255 to 500 ml) in the intervention and control groups, respectively (p for noninferiority <0.001). The median waiting period between the decision to undergo CABG and the procedure was 112 h (IQR: 66 to 142 h) and 136 h (IQR: 112 to 161 h) (p < 0.001), respectively. In the intention-to-treat analysis, a 6.4% decrease in the median in-hospital expenses was observed in the intervention group (p = 0.014), with 11.2% decrease in the analysis per protocol (p = 0.003)., Conclusions: A strategy based on platelet reactivity-guided is noninferior to the standard of care in patients with ACS awaiting CABG regarding peri-operative bleeding, significantly shortens the waiting time to CABG, and decreases hospital expenses. (Evaluation of Platelet Aggregability in the Release of CABG in Patients With ACS With DAPT; NCT02516267)., Competing Interests: Funding Support and Author Disclosures This study was financed in part by the Coordination for the Improvement of Higher Education Personnel-Brazil (CAPES) – Finance Code 001. Dr. Furtado has received grants and personal fees from AstraZeneca; personal fees from Servier; and grants from EMS, Pfizer, Novo Nordisk, DalCor, Novartis, and Janssen, all outside the submitted work. Dr. Baracioli has received personal fees from Sandoz. Dr. Barbosa has received personal fees from Bayer, Daiichi-Sankyo, and Servier. Dr. Britto has received research grants from Novo Nordisk, DalCor, AstraZeneca, and Novartis. Dr. Farkouh has received research grants from Amgen, Novartis, and Novo Nordisk. Dr. Gurbel has received consultant and/or receives honoraria from Bayer, Merck, Janssen, Medicure, and USWorld Meds; has received grants from the National Institutes of Health, Janssen, Merck, Bayer, Haemonetics, Instrumentation Labs, and Amgen; holds stock or stock options in Merck, Medtronic, and Pfizer; and holds patents in the area of personalized antiplatelet therapy and interventional cardiology. Dr. Nicolau has received personal fees from AMGEN; has received grants from AstraZeneca, Bristol Myers Squibb, CLS Behring, Dalcor, Janssen, NovoNordisk, and Vifor; has received grants and personal fees from Bayer, Novartis, and Sanofi; and has received personal fees from Daiichi-Sankyo and Servier. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Increased risk of new-onset diabetes with statins challenges the long-term safety of this drug class. However, few reports have analyzed this issue during acute coronary syndromes (ACS)., Objective: To explore the association between early initiation of statin therapy and blood glucose levels in patients admitted with ACS., Methods: This was a retrospective analysis of patients hospitalized with ACS. Statin-naïve patients were included and divided according to their use or not of statins within the first 24 hours of hospitalization. The primary endpoint was incidence of in-hospital hyperglycemia (defined as peak blood glucose > 200 mg/dL). Multivariable linear and logistic regression models were used to adjust for confounders, and a propensity-score matching model was developed to further compare both groups of interest. A p-value of less than 0.05 was considered statistically significant., Results: A total of 2,357 patients were included, 1,704 of them allocated in the statin group and 653 in the non-statin group. After adjustments, statin use in the first 24 hours was associated with a lower incidence of in-hospital hyperglycemia (adjusted OR=0.61, 95% CI 0.46-0.80; p < 0.001) and lower need for insulin therapy (adjusted OR = 0.56, 95% CI 0.41-0.76; p < 0.001). These associations remained similar in the propensity-score matching models, as well as after several sensitivity analyses, such as after excluding patients who developed cardiogenic shock, severe infection or who died during index-hospitalization., Conclusions: Among statin-naïve patients admitted with ACS, early statin therapy was independently associated with lower incidence of in-hospital hyperglycemia. (Arq Bras Cardiol. 2021; 116(2):285-294).

Objectives: Returning to work after an episode of acute coronary syndrome (ACS) is challenging for many patients, and has both personal and social impacts. There are limited data regarding the working status in the very long-term after ACS., Methods: We retrospectively analyzed 1,632 patients who were working prior to hospitalization for ACS in a quaternary hospital and were followed-up for up to 17 years. Adjusted models were developed to analyze the variables independently associated with actively working at the last contact, and a prognostic predictive index for not working at follow-up was developed., Results: The following variables were significantly and independently associated with actively working at the last contact: age>median (hazard-ratio [HR], 0.76, p<0.001); male sex (HR, 1.52, p<0.001); government health insurance (HR, 1.36, p<0.001); history of angina (HR, 0.69, p<0.001) or myocardial infarction (MI) (HR, 0.76, p=0.005); smoking (HR, 0.81, p=0.015); ST-elevation MI (HR, 0.81, p=0.021); anterior-wall MI (HR, 0.75, p=0.001); non-primary percutaneous coronary intervention (PCI) (HR, 0.77, p=0.002); fibrinolysis (HR, 0.61, p<0.001); cardiogenic shock (HR, 0.60, p=0.023); statin (HR, 3.01, p<0.001), beta-blocker (HR, 1.26, p=0.020), angiotensin-converting enzyme (ACE) inhibitor/angiotensin II receptor blocker (ARB) (HR, 1.37, p=0.001) at hospital discharge; and MI at follow-up (HR, 0.72, p=0.001). The probability of not working at the last contact ranged from 24.2% for patients with no variables, up to 80% for patients with six or more variables., Conclusions: In patients discharged after ACS, prior and in-hospital clinical variables, as well as the quality of care at discharge, have a great impact on the long-term probability of actively working.

Introduction: Lipoprotein (a) [Lp(a)] is a risk factor for coronary artery disease (CAD). To the best of our knowledge, this is the first study addressing the relationship between Lp(a) and platelet reactivity in primary and secondary prevention., Methods: Lp(a) was evaluated in 396 individuals with (82.3%) and without (17.7%) obstructive CAD. The population was divided into two groups according to Lp(a) concentrations with a cutoff value of 50 mg/dL. The primary objective was to evaluate the association between Lp(a) and adenosine diphosphate (ADP)-induced platelet reactivity using the VerifyNow™ P2Y 12 assay. Platelet reactivity was also induced by arachidonic acid and collagen-epinephrine (C-EPI) and assessed by Multiplate™, platelet function analyzer™ 100 (PFA-100), and light transmission aggregometry (LTA) assays. Secondary objectives included the assessment of the primary endpoint in individuals with or without CAD., Results: Overall, 294 (74.2%) individuals had Lp(a) < 50 mg/dL [median (IQR) 13.2 (5.8-27.9) mg/dL] and 102 (25.8%) had Lp(a) ≥ 50 mg/dL [82.5 (67.6-114.5) mg/dL], P < 0.001. Univariate analysis in the entire population revealed no differences in ADP-induced platelet reactivity between individuals with Lp(a) ≥ 50 mg/dL (249.4 ± 43.8 PRU) versus Lp(a) < 50 mg/dL (243.1 ± 52.2 PRU), P = 0.277. Similar findings were present in individuals with (P = 0.228) and without (P = 0.669) CAD, and regardless of the agonist used or method of analysis (all P > 0.05). Finally, multivariable analysis did not show a significant association between ADP-induced platelet reactivity and Lp(a) ≥ 50 mg/dL [adjusted OR = 1.00 [(95% CI 0.99-1.01), P = 0.590]., Conclusion: In individuals with or without CAD, Lp(a) ≥ 50 mg/dL was not associated with higher platelet reactivity.

Aims: Diagnostic and therapeutic tools have a significant impact on morbidity and mortality associated with acute coronary syndromes (ACS). Data about ACS performance measures are scarce in Brazil, and improving its collection is an objective of the Brazilian Registry in Acute Coronary syndromEs (BRACE)., Methods and Results: The BRACE is a cross-sectional, observational epidemiological registry of ACS patients. Stratified 'cluster sampling' methodology was adopted to obtain a representative picture of ACS. A performance score (PS) varying from 0 to 100 was developed to compare studied parameters. Performance measures alone and the PS were compared between institutions, and the relationship between the PS and outcomes was evaluated. A total of 1150 patients, median age 63 years, 64% male, from 72 hospitals were included in the registry. The mean PS for the overall population was 65.9% ± 20.1%. Teaching institutions had a significantly higher PS (71.4% ± 16.9%) compared with non-teaching hospitals (63.4% ± 21%; P < 0.001). Overall in-hospital mortality was 5.2%, and the variables that correlated independently with in-hospital mortality included: PS-per point increase (OR = 0.97, 95% CI 0.95-0.98, P < 0.001), age-per year (OR = 1.06, 95% CI 1.03-1.09, P < 0.001), chronic kidney disease (OR = 3.12, 95% CI 1.08-9.00, P = 0.036), and prior angioplasty (OR = 0.25, 95% CI 0.07-0.84, P = 0.025)., Conclusions: In BRACE, the adoption of evidence-based therapies for ACS, as measured by the performance score, was independently associated with lower in-hospital mortality. The use of diagnostic tools and therapeutic approaches for the management of ACS is less than ideal in Brazil, with high variability especially among different regions of the country., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Introduction: The interaction between anticoagulants and platelet function is complex. Previous publications showed mixed results regarding the role of heparins in platelet aggregation. On the other hand, the direct thrombin inhibitor (DTI) dabigatran might enhance the risk of myocardial infarction in patients with atrial fibrillation, which could be related to increased platelet aggregability., Methods: This was a prospective, interventional study of patients with chronic coronary artery disease (CAD) taking low-dose aspirin. The objective of the current study was to compare the effects of dabigatran versus enoxaparin on platelet aggregability. Subjects initially were on orally administered dabigatran for 5 days followed by subcutaneously administered enoxaparin after a 30-day washout period. Platelet function was assessed at baseline and after each intervention by multiple electrode aggregometry (MEA-ASPI) (primary endpoint), serum thromboxane B2 (TXB2), VerifyNow Aspirin™, and coagulation tests (secondary endpoints)., Results: Compared to baseline MEA-ASPI values, dabigatran increased platelet aggregation while enoxaparin decreased platelet aggregation (+ 5 U ± 24.1 vs - 6 U ± 22.2, respectively, p = 0.012). The TXB2 assay showed the same pattern (+ 2 pg/ml for dabigatran vs - 13 pg/ml for enoxaparin, p = 0.011). None of the additional tests showed significant differences between the groups. Individually, compared to baseline TXB2 results, enoxaparin significantly decreased platelet activation [33 (16.5-95) pg/mL vs 20 (10-52) pg/mL, respectively, p = 0.026], but no significant differences were observed with dabigatran., Conclusions: DTI and anti-Xa drugs exert opposite effects on platelet function. A significant decrease in platelet activation through COX1 (also known as prostaglandin G/H synthase 1) was observed with enoxaparin, but no significant differences in platelet function were observed with dabigatran., Trial Registration: ClinicalTrials.gov identifier, NCT02389582.

Objectives: Ischemic stroke (IS) or transient ischemic attack (TIA) history is present in 4-17% of patients with coronary artery disease (CAD). This subgroup of patients is at high risk for both ischemic and bleeding events. The aim of this study was to determine the role of platelet aggregability, coagulation and endogenous fibrinolysis in patients with CAD and previous IS or TIA., Methods: A prospective case-control study that included 140 stable CAD patients divided into two groups: the CASE group (those with a previous IS/TIA, n=70) and the CONTROL group (those without a previous IS/TIA, n=70). Platelet aggregability (VerifyNow Aspirin® and VerifyNow P2Y12®), coagulation (fibrinogen and thromboelastography by Reorox®) and endogenous fibrinolysis (D dimer and plasminogen activator inhibitor-1) were evaluated., Results: Patients in the CASE group presented significantly higher systolic blood pressure levels (135.84±16.09 vs 123.68±16.11, p<0.01), significantly more previous CABG (25.71% vs 10%, p=0.015) and significantly higher calcium channel blocker usage (42.86% vs 24.29%, p=0.02) than those in the control group. In the adjusted models, low triglyceride values, low hemoglobin values and higher systolic blood pressure were significantly associated with previous IS/TIA (CASE group). Most importantly, platelet aggregability, coagulation and fibrinolysis tests were not independently associated with previous cerebrovascular ischemic events (CASE group)., Conclusion: Platelet aggregability, coagulation and endogenous fibrinolysis showed similar results among CAD patients with and without previous IS/TIA. Therefore, it remains necessary to identify other targets to explain the higher bleeding risk presented by these patients.

Recent reports have suggested that aspirin effect might be influenced by bodyweight, with decreased efficacy in heavier individuals. We investigated the influence of bodyweight on aspirin pharmacodynamics in two independent datasets of patients taking non-enteric coated aspirin 100 mg QD for coronary artery disease (CAD). In the first dataset, 368 patients had their platelet aggregation assessed using VerifyNow Aspirin and measured in Aspirin Reaction Units (ARU). In the second dataset, 70 patients had serum thromboxane B2 (TXB2) dosage assessed by an ELISA assay and measured in pg/mL. Platelet aggregation was independently associated with bodyweight, with 8.41 (95% CI 1.86-14.97; adjusted p-value = 0.012) increase in ARU for every 10 kg. Furthermore, the rate of non-response to aspirin (defined as ARU ≥ 550) was significantly associated with increased bodyweight (adjusted p-value = 0.007), with OR = 1.23 (95% CI 1.06-1.42) for every 10 kg. Similar results were found considering body mass index (in kg/m 2 ), with 15.5 (95% CI 5.0 to 25.9; adjusted p-value = 0.004) increase in ARU for every 10 kg and non-response OR = 1.43 (95% CI 1.13 to 1.81, adjusted p-value = 0.003) for every 5 kg/m 2 . Moreover, serum TXB2 was higher in patients weighting more than 70 kg (222.6 ± 62.9 versus 194.9 ± 61.9 pg/mL; adjusted p-value = 0.018). In two different datasets of patients with CAD on non-enteric coated aspirin 100 mg QD, increased bodyweight was independently associated with impaired response to aspirin.

Background: The role of beta-blockers in patients with acute coronary syndromes is mainly derived from studies including patients with ST-segment elevation myocardial infarction. Little is known about the use of beta-blockers and associated long-term clinical outcomes in patients with non-ST-elevation acute coronary syndromes (NSTEACS)., Methods: We analyzed short- and long-term clinical outcomes of 2921 patients with NSTEACS using or not oral beta-blockers in the first 24 h of the acute coronary syndromes (ACS) presentation. The association between beta-blocker use and mortality was assessed using a propensity score adjusted analysis (N = 1378)., Results: Patients starting oral beta-blockers in the first 24 h of hospitalization, compared with patients who did not, had lower rates of in-hospital mortality (OR = 0.52, 95% CI 0.33 to 0.74, P = 0.002) and higher mean survival times in the long-term follow-up (11.86±0.4 years vs. 9.92±0.39 years, P < 0.001)., Conclusion: The use of beta-blockers in the first 24 h of patients presenting with NSTEACS was associated with better in-hospital and long-term mortality outcomes.

Introduction: Cardiovascular disease (CVD) is the main cause of death in the world. Coronary artery disease (CAD) is the most common form of CVD presentation, but the prevalence of peripheral artery disease (PAD) is increasing. Patients with polyvascular disease comprise a very high-risk population that has been infrequently studied. Areas covered: The authors review the current evidence of the efficacy and safety of ticagrelor in the setting of acute coronary syndrome and stable patients post-MI with and without PAD and summarize its pharmacokinetics, pharmacodynamics, and regulatory issues. Expert opinion: Randomized studies showed that ticagrelor is superior to clopidogrel in patients with acute coronary syndromes, and is superior to placebo in the chronic phase (>1 year) post-myocardial infarction. Sub-analyses of these studies suggest that patients with myocardial infarction and PAD, compared to patients without these characteristics, may have greater benefit with ticagrelor. Nonetheless, the global evidence about the role of ticagrelor in patients with myocardial infarction and PAD remains relatively sparse, and a prospective randomized trial testing this hypothesis would be necessary to provide more definite data regarding the efficacy and safety of ticagrelor in this very high-risk population.

Background: Data from over 4 decades have reported a higher incidence of silent infarction among patients with diabetes mellitus (DM), but recent publications have shown conflicting results regarding the correlation between DM and presence of pain in patients with acute coronary syndromes (ACS)., Objective: Our primary objective was to analyze the association between DM and precordial pain at hospital arrival. Secondary analyses evaluated the association between hyperglycemia and precordial pain at presentation, and the subgroup of patients presenting within 6 hours of symptom onset., Methods: We analyzed a prospectively designed registry of 3,544 patients with ACS admitted to a Coronary Care Unit of a tertiary hospital. We developed multivariable models to adjust for potential confounders., Results: Patients with precordial pain were less likely to have DM (30.3%) than those without pain (34.0%; unadjusted p = 0.029), but this difference was not significant after multivariable adjustment, for the global population (p = 0.84), and for subset of patients that presented within 6 hours from symptom onset (p = 0.51). In contrast, precordial pain was more likely among patients with hyperglycemia (41.2% vs 37.0% without hyperglycemia, p = 0.035) in the overall population and also among those who presented within 6 hours (41.6% vs. 32.3%, p = 0.001). Adjusted models showed an independent association between hyperglycemia and pain at presentation, especially among patients who presented within 6 hours (OR = 1.41, p = 0.008)., Conclusion: In this non-selected ACS population, there was no correlation between DM and hospital presentation without precordial pain. Moreover, hyperglycemia correlated significantly with pain at presentation, especially in the population that arrived within 6 hours from symptom onset.

Introduction: The oxidative process plays a fundamental role in the pathophysiology of sickle cell anemia (SCA), and population and environmental characteristics may influence redox balance. The aim of this study was to evaluate lipid peroxidation and antioxidant capacity in Brazilian Hb S carriers undergoing different therapies., Methods: Blood samples from 270 individuals were analyzed (Hb SS, n = 68; Hb AS, n = 53, and Hb AA, n = 149). Hemoglobin genotypes were assessed through cytological, electrophoretic, chromatographic, and molecular methods. Plasma lipid peroxidation and antioxidant capacity were measured by spectrophotometric methods., Results: Patients with SCA who used iron-chelating drugs combined with hydroxyurea, associated with regular transfusions, showed lower levels of TBARS (P ≤ 0.05), higher levels of TEAC (P ≤ 0.01), and lower TBARS/TEAC ratio (R = 255.8). The redox profile of Hb AS subjects was not statistically different (P > 0.05) from that of Hb AA subjects., Conclusion: The data suggest that oxidative stress is lower in the patients with SCA who received regular blood transfusions associated with the combined use of HU and iron chelators than the group received only HU. The redox system of the Hb AS carriers is compatible with the control group., (© 2013 John Wiley & Sons Ltd.)

Background: It is well known that the occurrence of bleeding increases in-hospital mortality in patients with acute coronary syndromes (ACS), and there is a good correlation between bleeding risk scores and bleeding incidence. However, the role of bleeding risk score as mortality predictor is poorly studied., Objective: The main purpose of this paper was to analyze the role of bleeding risk score as in-hospital mortality predictor in a cohort of patients with ACS treated in a single cardiology tertiary center., Methods: Out of 1655 patients with ACS (547 with ST-elevation ACS and 1118 with non-ST-elevation ACS), we calculated the ACUITY/HORIZONS bleeding score prospectively in 249 patients and retrospectively in the remaining 1416. Mortality information and hemorrhagic complications were also obtained., Results: Among the mean age of 64.3 ± 12.6 years, the mean bleeding score was 18 ± 7.7. The correlation between bleeding and mortality was highly significant (p < 0.001, OR = 5.296), as well as the correlation between bleeding score and in-hospital bleeding (p < 0.001, OR = 1.058), and between bleeding score and in-hospital mortality (adjusted OR = 1.121, p < 0.001, area under the ROC curve 0.753, p < 0.001). The adjusted OR and area under the ROC curve for the population with ST-elevation ACS were, respectively, 1.046 (p = 0.046) and 0.686 ± 0.040 (p < 0.001); for non-ST-elevation ACS the figures were, respectively, 1.150 (p < 0.001) and 0.769 ± 0.036 (p < 0.001)., Conclusions: Bleeding risk score is a very useful and highly reliable predictor of in-hospital mortality in a wide range of patients with acute coronary syndromes, especially in those with unstable angina or non-ST-elevation acute myocardial infarction.

Background: Hyperglycemia in the acute phase of myocardial infarction is an important prognostic factor. However, its pathophysiology is not fully understood., Objective: To analyze simultaneously the correlation between hyperglycemia and biochemical markers related to stress, glucose and lipid metabolism, coagulation, inflammation, and myocardial necrosis. METHODS Eighty patients with acute myocardial infarction were prospectively included. The following parameters were analyzed: blood glucose; stress hormones (cortisol and norepinephrine); glucose metabolism factors [glycated hemoglobin (HbA1c); insulin]; lipoproteins (total cholesterol, LDL, HDL, minimally modified electronegative LDL, and adiponectin); glycerides (triglycerides, VLDL and fatty acids); coagulation factors (factor VII, fibrinogen, plasminogen activator inhibitor-1); inflammation (high-sensitivity C reactive protein); and myocardial necrosis (CK-MB and troponin). Continuous variables were converted into degrees of relevance using fuzzy logic., Results: Significant correlation was observed between hyperglycemia and glucose metabolism (p < 0.001), lipoproteins (p = 0.03), and necrosis factors (p = 0.03). In the multivariate analysis, only glucose metabolism (OR = 4.3; CI = 2.1-68.9; and p < 0.001) and myocardial necrosis (OR = 22.5; CI = 2-253; and p = 0.012) showed independent and significant correlation. For the analysis of the influence of history of diabetes mellitus, a regression model including only patients without diabetes mellitus was developed, and the results did not change. Finally, in the model adjusted for age, gender, and clinical variables (history of diabetes mellitus, hypertension and dyslipidemia), three variables maintained a significant and independent association with hyperglycemia: glucose metabolism (OR = 24.1; CI = 4.8-122.1; and p < 0.001), myocardial necrosis (OR = 21.9; CI = 1.3-360.9; and p = 0.03), and history of DM (OR = 27; CI = 3.7-195.7; and p = 0.001)., Conclusion: Glucose metabolism and myocardial necrosis markers were the best predictors of hyperglycemia in patients with acute myocardial infarction.

In the past two years we observed several changes in the diagnostic and therapeutic approach of patients with acute heart failure (acute HF), which led us to the need of performing a summary update of the II Brazilian Guidelines on Acute Heart Failure 2009. In the diagnostic evaluation, the diagnostic flowchart was simplified and the role of clinical assessment and echocardiography was enhanced. In the clinical-hemodynamic evaluation on admission, the hemodynamic echocardiography gained prominence as an aid to define this condition in patients with acute HF in the emergency room. In the prognostic evaluation, the role of biomarkers was better established and the criteria and prognostic value of the cardiorenal syndrome was better defined. The therapeutic approach flowcharts were revised, and are now simpler and more objective. Among the advances in drug therapy, the safety and importance of the maintenance or introduction of beta-blockers in the admission treatment are highlighted. Anticoagulation, according to new evidence, gained a wider range of indications. The presentation hemodynamic models of acute pulmonary edema were well established, with their different therapeutic approaches, as well as new levels of indication and evidence. In the surgical treatment of acute HF, CABG, the approach to mechanical lesions and heart transplantation were reviewed and updated. This update strengthens the II Brazilian Guidelines on Acute Heart Failure to keep it updated and refreshed. All clinical cardiologists who deal with patients with acute HF will find, in the guidelines and its summary, important tools to help them with the clinical practice for better diagnosis and treatment of their patients.

It is well documented that Hb S and iron affect blood cells, and trigger oxidative processes and generation of free radicals with potential for lipid peroxidation. We evaluated the frequency of polymorphisms in the HFE gene in Hb AS blood donors and how these polymorphisms influenced lipid peroxidation and antioxidant capacity. Blood samples were collected from 211 Hb AS blood donors, 119 Hb AA blood donors as a control group, and 28 sickle cell disease patients (Hb SS). The H63D allele was found at a frequency of 10.5% in the Hb AS samples, and the C282Y allele frequency was 0.7%. In the control group, the frequencies of the H63D and C282Y alleles were 13.4 and 2.1%, respectively. In the sickle-cell disease patients, the H63D and the C282Y allele frequencies were 10.7 and 3.5%, respectively. The frequencies of the C282Y and H63D polymorphisms in Hb AS blood donors are similar to those reported for the Brazilian population. Serum malondialdehyde values, indicative of lipid peroxidation, were highest in sickle cell patients, independent of the polymorphisms in the HFE gene, with significant differences, showing the influence of Hb S allele in the levels of lipid peroxidation. However, the trolox equivalent antioxidant capacity average levels, indicative of the antioxidant capacity, were reduced with significant differences, indicating that in spite of a lipid peroxidation raise, this is not followed by the increased of the antioxidant capacity, leading to oxidative stress.

Introduction: In elderly patients with acute myocardial infarction, very little is known about the role of surgical myocardial revascularization and percutaneous coronary intervention (invasive therapies--IT), especially in the context of long-term outcomes after hospital discharge., Methods: We analyzed 1588 patients with MI who had been included prospectively in a databank and followed for up to 7.5 years. In this population, 548 patients were >70 years old (elderly group--EG), and 1040 were <70 years of age (younger group--YG); 1088 underwent IT during hospitalization, and the remaining 500 were treated medically (conservative therapy--CT). Patients were monitored either by visit or by phone at least once a year. A standard questionnaire was administered to all patients. The impact of IT was analyzed with both non-adjusted and adjusted models., Results: By the end of the follow-up period, the survival rates for the IT and CT groups were, respectively, 71.9% versus 47.2% in the global population (hazard ratio=0.55, P<0.001), 81.5% versus 66.6% in the YG (hazard ratio=0.68, P=0.018) and 48.8% versus 20.3% in the EG (hazard ratio=0.58, P<0.001). In the adjusted models, the hazard ratios were 0.62 (P<0.001) in the global population, 0.74 in the YG (P=0.073) and 0.64 (P=0.001) in the EG., Conclusion: Long-term follow-up of patients with myocardial infarction revealed that IT during the in-hospital phase was at least as effective in elderly patients as in younger patients.

Background: Little is known, especially in our country, about the influence of health insurance plans on the long term outcome of patients after acute myocardial infarction (AMI)., Objective: To assess the outcome of patients with AMI who are covered by the National Health System (SUS) or other health insurance plans., Methods: We analyzed 1,588 patients with AMI (mean age of 63.3 + 12.9 years, 71.7% male) who were included prospectively into a specific database and followed up for up to 7.55 years. Of this total, 1,003 were placed in the "SUS" group and 585 in the "other insurance plans" group. We applied chi-square, log-rank and Cox (stepwise) to the different statistical analyses. The long term multivariate model with mortality as a dependent variable included 18 independent variables., Results: In-hospital mortality rates in the "other insurance plans" and "SUS" groups were 11.4% and 10.3%, respectively (p = 0.5); in the long term, survival chances in the groups were respectively, 70.4% + 2.9 and 56.4% + 4.0 (p = 0.001, hazard-ratio = 1.43, or a 43% higher chance of death in the "SUS" group). In the adjusted model, the 'SUS' group had a significantly higher chance of death (a 36% higher chance, p = 0.005). Surgical revascularization and angioplasty improved the prognosis of these patients, whereas age and previous history of infarction, diabetes or heart failure worsened the prognosis., Conclusions: Relative to patients with other insurance plans, SUS users present similar mortality rates during hospital stay, but their prognosis is worse in the long term, thus reinforcing the need for additional efforts to improve the care provided to these patients after hospital discharge.

Objective: To assess preoperative predictors of mortality in patients undergoing coronary artery bypass grafting (CABG) within the first 30 days of acute myocardial infarction (AMI)., Methods: Between March 1998 and July 2002, 753 AMI patients were consecutively and prospectively entered into a database, 135 (17.9%) of whom underwent isolated CABG and were enrolled in this study. The following prognostic factors were assessed by multivariate analysis: age, gender, diabetes, history of previous AMI, CABG or coronary angioplasty (PTCA), anterior infarct location, Q-wave AMI, the use of fibrinolytics, elapsed time from AMI to the procedure, and presence of complications in the preoperative period., Results: Overall in-hospital mortality was 6.7%, ranging from 12.5% in patients with preoperative complications to 1.4% in those with no complications. Only history of previous angioplasty (p = 0.037) and cardiogenic shock (p = 0.002) showed a statistically significant correlation with postoperative mortality. The use of thrombolytics, on the other hand, in the initial management of AMI showed a negative correlation with mortality (p = 0.035)., Conclusion: CABG in the acute phase of MI is associated with distinct operative mortality, depending on the patients preoperative clinical condition. Among those factors analyzed, preoperative cardiogenic shock and history of previous angioplasty were predictive of worse prognosis in this group of patients.

In patients with acute myocardial infarction (AMI), little is known about the correlation between prognostic variables and aspects of ruptured plaque at the coronary angiography. Five hundred patients with acute myocardial infarction were studied in a consecutive and prospective manner; of these, 264 patients were excluded mainly because of the presence of an occluded culprit coronary artery. The remaining 236 patients were divided according to the presence (113, 52%) or absence (126, 48%) of angiographic aspects suggestive of ruptured plaque, and correlated with 49 clinical, electrocardiographic, in-hospital complications, procedures, and other angiographic prognostic variables. The variables that correlated significantly and independently with angiographic aspects of ruptured plaque were: presence of thrombi and higher degree of residual stenosis at the culprit coronary artery, as well as white ethnic group.

Orbofiban is a unique antiplatelet agent that inhibits the binding of fibrinogen to gycoprotein (GP) IIb/IIIa integrin receptors and thus prevents platelet aggregation induced by various agents. However, recent studies indicate that treatment with orbofiban does not reduce the incidence of recurrent ischemic events. The mechanisms underlying the lack of benefit of orbofiban in patients with acute coronary syndromes are not completely clear. The purpose of this study was to characterize the effects of orbofiban on cellular activation (neutrophil superoxide generation) and surface expression of adhesion molecules of circulating neutrophils (CD18, CD11b, and L-selectin) and platelets (P-selectin and GP IIb/IIIa) in patients with acute coronary syndromes. After 5-7 days, orbifiban (50 mg BID) did not reduce PMN adhesion molecule expression and ex vivo-stimulated PMN superoxide generation--as was observed in the placebo group, without orbofiban. In contrast, orbofiban induced marked reductions in GP IIb/IIIa and P-selectin expressions after 5-7 days of treatment. The sustained neutrophil activation observed with orbofiban may have a role on the recurrent thrombotic events observed with orbofiban treatment in the OPUS-TIMI 16 trial.

A woman aged 98 years entered the tertiary hospital service with a picture of acute myocardial infarction of the extensive anterior wall, which began 4 hours earlier. Due to the large myocardial risk area suggested by the electrocardiogram, the patient was taken to the hemodynamics laboratory for the performance of emergency coronary arteriography, which revealed occlusion in the proximal third of the anterior descending artery. Primary angioplasty followed by stent grafting was successfully performed. The patient had a satisfactory evolution (Killip I) and was discharged from the hospital on the seventh postinfarction day. We discuss here aspects of thrombolysis and coronary percutaneous interventions in the aged.