Prediction of enzymatic infarct size in ST-segment elevation myocardial infarction

Objectives Predictors of adverse outcomes following myocardial infarction (MI) are well established; however, little is known about what predicts enzymatically estimated infarct size in patients with acute ST-elevation MI. The Complement And Reduction of INfarct size after Angioplasty or Lytics trials of pexelizumab used creatine kinase (CK)-MB area under the curve to determine infarct size in patients treated with primary percutaneous coronary intervention (PCI) or fibrinolysis. Methods Prediction of infarct size was carried out by measuring CK-MB area under the curve in patients with ST-segment elevation MI treated with reperfusion therapy from January 2000 to April 2002. Infarct size was calculated in 1622 patients (PCI=817; fibrinolysis=805). Logistic regression was used to examine the relationship between baseline demographics, total ST-segment elevation, index angiographic findings (PCI group), and binary outcome of CK-MB area under the curve greater than 3000 ng/ml. Results Large infarcts occurred in 63% (515) of the PCI group and 69% (554) of the fibrinolysis group. Independent predictors of large infarcts differed depending on mode of reperfusion. In PCI, male sex, no prior coronary revascularization and diabetes, decreased systolic blood pressure, sum of ST-segment elevation, total (angiographic) occlusion, and nonright coronary artery culprit artery were independent predictors of larger infarcts (C index=0.73). In fibrinolysis, younger age, decreased heart rate, white race, no history of arrhythmia, increased time to fibrinolytic therapy in patients treated up to 2 h after symptom onset, and sum of ST-segment elevation were independently associated with a larger infarct size (C index=0.68). Conclusion Clinical and patient data can be used to predict larger infarcts on the basis of CK-MB quantification. These models may be helpful in designing future trials and in guiding the use of novel pharmacotherapies aimed at limiting infarct size in clinical practice. Coron Artery Dis 23:118-125 (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

In-hospital death in acute coronary syndrome was related to admission glucose in men but not in women

Background: Admission hyperglycaemia is associated with mortality in patients with acute coronary syndrome (ACS), but controversy exists whether hyperglycaemia uniformly affects both genders. We evaluated coronary risk factors, gender, hyperglycaemia and their effect on hospital mortality. Methods: 959 ACS patients (363 women and 596 men) were grouped based on glycaemia >= or < 200 mg/dL and gender: men with glucose < 200 mg/dL (menG-); women with glucose < 200 mg/dL (womenG-); men with glucose >= 200 mg/dL (menG+); and women with glucose >= 200 mg/dL (womenG+). A logistic regression analysis compared the relation between gender and glycaemia groups and death, adjusted for coronary risk factors and laboratory data. Results group: menG- had lower mortality than menG+ (OR = 0.172, IC95% 0.062-0.478), and womenG+ (OR = 0.275, IC95% 0.090-0.841); womenG- mortality was lower than menG+ (OR = 0.230, IC95% 0.074-0.717). No difference was found between menG+ vs womenG+ (p = 0.461), or womenG- vs womenG+ (p = 0.110). Age (OR = 1.067, IC95% 1.031-1.104), EF (OR = 0.942, IC95% 0.915-0.968), and serum creatinine (OR = 1.329, IC95% 1.128-1.566) were other independent factors related to in-hospital death. Conclusions: Death was greater in hyperglycemic men compared to lower blood glucose men and women groups, but there was no differences between women groups in respect to glycaemia after adjustment for coronary risk factors.

Thrombin-Receptor Antagonist Vorapaxar in Acute Coronary Syndromes

BACKGROUND Vorapaxar is a new oral protease-activated receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. METHODS In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. RESULTS Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5010 vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups. CONCLUSIONS In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.)

Prasugrel versus Clopidogrel for Acute Coronary Syndromes without Revascularization

Background The effect of intensified platelet inhibition for patients with unstable angina or myocardial infarction without ST-segment elevation who do not undergo revascularization has not been delineated. Methods In this double-blind, randomized trial, in a primary analysis involving 7243 patients under the age of 75 years receiving aspirin, we evaluated up to 30 months of treatment with prasugrel (10 mg daily) versus clopidogrel (75 mg daily). In a secondary analysis involving 2083 patients 75 years of age or older, we evaluated 5 mg of prasugrel versus 75 mg of clopidogrel. Results At a median follow-up of 17 months, the primary end point of death from cardiovascular causes, myocardial infarction, or stroke among patients under the age of 75 years occurred in 13.9% of the prasugrel group and 16.0% of the clopidogrel group (hazard ratio in the prasugrel group, 0.91; 95% confidence interval [CI], 0.79 to 1.05; P = 0.21). Similar results were observed in the overall population. The prespecified analysis of multiple recurrent ischemic events (all components of the primary end point) suggested a lower risk for prasugrel among patients under the age of 75 years (hazard ratio, 0.85; 95% CI, 0.72 to 1.00; P = 0.04). Rates of severe and intracranial bleeding were similar in the two groups in all age groups. There was no significant between-group difference in the frequency of nonhemorrhagic serious adverse events, except for a higher frequency of heart failure in the clopidogrel group. Conclusions Among patients with unstable angina or myocardial infarction without ST- segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.)

Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes and a History of Stroke or Transient Ischemic Attack

Background-Patients with acute coronary syndromes and history of stroke or transient ischemic attack (TIA) have an increased rate of recurrent cardiac events and intracranial hemorrhages. Methods and Results-We evaluated treatment effects of ticagrelor versus clopidogrel in patients with acute coronary syndrome with and without a history of prior stroke or TIA in the PLATelet inhibition and patient Outcomes (PLATO) trial. Of the 18 624 randomized patients, 1152 (6.2%) had a history of stroke or TIA. Such patients had higher rates of myocardial infarction (11.5% versus 6.0%), death (10.5% versus 4.9%), stroke (3.4% versus 1.2%), and intracranial bleeding (0.8% versus 0.2%) than patients without prior stroke or TIA. Among patients with a history of stroke or TIA, the reduction of the primary composite outcome and total mortality at 1 year with ticagrelor versus clopidogrel was consistent with the overall trial results: 19.0% versus 20.8% (hazard ratio, 0.87; 95% confidence interval, 0.66-1.13; interaction P=0.84) and 7.9% versus 13.0% (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91). The overall PLATO-defined bleeding rates were similar: 14.6% versus 14.9% (hazard ratio, 0.99; 95% confidence interval, 0.71-1.37), and intracranial bleeding occurred infrequently (4 versus 4 cases, respectively). Conclusions-Patients with acute coronary syndrome with a prior history of ischemic stroke or TIA had higher rates of clinical outcomes than patients without prior stroke or TIA. However, the efficacy and bleeding results of ticagrelor in these high-risk patients were consistent with the overall trial population, with a favorable clinical net benefit and associated impact on mortality.

Summary of the II Brazilian Guideline Update on Acute Heart Failure 2009/2011

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.

High sodium intake adversely affects oxidative-inflammatory response, cardiac remodelling and mortality after myocardial infarction

Objective: Enhanced sodium intake increases volume overload, oxidative stress and production of proinflammatory cytokines. In animal models, increased sodium intake favours ventricular dysfunction after myocardial infarction (MI). The aim of this study was to investigate, in human subjects presenting with ST-segment elevation MI (STEMI), the impact of sodium intake prior the coronary event. Methods: Consecutive patients (n = 372) admitted within the first 24 h of STEMI were classified by a food intake questionnaire as having a chronic daily intake of sodium higher (HS) or lower (LS) than 1.2 g in the last 90 days before MI. Plasma levels of 8-isoprostane, interleucin-2 (IL-2), tumour necrosis factor type alpha (TNF-alpha), C-reactive protein (CRP) and brain natriuretic peptide (BNP) were measured at admission and at the fifth day. Magnetic resonance imaging was performed immediately after discharge. Total mortality and recurrence of acute coronary events were investigated over 4 years of follow-up. Results: The decrease of 8-isoprostane was more prominent and the increase of IL-2, TNF-alpha and CRP less intense during the first 5 days in LS than in HS patients (p < 0.05). Sodium intake correlated with change in plasma BNP between admission and fifth day (r = 0.46; p < 0.0001). End-diastolic volumes of left atrium and left ventricle were greater in HS than in LS patients (p < 0.05). In the first 30 days after MI and up to 4 years afterwards, total mortality was higher in HS than in LS patients (p < 0.05). Conclusion: Excessive sodium intake increases oxidative stress, inflammatory response, myocardial stretching and dilatation, and short and long-term mortality after STEMI. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

BNP and Admission Glucose as In-Hospital Mortality Predictors in Non-ST Elevation Myocardial Infarction

Objectives. Admission hyperglycemia and B-type natriuretic peptide (BNP) are associated with mortality in acute coronary syndromes, but no study compares their prediction in-hospital death. Methods. Patients with non-ST-elevation myocardial infarction (NSTEMI), in-hospital mortality and two-year mortality or readmission were compared for area under the curve (AUC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and accuracy (ACC) of glycemia and BNP. Results. Respectively, AUC, SEN, SPE, PPV, NPV, and ACC for prediction of in-hospital mortality were 0.815, 71.4%, 84.3%, 26.3%, 97.4%, and 83.3% for glycemia = 200 mg/dL and 0.748, 71.4%, 68.5%, 15.2%, 96.8% and 68.7% for BNP = 300 pg/mL. AUC of glycemia was similar to BNP (P = 0.411). In multivariate analysis we found glycemia >= 200mg/dL related to in-hospital death (P = 0.004). No difference was found in two-year mortality or readmission in BNP or hyperglycemic subgroups. Conclusion. Hyperglycemia was an independent risk factor for in-hospital mortality in NSTEMI and had a good ROC curve level. Hyperglycemia and BNP, although poor in-hospital predictors of unfavorable events, were independent risk factors for death or length of stay >10 days. No relation was found between hyperglycemia or BNP and long-term events.

ST Elevation Myocardial Infarction in the elderly

Acute coronary syndromes (ACS) are the leading causes of death in the elderly. The suspicion and diagnosis of ACS in this age group is more difficult, since typical angina is less frequent. The morbidity and mortality is greater in older age patients presenting ACS. Despite the higher prevalence and greater risk, elderly patients are underrepresented in major clinical trials from which evidence based recommendations are formulated. The authors describe, in this article, the challenges in the diagnosis and management of ST elevation myocardial infarction in the elderly, and discuss the available evidence.

Air pollution and health: bridging the gap from sources to health outcomes: conference summary

Air Pollution and Health: Bridging the Gap from Sources to Health Outcomes, an international specialty conference sponsored by the American Association for Aerosol Research, was held to address key uncertainties in our understanding of adverse health effects related to air pollution and to integrate and disseminate results from recent scientific studies that cut across a range of air pollution-related disciplines. The Conference addressed the science of air pollution and health within a multipollutant framework (herein "multipollutant" refers to gases and particulate matter mass, components, and physical properties), focusing on five key science areas: sources, atmospheric sciences, exposure, dose, and health effects. Eight key policy-relevant science questions integrated across various parts of the five science areas and a ninth question regarding findings that provide policy-relevant insights served as the framework for the meeting. Results synthesized from this Conference provide new evidence, reaffirm past findings, and offer guidance for future research efforts that will continue to incrementally advance the science required for reducing uncertainties in linking sources, air pollutants, human exposure, and health effects. This paper summarizes the Conference findings organized around the science questions. A number of key points emerged from the Conference findings. First, there is a need for greater focus on multipollutant science and management approaches that include more direct studies of the mixture of pollutants from sources with an emphasis on health studies at ambient concentrations. Further, a number of research groups reaffirmed a need for better understanding of biological mechanisms and apparent associations of various health effects with components of particulate matter (PM), such as elemental carbon, certain organic species, ultrafine particles, and certain trace elements such as Ni, V, and Fe(II), as well as some gaseous pollutants. Although much debate continues in this area, generation of reactive oxygen species induced by these and other species present in air pollution and the resulting oxidative stress and inflammation were reiterated as key pathways leading to respiratory and cardiovascular outcomes. The Conference also underscored significant advances in understanding the susceptibility of populations, including the role of genetics and epigenetics and the influence of socioeconomic and other confounding factors and their synergistic interactions with air pollutants. Participants also pointed out that short-and long-term intervention episodes that reduce pollution from sources and improve air quality continue to indicate that when pollution decreases so do reported adverse health effects. In the limited number of cases where specific sources or PM2.5 species were included in investigations, specific species are often associated with the decrease in effects. Other recent advances for improved exposure estimates for epidemiological studies included using new technologies such as microsensors combined with cell phone and integrated into real-time communications, hybrid air quality modeling such as combined receptor-and emission-based models, and surface observations used with remote sensing such as satellite data.