Early assessment and treatment of myocardial infarction

Abstract

Although the detection and treatment of acute myocardial infarction (MI) has dramatically improved the last decades, ischemic heart disease is still a leading cause of death worldwide. Whereas mortality has declined in industrialized countries, it continues to rise in other parts of the world. Therefore improvement in the evaluation of chest pain patients and the treatment of MI is needed.

Diagnosing acute coronary syndromes (ACS) can be challenging, especially in the first hours after the onset of symptoms. The discovery and validation of early detectable biomarkers could greatly improve patient management and outcome. Extracellular vesicles (ECVs) are small vesicles that are shed by cells that are important in the pathogenesis of ACS, making them an interesting potential source of early detectable biomarkers for ACS. Serum levels of selected ECV proteins show associations with the presence of myocardial ischemia in chest pain patients. Although these proteins at this stage are not able to compete with currently used biomarkers, this study shows that ECV content changes within the first hours after ACS, identifying ECVs as a promising source of biomarkers for ACS.

Many studies have reported differences in cardiovascular risk factor profiles between Caucasians and Asian ethnic groups, as well as inter-ethnic differences within Asia. We investigated the influence of ethnicity on clinical outcome in chest pain patients from four major ethnic groups in the Netherlands and Singapore. This study showed that Caucasian and Malay chest pain patients had a higher chance of having an MI compared with Chinese and Indians. In contrast, Chinese and Indian patients had a higher prevalence of unstable angina. Furthermore, MI patients from all Asian ethnic groups had more severe coronary artery disease than Caucasian MI patients. These differences potentially influence the performance of risk stratification tools, such as the HEART score. In the same cohort it was shown that the HEART score tends to underestimate the risk of adverse cardiac events in certain Asian ethnic groups. Therefore, we recommend the consideration of ethnicity in risk stratification and clinical decision making in patients presenting to the emergency department with chest pain.

The treatment of acute MI by reperfusion of the ischemic myocardium comes at the cost of inducing several processes leading to additional myocardial injury, called ischemia-reperfusion (IR) injury. An exaggerated immune response is a major factor contributing to IR injury. Complement factor 5a (C5a) and leukotriene B4 (LTB4), as activation products of important inflammatory pathways, are powerful mediators of the immune response. Absence of C5aR, the receptor for C5a, on bone-marrow derived cells was shown to reduce infarct size and attenuate cardiac function by reducing influx of neutrophils and T cells into the infarcted myocardium following myocardial IR in mice. Furthermore selectively blocking BLT1, the receptor for LTB4, with a BLT1 antagonist directly after myocardial reperfusion reduced infarct size and improved cardiac function in a mouse model of myocardial IR injury by reducing leucocyte activation and myocardial apoptosis. Therefore, blocking these receptors forms a promising potential therapeutic option to limit myocardial IR injury.