Recent advances in the diagnosis and treatment of acute myocardial infarction

Abstract

The Third Universal Definition of Myocardial Infarction (MI) requires cardiac myocyte necrosis with an increase and/or a decrease in a patient’s plasma of cardiac troponin (cTn) with at least one cTn measurement greater than the 99^th percentile of the upper normal reference limit during: (1) symptoms of myocardial ischemia; (2) new significant electrocardiogram (ECG) ST-segment/T-wave changes or left bundle branch block; (3) the development of pathological ECG Q waves; (4) new loss of viable myocardium or regional wall motion abnormality identified by an imaging procedure; or (5) identification of intracoronary thrombus by angiography or autopsy. Myocardial infarction, when diagnosed, is now classified into five types. Detection of a rise and a fall of troponin are essential to the diagnosis of acute MI. However, high sensitivity troponin assays can increase the sensitivity but decrease the specificity of MI diagnosis. The ECG remains a cornerstone in the diagnosis of MI and should be frequently repeated, especially if the initial ECG is not diagnostic of MI.

There have been significant advances in adjunctive pharmacotherapy, procedural techniques and stent technology in the treatment of patients with MIs. The routine use of antiplatelet agents such as clopidogrel, prasugrel or ticagrelor, in addition to aspirin, reduces patient morbidity and mortality. Percutaneous coronary intervention (PCI) in a timely manner is the primary treatment of patients with acute ST segment elevation MI. Drug eluting coronary stents are safe and beneficial with primary coronary intervention. Treatment with direct thrombin inhibitors during PCI is non-inferior to unfractionated heparin and glycoprotein IIb/IIIa receptor antagonists and is associated with a significant reduction in bleeding. The intra-coronary use of a glycoprotein IIb/IIIa antagonist can reduce infarct size. Pre- and post-conditioning techniques can provide additional cardioprotection. However, the incidence and mortality due to MI continues to be high despite all these recent advances. The initial ten year experience with autologous human bone marrow mononuclear cells (BMCs) in patients with MI showed modest but significant increases in left ventricular (LV) ejection fraction, decreases in LV end-systolic volume and reductions in MI size. These studies established that the intramyocardial or intracoronary administration of stem cells is safe. However, many of these studies consisted of small numbers of patients who were not randomized to BMCs or placebo. The recent LateTime, Time, and Swiss Multicenter Trials in patients with MI did not demonstrate significant improvement in patient LV ejection fraction with BMCs in comparison with placebo. Possible explanations include the early use of PCI in these patients, heterogeneous BMC populations which died prematurely from patients with chronic ischemic disease, red blood cell contamination which decreases BMC renewal, and heparin which decreases BMC migration. In contrast, cardiac stem cells from the right atrial appendage and ventricular septum and apex in the SCIPIO and CADUCEUS Trials appear to reduce patient MI size and increase viable myocardium. Additional clinical studies with cardiac stem cells are in progress.

Keywords: Myocardial necrosis, Type 1-5 myocardial infarctions, Troponin assays, Percutaneous coronary intervention, Fibrinolytic therapy, Thienopyridines, Cardioprotection, Bone marrow stem cells, Cardiac stem cells

Core tip: The Third Universal Definition of myocardial infarction (MI) combines clinical symptoms, cardiac biomarkers and electrocardiogram (ECG) changes. Small amounts of myocardial necrosis may occur with heart failure, renal failure, myocarditis, arrhythmias, pulmonary embolism or uneventful percutaneous or surgical coronary revascularization and should be termed myocardial injury. High sensitivity troponin assays increase the sensitivity but decrease the specificity of MI diagnosis. The ECG remains a cornerstone of MI diagnosis. Primary percutaneous coronary intervention in a timely manner is the primary treatment of patients with acute ST segment elevation MI. Antiplatelet agents (clopidogrel, prasugrel or ticagrelor), in addition to aspirin, reduce patient MI morbidity and mortality. The recent LateTime, Time, and Swiss Multicenter Trials of bone marrow stem cells in MI treatment did not demonstrate significant improvement in patient LV ejection fraction in comparison with placebo. In contrast, cardiac stem cells from the right atrial appendage or ventricular septum/apex in the SCIPIO and CADUCEUS Trials reduced patient MI size and increased viable myocardium. Studies with cardiac stem cells are continuing.