Paul A. Schurmann, MD and Glenn N. Levine, MD, FACC, FAHA

1. What is non–ST segment elevation acute coronary syndrome?

    It is now recognized that unstable angina, non–Q wave myocardial infarction (MI), non–ST segment elevation MI, and ST segment elevation myocardial infarction (STEMI) are all part of a continuum of the pathophysiologic process in which a coronary plaque ruptures, thrombus formation occurs, and partial or complete, transient or more sustained vessel occlusion may occur (Fig. 17-1). This process is deemed acute coronary syndrome when it is clinically recognized and causes symptoms. Acute coronary syndromes can be subdivided for treatment purposes into non–ST segment elevation acute coronary syndrome (NSTE-ACS) and ST segment elevation acute coronary syndrome (STE-ACS).

    The American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines have traditionally used the terms unstable angina/non–ST elevation MI (UA/NSTEMI) when referring to patients with NSTE-ACS, whereas the European Society of Cardiology (ESC) guidelines prefer the term acute coronary syndrome without ST elevation.

2. What is the current definition of a myocardial infarction?

    According to the 2007 joint ESC/ACCF/AHA/World Heart Federation statement, the term myocardial infarction should be used “when there is evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia.” For patients with acute coronary syndromes, this includes detection of the rise or fall of cardiac biomarkers (preferably troponin) with at least one value above the ninety-ninth percentile of the upper reference limit, and evidence of myocardial ischemia with at least one of the following:

Note that using this definition, patients admitted with anginal chest pains and troponin elevations of as little as 0.04 to 0.08 ng/mL may now be diagnosed as having myocardial infarction, depending on locally established ninety-ninth percentile ranges of troponin values.

3. What other conditions besides epicardial coronary artery disease and acute coronary syndrome can cause elevations in troponin?

    Although troponins have extremely high myocardial tissue specificity and sensitivity with new assay, numerous conditions besides epicardial coronary artery disease and acute coronary syndromes may cause elevations of troponins. Such conditions include noncoronary cardiac disease (myocarditis, acute congestive heart failure [CHF] exacerbation, cardiac contusion, apical ballooning syndrome), acute vascular pathology (hypertensive crisis, aortic dissection, pulmonary embolus), infiltrative diseases (amyloidosis, sarcoidosis), and systemic illnesses (anemia, chromic kidney disease [CKD], hypothyroidism, hypoxemia). Conditions that have been associated with elevation of troponin levels are given in Table 17-1.

4. What are the factors that make up the Thrombolysis in Myocardial Infarction (TIMI) Risk Score?

    The seven factors that make up the TIMI Risk Score are shown in the list that follows. Each factor counts as 1 point. A total score of 0 to 2 is a low TIMI Risk Score and is associated with a 4.7% to 8.3% 2-week risk of adverse cardiac events; a total score of 3 to 5 is an intermediate TIMI Risk Score and is associated with a 13.2 to 26.2% 2-week risk of adverse cardiac events; and a total score of 6 to 7 is a high TIMI Risk Score and is associated with a 40.9% risk of adverse cardiac events.

5. What are the components of the Global Registry of Acute Coronary Events (GRACE) ACS Risk Model (at the time of admission)?

    The components of the GRACE ACS Risk Model at the time of admission consist of:

Scores are calculated based on established criteria. Calculation algorithms are easily downloadable to computers and handheld devices. A low-risk score is considered 108 or less and is associated with a less than 1% risk of in-hospital death. An intermediate score is 109 to 140 and is associated with a 1% to 3% risk of in-hospital death. A high-risk score is greater than 140 and associated with a more than 3% risk of in-hospital death.

6. What other biomarkers and measured blood levels have been shown to correlate with increased risk of adverse cardiovascular outcome?

    Multiple biomarkers can be measured in the blood, but it is important to understand what they represent. The most common are creatine kinase–MB (CK-MB) and troponin T and I levels, which are related to myocardial injury and are independent predictors of adverse cardiovascular outcomes.

    Common inflammatory biomarkers like C-reactive protein (CRP), matrix metalloproteinase (MMP-9), myeloperoxidase (MPO), B-type natriuretic peptide (BNP), and ischemia modified albumin (IMA) have been shown to be independent predictors of adverse cardiovascular outcomes. How these findings should be used in clinical practice is subject to continued investigation and debate. Additional markers are expected to emerge over the next several years.

7. What are the differences between the oral antiplatelet agents?

    The first thienopyridine was ticlopidine (Ticlid), which was used along with aspirin for the prevention of stent thrombosis. Ticlopidine was replaced in clinical practice by clopidogrel, which was a once-daily agent with similar efficacy to ticlopidine, but better tolerated.

    More recently, the thienopyridine prasugrel and the triazolopyrimidine ticagrelor have been approved for use. These two agents have been studied in patients with ACS undergoing stent implantation. Like clopidogrel, both are P2Y₁₂ blockers. Both these newer agents are more potent than clopidogrel, leading to greater and more reliable platelet inhibition than clopidogrel. They also both have a shorter onset of action than clopidogrel. Like clopidogrel, prasugrel irreversibly inhibits the platelet. Although ticagrelor does not irreversibly inhibit the platelet, there nevertheless is effective platelet inhibition for days following discontinuation of ticagrelor. The characteristics of these 3 agents are summarized in Table 17-2.