In the United States, there are 1.19 million hospital admissions for ACS annually. UA/NSTEMI patients constitute 845 million, or ∽71% of the total, while STEMI patients make up a smaller fraction. The overall incidence of both NSTE-ACS and STEMI has decreased in the past decade, likely due to decreased smoking rates and improved medical therapy (especially statins) (2).

The acute in-hospital mortality of STEMI (7%) is higher than that of NSTE-ACS (3%—5%), but equalizes by 6 months. Longerterm follow-up demonstrates that NSTE-ACS has a higher mortality rate than STEMI. This is explained by different patient profiles: NSTE-ACS patients on average tend to be older and have more comorbidities such as diabetes and renal failure, whereas STEMI patients tend to be younger smokers.

ACS result from coronary artery obstruction causing myocardial ischemia and NSTEMI and STEMI myocardial necrosis. Acute coronary artery obstruction typically results from thrombosis of a ruptured coronary plaque, with or without concomitant vasoconstriction. In contrast to the previous conception that coronary artery disease (CAD) is a slowly progressive disease, the current understanding of CAD (see Chapter 1) is that of a stuttering inflammatory process of repeated plaque rupture and healing on top of a lipid core. Abrupt thrombotic occlusion may rapidly progress in plaques that are not obstructive at baseline.

Coronary thrombosis involves endothelial dysfunction and disruption, platelet activation, and circulating coagulation proteins. The platelet is a central actor and regulates the process of thrombosis (see Chapter 5). When endothelial cells are injured, thrombosis begins with rapid adhesion of platelets to the site of injury. Within seconds, the platelets are activated, degranulate, and recruit additional platelets to the developing thrombus. The secretory granules release adenosine diphosphate (ADP), which stimulates further platelet activation, and thrombin, which initiates the coagulation system. Thromboxane is generated from the platelet phospholipase A2, and has an additional effect on platelet activation. Ultimately, glycoprotein (GP) IIb/IIIa receptors on the platelet are activated. GP IIb/IIIa receptors bind to fibrinogen, cross-linking platelets together. Repetitive platelet activation and fibrinogen cross-linking brings about platelet aggregation, which can then lead to occlusive thrombus formation. Although there are multiple pathways to platelet activation, the platelet GP IIb/IIIa
receptor is the final common pathway in platelet aggregation that would lead to NSTEMI.

When plaque rupture results in complete (100%) thrombotic occlusion and is sustained, the myocardial infarction (MI) that results is typically transmural and associated with ST-segment elevation. Without reperfusion, this ultimately leads to a Q-wave infarction. With subtotal (99% or less) or transient occlusion, the presentation may be either UA or NSTEMI, depending upon the degree and duration of ischemia. When ischemia is sufficient to cause myonecrosis detectable by serum biomarkers, NSTEMI is diagnosed. With the use of sensitive troponin assays, patients who would have formerly been categorized as UA (based on negative creatine kinase) are increasingly diagnosed as NSTEMI.

Other less common causes of ACS include spontaneous coronary dissection, spasm (Prinzmetal angina, cocaine), inflammatory arteritis, trauma, and thromboembolism. These rare causes should be considered in patients lacking CAD risk factors. For instance, a younger peripartum woman with chest pain and changes in electrocardiogram (ECG) may be more likely to have spasm or coronary dissection than atherosclerotic disease.

The clinical presentation of ACS classically includes substernal chest discomfort associated with diaphoresis and dyspnea. This sensation may variably be described as pressure or sharp pain, depending on the patient. The chest discomfort may radiate to the left arm, and also to the shoulder, neck, or jaw. Relief of chest pain with nitroglycerin and exacerbation of the chest pain with manual pressure may point toward a noncardiac cause for chest pain, but these signs are insufficiently reliable for clinical diagnosis.

Atypical presentations occur frequently, particularly among diabetic patients and women. Dyspnea, epigastric pain, nausea, syncope, or unexplained tachycardia may be the only symptoms to suggest a cardiac pathology.

Physical examination of the ACS patients is often unremarkable. Signs of left ventricular dysfunction (rales, third heart sound, hypotension, jugular venous distention) or cardiogenic shock (cold clammy extremities, tachycardia) may be present in patients with extensive MI or prior injury. Transient ischemia may be associated with papillary muscle dysfunction and intermittent murmur of mitral regurgitation.

Patients with chest pain require prompt triage and risk assessment in an emergency room. An ECG should be immediately performed, with a goal of within 10 minutes. Serial ECGs are also recommended for patients with nondiagnostic ECGs or for those who continue to be symptomatic. Comparison with prior ECGs can be extremely valuable, particularly in patients with baseline abnormalities such as hypertrophy or early repolarization. ECGs should be reviewed for ST-segment elevation (≥1 mm in two contiguous leads) or new left bundle branch block, which may indicate acute STEMI. Isolated ST-segment depression in right precordial leads (V1-V3) with tall R waves may indicate a true posterior infarction, which should also be treated as a STEMI. NSTE-ACS may present as ST-segment depression or T-wave inversions, or be electrically silent. Dynamic ST-segment or T-wave changes increase the specificity of the ECG for ACS.

Unfortunately, the history and physical examination, and ECG are sufficient to diagnose ACS in only <50% of cases. Cardiac biomarkers should thus be drawn on all patients with suspected ACS. Biomarkers may not be elevated in the first 4 hours after the onset of symptoms, and thus serial biomarkers should be drawn at 6- or 8-hour intervals. The preferred cardiac biomarker is the troponin assay (cTnI or cTnT), which has a very high (>95%) sensitivity for myocardial injury. Ultrahigh-sensitivity (>99%) troponin assays are increasingly becoming available, and may reduce the time to diagnosis of ACS (3). Abnormal troponin levels connote an increased risk for major adverse cardiac events and death, with higher concentrations indicating progressively elevated risk (4). The specificity of the cardiac troponin for ACS is reported to be very high (>95%) when used in patients with chest pain. However, when used in a patient population broader than that in clinical trials, the test may be positive for reasons besides ACS, and there may still be a role for less-sensitive (but more specific) markers such as CK-MB. For instance, following PCI, troponin assays are overly sensitive to clinically silent periprocedural necrosis, and do not carry the same prognostic value as elevations in CK-MB (5).

B-type natriuretic peptide (BNP) is increasingly used as a cardiac biomarker. Elevated levels may reflect either acquired or preexisting left ventricular dysfunction and are associated with an increased risk of complications (4).

With the advent of high-sensitivity troponin assays as the preferred cardiac marker, one of the most common consultations received by the interventional cardiologist is for the positive troponin, which in the absence of chest pain is often caused by demand ischemia, heart failure, or renal failure, rather than ACS (6). The 2012 universal definition of MI (Table 16-1) includes patients with positive biomarkers with either ischemic symptoms, ECG changes of ischemia or infarction, or echocardiographic evidence of infarction. This definition includes infarctions because of ACS, supply-demand imbalance, sudden cardiac death, PCI complications, or post-CABG (7). The terminology is thus muddled, in that a patient may have a MI without having an ACS (NSTEMI or STEMI), particularly when nondiagnostic symptoms (especially dyspnea, hypotension) and ECG (T-wave inversions) are present. Changes in the concentration of troponin may be helpful in differentiating acute from chronic causes of myocardial damage, with a rise of 20% typically being used as a criterion for an acute injury, especially in patients with renal failure, heart failure, or left ventricular hypertrophy (8).

Antithrombotic therapies and PCI are beneficial only for patients with primary acute thrombotic coronary events. An incorrect diagnosis at best will be a distraction from underlying illness, at worst a therapeutic misadventure that will result in hemorrhagic or vascular complications.

ACC/AHA Guidelines for the management of UA/NSTEMI were issued in complete form in 2007 (9) and updated in 2011 (10). A thorough review of these guidelines is suggested for board preparation.