Patients with ischemic heart disease fall into two large groups: patients with chronic coronary artery disease (CAD) who most commonly present with stable angina (Chap. 243) and patients with acute coronary syndromes (ACSs). The latter group, in turn, is composed of patients with acute myocardial infarction (MI) with ST-segment elevation on their presenting electrocardiogram (ECG) (STEMI; Chap. 245) and those with unstable angina (UA) and non-ST-segment elevation MI (UA/NSTEMI; Fig. 245-1). Every year in the United States, approximately 1 million patients are admitted to hospitals with UA/NSTEMI as compared with ∼300,000 patients with acute STEMI. The relative incidence of UA/NSTEMI compared to STEMI appears to be increasing. More than one-third of patients with UA/NSTEMI are women, while less than one-fourth of patients with STEMI are women.
The diagnosis of UA is based largely on the clinical presentation. Stable angina pectoris is characterized by chest or arm discomfort that may not be described as pain but is reproducibly associated with physical exertion or stress and is relieved within 5–10 minutes by rest and/or sublingual nitroglycerin (Chaps. 12 and 343). UA is defined as angina pectoris or equivalent ischemic discomfort with at least one of three features: (1) it occurs at rest (or with minimal exertion), usually lasting >10 minutes; (2) it is severe and of new onset (i.e., within the prior 4–6 weeks); and/or (3) it occurs with a crescendo pattern (i.e., distinctly more severe, prolonged, or frequent than previously). The diagnosis of NSTEMI is established if a patient with the clinical features of UA develops evidence of myocardial necrosis, as reflected in elevated cardiac biomarkers.
UA/NSTEMI is most commonly caused by a reduction in oxygen supply and/or by an increase in myocardial oxygen demand superimposed on a lesion that causes coronary arterial obstruction, usually an atherothrombotic coronary plaque. Four pathophysiologic processes that may contribute to the development of UA/NSTEMI have been identified: (1) plaque rupture or erosion with a superimposed nonocclusive thrombus, believed to be the most common cause; in such patients, NSTEMI may occur with downstream embolization of platelet aggregates and/or atherosclerotic debris; (2) dynamic obstruction [e.g., coronary spasm, as in Prinzmetal's variant angina (PVA) (p. 2020)]; (3) progressive mechanical obstruction [e.g., rapidly advancing coronary atherosclerosis or restenosis following percutaneous coronary intervention (PCI)]; and (4) UA secondary to increased myocardial oxygen demand and/or decreased supply (e.g., tachycardia, anemia). More than one of these processes may be involved.
Among patients with UA/NSTEMI studied at angiography, approximately 5% have stenosis of the left main coronary artery, 15% have three-vessel CAD, 30% have two-vessel disease, 40% have single-vessel disease, and 10% have no apparent critical epicardial coronary artery stenosis; some of the latter may have obstruction of the coronary microcirculation. The "culprit lesion" may show an eccentric stenosis with scalloped or overhanging edges and a narrow neck on angiography. Angioscopy has been reported to show "white" (platelet-rich) thrombi, as opposed to "red" (fibrin- and cell-rich) thrombi; the latter are more often seen in patients with acute STEMI. Patients with UA/NSTEMI frequently have multiple plaques at risk of disruption (vulnerable plaques).
History and Physical Examination
The clinical hallmark of UA/NSTEMI is chest pain, typically located in the substernal region or sometimes in the epigastrium, that radiates to the neck, left shoulder, and/or the left arm (Chap. 12). This discomfort is usually severe enough to be described as frank pain. Anginal "equivalents" such as dyspnea and epigastric discomfort may also occur, and these appear to be more frequent in women. The physical examination resembles that in patients with stable angina (Chap. 243) and may be unremarkable. If the patient has a large area of myocardial ischemia or a large NSTEMI, the physical findings can include diaphoresis; pale, cool skin; sinus tachycardia; a third and/or fourth heart sound; basilar rales; and, sometimes, hypotension, resembling the findings of large STEMI.
In UA, ST-segment depression, transient ST-segment elevation, and/or T-wave inversion occur in 30 to 50% of patients. In patients with the clinical features of UA, the presence of new ST-segment deviation, even of only 0.05 mV, is an important predictor of adverse outcome. T-wave changes are sensitive for ischemia but less specific, unless they are new, deep T-wave inversions (≥0.3 mV).
Patients with UA/NSTEMI who have elevated biomarkers of necrosis, such as CK-MB and troponin (a much more specific and sensitive marker of myocardial necrosis), are at increased risk for death or recurrent MI. Elevated levels of these markers distinguish patients with NSTEMI from those with UA. There is a direct relationship between the degree of troponin elevation and mortality. However, in patients without a clear clinical history of myocardial ischemia, minor troponin elevations have been reported and can be caused by congestive heart failure (CHF), myocarditis, or pulmonary embolism, or they may be false-positive readings. Thus, in patients with an unclear history, small troponin elevations may not be diagnostic of an ACS.
(See also Chap. 12) Approximately six million persons per year in the United States present to hospital emergency departments (EDs) with a complaint of chest pain or other symptoms suggestive of ACS. A diagnosis of an ACS is established in 20 to 25% of such patients. The first step in evaluating patients with possible UA/NSTEMI is to determine the likelihood that CAD is the cause of the presenting symptoms. The American College of Cardiology/American Heart Association (ACC/AHA) Guidelines include, among the factors associated with a high likelihood of ACS, a prior history typical of stable angina, a history of established CAD by angiography, prior MI, CHF, new ECG changes, or elevated cardiac biomarkers.