Nonetheless, the burden of ACS remains significant both from a health care perspective and from an economic perspective. More than 1 million acute MIs occur in the United States annually, and 20% of affected patients die before reaching the hospital, primarily from arrhythmias during the first hours of symptoms.¹ Many survivors of acute MI are left with impaired cardiac function, which adversely affects their ability to perform activities of daily living and their quality of life. Approximately 6 million emergency department (ED) visits in the United States are made annually for the evaluation of chest pain, and as many as one in three of these patients are ultimately found to have ACS.² The annual cost of providing care for patients with ACS, both immediately and then later for those who survive, is more than $100 billion.³ Finally, despite advances in diagnostic techniques, 2% to 5% of patients with acute MI are discharged from the ED because their disease is not identified.⁴ These “missed MI” patients represent the highest mean payments for emergency medicine–related medical malpractice claims.

Definitions

Angina pectoris or, simply, angina is defined as transient and episodic discomfort in the chest occurring as a result of myocardial ischemia. Chronic stable angina can be reproduced with a specific level of physical or emotional stress and reliably resolves with rest, relief of the stress, or nitroglycerin therapy.

Unstable angina pectoris (UAP) is defined as angina of new onset that occurs at rest or in a crescendo pattern (with longer duration or intensity or with increasingly less exertion). If the angina is occurring at rest, it must be of at least 20 minutes’ duration to be characterized as unstable. Pathophysiologically, UAP is characterized by the presence of unstable coronary atherosclerotic plaque with thrombosis and partial obstruction of the involved coronary artery but without myocardial cell death. In contrast, chronic stable angina is generally related to fixed stable atherosclerotic lesions without rupture or thrombosis. Variant (or Prinzmetal) angina also occurs at rest but is due to coronary vasospasm rather than unstable coronary atherosclerotic plaque. It may be manifested as ST-segment elevation on an electrocardiogram (ECG) and mimic ST-segment elevation myocardial infarction (STEMI) but generally responds to nitroglycerin with resolution of the acute ECG abnormalities.

Myocardial infarction is defined as myocardial necrosis. Clinical criteria for the presence of an acute, evolving, or recent MI, which have been laid out jointly by the American College of Cardiology and the European Society of Cardiology, focus on any evidence of myocardial cell death. The exact definition of an acute or evolving MI is a rise above the upper limit of normal and subsequent fall in levels of cardiac biomarkers specific for myocardial necrosis (troponin or the MB fraction of creatine kinase MB [CK-MB]) along with at least one of the following ⁵:

• Symptoms consistent with ACS

• ECG evidence of myocardial ischemia, specifically, ST-segment elevation or depression or T-wave inversions

• Development of pathologic Q waves on the ECG

• Percutaneous coronary artery intervention

Myocardial infarction is further classified as STEMI and non–ST-elevation MI (NSTEMI). STEMI is present when the patient has (1) cardiac biomarkers for necrosis as previously defined and (2) new or presumed new ST-segment elevation in two or more contiguous ECG leads. The cutoff point for ST-segment elevation is 0.1 mV.⁶ Contiguous leads are defined in the chest leads as V₁ through V₆ and in the frontal plane as the sequence aVL, I, inverted aVR, II, aVF, and III. Patients who meet the clinical criteria for STEMI and left bundle branch block (LBBB) and are not old or who have ECG evidence of an isolated true posterior MI are also considered, for treatment algorithm purposes, to have STEMI. NSTEMI is present when the patient meets the criteria for MI as previously defined but exhibits no evidence of ST-segment elevation, new LBBB, or ECG evidence of an isolated posterior wall MI.

Acute coronary syndrome is the clinical manifestation of acute myocardial ischemia resulting from the presence of unstable coronary plaque. Accordingly, ACS is represented by the full spectrum of STEMI, NSTEMI, and UAP, which comprise a continuum of similar clinical and pathophysiologic features. STEMI and NSTEMI are differentiated by the findings on a 12-lead ECG, whereas UAP is identical to NSTEMI except that the cardiac biomarkers remain normal in the former. Given that a laboratory result is the only distinguishing feature between patients with UAP and those with NSTEMI, patients are treated identically on arrival by the initial health care provider.

Pathophysiology

The pathophysiology of acute myocardial ischemia is related to an imbalance between myocardial oxygen supply and demand. Specifically, myocardial ischemia occurs when coronary perfusion is insufficient to meet myocardial oxygen consumption needs. Myocardial oxygen needs depend on the heart rate, afterload conditions, and contractility of the myocardium. Insufficient coronary perfusion is generally due to atherosclerosis involving the coronary arteries. In patients with chronic stable angina, fixed atherosclerotic lesions partially obstruct flow of blood to the myocardium; when demand for oxygen increases (e.g., because of exercise), flow may become insufficient to meet the demand, and myocardial ischemia and anginal symptoms occur.

The pathophysiology of ACS begins when an atherosclerotic plaque within a coronary artery becomes unstable as a result of plaque rupture or hemorrhage into the plaque. The atherosclerotic plaque need not be causing critical stenosis before becoming unstable. Plaque rupture or hemorrhage exposes the lipid-rich core of the plaque and the basement membrane proteins of the blood vessel wall. As part of the resultant inflammatory cascade, platelets adhere to the core of the ruptured plaque and start to release platelet agonists—adenosine diphosphate, thrombin, and epinephrine. These agonists induce platelet activation, which is characterized by the expression of 50,000 to 80,000 glycoprotein (GP) IIb/IIIa receptors on the surface of each platelet. Fibrinogen, freely circulating in the bloodstream, is a bivalent molecule with binding sites on each end that are specific for the GP IIb/IIIa receptor. Fibrinogen thus facilitates platelet aggregation because each strand cross-links two platelets. The resultant platelet-fibrinogen web is further stabilized by thrombin, which is released by activated platelets and by activation of the coagulation cascade. Thrombin cross-links and modifies fibrinogen to the more stable fibrin.

As the platelet-fibrin aggregation grows, it traps red and white blood cells moving through the coronary artery, and a thrombus forms. At the same time, the inflammatory process leads to the release of vasoactive mediators, which may induce vasospasm, further compromising coronary blood flow. If this process leads to complete occlusion of the epicardial coronary artery at the site of plaque rupture, STEMI will result. If the thrombus is partially obstructing coronary blood flow and generating microemboli to smaller coronary arterioles, which in turn may become obstructed or exhibit spasms, NSTEMI (if myocardial cell death has occurred as shown by a rise in cardiac biomarkers) or UAP (if biomarkers remain normal) results.

Much less commonly, ACS may be due to primary vasospasm rather than primary plaque rupture. Generally the result of sympathetic overstimulation by endogenous epinephrine or serotonin, coronary vasospasm may lead to platelet activation and thrombus formation, even in the absence of underlying coronary artery atherosclerosis. Coronary vasospasm is more likely to cause UAP than MI.

Presenting Signs and Symptoms

History

Patients with ACS classically have chest discomfort in the substernal (precordial) area. Typically, this discomfort is described as pain, pressure, or tightness and may begin at rest or during exertion. It may also be located in the left or right anterior portion of the chest and may radiate to the shoulder, neck, jaw, arm, or back. Characteristically, the duration of discomfort ranges from several minutes to an hour. It is rare for the discomfort related to ACS to last only seconds or to persist continuously for hours. Associated symptoms that may be present are dyspnea, nausea, vomiting, diaphoresis, weakness, dizziness, and fatigue.

Atypical Presentations

The emergency physician (EP) should beware of atypical manifestations of ACS, which are common and portend a markedly worse clinical outcome. The quality of the chest discomfort cannot be relied on to exclude ACS. Patients with discomfort that is sharp or stabbing in quality or is pleuritic, palpable, or positional in nature make up a significant minority of patients with ACS. Furthermore, any of the associated symptoms listed previously can occur either alone or together without chest discomfort and still represent ACS. Findings of this type (without chest discomfort) are referred to as an anginal equivalent and require the same clinical management as cases manifested more classically. Other atypical manifestations include isolated back, neck, jaw, or arm discomfort; epigastric pain or burning; indigestion; isolated dyspnea; and generalized weakness. Elderly patients are particularly likely to have atypical symptoms, in particular, weakness and altered mentation. Other populations in whom ACS is likely to be manifested atypically are women, nonwhite patients, and diabetic patients. In all these groups ACS is much more likely to be misdiagnosed initially than in the overall population.

Physical Findings

Physical examination is often unrevealing in patients with ACS because most of the findings are related to complications of ACS. The vital signs should be evaluated carefully and monitored for evidence of arrhythmia, respiratory compromise, and cardiogenic shock. Jugular venous distention, rales, and a third heart sound (S₃) are signs of congestive heart failure complicating ACS. When these signs are coupled with altered mental status and hypotension, cardiogenic shock is likely.

Physical findings can also help suggest an alternative diagnosis. For example, fever and signs of consolidation on lung examination are suggestive of pneumonia rather than ACS, whereas unilateral absence of breath sounds suggests pneumothorax as the most likely diagnosis. Although chest wall tenderness is suggestive of a musculoskeletal etiology, ACS should not be excluded as a diagnosis solely on the basis of chest discomfort that is reproducible on palpation.

Differential Diagnosis and Medical Decision Making

The differential diagnosis in patients with ACS includes a host of other diseases that can be manifested as chest pain or dyspnea: stable angina, pericarditis, myocarditis, pulmonary embolism (PE), aortic dissection, pneumonia, pleurisy, pneumothorax, Boerhaave syndrome, esophageal reflux, esophageal spasm, gastritis, biliary colic, pancreatitis, peptic ulcer disease, musculoskeletal pain, and herpes zoster. One of the historical features that tends to favor a diagnosis of ACS is chest pressure or tightness rather than a sharp pain, which is more commonly associated with pericarditis, pleurisy, pneumothorax, PE, and aortic dissection. In addition, the chest discomfort in patients with ACS tends to gradually worsen, unlike the pain associated with PE or aortic dissection, which is generally worst at the onset and then persistently severe. Pain of a pleuritic nature tends to favor PE, pleurisy, or pneumothorax, whereas pain that is worse on palpation tends to suggest a chest wall musculoskeletal cause. Discomfort that is positional in nature tends to favor pericarditis or gastrointestinal causes rather than ACS. However, it is very important to remember that a significant percentage of patients with ACS have pleuritic, positional, or palpable chest pain and that these historical features cannot be used to exclude the diagnosis.⁷

Although the differential diagnosis of chest discomfort is long and includes entities from several different organ systems, some bear special mention because of the risk that they pose to patients. In each patient with chest discomfort, the EP should consider and reasonably exclude aortic dissection, PE, pneumonia, pneumothorax, and Boerhaave syndrome. This does not mean that these diagnoses must be excluded by definitive diagnostic techniques. They may be reasonably excluded on the basis of the history and physical findings, but this thought process should be documented clearly in the medical record.

Diagnostic Testing

Electrocardiogram

The 12-lead ECG is the most important diagnostic test for patients with suspected ACS. In addition to providing diagnostic information, the ECG can be used to assess progression of the syndrome and response to therapeutic interventions. In addition, ECG findings determine treatment pathways and assist with disposition decisions. The ECG in patients with suspected ACS should be carefully and systematically analyzed for evidence of ST-segment elevation, ST-segment depression, T-wave inversion, and pathologic Q waves as signs of myocardial ischemia or infarction. Also, the rate, rhythm, and intervals, along with QRS morphology, should be studied for evidence of complications of ACS. Finally, evidence of noncardiac causes of chest pain should be sought on the ECG, in particular, findings suggestive of PE and pericarditis.

It important to remember that many patients with confirmed ACS have normal or nondiagnostic findings on the ECG. Even in patients with acute MI, the ECG findings can be normal in a small percentage of cases. In addition, the ECG represents only one static point in time, and ACS is a dynamic process. Hence, a single nondiagnostic ECG cannot be relied on to exclude the diagnosis of ACS, and the history elicited from the patient remains more important than findings on the ECG, particularly when they are negative or nondiagnostic. Nonetheless, specific ECG findings of myocardial ischemia or infarction are often present and are very helpful in determining treatment and disposition.

Electrocardiographic Findings in ST-Segment Elevation Myocardial Infarction

The initial ECG abnormality that occurs in patients with epicardial coronary artery occlusion is peaked hyperacute T waves in the distribution supplied by the IRA. T waves become tall and sharply peaked within minutes of occlusion of the IRA (Fig. 55.1, A). Peaked T waves may also be seen in patients with hyperkalemia, pericarditis, early repolarization, and LBBB. In the next several minutes, ST-segment elevation becomes evident on the ECG (see Fig. 55.1, B). To be diagnostic, the ST-segment elevation must be at least 1 mm above the baseline; this is generally considered the TP segment. Most typically, this ST elevation is convex or domed, though less commonly it may be straight or, rarely, concave. Concave ST-segment elevations are more characteristic of other conditions associated with ST-segment elevation (Box 55.1).