Acute Coronary Syndrome

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Chapter 78

Acute Coronary Syndrome

Acute coronary syndrome (ACS) refers to the constellation of clinical diseases occurring as a result of acute myocardial ischemia. ACS includes a spectrum of clinical presentations ranging from unstable angina (UA) to non–ST segment elevation myocardial infarction (NSTEMI) and ST segment elevation myocardial infarction (STEMI). ACS and in particular acute myocardial infarction (AMI) remain the leading causes of death in much of the developed world.

Historical Perspective

Several advances in the mid-20th century drastically changed the approach to acute coronary care. The development of external defibrillators and cardiac pacemakers as well as new pharmacologic agents provided physicians with effective approaches for treating life-threatening dysrhythmias. The introduction of selective coronary arteriography by Sones in 1959 revolutionized the management of patients with coronary artery disease (CAD). In 1960, Kouwenhoven inaugurated the era of cardiopulmonary resuscitation (CPR).

These developments led to the recognition that the time between onset of symptoms and the initiation of therapy is critical. Day organized a cardiac arrest team in 1960 and established the first coronary care unit 2 years later, reducing AMI mortality by half. In the 1980s, DeWood performed coronary angiography early in the course of AMI and demonstrated coronary occlusion in the infarct-related artery. The early experience of Rentrop with the intracoronary administration of streptokinase in AMI ushered in the era of thrombolysis, now termed fibrinolytic therapy.

Recognition that the majority of sudden deaths from ischemic heart disease occur outside the hospital led to numerous advances for preadmission ACS care. In 1969, advanced prehospital cardiac care was initiated in Belfast with Pantridge’s mobile cardiac care units. In 1970, Nagel reported the benefits of preadmission telemetry for field providers of advanced cardiac life support in patients experiencing dysrhythmias or sudden cardiac death. In the 1980s portable 12-lead electrocardiograms (ECGs) were introduced into the emergency medical services (EMS) environment. Although the ECG is the cornerstone of the diagnostic evaluation of ACS, diagnostic tools such as echocardiography, stress testing, nuclear imaging, and computed tomography (CT) play increasingly important roles, particularly when the diagnosis is not straightforward.

Fibrinolytic therapy and interventional, catheter-based techniques revolutionized the treatment of patients with STEMI during the 1980s. Combination therapies with antiplatelet, antithrombotic, and fibrinolytic agents continue to be studied for STEMI patients. Interventional success is improving with the use of newer stenting devices and various platelet and coagulation system inhibitors. STEMI systems of care address the management of STEMI from a systems-based perspective, starting with EMS in the prehospital setting, through the emergency department (ED) to the cardiac catheterization laboratory, and to the coronary care unit. This systems-based approach stresses a number of factors crucial in the management of STEMI, including the time-sensitivity of treatment, the multidisciplinary composition of the management team, and the multistep nature of the overall process. In addition to further development of the STEMI systems of care approach, current efforts focus on the establishment of regional cardiac centers and the expansion of interventional capabilities to smaller hospitals. Furthermore, appropriate methods of evaluation of potential ACS patients without obvious STEMI or other diagnostic findings continue to mature. The observation unit–based “rule-out myocardial infarction (MI)” strategy has been shortened in total time, rendered more efficient in process, and made safer with respect to medical management and detection of ACS events. Although this strategy of chest pain evaluation is more efficient than previous approaches, further improvements in reducing the missed MI in the ED are under development.


Ischemic heart disease and CAD continue to be the leading causes of death among adults in many developed countries. Ischemic heart disease accounts for nearly 1 million deaths in the United States annually, of which approximately 160,000 occur in persons 65 years of age or younger. More than half of all deaths from cardiovascular disease occur in women, and CAD remains a major cause of morbidity and mortality in women beyond their middle to late fifties. The incidence of cardiovascular disease is expected to continue to increase owing to lifestyle and behavioral changes that promote heart disease.1

A significant reduction in age-adjusted mortality from CAD has occurred in the United States over the past four decades.2,3 In large part, the decline has been accompanied by diminished mortality from AMI. This decrease is a result of a reduction in the incidence of AMI by 25% and a sharp drop in the case-fatality rate. Reduction in cigarette smoking, management of lipids, and improved management of hypertension and diabetes mellitus undoubtedly play a role, along with significant advances in medical treatment.

In 2005, 5.8 million patients were evaluated for chest pain or related complaints in EDs in the United States, constituting 5% of all ED visits. In 2004, 4.1 million visits to the ED had a primary diagnosis of cardiovascular disease, and over 1.5 million patients were hospitalized for a primary or secondary diagnosis of ACS.47 In addition, approximately 2% of patients with ACS are discharged from the ED. In the United States, approximately 900,000 persons every year experience an AMI, of whom 20% die before reaching the hospital, and 30% die within 30 days.8,9 The majority of fatalities from CAD occur outside the hospital, usually from an ACS-related dysrhythmia within 2 hours of onset of symptoms. For many patients who experience a nonfatal AMI, their lives are limited by an impaired functional status, anginal symptoms, and a diminished quality of life. The economic cost of ACS is estimated to be $100 to $120 billion annually.10

Spectrum of Disease

Coronary heart disease includes the spectrum from asymptomatic CAD and stable angina to UA, AMI, and sudden cardiac death. ACS includes the “acute” subtypes of coronary heart disease, including UA, AMI, and sudden cardiac death.

Stable Angina

Stable angina pectoris is transient, episodic chest discomfort resulting from myocardial ischemia. This discomfort is typically predictable and reproducible, with the frequency of attacks constant over time. Physical or psychological stress (physical exertion, emotional stress, anemia, dysrhythmias, or environmental exposures) may provoke an attack of angina that resolves spontaneously over a constant, predictable period of time with rest or nitroglycerin (NTG).

The Canadian Cardiovascular Society classification for angina is defined as follows: class I, no angina with ordinary physical activity; class II, slight limitation of normal activity as angina occurs with walking, climbing stairs, or emotional stress; class III, severe limitation of ordinary physical activity as angina occurs on walking one or two blocks on a level surface or climbing one flight of stairs in normal conditions; and class IV, inability to perform any physical activity without discomfort as anginal symptoms occur at rest.

Unstable Angina

Unstable angina is broadly defined as angina occurring with minimal exertion or at rest, new-onset angina, or a worsening change in a previously stable anginal syndrome in terms of frequency or duration of attacks, resistance to previously effective medications, or provocation with decreasing levels of exertion or stress. Rest angina is defined as angina occurring at rest, lasting longer than 20 minutes, and occurring within 1 week of presentation. New-onset angina is angina of at least class II severity with onset within the previous 2 months. Increasing or progressive angina is diagnosed when a previously known angina becomes more frequent, longer in duration, or increased by one class within the previous 2 months of at least class III severity. Symptoms that last longer than 20 minutes despite cessation of activity are consistent with angina at rest and reflect UA.

UA is often referred to as preinfarction angina, accelerating or crescendo angina, intermediate coronary syndrome, and preocclusive syndrome, underscoring its difference from stable angina. UA should be considered a possible harbinger of AMI and hence should be treated aggressively. A patient with a diagnosis of angina in the ED should be presumed to have UA until a thorough clinical evaluation reliably determines otherwise.

UA can also be defined from a pathophysiologic perspective. Plaque rupture accompanied by thrombus formation and vasospasm illustrate the intracoronary events of UA. This is frequently characterized by an electrocardiographic abnormality, including T wave and ST segment changes.

Variant angina—also known as Prinzmetal’s angina—is caused by coronary artery vasospasm at rest with minimal fixed coronary artery lesions; it may be relieved by exercise or NTG. The ECG reveals ST segment elevation that is impossible to discern from AMI electrocardiographically and, at times, clinically.

Acute Myocardial Infarction

Acute myocardial infarction is defined as myocardial cell death and necrosis of the myocardium. The four-decade-old World Health Organization (WHO) definition for AMI has been replaced by clinical criteria developed jointly by the European Society for Cardiology and American College of Cardiology (ACC) that focus on defining infarction as any evidence of myocardial necrosis. This definition for an acute, evolving, or recent MI requires a typical rise and fall of a cardiac biochemical marker, currently troponin, with clinical symptoms, ECG changes, or coronary artery abnormalities based on interventional evaluation.11 The actual definition,11 referred to as the “Universal Definition of Myocardial Infarction,” includes the following; either one of these criteria satisfies the diagnosis for an acute, evolving, or recent MI:

Furthermore, regarding an established MI, any one of the following criteria satisfies this diagnosis11:

Considering the myriad clinical situations in which MI is encountered, the five primary “types” of infarction are described by the following categorization:

• Type 1—Spontaneous MI related to ischemia resulting from a primary coronary event, such as plaque erosion rupture, erosion, fissuring, or dissection with accompanying thrombus formation and vasospasm. Type 1 infarctions represent the “true” ACS event.

• Type 2—MI secondary to ischemia caused by either increased oxygen demand or decreased supply, as seen in coronary artery spasm, coronary embolism, severe anemia, compromising arrhythmias, or significant systemic hypotension.

• Type 3—Sudden unexpected cardiac death, including cardiac arrest, often with symptoms suggestive of myocardial ischemia, accompanied by presumably new ST segment elevation or new left bundle branch block (LBBB) pattern. Fresh coronary thrombus is noted via either angiography or autopsy; death occurs before appropriate sampling of the blood to detect the abnormal cardiac biomarker.

• Type 4—MI associated with coronary instrumentation, such as occurring after percutaneous coronary intervention (PCI). For PCIs in patients with normal baseline troponin values, elevations of cardiac biomarkers above the 99th percentile URL are indicative of periprocedural myocardial necrosis. By convention, increases of biomarkers greater than 3 times the 99th percentile URL are designated as defining PCI-related MI. A subtype related to a documented stent thrombosis is similarly recognized.

• Type 5—MI associated with coronary artery bypass grafting (CABG). For CABG in patients with normal baseline troponin values, elevations of cardiac biomarkers above the 99th percentile URL are indicative of periprocedural myocardial necrosis. By convention, increases of biomarkers greater than five times the 99th percentile URL plus any of the following are designated as defining CABG-related MI:

This categorization is more than a simple semantic description of AMI. Diagnostic and management issues clearly are different depending on the subtype of MI encountered. For instance, the type 1 event should be approached with attention to platelet, coagulation system, and vasospasm considerations, whereas the type 2 infarction should have attention paid to the frequent primary, inciting pathophysiologic situations that are actually causing the AMI.

AMI is further classified by findings on the ECG at presentation, as either STEMI or NSTEMI. Previous descriptors, such as transmural and nontransmural, as well as Q wave and non–Q wave MI, fail to adequately describe the coronary event and its related pathophysiology, electrocardiographic presentation, and pathologic outcome. The differentiation between STEMI and NSTEMI has important implications in terms of management, outcome, and prognosis for patients with AMI. In fact, the ACC and the American Heart Association (AHA) have separate clinical guidelines for the management of patients with UA/NSTEMI and those patients with STEMI.6,7,12


The underlying pathophysiology of ACS is myocardial ischemia as a result of inadequate perfusion to meet myocardial oxygen demand. Myocardial oxygen consumption is determined by heart rate, afterload, contractility, and wall tension. Inadequate perfusion most commonly results from coronary arterial vessel stenosis as a result of atherosclerotic CAD. Usually the reduction of coronary blood flow does not cause ischemic symptoms at rest until the vessel stenosis exceeds 95%. Myocardial ischemia, however, may occur with exercise and increased myocardial oxygen consumption with as little as 60% vessel stenosis.13

CAD is characterized by thickening and obstruction of the coronary vessel arterial lumen by atherosclerotic plaques. Although atherosclerosis is usually diffuse and multifocal, individual plaques vary greatly in composition. Fibrous plaques are considered stable but can produce anginal symptoms with exercise and increased myocardial oxygen consumption because of the reduction in coronary artery blood flow through the fixed, stenotic lesions. Vulnerable or unstable fibrolipid plaques consist of a lipid-rich core separated from the arterial lumen by a fibromuscular cap. These lesions are likely to rupture, resulting in a cascade of inflammatory events, thrombus formation, and platelet aggregation that can cause acute obstruction of the arterial lumen and myocardial necrosis.14

Thrombus formation is considered an integral factor in ACS, including all subtypes ranging from UA to NSTEMI and STEMI. These syndromes are initiated by endothelial damage and atherosclerotic plaque disruption, which leads to platelet activation and thrombus formation. Platelets play a major role in the thrombotic response to rupture of coronary artery plaque and subsequent ACS. Platelet-rich thrombi are also more resistant to fibrinolysis than fibrin- and erythrocyte-rich thrombi. The resulting thrombus can occlude the vessel lumen, leading to myocardial ischemia, hypoxia, acidosis, and eventually infarction. The consequences of the occlusion depend on the extent of the thrombotic process, the characteristics of the preexisting plaque, the extent of the vessel obstruction, and the availability of collateral circulation.

In the setting of UA, acute stenosis of the vessel is noted; complete obstruction, however, is encountered in only 20% of cases. In these cases, it is likely that extensive collateral vessel circulation prevents total cessation of blood flow, averting frank infarction.13 With AMI, the occlusive fibrin-rich thrombus is fixed and persistent, resulting in myonecrosis of the cardiac tissue supplied by the affected artery. Angiographic studies demonstrate that the preceding coronary plaque lesion is often less than 50% stenotic, indicating that the most important factors in the infarction are the acute events of plaque rupture, platelet activation, and thrombus formation rather than the severity of the underlying coronary artery stenosis.

Another important aspect of ACS is vasospasm. After significant coronary vessel occlusion, local mediators and vasoactive substances are released, inducing vasospasm, which further compromises blood flow. Central and sympathetic nervous system input increases within minutes of the occlusion, resulting in vasomotor hyperreactivity and coronary vasospasm. Sympathetic stimulation by endogenous hormones, such as epinephrine and serotonin may also result in increased platelet aggregation and neutrophil-mediated vasoconstriction. Approximately 10% of MIs occur as a result of coronary artery spasm and subsequent thrombus formation without significant underlying CAD. This mechanism may be more prevalent during UA and other coronary syndromes that do not result in infarction.

Further myocardial injury occurs at the cellular level as inflammatory, thrombotic, and other debris from the occlusive plaque lesion is released and embolizes into the distal vessel. Such embolization can result in obstruction at the microvasculature, leading to hypoperfusion and ischemia of the distal myocardial tissue, even after reopening of the more proximal, initial, obstructing lesion. In particular, the introduction of calcium, oxygen, and cellular elements into ischemic myocardium can lead to irreversible myocardial damage that causes reperfusion injury, prolonged ventricular dysfunction (known as myocardial stunning), or reperfusion dysrhythmias. Neutrophils probably play an important role in reperfusion injury, occluding capillary lumens, decreasing blood flow, accelerating the inflammatory response, and resulting in the production of chemoattractants, proteolytic enzymes, and reactive oxygen species.

Clinical Features

Clinical features associated with ACS vary based on the patient type, including gender, comorbid conditions, and age considerations. Women, patients with diabetes mellitus, and the elderly, among other populations, can exhibit differing presentations of ACS. Women demonstrate less remarkable, if not subtle, ACS presentations. Diabetic patients frequently exhibit nontraditional symptoms of AMI, such as dyspnea. The elderly commonly note only weakness, confusion, or other nonclassic symptoms as the primary manifestation of ACS. The detection of AMI, ACS, and symptomatic obstructive coronary lesions are all part of the focus on ED management. The primary focus of the diagnostic effort changes significantly at different phases of the ED evaluation. Early, usually within the initial 15 minutes of presentation, the principal task is the identification of STEMI. Once STEMI has been excluded (and the patient remains clinically stable), the evaluation over the next several hours then focuses on the detection of ACS, including UA and NSTEMI. If excluded (and again, in a stable patient), the identification of symptomatic coronary obstructive lesions is the evaluation’s goal; this last task can be accomplished during the initial ED presentation or later at follow-up.

Preadmission Evaluation

Appropriate pharmacotherapy for persistent anginal chest pain in the preadmission setting includes sublingual NTG, oral aspirin (acetylsalicylic acid [ASA]) that is preferably chewed, and intravenous morphine sulfate; the acronym MONA summarizes preadmission pharmacotherapeutic interventions (morphine, oxygen, nitroglycerin, and aspirin). Establishment of the diagnosis of ACS in this setting is difficult, however, as chest pain is a poor predictor of the diagnosis and adjunctive tools are limited.15 Preadmission 12-lead ECG offers high specificity (99%) and positive predictive value (93%) for AMI in patients with atraumatic chest pain while increasing the paramedic scene time by an average of only 3 minutes. This approach offers many advantages, including (1) earlier detection of STEMI, (2) ability to base the destination on the availability of PCI, and (3) more rapid reperfusion therapy.7 Preadmission 12-lead ECG would be necessary in the limited populations in whom preadmission fibrinolytic therapy might be applicable, such as those with prolonged out-of-hospital times (90-120 minutes).

Emergency Department Evaluation

The History

The character of the chest discomfort as well as the onset, location, radiation, duration, prior presence, and any exacerbating or alleviating factors should be sought. Associated symptoms, especially of a cardiac, pulmonary, gastrointestinal, and neurologic nature, should be elicited. Results from any prior cardiac testing should be obtained.

Traditionally, a history of risk factors for CAD is sought; these include male gender, age, tobacco smoking, hypertension, diabetes mellitus, hyperlipidemia, family history, artificial or early menopause, and chronic cocaine abuse. Approximately 80% of a population of more than 122,000 patients with known CAD had at least one of the four conventional risk factors (diabetes mellitus, cigarette smoking, hypertension, or hyperlipidemia).16 Cardiac risk factor burden has little impact on the ED diagnosis of ACS; however, in patients older than 40 years, ACS is 22 times more likely if four of the five major risk factors (diabetes mellitus, smoking, hypertension, hyperlipidemia, and family history) are present (compared with none).17 Nevertheless, Bayesian analysis indicates that risk factors are a populational phenomenon and do not increase or decrease the likelihood of any condition in any one patient. Thus the presence of an individual risk factor or a collection of risk factors is far less important in diagnosing acute cardiac ischemia in the ED than the history of presenting illness, prior diagnosis of ischemic cardiac disease in the patient, the presence of ST segment or T wave changes, or cardiac marker abnormalities.18

Risk assessment tools, such as the PURSUIT (Platelet Glycoprotein IIb-IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) risk model, the GRACE (Global Registry of Acute Coronary Events) risk model, and the TIMI (Thrombolysis in Myocardial Infarction) risk score, can be used to determine risk of death and ischemia in NSTEMI and STEMI. The TIMI risk score assigns a point each for seven factors based on history, cardiac markers, and the ECG. It can be accessed at Although these tools may aid in decision-making and in risk stratification for patients to properly determine their disposition (telemetry bed vs. intensive care unit), none of them are designed to identify patients who may safely be discharged home.

There are several nontraditional risk factors for coronary disease. Antiphospholipid syndrome, rheumatoid arthritis, human immunodeficiency virus (HIV),19 and particularly systemic lupus erythematosus (SLE) are associated with a higher risk of cardiovascular disease.20 Women with SLE who are 35 to 44 years of age are over more than 50 times more likely to have an MI than a similar age- and gender-matched Framingham population.21

The Classic History

The term angina refers to “tightening,” not pain. Classic angina pectoris may not be pain at all but rather a “discomfort,” with a “squeezing,” “pressure,” “tightness,” “fullness,” “heaviness,” or “burning” sensation. Classically, it is substernal or precordial in location and may radiate to the neck, jaw, shoulders, or arms. If the discomfort does extend down the arm, it classically involves the ulnar aspect. Discomfort in the left chest and radiation to left-sided structures is typical, but location and radiation to both sides or to only the right side may be consistent with angina. Radiation of the discomfort to the right arm or shoulder, or to both arms or shoulders, exceeds radiation to the left arm or shoulder in terms of likelihood of the chest pain being caused by ACS, although all exceed a positive likelihood ratio of 2.22,23

Furthermore, classic features of angina pectoris include exacerbation with exertion, a heavy meal, stress, or cold, and alleviation with rest. The onset of pain at rest in no way excludes the diagnosis of angina. Anginal discomfort characteristically lasts from 2 to 5 minutes up to 20 minutes, and it is rare for it to last only a few seconds or to endure for hours or incessantly, “all day” (Table 78-1).

Table 78-1

Clinical Characteristics of Classic Anginal Chest Discomfort

Type of pain Dull, pressure Sharp, stabbing
Duration 2-5 min, often 15-20 min Seconds or hours
Onset Gradual Rapid
Location Substernal Lateral chest wall, back
Reproducible With exertion With inspiration
Associated symptoms Present Absent
Palpation of chest wall Not painful Painful, exactly reproduces pain complaint

Adapted from Zink BJ: Angina and unstable angina. In Gibler WB, Aufderheide TP (eds): Emergency Cardiac Care. St. Louis, Mosby, 1994.

Symptoms characteristically associated with angina pectoris, or other entities of ACS, include dyspnea, nausea, vomiting, diaphoresis, weakness, dizziness, excessive fatigue, or anxiety (Table 78-2). If these symptoms arise, either alone or in combination, as a presenting pattern of known ischemic coronary disease, they are termed anginal equivalent symptoms. Recognition that coronary ischemia may arise with an anginal equivalent rather than a classic symptom is the key to understanding the atypical presentation of ACS. Complaints of “gas,” “indigestion,” or “heartburn” in the absence of a known history of gastroesophageal reflux disease, or if the heartburn is different from the patient’s usual gastroesophageal reflux, or reproducible pain on abdominal palpation should raise suspicion of ACS. Gastroesophageal reflux disease is a common misdiagnosis in cases of missed ACS.

The Atypical History

A description of typical symptoms (crushing, retrosternal chest pain or pressure) is often lacking in ACS; this may be a result of atypical features of the pain (e.g., character, location, duration, exacerbating and alleviating factors) or the presence of anginal equivalent symptoms (e.g., dyspnea, nausea, vomiting, diaphoresis, indigestion, syncope). Patients with an ultimate diagnosis of AMI or UA can have pain that is pleuritic, positional, or reproduced by palpation. Some patients describe their pain as burning or indigestion, sharp, or stabbing (see Table 78-2).23,24

In a large study of nearly 435,000 patients ultimately diagnosed with AMI, one third did not have chest pain on presentation.25 Multiple studies have identified risk factors for atypical presentation of ACS: diabetes mellitus, older age, female gender, nonwhite ethnicity, dementia, no prior history of MI or hypercholesterolemia, no family history of coronary disease, and previous history of congestive heart failure (CHF) or stroke.2527 In patients with AMI or UA, atypical presenting complaints include dyspnea, nausea, diaphoresis, syncope, or pain in the arms, epigastrium, shoulder, or neck.

Atypical features of ACS are present with increasing frequency in sequentially older populations. Before age 85, chest pain is found in the majority of patients with acute MI, although dyspnea, stroke, weakness, and altered mental status are notably present. In those older than 85 years, however, atypical symptoms are more common than chest pain, with 60 to 70% of patients older than 85 having an anginal equivalent complaint, especially dyspnea.27 Coincident ACS is more likely to occur in the elderly; patients with another acute condition (e.g., trauma, infection) should be scrutinized for concurrent ACS.28

Patients with diabetes mellitus are at heightened risk for ACS as well as an atypical presentation, such as dyspnea, nausea or vomiting, confusion, or fatigue. Medically unrecognized AMI can occur in 40% of patients with diabetes mellitus compared with 25% of a nondiabetic population, and myocardial scar unaccompanied by antemortem diagnosis of MI is three times more likely in diabetics.29

As with age and diabetes, female gender is an important risk factor for MI without chest pain. In some series, less than 60% of women reported chest discomfort at the time of their MI, with others reporting dyspnea, indigestion, or vague symptoms, such as weakness, unusual fatigue, cold sweats, sleep disturbance, anxiety, or dizziness.30

Finally, nonwhite racial and ethnic populations may have atypical symptoms in ACS.25 Compelling data demonstrate a disparity in treatment approach related to race in patients with acute manifestations of coronary heart disease.31 Whether this is related to the atypical nature of presenting symptoms in different racial groups is not clear. Although certain features of the chest pain history serve to increase or decrease the likelihood of ACS, none of them is strong enough to endorse discharge of the patient based on the history alone.24

Physical Examination

The physical examination focuses on the cardiac, pulmonary, abdominal, and neurologic examinations, looking for signs of complications of ACS as well as alternative diagnoses for chest pain and the anginal equivalent syndromes (Table 78-3). Altered mental status, diaphoresis, and signs of CHF are all ominous findings in patients with symptoms consistent with ACS. Historical studies using untrained physicians identified chest wall tenderness or “reproducible” chest wall tenderness in up to 15% of patients ultimately diagnosed with AMI, but these data are highly suspect. The real incidence of truly reproducible chest wall tenderness (i.e., when the patient reliably identifies to the examiner that the pain produced on palpation is identical to the pain causing the patient’s presentation) in ACS is probably very small. It is suggested that patients with chest pain that is fully pleuritic, positional, or reproducible by palpation (the three Ps) are at low risk (yet not no risk) for ACS.22

Table 78-3

Key Entities in the Differential Diagnosis of Chest Pain

Acute myocardial infarction Unstable angina
Stable angina Prinzmetal’s angina
Pericarditis Myocardial or pulmonary contusion
Pneumonia Pulmonary embolism
Pneumothorax Pulmonary hypertension
Pleurisy Aortic dissection
Boerhaave’s syndrome Gastroesophageal reflux
Peptic ulcer disease Gastritis or esophagitis
Esophageal spasm Mallory-Weiss syndrome
Cholecystitis or biliary colic Pancreatitis
Herpes zoster Musculoskeletal pain

Outcomes in Atypical Presentations

Not surprisingly, atypical presentation of patients with ACS is associated with a delay in diagnosis and poorer outcomes. In the Second National Registry of Myocardial Infarction (NRMI-2) study, patients with MI without chest pain were significantly more likely to die in the hospital (23 vs. 9% for patients with chest pain) and were more likely to experience stroke, hypotension, or heart failure that required intervention, possibly reflecting the older age and greater comorbidity in this group.25 Patients with atypical symptomatology seek medical care later and are less likely to receive standard therapies, such as aspirin, beta-adrenergic blockers, heparin, fibrinolysis, and emergent reperfusion therapy.25 Patients 65 years of age or younger with NSTEMI have a 1% chance of dying during their hospitalization, but this risk is increased to 10% for patients ages 85 years and older.28

Missed Diagnosis of Acute Coronary Syndrome

Approximately 2% to 4% of patients with acute MI in the ED are discharged without diagnosis.32 Missed ACS is the misdiagnosis that accounts for the largest amount of payment by emergency physicians in medical malpractice claims. Atypical presenting symptoms are an obvious causative consideration. Patients with undiagnosed ACS discharged from the ED are younger, more likely to be women or nonwhite, more likely to have atypical complaints, and less likely to have ECG evidence of acute ischemia.32,33 Among all patients with cardiac ischemia, women younger than 55 years seem to be at highest risk for inappropriate discharge. With respect to ECG findings, 53% of patients with missed AMI and 62% of patients with missed UA have normal or nondiagnostic ECGs. Finally, the risk-adjusted mortality ratio for all patients with acute cardiac ischemia is 1.9 times higher among nonhospitalized patients.32 Factors associated with misdiagnosis of ACS in medical malpractice closed claims analysis include physicians with less experience who document histories less clearly, admit fewer patients, and misinterpret the ECG.

Early Complications of Acute Myocardial Infarction

Bradydysrhythmia and atrioventricular (AV) conduction block occur in 25 to 30% of patients with AMI; sinus bradycardia is most commonly seen.3436 Symptomatic bradydysrhythmias in the first few hours after inferior AMI tend to be atropine responsive; conduction abnormalities that appear beyond 24 hours of MI tend not to respond to atropine.37 Patients with AV block in the setting of anterior AMI tend to respond poorly to therapy and have a poor prognosis.

Tachydysrhythmias are quite common in the setting of AMI and may be atrial in origin (e.g., sinus tachycardia and atrial fibrillation) or ventricular (e.g., ventricular tachycardia and fibrillation). Not all require treatment, such as a compensatory sinus tachycardia in patients with AMI complicated by CHF. Primary ventricular fibrillation occurs in an estimated 4 to 5% of patients with AMI, with 60% of those cases occurring in the first 4 hours and 80% within 12 hours.

Cardiogenic shock is hypotension with end-organ hypoperfusion resulting from decreased cardiac output that is unresponsive to restoration of adequate preload. Patients at risk include those with large infarcts, prior MI, low ejection fraction on presentation (<35%), older age, and diabetes mellitus. Although some differential diagnoses can usually be reasonably excluded (e.g., sepsis, anaphylaxis, adrenal crisis, and hypovolemic or hemorrhagic states), other causes of shock with similar presentations should be considered, such as aortic dissection, pulmonary embolism (PE), pericardial tamponade, and ventricular free wall rupture accompanying acute MI. Adjunctive diagnostic measures include bedside echocardiography and invasive hemodynamic monitoring, with the latter demonstrating systemic hypotension, low cardiac output, elevated filling pressures, and increased systemic vascular resistance. Therapeutic measures include vasopressor and inotropic support, intra-aortic balloon counterpulsation, and early revascularization; fibrinolytic therapy does not decrease mortality in cardiogenic shock.

Left ventricular free wall rupture is uncommon. Approximately one third of cases occur in the first 24 hours, and the remainder occur 3 to 5 days after transmural MI. Clinically, free wall rupture may occur with sudden death, pulseless electrical activity, or precipitous deterioration in the presence of AMI. Subacute presentations include agitation, chest discomfort, and repetitive vomiting. Signs of pericardial effusion on the ECG or echocardiogram are suggestive of the diagnosis in the setting of acute or recent MI. Free wall rupture is almost universally fatal, although prompt diagnosis followed by emergent surgical intervention may rarely be lifesaving; pericardiocentesis is indicated as an immediate temporizing intervention.

Rupture of the interventricular septum may also occur; it may arise similarly to cardiogenic shock and free wall rupture of the ventricle. The clue to this diagnosis on physical examination is the development of a new, harsh, loud holosystolic murmur heard best at the left lower sternal border. The diagnosis can be confirmed by echocardiography with color flow Doppler imaging. The presentation of acute, catastrophic deterioration with a new, harsh systolic murmur should prompt immediate cardiac surgery consultation for repair of a septal defect or ruptured papillary muscle of the mitral valve. Medical therapy including vasopressor and inotropic support, as well as intra-aortic balloon counterpulsation, is an important bridge to the definitive surgical treatments of valve repair or replacement.

Pericarditis, when associated with AMI, can occur early or in a delayed fashion; the former is termed infarct pericarditis, and the latter is known as post-MI syndrome or Dressler’s syndrome. Infarct pericarditis is associated with transmural insult and thus principally involves the pinnacle of the infarct zone near the epicardium. Although the characteristic ST segment changes may be obscured by ST segment abnormalities related to the infarction itself, if they are evident, they are logically quite localized. Infarct pericarditis is a common cause of new chest pain in the first week after MI. This pain is characteristically pleuritic and worse in the supine position. Embolic complications are more common in patients with infarct pericarditis; linked to this is the higher rate of ventricular aneurysm development in this population.

Dresslers syndrome, unlike infarct pericarditis, does not require transmural involvement. It is a relatively uncommon, late complication occurring from 1 week to several months after the MI. Clinical features include fever, malaise, pleuropericardial pain, and at times the presence of a rub on cardiac auscultation. Laboratory findings are highly nonspecific and include an elevated erythrocyte sedimentation rate and leukocyte count. The ECG may show ST segment–T wave findings of pericarditis, although as with infarct pericarditis, these changes may be overshadowed by the evolving changes of the recent MI. PR segment depression is a telltale clue. Pericardial or pleural effusions may be evident and can be serous or bloody. Echocardiography assesses pericardial fluid and risk of tamponade. The pericardial reaction is believed to be immune mediated, and treatment includes anti-inflammatory agents.

Stroke may also complicate AMI, most commonly ischemic or thromboembolic. The major predisposing mechanisms with a recent MI are embolization from left ventricular mural thrombus with decreased ejection fraction, embolization from the left atrial appendage with atrial fibrillation, and hypercoagulability with concomitant carotid arterial disease. The rate of stroke is higher in the setting of MI (0.9% tapering to 0.1% at day 28 after MI) than in control subjects (0.014%).38

Hemorrhagic stroke is an obvious concern in the patient undergoing fibrinolytic therapy. The rate of hemorrhagic stroke with varying fibrinolytic agents is less than 1%, although the rate climbs in older patients. PCI lowers the overall risk of stroke compared with fibrinolytic therapy. Analysis of only fibrinolytic-eligible patients from the NRMI-2 database yields more than 24,000 patients treated with alteplase and more than 4000 who received primary angioplasty. The difference in stroke rate is highly significant (1.6% in the fibrinolytic group vs. 0.7% in the angioplasty group). Considering hemorrhagic strokes, the difference is again dramatic (1.0% in the fibrinolytic group vs. 0.1% in the angioplasty group).39

Hyperglycemia in the setting of AMI may be viewed as a complication, as well as a complicating disease process in AMI. Hyperglycemia is present in up to one half of all patients with STEMI, yet only one fifth to one fourth of those patients are recognized diabetics. Elevated glucose at the time of admission has independent negative implications for mortality rates in AMI patients. Although fasting blood sugar the day after presentation is a better predictor, an admission blood glucose level higher than 200 mg/dL is linked to similar mortality rates among diabetics and nondiabetics. There is a 4% mortality increase for nondiabetic patients for every 18-mg/dL elevation in blood glucose level. Hyperglycemia seems to induce a complex set of unfavorable cellular and biochemical circumstances, including negative effects on coronary flow and microvascular perfusion, as well as adverse effects on platelet function, fibrinolysis, and coagulation. Intravenous insulin therapy for glucose normalization is linked to improved outcomes in patients with STEMI as well as those in the medical intensive care unit. ACC/AHA guidelines acknowledge that tight control of blood glucose during and after STEMI decreases acute and 1-year mortality rates.40

Adverse events of ACS therapy