1. Typical rise and gradual fall or more rapid rise and fall of biochemical markers of myocardial necrosis with at least one value above the 99th percentile of the upper reference limit (URL) and with at least one of the following clinical parameters:

2. Pathologic findings of an AMI

• Development of new pathologic Q waves on serial ECGs. The patient may or may not remember previous symptoms. Biochemical markers of myocardial necrosis may have normalized, depending on the length of time since the infarct developed.

• Imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a nonischemic cause.

• Pathologic findings of a healed or healing MI.

• 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:

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 www.timi.org.⁶ 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).

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.^25–27 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

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.34–36 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.

Dressler‘s 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 should also be considered as potential complications, including hemorrhage associated with medications and resulting from invasive procedures. The various antiplatelet, anticoagulant, and fibrinolytic therapies (as noted earlier) are all associated with hemorrhage as a major complicating issue. In fact, within a single class of medications, many of these agents are so similar in efficacy that superiority is determined by the rate of occurrence of adverse effects. Aggressive supportive care coupled with “antidote” therapy is the most appropriate approach to patients with hemorrhagic complication from medications. Protamine can be helpful in the reversal of the heparins. Fresh frozen plasma (FFP) and platelet infusions are of value in certain anticoagulant and antiplatelet scenarios. The low-molecular-weight heparins (LMWHs) cannot be reversed. Fibrinolytic agents also cannot be reversed; rather, therapy including FFP and packed red blood cell (PRBC) transfusions is most appropriate. These various antidotal agents should be considered only with life-threatening hemorrhage. The clinician at the bedside, who can evaluate the risks and benefits of these treatments in the setting of a complicated ACS event, is in the best position to determine management strategies.

Procedural complications include arterial injury with hemorrhage related to percutaneous interventions; the most typical is a pseudoaneurysm of the femoral artery with hemorrhage into the thigh compartment or retroperitoneal area. The diagnosis is made based on a high degree of clinical suspicion in a patient with recent femoral artery cannulization. Physical examination findings, including extensive bruising in the thigh and bruits over the femoral artery, are suggestive; ultrasonography or CT of the thigh or retroperitoneal area can confirm the diagnosis.