Acute Myocardial Infarction

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75 Acute Myocardial Infarction

Angina pectoris was recognized in the 18th century; myocardial infarction (MI), however, was described approximately 200 years later. Simultaneous to the identification of MI was the initial introduction and subsequent application of the electrocardiogram (ECG)—the first objective method of assessing the coronary origin of the presentation. In fact, early clinician investigators described the evolving “electrographic” changes during angina in 1918.¹ Over the next 50 years, angina pectoris and MI were further characterized and diagnosed; unfortunately, however, the management of ischemic heart disease did not progress as significantly. From this point in medical history until the 1960s, management consisted primarily of pain relief coupled with strict bed rest for prolonged periods and management of resultant congestive heart failure (CHF); acute complications such as cardiogenic shock and sudden cardiac death were invariably fatal events. Subsequently, the introduction and widespread use of cardiopulmonary resuscitation, external defibrillation, and antidysrhythmic agents gave the clinician powerful new tools in the management of sudden cardiac death and other malignant dysrhythmias. Overall management, however, was still aimed at the complications of ischemic heart disease rather than the syndrome itself.

With recognition of the thrombotic nature of the acute coronary syndrome within the last several decades, the stage was set for the next most significant advance in the management of more acute forms of ischemic heart disease, namely acute myocardial infarction (AMI). Early coronary angiography coupled with intraarterial administration of streptokinase ushered in the era of acute reperfusion therapies, certainly the most significant advancement in the recent past. Clinicians were now able not only to treat the acute complications of the illness but also to interrupt, if not halt, the primary process, thereby markedly reducing morbidity and mortality. Furthermore, aggressive antiplatelet and anticoagulant therapies as well as intracoronary stenting have increased rates of patency and reduced coronary reocclusion and reinfarction.

The most recent efforts in this important area of acute cardiac care focus on rapid recognition of acute coronary syndrome (ACS), use of various adjunctive therapies, and restoration of coronary perfusion. When applied to the patient with ST-segment elevation myocardial infarction (STEMI), this process can be described as a STEMI “system of care.” In this system of care, STEMI is rapidly recognized; emergent reperfusion therapy, whether it be accomplished via medical fibrinolysis or catheter-based percutaneous coronary intervention (PCI), is quickly initiated while adjunctive antiplatelet and anticoagulant therapies are administered. This system of care spans from the ambulance with prehospital 12-lead ECG through the emergency department (ED) to the cardiac catheterization laboratory and coronary care unit (CCU).

Epidemiology

Globally, cardiovascular disease now ranks as the leading cause of death. It now causes one third of all deaths worldwide. The World Health Organization (WHO) in conjunction with the Centers for Disease Control and Prevention (CDC) published the Atlas of Heart Disease and Stroke; in this report, the WHO/CDC note a combined death toll of 17 million persons per year, with a potential increase to 24 million people per year by 2030.² In the United States, ischemic heart disease, particularly acute forms of the illness, is the leading cause of death for adults. Unfortunately, half of these deaths result from sudden cardiac death unrelated to ACS, usually within the first 2 hours of symptom onset, either out of hospital or soon after arrival in the ED. Fifteen percent of the fatalities occur prior to age 65 years, with the majority in women. The “burden” placed on medical centers and other acute care facilities is tremendous, with an approximate 8 million people having been admitted to hospital in the past 20 years; 20% of these admissions involve AMI. Furthermore, while death from coronary heart disease has decreased in North America and many western European countries, there is an increased mortality in developing countries.^3,⁴

According to the American Heart Association,⁵ coronary heart disease caused approximately 1 of every 6 deaths in the United States in 2006. In 2010, an estimated 785,000 Americans will have a new coronary event, and approximately 470,000 will have a recurrent attack. It is estimated that an additional 195,000 “silent” first MIs occur each year. These events usually occur in patients over the age of 40 years, with an increasing occurrence as one ages. Approximately every 25 seconds, someone in the United States will have a coronary event, and approximately every minute someone will die of one such event.⁵

Pathophysiology

Ischemic heart disease describes an entire spectrum of illness, ranging from acute to chronic entities related to coronary artery disease, including angina pectoris, AMI, cardiomyopathy and malignant dysrhythmia. Acute coronary syndromes have been defined as unstable angina pectoris (USAP) and AMI. In the past, AMI was separated into Q-wave (transmural) and non–Q wave (nontransmural) events. This terminology was replaced by myocardial infarction with associated ST elevation (STEMI) and infarction without elevation of the ST segment (non-STEMI or NSTEMI). In STEMI, the patient’s symptoms and ECG are relied upon to drive treatment. When diagnostically abnormal ST-segment elevation is not present, a rise in serum markers over time can indicate an NSTEMI, assuming the appropriate clinical conditions exist. While this terminology is still used, MI has been further defined and categorized to reflect the many possible clinical situations (please refer to the following discussions for further delineation of AMI).

Historically, the two primary intracoronary pathophysiologic events underlying the development of ACS include thrombus formation and vasospasm. In the setting of either a structurally normal artery or preexisting coronary artery disease, initial endothelial damage produces platelet aggregation and resultant thrombus formation. In most cases, disruption of an atherosclerotic plaque provides the endothelial injury. Occlusion of the coronary artery then results, ranging from minimal, transient, asymptomatic obstruction to complete occlusion usually associated with prominent symptomatology, namely AMI. Coronary artery obstruction can lead to myocardial ischemia, hypoxia, acidosis, and ultimately AMI. Vasospasm results when locally active substances are coupled with systemic mediators to produce a cascade of events resulting in worsened myocardial perfusion. Isolated vasospasm followed by thrombus is involved in approximately 10% of AMIs. Refer to Figure 75-1 for a depiction of the acute pathophysiology of AMI.

Figure 75-1 Pathophysiology of acute myocardial infarction.

A, Normal coronary flow without obstructive lesions. B, Lipid accumulation with plaque formation and ultimate rupture, leading to thrombus formation and vasospasm. C, Significant compromised flow within the coronary artery, resulting in clinical manifestation, as noted in D, with ST-segment elevation, likely accompanied by chest discomfort or other symptoms.

(Figures courtesy Ashok Subramanian, MD.)

In the last decade, the definition of MI has evolved. The European Society of Cardiology and the American College of Cardiology published consensus criteria for “redefinition” of MI in 2000.⁶ These criteria reflected the improvements in biomarker testing. Then in 2007, working groups from these organizations along with the World Heart Federation and American Heart Association published the “Universal Definition of Myocardial Infarction.”⁶ This expanded definition classifies infarction based on clinical situations resulting in myocardial necrosis/cell death.⁶

The term myocardial infarction should be used when there is evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Under these conditions, any one of the following criteria meets the diagnosis for myocardial infarction; the various subcategories of acute myocardial infarction are referred to as types 1 to 5 ⁶:

Type 1. Spontaneous myocardial infarction related to ischemia due to a primary coronary event such as plaque erosion. The type 1 AMI demonstrates a typical rise and/or fall of cardiac biomarkers (preferably troponin), with at least one value above the 99th percentile of the upper reference limit (URL) together with evidence of myocardial ischemia manifested by at least one of the following:

• Symptoms of ischemia

• ECG changes indicative of new ischaemia (new ST-segment and/or T-wave changes or a new left bundle branch block [LBBB])

• Development of pathologic Q waves on the ECG

• Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality

Type 2. Myocardial infarction secondary to ischemia due to either increased oxygen demand or decreased supply (e.g., coronary artery spasm, coronary embolism, anemia, arrhythmias, severe hypertension, or significant hypotension)

Type 3. Sudden, unexpected cardiac death involving cardiac arrest, often with symptoms suggestive of myocardial ischemia, and accompanied by presumably new ST elevation, or new LBBB, and/or evidence of fresh thrombus by coronary angiography and/or at autopsy, but death occurring before blood samples could be obtained or at a time before the appearance of cardiac biomarkers in the blood

Type 4. Myocardial infarction associated with PCI, without or without intracoronary stent. For percutaneous coronary interventions (PCI) 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 × 99th percentile URL have been designated as defining PCI-related myocardial infarction. A subtype related to a documented stent thrombosis is recognized.

Type 5. Myocardial infarction associated with CABG. For coronary artery bypass grafting (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 5 × 99th percentile URL plus either new pathologic Q waves, or new LLLB, or angiographically documented new graft or native coronary artery occlusion, or imaging evidence of new loss of viable myocardium have been designated as defining CABG-related myocardial infarction. Also, pathologic findings of an acute myocardial infarction define the type 5 AMI.⁶

Criteria for prior MI includes the following ⁶:

• Development of new pathologic Q waves with or without symptoms

• 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

Additional issues to consider in the pathophysiology of AMI focus on initial primary illness or concurrent medical events. Such considerations obviously have significant potential for impact on additional diagnostic and therapeutic issues; these presentations are reasonably likely in the undifferentiated, ill critical care patient. In the type 2 AMI presentation, the patient with shock of varying causes may experience AMI secondary to the physiologic insult placed on the heart. For instance, the patient with distributive shock resulting from urosepsis or the patient with hypovolemic shock due to gastrointestinal hemorrhage may experience either NSTEMI or STEMI. Furthermore, metabolic poisons such as cyanide, carbon monoxide, and hydrogen sulfide can disrupt myocardial cellular function, resulting in ACS.

Clinical Features

The history—and the clinician’s interpretation of the available history—is vital. In the critical care unit, however, the patient may be unable to offer a thorough history because of either active illness or instrumentation such as endotracheal intubation. If available, an appropriate history will enable the clinician to focus the evaluation, provide adequate therapies, secure a safe disposition, and minimize the need for additional investigations.

Angina pectoris, the chest pain associated with ACS, by definition includes a sense of choking, strangulation, or constriction. Common descriptions of the discomfort include not only pain but also pressure, squeezing, fullness, or heaviness. In some patients, the symptoms are perceived as gastrointestinal. The location for angina is substernal and left chest with radiation to the shoulders, arms, neck, or jaw. Patients with AMI, however, may also present with pain in the right chest. The duration of chest pain is valuable in determining its cause. Angina pectoris generally is short-lived, lasting less than 15 minutes. Patients with AMI usually experience more than 30 minutes of chest pain. Intermittent, sharp, localized chest discomfort lasting less than several seconds usually is not due to ACS. The symptoms of angina pectoris improve dramatically within 2 to 5 minutes after rest or nitroglycerin. If the pain persists for more than 10 minutes, the diagnosis of ACS or a noncardiac origin should be considered. Caution is also advised in the chest pain patient who appears to respond to an antacid; overreliance on this response as a major decision point in “ruling out” ACS is not encouraged. Many AMI patients experience associated symptoms such as dyspnea, diaphoresis, nausea, vomiting, dizziness, and anxiety; these various symptoms may be the primary complaint in patients presenting with AMI.

Risk factors that increase the likelihood for atherosclerosis and AMI—male gender, family history, cigarette smoking, hypertension, hypercholesterolemia, and diabetes mellitus—should be sought. Personal habits such as cigarette smoking and use of illicit drugs, particularly sympathomimetic substances such as cocaine, should be reviewed. Artificial or early menopause and the use of contraceptive pills may increase the likelihood of ischemic heart disease in women. If a patient has a history of coronary artery disease, a risk-factor analysis is unwarranted, because the risk of coronary artery disease is 100%.

There has been disagreement over whether these coronary risk factors should be considered in the clinician’s medical decision making. An early report ⁵ suggested that such factors, which were initially derived because of their ability to predict the development of coronary atherosclerosis and its complications over decades in association with other clinical variables such as ECG interpretation, have minimal predictive value acutely as to whether a patient is currently experiencing an AMI. More contemporary investigation in possible ACS patients suggests that the coronary risk factors do in fact have significant predictive value.^7,^8,⁹ This important issue is still debated by the epidemiologists; for the clinician, a consideration of the risk-factor burden is one feature of the overall diagnostic analysis.

Because angina is a visceral sensation that is often diffuse, some patients may have an anginal equivalent syndrome. Such anginal equivalent presentations describe patients who are experiencing ACS yet do not complain of typical chest pain; rather, these patients note atypical pain, dyspnea, weakness, diaphoresis, or emesis—these complaints, in fact, are the manifestation of the ACS event. Patients with altered cardiac pain perception (e.g., the elderly or patients with long-standing diabetes mellitus) are potentially at risk to present with anginal equivalent syndromes. A recent large survey of 434,877 confirmed AMI patients reported that a significant minority of these individuals—approximately 30%—lacked chest pain on presentation, noting only the anginal equivalent complaints.¹⁰ The most frequently encountered anginal equivalent chief complaint is dyspnea, which is found in 10% to 30% of patients with AMI, often due to pulmonary edema.^10,^11,¹² Isolated emesis and diaphoresis are quite rare.^11,¹²

The geriatric patient may also present atypically with acute weakness (3%–8%) and syncope (3%–5%).¹³ Unexplained sinus tachycardia, bronchospasm resulting from cardiogenic asthma, and new-onset lower extremity edema have all been reported as anginal equivalent presentations for AMI in this age group. Among the very elderly, anginal equivalent syndromes typically involve neurologic presentations with acute mental status abnormalities and stroke. From the perspective of acute delirium, less than 1% of such patients in an ED population with altered mentation will be found to have AMI. AMI associated with acute stroke is noted in approximately 5% to 9% of patients.¹³

Physical Examination

The physical examination in the patient with AMI rarely provides diagnostic confirmation of the illness; the examination can certainly suggest MI yet not confirm its presence. The ECG, serum markers, and other investigations interpreted in the context of the clinical event confirm the diagnosis. Specific examination findings resulting directly from ACS include anxiety, pale appearance, and diaphoresis. In fact, the presence of significant diaphoresis as a physical examination finding is strongly suggestive of AMI.¹⁴ Significant physical examination findings encountered in the AMI patient most often result indirectly from the coronary event and result directly from complications of the AMI. These findings include hypotension, altered mentation, various other signs of poor perfusion, rales and low oxygen saturations related to pulmonary congestion, and heart sounds related to myocardial and/or valvular dysfunction.¹⁵ Both brady- and tachydysrhythmias are seen as well. And, of course, the combination of poor peripheral perfusion—manifested by hypotension unresponsive to hemodynamic support—and pulmonary edema is considered cardiogenic shock.

The physical examination, although crucial to many life-threatening disease processes, is often unhelpful in diagnosing AMI; AMI may be suggested, however, in the patient with obvious cardiac dysfunction manifested by acute pulmonary edema or cardiogenic shock, or both. A change in mental status, poor peripheral perfusion, pronounced tachycardia, hypotension, diaphoresis, rales, jugular venous distension, and S₃ and S₄ heart sounds often provide evidence of significant myocardial dysfunction in patients with AMI. Patients with evidence of myocardial dysfunction, including S₃ heart sound, S₄ heart sound, or rales, on initial presentation are at much greater risk for adverse cardiovascular events, including nonfatal AMI, death, stroke, life-threatening dysrhythmia, and the requirement for cardiac surgery.

Caution should be exercised when attributing a chest wall source for pain based on palpation or movement. To safely relate the chest discomfort to a chest wall origin, the pain must be described as sharp or stabbing (i.e., pleuritic in nature) and be completely reproducible by palpation.¹⁶ Up to 15% of patients with AMI may have some form of tenderness on chest wall palpation.¹⁷

Diagnostic Strategies

Electrocardiogram

In the chest pain patient (or patient with acute cardiorespiratory decompensation suspected of AMI), the ECG can be used to establish the diagnosis of AMI or other noncoronary ailment, select appropriate therapy, determine the response to treatments, determine the correct inpatient disposition location, and predict risk of both cardiovascular complication and death. The ECG is an extremely powerful diagnostic study, which, if used in appropriate fashion, can guide the clinician in the evaluation of the chest pain patient suspected of AMI. In fact, the ECG provides pivotal information in the patient with STEMI, allowing its diagnosis and guiding acute resuscitative therapies. In other coronary-related ailments, the ECG can provide useful information regarding diagnosis and management. An understanding of its shortcomings, however, in this application will only improve its use. From the perspective of the ECG diagnosis of AMI, the ECG has numerous shortcomings, including the “normal” and “nondiagnostic” interpretations, evolving AMI patterns, the NSTEMI ECG presentation, confounding and mimicking patterns, and the isolated acute posterior wall AMI.

The ECG may manifest a range of ECG abnormalities (Figure 75-2) in the patient with potential AMI, including the prominent T wave, T-wave inversion, ST-segment depression, ST-segment elevation, and QA waves, among other findings. The earliest ECG finding resulting from STEMI is the hyperacute T wave, which may appear minutes after the interruption of blood flow; the R wave also increases in amplitude at this stage. The hyperacute T wave, a short-lived structure that evolves rapidly on to ST-segment elevation over a 5- to 30-minute period, is often asymmetric with a broad base; these T waves are also associated not infrequently with reciprocal ST-segment depression in other ECG leads. Such a finding on the ECG is transient in the AMI patient; either apparent or progressive ST-segment elevation is usually encountered at this stage. As the infarction progresses, the hyperacute T wave evolves into the giant R wave, particularly in the anterior wall AMI. The giant R wave is a transition structure from the hyperacute T wave to typical ST-segment elevation; it essentially is a large monophasic R wave with pronounced ST-segment elevation. Prominent T waves may be seen in patients with AMI as well as hyperkalemia, acute myopericarditis, benign early repolarization, left ventricular hypertrophy, and bundle branch block.

Figure 75-2 Electrocardiographic findings of acute myocardial infarction (AMI): (1) T-wave abnormalities of AMI. A, Prominent “hyperacute” T wave. B-E, T-wave inversions of non–ST-segment elevation MI (NSTEMI). (2) ST-segment depression. A, Flat. B, Downsloping. C, Upsloping. (3) ST-segment elevation. A, Convex ST-segment elevation. B, Obliquely straight ST-segment elevation. C, Convex ST-segment elevation. (4) Pathologic Q waves. A, Pathologic Q wave of completed myocardial infarction. B, Simultaneous ST-segment elevation with pathologic Q wave 2 hours into the course of ST-segment elevation MI (STEMI).

Within moments, the ST segment assumes a more easily recognized morphology. In approximately 85% of STEMI patients, the initial upsloping portion of the ST segment is either convex or flat; if the ST segment is flat, it may be either horizontally or obliquely so. An analysis of the ST-segment waveform can be particularly helpful in distinguishing among the various causes of ST-segment elevation and identifying the AMI case. This technique uses the morphology of the initial portion of the ST segment/T wave—defined as beginning at the J point and ending at the apex of the T wave. Patients with noninfarctional ST-segment elevation (i.e., early repolarization or left ventricular hypertrophy-related change) tend to have a concave morphology of the waveform. Conversely, patients with ST-segment elevation due to AMI have either obliquely flat or convex waveforms. The use of this ST-segment elevation waveform analysis in emergency room chest pain patients increases specificity for the AMI diagnosis.¹⁸ This morphologic observation should be used only as a guideline. As with most guidelines, it is not infallible.

Significant ST-segment elevation occurring in at least two anatomically oriented leads is the primary ECG indication for fibrinolysis or urgent PCI. In that ST-segment elevation represents a significant finding, a brief review of the various causes of ST-segment elevation in the chest pain patient is warranted. Unfortunately, ST-segment elevation in the chest pain patient less often results from AMI; in fact, only 20% to 30% of chest pain patients will have STEMI—the remainder of these patients will have noninfarctional causes of the ST-segment elevation.^18,¹⁹ Patients with chest pain may present electrocardiographically with ST-segment elevation due to AMI, confounding patterns, or masquerading syndromes. In most instances, ST-segment elevation resulting from AMI is easily noted. Confounding patterns such as LBBB, ventricular paced rhythms, and left ventricular hypertrophy may obscure the typical ECG findings of AMI as well as produce noninfarctional ST-segment elevation, which may lead the uninformed clinician astray. Other ST-segment elevation patterns, including benign early repolarization and acute pericarditis, occur in the individual with chest discomfort and may suggest the incorrect diagnosis of AMI, exposing the patient to unnecessary and potentially dangerous therapies.

ST-segment depression is generally considered to represent subendocardial, noninfarctional ischemia, although it may be the presenting ECG finding in the NSTEMI patient. The morphology of subendocardial ischemic ST-segment depression is classically horizontal or downsloping; upsloping ST-segment depression is also seen, yet is less often associated with acute ischemia. With subendocardial ischemia, the ST-segment depression is often diffuse and can be located in both the anterior and the inferior leads. ST-segment depression also occurs as the primary ECG finding in NSTEMI as well as a secondary, though important, manifestation in STEMI, namely reciprocal ST-segment depression. Also, ST-segment depression in the right precordial leads may represent posterior wall AMI. Nonischemic causes of ST-segment depression include digoxin effect and repolarization changes seen in left ventricular hypertrophy, bundle branch block, and ventricular paced rhythm presentations.

Reciprocal ST-segment depression, also known as reciprocal change, is defined as ST-segment depression in leads separate and distinct from leads reflecting ST-segment elevation. Importantly, this form of ST-segment depression is not associated with situations in which altered intraventricular conduction produces deviation—such as bundle branch block, left ventricular hypertrophy, and ventricular paced rhythms. Reciprocal change in the setting of a STEMI identifies a patient with an increased chance of poor outcome and, therefore, an individual who may benefit from a more aggressive approach. Furthermore, its presence on the ECG supports the diagnosis of AMI with very high sensitivity and positive predictive values greater than 90%. The use of reciprocal change in both prehospital and emergency room chest pain patients increases the diagnostic accuracy in the ECG recognition of AMI.^20,²¹ Reciprocal change is seen in approximately 75% of cases of inferior wall AMI and much less often in cases of anterior wall MI (30%).^20,²¹

Inverted T waves produced by ACS are classically narrow and symmetric; they are morphologically characterized by an isoelectric ST segment that is usually bowed upward (i.e., concave) and followed by a sharp symmetric downstroke. The terms coronary T wave and coved T wave have been used to describe these T-wave inversions. Prominent, deeply inverted, and widely splayed T waves are more characteristic of the noninfarctional, nonischemic conditions such as cerebrovascular accident. An important subgroup of patients with noninfarctional angina often have deep T-wave inversions in the precordial leads (V₁ through V₄); the T wave may also be biphasic in this same distribution. The syndrome, termed the left anterior descending T wave or Wellen syndrome, is important to recognize because it is highly specific for stenosis of the left anterior descending coronary artery with anterior wall AMI as the natural history. T-wave inversion can also be caused by NSTEMI and evolving states of STEMI.

In general, Q waves represent established myocardial necrosis and rarely are the primary finding in the AMI patient. Pathologic Q waves may be caused by a previously unrecognized prior infarction, or conversely, a prior MI may mask ischemic extension in the same anatomic location. Q waves usually develop within 8 to 12 hours after a transmural AMI, yet they can be noted as early as 1 to 2 hours after the onset of complete coronary occlusion. As such, the simultaneous presence of Q waves and ST-segment elevation does not preclude consideration of fibrinolytic therapy.

The ECG changes discussed previously may all be encountered in the AMI patient. Two basic ECG presentations of AMI, the STEMI and NSTEMI, warrant further comment. The STEMI presents with ST-segment elevation in at least two anatomically contiguous leads—a reasonably straightforward principle. On the contrary, the NSTEMI can manifest with a range of ECG abnormalities, representing a diagnostic challenge and a potential failing of the ECG. Patients with NSTEMI may present with obvious abnormality such as ST-segment depression or T-wave abnormalities; these findings can be transient. In these cases, symmetric convex downward ST-segment depression or inverted or biphasic T waves are characteristically seen. Alternatively, the ECG may only reveal nonspecific findings or appear initially normal. Lastly, the NSTEMI patient may demonstrate only a confounding pattern such as LBBB. Regardless of the non–ST-segment elevation presentation, the NSTEMI patient is diagnosed with AMI only after the return of a positive serum marker.

Several ECG patterns confound the diagnosis of AMI, including LBBB, ventricular paced rhythms, and left ventricular hypertrophy. In the patient with LBBB, the anticipated or expected ST-segment/T-wave configurations are discordant, directed on the opposite side of the isoelectric baseline from the terminal portion of the QRS complex. This relationship is called QRS complex–T wave axes discordance (Figure 75-3).^22,²³ Loss of this discordance in patients with LBBB may imply AMI. The clinician must realize, however, that the ECG is markedly compromised as a diagnostic tool in this setting. As with the LBBB pattern, the right ventricular paced rhythm and left ventricular hypertrophy patterns can both mimic and mask the manifestations of AMI. In ventricular paced rhythms, the principle of appropriate discordance should also be followed. An inspection of the ECG in patients with ventricular paced rhythms must be performed, looking for a loss of this QRS complex–T wave axes discordance. Loss of this normal discordance in patients with ventricular paced rhythms can suggest AMI.²⁴ Left ventricular hypertrophy is not uncommonly encountered on the ECG of chest pain patients. Its presence on the ECG, particularly the repolarization changes that alter the morphology of the ST segment and/or the T wave, can confound the early evaluation. These repolarization changes are seen in approximately 70% of cases and represent the new norm for the patient with electrocardiographic left ventricular hypertrophy.²⁵ Left ventricular hypertrophy is associated with poor R wave progression, producing a QS pattern in the right to mid-precordial leads. In most instances, the ST-segment elevation is seen here along with prominent T waves. ST-segment depression with inverted T wave is also seen in the lateral leads.

Figure 75-3 Electrocardiographic indications for reperfusion therapy in the left bundle branch block presentation.

Several additional ECG tools can be employed by the clinician to further evaluate the chest pain patient suspected of AMI. These tools include additional ECG leads and ST-segment surveillance. The additional-lead ECG improves the diagnostic power of the standard 12-lead ECG; with the addition of three leads, the 15-lead ECG is produced. In the 15-lead ECG, the posterior leads V₈ and V₉ image the posterior wall of the left ventricle (posterior AMI) and lead V₄R evaluates the right ventricle (right ventricular infarction). The use of the additional leads can not only confirm the presence of AMI but also alter treatment decisions in ACS patients. In a study of all emergency room chest pain patients initially evaluated with a 12-lead ECG, Brady el al.²⁶ reported that the 15-lead ECG provided a more accurate description of myocardial injury in those patients with AMI yet failed to alter rates of diagnoses or the use of reperfusion therapies or change disposition locations. Looking at a more select population of chest pain patients, Zalenski and colleagues²⁷ investigated the use of the 15-lead ECG in chest pain patients with a moderate to high pretest probability of AMI who were already identified as candidates for critical care admission. In this study, the authors reported an approximate 12% increase in sensitivity for the diagnosis of AMI. Potential clinical indications for obtaining the 15-lead ECG in chest pain patients include: (1) ST-segment depression in leads V₁ through V₃; (2) STEMI of the lateral or inferior wall; (3) isolated ST-segment elevation in lead V₁ or ST-segment elevation in leads V₁ and V₂; and (4) the inferior or lateral AMI complicated by hypotension on presentation or after preload reducing medication administration. Figure 75-4, A is an example of a 15-lead ECG with inferoposterior AMI with right ventricular infarction. Note the ST-segment elevation in leads II, III, and aVf (inferior AMI), RV₄ (right ventricular infarction), and leads V₈ and V₉ (posterior AMI); the ST-segment depression with prominent R wave is also seen in leads V₁ to V₃.

Figure 75-4 A, A 15-lead electrocardiogram showing inferoposterior acute myocardial infarction (AMI) with right ventricular (RV) infarction. Note the ST-segment elevation in leads II, III, and aVf (inferior AMI), RV₄ (RV infarction), and leads V₈ and V₉ (posterior AMI). The ST-segment depression with prominent R wave is also seen in leads V₁ to V₃. B, ECG body mapping. i. Non-diagnostic 12-lead ECG in an acutely ill patient with pulmonary edema. ii. Torso map demonstrating acute posterior and RV infarctions signified by the red coloration in the appropriate anatomic regions. iii. An 80-lead ECG with ST-segment elevation in the RV and posterior left ventricular leads, consistent with acute posterior AMI with RV infarction.

ECG body mapping, an extrapolation of the additional-lead concept, more completely images the heart in an electrical sense. Contemporary body mapping systems rely on a more widely distributed lead distribution, focusing on areas of the myocardium which are not imaged appropriately by the traditional 12-lead ECG, including the electrocardiographically “near-silent” and “silent” areas. The “near-silent” areas include the far inferior and lateral walls as well as the septal region of the left ventricle; the “silent” areas include the posterior wall of the left ventricle and the entire right ventricle. Various systems are available in today’s market, and most rely on a combination of torso mapping with ECG determination. An example of a body map is depicted in Figure 75-4, B; note the torso imaging with colorimetric depictions (green indicating normal ST segments, blue indicating ST-segment depression, and red indicating ST-segment elevation). The various ECG waveforms are also displayed for the entire body map, much more completely describing the heart when compared to the somewhat limited imaging of the 12-lead electrocardiogram. While body mapping has demonstrated increased rates of STEMI diagnosis, at this time, conclusive data noting improved patient outcomes is lacking.²⁸

Serial monitoring of the ST segment can also aid the clinician in the diagnosis of AMI as well as monitor the response to therapy. This can be accomplished using two different approaches: serial 12-lead ECG acquisition or ST-segment trend monitoring. Either technique can demonstrate the evolution of ST-segment/T-wave changes in a number of different clinical scenarios, including the initially nondiagnostic ECG, the continuous chest pain patient with an initially nondiagnostic ECG, and the individual with a confounding or masquerading ECG pattern. This increased level of monitoring may provide earlier evidence of coronary occlusion in patients with non-AMI ACS presentations. Potentially, serial ECGs can furnish an increased level of ECG monitoring in patients presenting with chest pain and a nondiagnostic ECG on presentation.²⁹^–³³ In the coronary care unit setting, serial ST-segment surveillance initiated at admission offers additional clinical data, with approximately 20% of patients revealing dynamic ECG change in the early stages of the hospital course.³⁴ ST-segment monitoring has proved to be an effective method for noninvasive evaluation of reperfusion after delivery of fibrinolytic therapy in multiple investigations. In one series, Krucoff and colleagues³³ noted that angiographically proven reperfusion was detected with a sensitivity of 89% using serial ST-segment trend monitoring, with a corresponding specificity of 82%.

Serum Markers

The elevation of serum cardiac markers over several days of hospitalization has traditionally been the standard method for diagnosing AMI. Whereas creatine phosphokinase (CK)-MB fraction once was the typical marker used by most clinical laboratories to indicate myocardial necrosis, now the troponins are the most commonly used serologic tests in the regions with established acute cardiac care. Previously, detection of AMI by enzyme elevations over 48 to 72 hours was sufficient to establish the diagnosis of AMI. Because of the evolution of acute interventional modalities, however, significant time-sensitive pressure now exists to identify patients with AMI earlier after onset of the ailment. Particularly in patients with a nondiagnostic ECG, early serum markers of myocardial necrosis have the potential to alter the diagnostic course and treatment plans. Further, there are now clear data that indicate that elevations in serum markers, even in those not meeting traditional criteria for AMI, independently identify those patients at risk for poor outcome.³⁵^–³⁷

In the last decade, the ability to measure serum markers has improved greatly. This improved sensitivity has been mirrored by improved specificity. The current “gold standard” is the troponin molecule (specifically I and T). This intracellular peptide controls the interaction of actin and myosin in the cardiac myocyte. When injury occurs, these markers are released from the cell. Changes in the absolute value of these markers can be detected as soon as 2 to 3 hours in 80% of patients following MI, thus “ruling in” for MI. “Ruling out” MI can take longer. While most patients display positive markers in 6 hours, and a few more patients become positive after 8 hours, a full 12-hour rule out should be performed in highly suspicious clinical situations.

Once released into the blood, these markers are then cleared by the kidneys. A baseline elevation of these markers in the absence of MI has been termed a troponin leak and has been noted to occur under multiple clinical conditions (Box 75-1). In fact, previous studies have demonstrated elevated troponin levels in up to half of critical care patients, many of whom do not have evidence of clinically significant coronary artery disease or ACS. However, regardless of etiology, patients with elevated troponin values have a higher incidence of adverse outcome, including mortality. It is the rise or fall of theses values, with one above the 99th percentile of the upper reference limit (URL), coupled with evidence of myocardial ischemia that differentiates MI from other causes of high troponin. Troponin elevations can persist for 1 to 2 weeks following injury. However, they are usually not rising or falling rapidly at his time. A greater than or equal to 20% increase in the value of the sample during this period can indicate re-injury.

As already noted, two myocardial-specific proteins—myocardial troponin T and troponin I—are extremely important in the evaluation of patients suspected of having AMI and have largely replaced CK for biochemical determination of infarction. The cardiac troponins I and T are genetically distinct from those forms found in skeletal muscle, making them highly cardiac-specific markers. The biokinetics of troponin release are related to the location of the protein within the cell. Normally, small quantities of troponins are free in the cytosol, whereas the majority is entwined in the muscle fiber. Following injury, a biphasic rise in serum troponins is seen. This two-component pattern corresponds to the early release of the free cytoplasmic proteins followed by a prolonged rise with disruption of the actual muscle fiber, resulting in a sustained release of the troponins for approximately 7 days. Serum troponin concentrations begin to rise measurably in the serum at about the same time as CK-MB elevations become detectable—as early as 3 hours after onset—and therefore offer no particular benefit over the CK-MB regarding early detection of the event. The troponins, however, remain elevated for prolonged periods of time, ranging from 7 to 10 days. The cardiac-specific troponins are highly sensitive for the early detection of myocardial injury in patients with AMI. A positive test result is associated with significant risk, whereas negative study (i.e., serial troponins) findings predict low risk.³⁸

The sensitivity of the troponins approaches 50% within 3 to 4 hours of the event. The test finding is positive for AMI in about 75% at 6 hours after onset of symptoms; at 12 hours, the test is almost 100% sensitive for AMI.³⁹ Moreover, the presence of a positive troponin, even in the face of a nondiagnostic ECG and negative CK-MB assay, independently confers a prognosis on the patient that is similar to those suffering STEMIs.^40,⁴¹ Thus, elevated troponin values appear to be excellent indicators of risk of subsequent death, AMI, and acute cardiovascular complications in all ACS patients, even those who do not meet traditional criteria for AMI. A negative test result, however, does not necessarily imply a favorable prognosis. One caveat for the troponins is that a number of systemic diseases can cause elevations in the serum levels of troponins without ACS.

If unable to measure troponin, then CK-MB should be measured by mass assay. It too should be scrutinized to the same URL as noted above. Unfortunately, CK-MB is less sensitive than the troponins in this determination and less frequently used by many health systems and medical centers. It typically rises in 2 to 4 hours and falls in 1 to 2 days.

Another widely employed serum marker is myoglobin. Myoglobin is a theoretically attractive indicator for myocardial injury, because levels are elevated in the serum within 1 to 2 hours after symptom onset and peak 4 to 5 hours after AMI. The sensitivity of myoglobin for AMI approaches 100% at 3 hours. Yet, its considerable lack of specificity markedly reduces the power of this test. Currently, myocardial myoglobin is not biochemically distinguishable from skeletal muscle myoglobin, reducing its specificity to approximately 80% compared with 94% for immunochemical CK-MB determination 3 hours after emergency room presentation. As with the troponins, myoglobin level is elevated in patients with renal failure because of reduced clearance, making this marker less useful in a patient population that tends to be at an elevated risk for ACS. Additionally, it also will be elevated in any clinical situation involving the skeletal muscle, such as trauma, exercise, and significant systemic illness.

Medical decision making regarding serum marker use in the suspected AMI patient is complex. Serum markers are most often used in a serial fashion. Relying solely on the result of a single negative assay can result in a missed diagnosis in up to 74% of patients.⁴² Single testing strategies, however, may be of value when the clinician is evaluating a nonspecific presentation with illness course lasting greater than 72 to 96 hours. Trending results over time significantly reduces the chance of a missed diagnosis, particularly in acute presentations of short course. A number of studies support the assertion that the troponins approach 100% sensitivity and specificity for cardiac ischemia at 12 hours following an event.³⁹ These studies all caution, however, that such elevations will occur only with cell injury; hence, they are not appropriate markers for non-AMI ACS presentations. In the setting of an appropriate clinical history or diagnostic ECG changes, a strategy of serial cardiac marker testing is relatively straightforward. Depending on the particular investigation employed, the clinician looks for the characteristic rise and fall of serial markers over a time course for the diagnosis of AMI.⁶ Most literature supports such serial testing in the acute setting for a period of 8 to 12 hours to adequately rule out MI.^6,^43,⁴⁴

The more challenging diagnostic situation is found in the critically ill patient with minimal rise in the serum marker and absence of a distinct cardiac event. It is clear, for instance, that troponin levels can be elevated in patients with renal failure or skeletal muscle diseases in the absence of ischemic coronary artery disease. In the renal failure patient, clinical suspicion of ACS must guide evaluation and management decisions; furthermore, the trending of values over time, seeking the characteristic rise and fall of serial markers as well as comparisons to “baseline” values, will also improve the clinician’s ability to use these diagnostic tests in appropriate fashion, thereby optimizing care. Patients with significant physiologic injury (e.g., sepsis, acute respiratory failure, multiple trauma, shock) have also been found to have elevated troponin values. In these populations, the elevated levels correlate with left ventricular function and the presence of organ dysfunction, yet the data addressing hospital survival and length of stay are conflicting.