Acute Myocardial Infarction

Acute myocardial infarction (AMI) is one of the most common diagnoses in hospitalized patients in industrialized countries. In the United States, approximately 1.1 million AMIs occur each year. The mortality rate with AMI is approximately 30%, with more than half of these deaths occurring before the stricken individual reaches the hospital. Although the mortality rate after admission for AMI has declined by about 30% over the last two decades, approximately 1 of every 25 patients who survives the initial hospitalization dies in the first year after AMI. Survival is markedly reduced in elderly patients (over age 75), whose mortality rate is 20% at 1 month and 30% at 1 year after AMI.

Pathophysiology: Role of Acute Plaque Rupture

AMI generally occurs when coronary blood flow decreases abruptly after a thrombotic occlusion of a coronary artery previously narrowed by atherosclerosis. Slowly developing, high-grade coronary artery stenoses usually do not precipitate AMI because of the development of a rich collateral network over time. Instead, AMI occurs when a coronary artery thrombus develops rapidly at a site of vascular injury. This injury is produced or facilitated by factors such as cigarette smoking, hypertension, and lipid accumulation. In most cases, infarction occurs when an atherosclerotic plaque fissures, ruptures, or ulcerates and when conditions (local or systemic) favor thrombogenesis, so that a mural thrombus forms at the site of rupture and leads to coronary artery occlusion (Fig. 243-5). Histologic studies indicate that the coronary plaques prone to rupture are those with a rich lipid core and a thin fibrous cap (Chap. 241). After an initial platelet monolayer forms at the site of the ruptured plaque, various agonists (collagen, ADP, epinephrine, serotonin) promote platelet activation. After agonist stimulation of platelets, there is production and release of thromboxane A2 (a potent local vasoconstrictor), further platelet activation, and potential resistance to thrombolysis.

Figure 243-5

Figure 243-5: Diagram of arterial thrombus responsible for acute myocardial infarction. Platelet adhesion and aggregation occur at the site of plaque rupture. Activated platelets exert procoagulant effects and the soluble coagulation cascade is activated. Fibrin strands and erythrocytes predominate within the lumen of the vessel and downstream in the 'body' and 'tail' of the thrombus.[From NS Kleiman: Antiplatelet therapy, in RM Califf (volume ed): Acute Myocardial Infarction and Other Acute Ischemic Syndromes, in E Braunwald (series ed): Atlas of Heart Diseases, Philadelphia: Current Medicine, 1996, p. 8.2.]

In addition to the generation of thromboxane A2, activation of platelets by agonists promotes a conformational change in the glycoprotein IIb/IIIa receptor (Chap. 116). Once converted to its functional state, this receptor develops a high affinity for amino acid sequences on soluble adhesive proteins (i.e., integrins) such as von Willebrand factor (vWF) and fibrinogen. Since vWF and fibrinogen are multivalent molecules, they can bind to two different platelets simultaneously, resulting in platelet cross-linking and aggregation.

The coagulation cascade is activated on exposure of tissue factor in damaged endothelial cells at the site of the ruptured plaque. Factors VII and X are activated, ultimately leading to the conversion of prothrombin to thrombin, which then converts fibrinogen to fibrin (Chap. 117). Fluid-phase and clot-bound thrombin participate in an autoamplification reaction that leads to further activation of the coagulation cascade. The culprit coronary artery eventually becomes occluded by a thrombus containing platelet aggregates and fibrin strands.

In rare cases, AMI may be due to coronary artery occlusion caused by coronary emboli, congenital abnormalities, coronary spasm, and a wide variety of systemic-particularly inflammatory-diseases. The amount of myocardial damage caused by coronary occlusion depends on (1) the territory supplied by the affected vessel, (2) whether or not the vessel becomes totally occluded, (3) the duration of coronary occlusion, (4) the quantity of blood supplied by collateral vessels to the affected tissue, (5) the demand for oxygen of the myocardium whose blood supply has been suddenly limited, (6) native factors that can produce early spontaneous lysis of the occlusive thrombus, and (7) the adequacy of myocardial perfusion in the infarct zone when flow is restored in the occluded epicardial coronary artery.

Patients at increased risk of developing AMI include those with multiple coronary risk factors (Chap. 241) and those with unstable angina or Prinzmetal's variant angina (Chap. 244). Less common underlying medical conditions predisposing patients to AMI include hypercoagulability, collagen vascular disease, cocaine abuse, and intracardiac thrombi or masses that can produce coronary emboli.

Clinical Presentation

In up to one-half of cases, a precipitating factor appears to be present before AMI, such as vigorous physical exercise, emotional stress, or a medical or surgical illness (Fig. 243-6). Although AMI may commence at any time of the day or night, circadian variations have been reported such that clusters are seen in the morning within a few hours of awakening. The increased frequency early in the day may be due to a combination of an increase in sympathetic tone and an increased tendency to thrombosis between 6:00 A.M. and 12 noon.

Figure 243-6

Figure 243-6: Hypothetical steps in the triggering of coronary thrombosis. Plaque disruption with thrombus formation occurs at a critical moment when a threshold combination of hemodynamic, prothrombotic, and vasoconstrictive forces (acute risk factors) is rapidly generated by external stressors (triggers) during a period of plaque vulnerability. Disruption of the plaque may be severe enough to produce a thrombogenic stimulus sufficiently intense to cause occlusive coronary thrombosis, leading to myocardial infarction (MI) or sudden cardiac death.[From S Waxman, JE Muller: Risk factors for an acute ischemic event, in RM Califf (volume ed): Acute Myocardial Infarction and Other Acute Ischemic Syndromes, in E Braunwald (series ed): Atlas of Heart Diseases, Philadelphia: Current Medicine, 1996, p. 2.11.]

Pain is the most common presenting complaint in patients with AMI. In some instances, it may be severe enough to be described asthe worst pain the patient has ever felt. The pain is deep and visceral; adjectives commonly used to describe it are heavy, squeezing, and crushing, although occasionally it is described as stabbing or burning (Chap. 13). It is similar in character to the discomfort of angina pectoris but usually is more severe and lasts longer. Typically the pain involves the central portion of the chest and/or the epigastrium, and on occasion it radiates to the arms. Less common sites of radiation include the abdomen, back, lower jaw, and neck. The frequent location of the pain beneath the xiphoid and patients' denial that they may be suffering a heart attack are chiefly responsible for the common mistaken impression of indigestion. The pain of AMI may radiate as high as the occipital area but not below the umbilicus. It is often accompanied by weakness, sweating, nausea, vomiting, anxiety, and a sense of impending doom. The pain may commence when the patient is at rest. When the pain begins during a period of exertion, it does not usually subside with cessation of activity, in contrast to angina pectoris.

Although pain is the most common presenting complaint, it is by no means always present. The proportion of painless AMIs is greater in patients with diabetes mellitus, and it increases with age. In the elderly, AMI may present as sudden-onset breathlessness, which may progress to pulmonary edema. Other less common presentations, with or without pain, include sudden loss of consciousness, a confusional state, a sensation of profound weakness, the appearance of an arrhythmia, evidence of peripheral embolism, or merely an unexplained drop in arterial pressure. The pain of AMI can simulate pain from acute pericarditis (Chap. 239), pulmonary embolism (Chap. 261), acute aortic dissection (Chap. 247), costochondritis, and gastrointestinal disorders. These conditions should therefore be considered in the differential diagnosis.

Physical Findings

Most patients are anxious and restless, attempting unsuccessfully to relieve the pain by moving about in bed, altering their position, and stretching. Pallor associated with perspiration and coolness of the extremities occurs commonly. The combination of substernal chest pain persisting for >30 min and diaphoresis strongly suggests AMI. Although many patients have a normal pulse rate and blood pressure within the first hour of AMI, about one-fourth of patients with anterior infarction have manifestations of sympathetic nervous system hyperactivity (tachycardia and/or hypertension), and up to one-half with inferior infarction show evidence of parasympathetic hyperactivity (bradycardia and/or hypotension).

The precordium is usually quiet, and the apical impulse may be difficult to palpate. In patients with anterior wall infarction, an abnormal systolic pulsation caused by dyskinetic bulging of infarcted myocardium may develop in the periapical area within the first days of the illness and then may resolve. Other physical signs of ventricular dysfunction that may be present include, in order of decreasing incidence, fourth (S4) and third (S3) heart sounds, decreased intensity of heart sounds, and, in more severe cases, paradoxical splitting of the second heart sound (Chap. 225). A transient apical systolic murmur due to dysfunction of the mitral valve apparatus may be midsystolic or late systolic in timing. A pericardial friction rub is heard in many patients with transmural AMI at some time in the course of the disease, if they are examined frequently. The carotid pulse is often decreased in volume, reflecting reduced stroke volume. Jugular venous distention with clear lung fields should raise suspicion of right ventricular infarction. Temperature elevations up to 38C may be observed during the first week after AMI; however, a temperature exceeding 38C should prompt a search for other causes. The arterial pressure is variable; in most patients with transmural infarction, systolic pressure declines by approximately 10 to 15 mmHg from the preinfarction state

Laboratory Findings

Myocardial infarction (MI) progresses through the following temporal stages: (1) acute (first few hours to 7 days), (2) healing (7 to 28 days),and (3) healed (29 days and beyond). When evaluating the results of diagnostic tests for AMI, the temporal phase of the infarction process must be considered. The laboratory tests of value in confirming the diagnosis may be divided into 4 groups: (1) electrocardiogram (ECG), (2) serum cardiac markers, (3) cardiac imaging, and (4) nonspecific indexes of tissue necrosis and inflammation


The electrocardiographic manifestations of AMI are described in Chap. 226. During the initial stage of the acute phase of MI, total occlusion of the infarct artery produces ST-segment elevation. Most patients initially presenting with ST-segment elevation evolve Q waves on the ECG and are ultimately diagnosed as having sustained a Q-wave MI. A small proportion may sustain only a non-Q-wave MI. When the obstructing thrombus is not totally occlusive, obstruction is transient, or if a rich collateral network is present, no ST-segment elevation is seen. Such patients are initially considered to be experiencing either unstable anigna or a non-ST-segment elevation MI (NSTEMI). Among patients presenting without ST-segment elevation, if a serum cardiac marker is detected and no Q wave develops, the diagnosis of non-Q-wave MI is ultimately made. A minority of patients who present initially without ST-segment elevation may develop a Q-wave MI. Previously it was believed that transmural MI is present if the ECG demonstrates Q waves or loss of R waves, and nontransmural MI may be present if the ECG shows only transient ST-segment and T-wave changes. However, electrocardiographic-pathologic correlations are far from perfect; and therefore a more rational nomenclature for designating electrocardiographic infarction is now commonly in use, with the terms Q-wave and non-Q-wave MI replacing the terms transmural and nontransmural MI, respectively.

The presentations that comprise the spectrum ranging from unstable angina through non-Q-wave MI to Q-wave MI are called the acute coronary syndromes (Fig. 243-1). This classification scheme provides a conceptual framework for interpreting the diagnostic and prognostic information gleaned from serum cardiac marker measurements as well as for planning antithrombotic therapy.

Figure 243-1

Figure 243-1: Acute coronary syndromes. Patients with ischemic discomfort may present with or without ST-segment elevation on the ECG. Of patients with ST-segment elevation, most (large arrow) ultimately develop a Q-wave AMI (QwMI), while a few (small arrow) develop a non-Q-wave AMI (NQMI). Patients who do not present with ST-segment elevation are suffering from either unstable angina or a non-ST segment elevation MI (NSTEMI) (large arrows), a distinction that is ultimately made on the presence or absence of a serum cardiac marker such as CKMB or a cardiac troponin detected in the blood. Most patients presenting with NSTEMI ultimately develop a NQMI on the ECG; a few may develop a QwMI. The spectrum of clinical presentations ranging from unstable angina through NQMI and QwMI are referred to as the actue coronary syndromes.

Serum Cardiac Markers

Certain proteins, called serum cardiac markers, are released into the blood in large quantities from necrotic heart muscle after AMI. The rate of liberation of specific proteins differs depending on their intracellular location and molecular weight, and the local blood and lymphatic flow. The temporal pattern of protein release is of diagnostic importance, but contemporary urgent reperfusion strategies necessitate making a decision (based largely on a combination of clinical and ECG findings) before the results of blood tests have returned from the central laboratory. Rapid whole-blood bedside assays for serum cardiac markers are now available and may facilitate management decisions, particularly in patients with nondiagnostic ECGs.

Creatine phosphokinase (CK) rises within 4 to 8 h and generally returns to normal by 48 to 72 h. An important drawback of total CK measurement is its lack of specificity for AMI, as CK may be elevated with skeletal muscle trauma. A two- to threefold elevation of total CK may follow an intramuscular injection, for example. This ambiguity may lead to the erroneous diagnosis of AMI in a patient who has been given an intramuscular injection of a narcotic for chest pain of noncardiac origin. Other potential sources of total CK elevation are (1) skeletal muscular diseases, including muscular dystrophy, myopathies, and polymyositis; (2) electrical cardioversion; (3) hypothyroidism; (4) stroke; (5) surgery; and (6) skeletal muscle damage secondary to trauma, convulsions, and prolonged immobilization.

The MB isoenzyme of CK has the advantage over total CK that it is not present in significant concentrations in extracardiac tissue and therefore is considerably more specific. However, cardiac surgery, myocarditis, and electrical cardioversion often result in elevated serum levels of the MB isoenzyme. A ratio (relative index) of CKMB mass:CK activity 0x0022652.5 suggests but is not diagnostic of a myocardial rather than a skeletal muscle source for the CKMB elevation. This ratio is less useful when levels of total CK are high owing to skeletal muscle injury or when the total CK level is within the normal range but CKMB is elevated.

Rather than attempting to make the diagnosis of AMI on the basis of a single measurement of CK and CKMB, clinicians should evaluate a series of measurements obtained over the first 24 h. Skeletal muscle release of CKMB typically produces a "plateau" pattern, whereas AMI produces a CKMB elevation that peaks approximately 20 h after the onset of coronary occlusion. When released into the circulation, the myocardial form of CKMB (CKMB2) is acted on by the enzyme carboxypeptidase, which cleaves a lysine residue from the carboxyl terminus to produce an isoform (CKMB1) with a different electrophoretic mobility. A CKMB2:CKMB1 ratio of >1.5 is highly sensitive for the diagnosis of AMI, particularly 4 to 6 h after the onset of coronary occlusion.

Cardiac-specific troponin T (cTnT) and cardiac-specific troponin I (cTnI) have amino acid sequences different from those of the skeletal muscle forms of these proteins. These differences have permitted the development of quantitative assays for cTnT and cTnI with highly specific monoclonal antibodies. Since cTnT and cTnI are not normally detectable in the blood of healthy individuals but may increase after AMI to levels over 20 times higher than the cutoff value (usually set only slightly above the noise level of the assay), the measurement of cTnT or cTnI is of considerable diagnostic usefulness, and they are now the preferred biochemical markers for MI. The cardiac troponins are particularly valuable when there is clinical suspicion of either skeletal muscle injury or a small MI that may be below the detection limit for CK and CKMB measurements. Levels of cTnI may remain elevated for 7 to 10 days after AMI, and cTnT levels may remain elevated for up to 10 to 14 days. Thus, measurement of cTnT or cTnI has replaced measurement of lactate dehydrogenase (LDH) and its isoenzymes in patients with suspected MI who come to medical attention more than 24 to 48 h after the onset of symptoms.

Myoglobin is released into the blood within only a few hours of the onset of AMI. Although myoglobin is one of the first serum cardiac markers that rises above the normal range after AMI, it lacks cardiac specificity, and it is rapidly excreted in the urine, so that blood levels return to the normal range within 24 h of the onset of infarction.

Many hospitals are using cTnT or cTnI rather than CKMB as the routine serum cardiac marker for diagnosis of AMI, although any of these analytes remains clinically acceptable. It is not cost-effective to measure both a cardiac-specific troponin and CKMB at all time points in every patient. However, in view of the prolonged elevation of cardiac-specific troponins (>1 week), episodes of recurrent ischemic discomfort and suspected recurrent MI are more readily diagnosed with a serum cardiac marker that remains elevated in the blood more briefly, such as CKMB or myoglobin.

While it has long been recognized that the total quantity of protein released correlates with the size of the infarct, the peak protein concentration correlates only weakly with infarct size. Recanalization of a coronary artery occlusion (either spontaneously or by mechanical or pharmacologic means) in the early hours of AMI causes earlier and higher peaking (at about 8 to 12 h after reperfusion) of serum cardiac markers.

Characteristic rises occur in serum cardiac markers in virtually all patients with clinically proven MI. CK and CKMB levels generally do not rise in unstable angina. However, approximately one-third of patients who are considered to have unstable angina on the basis of a lack of CK or CKMB elevation have elevations of cTnT or cTnI, probably indicating the presence of microinfarction. The finding of an elevated cardiac-specific troponin level, even in the presence of normal CK and CKMB values, is indicative of an adverse prognosis, and such patients should be considered to have sustained MI and managed as described below.

For the purposes of confirming the diagnosis of MI, serum cardiac markers should be measured on admission, 6 to 9 h after admission, and 12 to 24 h after admission if the diagnosis remains uncertain.

The nonspecific reaction to myocardial injury is associated with polymorphonuclear leukocytosis, which appears within a few hours after the onset of pain, persists for 3 to 7 days, and often reaches levels of 12,000 to 15,000 leukocytes per microliter. The erythrocyte sedimentation rate rises more slowly than the white blood cell count, peaking during the first week and sometimes remaining elevated for 1 or 2 weeks.

Cardiac Imaging

Two-dimensional echocardiography (Chap. 227) is the most frequently employed imaging modality in patients with AMI. Abnormalities of wall motion are almost universally present (Fig. 243-7). Even when no ST-segment elevation is seen, echocardiographically detectable wall motion abnormalities may be observed. Although AMI cannot be distinguished from an old myocardial scar or from acute severe ischemia by echocardiography, the ease and safety of the procedure make its use appealing as a screening tool. In the emergency department setting, early detection of the presence or absence of wall motion abnormalities by echocardiography can aid in management decisions, such as whether the patient should receive reperfusion therapy [e.g., thrombolysis or a percutaneous coronary intervention (PCI)]. Echocardiographic estimation of left ventricular (LV) function is useful prognostically; detection of reduced function serves as an indication for therapy with an angiotensin-converting enzyme inhibitor (see "Angiotensin-Converting Enzyme Inhibitors," below). Echocardiography may also identify the presence of right ventricular (RV) infarction, ventricular aneurysm, pericardial effusion, and LV thrombus. In addition, Doppler echocardiography is useful in the detection and quantitation of a ventricular septal defect and mitral regurgitation, two serious complications of AMI (see below).

Figure 243-7

Figure 243-7: Echocardiographic wall motion abnormality coronary artery disease. A, Two-dimensional echocardiographic apical four-chamber view at end-diastole. B, Two-dimensional echocardiographic apical four-chamber view at end-systole. The right ventricle (RV) and the septal and lateral walls at the base of the left ventricle (LV) demonstrate normal inward motion from diastole through systole; however, the distal septum and apex demonstrate akinesis (arrows in B). The wall motion. abnormality demonstrated in this frame was caused by ischemia from a lesion in the mid-left anterior descending artery. LAnleft atrium; RA--right atrium. [From MH Picard, AE Weyman: Echocardiography in chronic ischemic heart disease, in GA Beller (ed): Chronic Ischemic Heart Disease, vol 5, in E Braunwald (series ed): Atlas of Heart Diseases, Philadelphia: Current Medicine, 1996, pp. 4.2.]

Several radionuclide imaging techniques are available for evaluating patients with suspected AMI. However, these imaging modalities are used less often than echocardiography because they are more cumbersome and they lack sensitivity and specificity in many clinical circumstances. Myocardial perfusion imaging with 201Tl or 99mTc-sestamibi, which are distributed in proportion to myocardial blood flow and concentrated by viable myocardium (Chap. 244) reveal a defect ("cold spot") in most patients during the first few hours after development of a transmural infarct. However, although perfusion scanning is extremely sensitive, it cannot distinguish acute infarcts from chronic scars and thus is not specific for the diagnosis of acute MI. Radionuclide ventriculography, carried out with 99mTc-labeled red blood cells, frequently demonstrates wall motion disorders and reduction in the ventricular ejection fraction in patients with AMI. While of value in assessing the hemodynamic consequences of infarction and in aiding in the diagnosis of RV infarction when the RV ejection fraction is depressed, this technique is also quite nonspecific, as many cardiac abnormalities other than MI alter the radionuclide ventriculogram.


Prehospital Care

The prognosis in AMI is largely related to the occurrence of two general classes of complications: (1) electrical complications (arrhythmias) and (2) mechanical problems ("pump failure"). Most out-of-hospital deaths from AMI are due to the sudden development of ventricular fibrillation. The vast majority of deaths due to ventricular fibrillation occur within the first 24 h of the onset of symptoms, and, of these, over half occur in the first hour. Therefore, the major elements of prehospital care of patients with suspected AMI include (1) recognition of symptoms by the patient and prompt seeking of medical attention; (2) rapid deployment of an emergency medical team capable of performing resuscitative maneuvers, including defibrillation; and (3) expeditious transportation of the patient to a hospital facility that is continuously staffed by physicians and nurses skilled in managing arrhythmias, providing advanced cardiac life support, and (4) expeditious implementation of reperfusion therapy. The biggest delay usually occurs not during transportation to the hospital but rather between the onset of pain and the patient's decision to call for help. This delay can best be reduced by education of the public by health care professionals concerning the significance of chest pain and the importance of seeking early medical attention. Increasingly, monitoring and treatment are carried out by trained personnel in the ambulance, further shortening the time between the onset of the infarction and appropriate treatment.


Figure 243-8

Figure 243-8: Major goals of medical therapy for acute coronary syndromes. Once coronary atherosclerosis has developed, patients may present with chronic exertional angina pectoris or one of the features of the acute coronary syndromes: unstable angina pectorisjnon-Q-wave myocardial infarction (NQMI) or Q-wave MI. A common pathophysiologic mechanism precipitating the acute coronary syndromes is destabilization of an atherosclerotic plaque due to fissuring of its surface.

Initial Management in the Emergency Department

In the emergency department, the goals for the management of patients with suspected AMI include control of cardiac pain, rapid identification of patients who are candidates for urgent reperfusion therapy, triage of lower-risk patients to the appropriate location in the hospital, and avoidance of inappropriate discharge of patients with AMI. Many aspects of the treatment of AMI are initiated in the emergency department and then continued during the in-hospital phase of management.

Aspirin is now considered an essential element in the management of patients with suspected AMI and is effective across the entire spectrum of acute coronary syndromes (Fig. 243-2 and 243-3). Rapid inhibition of cyclooxygenase in platelets followed by a reduction of thromboxane A2 levels is achieved by buccal absorption of a chewed 160 to 325 mg tablet in the emergency department. This measure should be followed by daily oral administration of aspirin in a dose of 160 to 325 mg.

Figure 243-2

Figure 243-2: Management strategy for patients suspected of having an ST-segment elevation. AMI patients should receive aspirin (ASA), beta blockers (in the absence of contraindications), and an antithrombin (particularly if a relatively fibrin-specific thrombolytic agent is used). Adjunctive antithrombin therapy is probably not required for patients receiving streptokinase. Patients treated within 12 h who are eligible for thrombolytic therapy should expeditiously receive such treatment or be considered for primary percutaneous transluminal coronary angioplasty (PCI). Immediate, primary PCI is also to be considered when lytic therapy is contraindicated. An intravenous glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitor may be helpful for reducing thrombotic complications during primary PCI.

Figure 243-3

Figure 243-3: Management strategy for patients with unstable angina and AMI without ST-segment elevation. These patients should be treated with an antithrombin and aspirin. Nitrates should be administered for recurrent episodes of angina. The risk of death and cardiac ischemic events may be reduced in high risk patients if an intravenous GPIIb/IIIa inhibitor is administered. Adequate beta blockade should be established; when that is not possible or contraindications exist, a calcium antagonist can be considered. Patients at high risk should be triaged to cardiac catheterization with plans for revascularization if clinically suitable, while patients who are clinically stable can be treated more conservatively with continued observation in the hospital and consideration of a stress test to screen for any provocable myocardial ischemia. CABG, coronary artery bypass grafting; LV, left ventricular.

Since patients with AMI may develop hypoxemia secondary to ventilation-perfusion abnormalities from LV failure and intrinsic pulmonary disease, it has been a common practice to routinely administer supplemental oxygen. In patients whose arterial oxygen saturation is normal as estimated by pulse oximetry or measured by an arterial blood gas specimen, supplemental oxygen is of limited if any clinical benefit and therefore is not cost effective. However, when hypoxemia is present, oxygen should be administered by nasal prongs or face mask (2 to 4 L/min) for the first 6 to 12 h after infarction; the patient should then be reassessed to determine if there is a continued need for such treatment.

Control of Pain

Morphine is a very effective analgesic for the pain associated with AMI. However, it may reduce sympathetically mediated arteriolar and venous constriction, and the resulting venous pooling may reduce cardiac output and arterial pressure. This complication does not contraindicate the use of morphine. Hypotension associated with venous pooling usually responds promptly to elevation of the legs, but in some patients volume expansion with intravenous saline is required. The patient may experience diaphoresis and nausea, but these events usually pass and are replaced by a feeling of well-being associated with the relief of pain. Morphine also has a vagotonic effect and may cause bradycardia or advanced degrees of heart block, particularly in patients with posteroinferior infarction. These side effects usually respond to atropine (0.5 mg intravenously). Morphine is routinely administered by repetitive (every 5 min) intravenous injection of small doses (2 to 4 mg) rather than by the subcutaneous administration of a larger quantity, because absorption may be unpredictable by the latter route.

Before morphine is administered, sublingual nitroglycerin can be given safely to most patients with AMI. Up to three 0.4-mg doses should be administered at about 5-min intervals. In addition to diminishing or abolishing chest discomfort, nitroglycerin, once considered contraindicated in the setting of AMI, may be capable of both decreasing myocardial oxygen demand (by lowering preload) and increasing myocardial oxygen supply (by dilating infarct-related coronary vessels or collateral vessels). In patients whose initially favorable response to sublingual nitroglycerin is followed by the return of chest pain, particularly if accompanied by other evidence of ongoing ischemia such as further ST-segment or T-wave shifts, the use of intravenous nitroglycerin should be considered. Therapy with nitrates should be avoided in patients who present with low systolic arterial pressure (<100 mmHg) or in whom there is clinical suspicion of right ventricular infarction (inferior infarction on electrocardiogram, elevated jugular venous pressure, clear lungs, and hypotension). Nitrates should not be administered to patients who have taken the phosphodiasterase 5 inhibitor sildenafil for erectile dysfunction within the preceding 24 h since it may potentiate the hypotensive effects of nitrates. An idiosyncratic reaction to nitrates, consisting of sudden marked hypotension, sometimes occurs but can usually be reversed promptly by the rapid administration of intravenous atropine.

Intravenous beta blockers are also useful in the control of the pain of AMI. These drugs control pain effectively in some patients, presumably by diminishing myocardial oxygen demand and hence ischemia. More important, there is evidence that intravenous beta blockers reduce in-hospital mortality, particularly in high-risk patients (see "0x0003b2-Adrenoceptor Blockers," below). A commonly employed regimen is metoprolol, 5 mg every 2 to 5 min for a total of three doses, provided the patient has a heart rate >60 beats per minute (bpm), systolic pressure >100 mmHg, a PR interval <0.24 s, and rales that are no higher than 10 cm up from the diaphragm. Fifteen minutes after the last intravenous dose, an oral regimen is initiated of 50 mg every 6 h for 48 h followed by 100 mg every 12 h.

Unlike beta blockers, calcium antagonists are of little value in the acute setting, and there is evidence that short-acting dihydropyridines may be associated with an increased mortality risk.

Management Strategies (Figs. 243-2 and 243-3)

The primary tool for screening patients and making triage decisions is the initial 12-lead ECG. When ST-segment elevation in at least two contiguous leads of at least 2 mm in V1-V3 and 1 mm in other leads is present, a patient should be considered a candidate for reperfusion therapy (Fig. 243-2 (Fig. 243-9). If no contraindications are present (see "Contraindications and Complications," under "Thombolysis," below), thrombolytic therapy should ideally be initiated within 30 min. The process of selecting patients for thrombolysis versus primary PCI (angioplasty, or stenting) (Chap. 245) is discussed below. In the absence of ST-segment elevation, thrombolysis is not helpful, and evidence exists suggesting that it may be harmful. Pharmacotherapy for patients presenting without ST-segment elevation (Fig. 243-3) typically includes measures to control cardiac pain (as discussed above), aspirin, antithrombin therapy (preferably with low-molecular-weight heparin), and infusion of nitroglycerin as needed to control recurrent ischemia. For high-risk patients an intravenous infusion of a glycoprotein IIb/IIIa inhibitor should be considered. Further management recommendations for patients without ST-segment elevation are outlined in Fig. 243-3.

Figure 243-9

Figure 243-9: Expansion of the paradigm of the beneficial actions of early reperfusion therapy. The original paradigm appears on the left and the expanded paradigm is on the right. Restoration of coronary flow during the early (salvage) phase of acute myocardial infarction (MI) is administered to reduce MI size. Recent observations of the influence of infarct vessel patency on left ventricular (LV) remodeling and electrical stability led to an expansion of the original paradigm. [From MA Pfeffer: Cardiac remodeling and its prevention, in WS Colucci: Heart Failure: Cardiac Function and Dysfunction, in E Braunwald (series ed): Atlas of Heart Diseases, vol 4. Philadelphia: Current Medicine, 1995, p. 5.11. Adapted from C Kim, E Braunwald: Potential benefits of late reperfusion of infarcted myocardium: the open artery hypothesis. Circulation 88:2426-2436, 1993.]

Limitation of Infarct Size

The quantity of myocardium that becomes necrotic as a consequence of a coronary artery occlusion is determined by factors other than just the site of occlusion. While the central zone of the infarct contains necrotic tissue that is irretrievably lost, the fate of the surrounding ischemic myocardium may be improved by timely restoration of coronary perfusion, reduction of myocardial oxygen demands, prevention of the accumulation of noxious metabolites, and blunting of the impact of mediators of reperfusion injury (e.g., calcium overload and oxygen-derived free radicals). Up to one-third of patients with AMI may achieve spontaneous reperfusion of the infarct-related coronary artery within 24 h and experience improved healing of infarcted tissue. Reperfusion either pharmacologically (by thrombolysis) or mechanically (by angioplasty and/or stenting) accelerates the process of opening the occluded infarct-related artery in those patients in whom spontaneous thrombolysis ultimately would have occurred and also greatly increases the number of patients in whom restoration of flow in the infarct-related artery is accomplished. Timely restoration of flow in the epicardial infarct-related artery combined with improved perfusion of the downstream zone of infarcted myocardium results in a limitation of infarct size. Protection of the ischemic myocardium by the maintenance of an optimal balance between myocardial oxygen supply and demand through pain control, treatment of congestive heart failure, and minimization of tachycardia and hypertension extends the "window" of time for the salvage of myocardium by reperfusion strategies.

Glucocorticoids and nonsteroidal anti-inflammatory agents, with the exception of aspirin, should be avoided in the setting of AMI. They can impair infarct healing and increase the risk of myocardial rupture, and their use may result in a larger infarct scar. In addition, they can increase coronary vascular resistance, thereby potentially reducing flow to ischemic myocardium.


The thrombolytic agents tissue plasminogen activator (tPA), streptokinase, anisoylated plasminogen streptokinase activator complex (APSAC) and reteplase (rPA) have been approved by the Food and Drug Administration for intravenous use in the setting of AMI. These drugs all act by promoting the conversion of plasminogen to plasmin, which subsequently lyses fibrin thrombi. Although considerable emphasis was first placed on a distinction between more fibrin-specific agents, such as tPA, and non-fibrin-specific agents, such as streptokinase, it is now recognized that these differences are only relative, as some degree of systemic fibrinolysis occurs with tPA. The principal goal of thrombolysis is prompt restoration of coronary arterial patency.

When assessed angiographically, flow in the culprit coronary artery is described by a simple qualitative scale called the TIMI grading system: grade 0 indicates complete occlusion of the infarct-related artery; grade 1 indicates some penetration of the contrast material beyond the point of obstruction but without perfusion of the distal coronary bed; grade 2 indicates perfusion of the entire infarct vessel into the distal bed but with flow that is delayed compared with that of a normal artery; and grade 3 indicates full perfusion of the infarct vessel with normal flow. Early reports frequently lumped TIMI grades 2 and 3 under the general category of patency, but it is now recognized that grade 3 flow is the goal of reperfusion therapy, because full perfusion of the infarct-related coronary artery yields far better results in terms of infarct size, maintenance of LV function, and reduction of both short- and long-term mortality rates. Relatively new methods of angiographic assessment of the efficacy of thrombolysis include counting the number of frames required on the cine film for dye to flow from the origin of the infarct-related artery to a landmark in the distal vascular bed (TIMI frame count) and determining the rate of entry and exit of contrast dye from the microvasculature in the myocardial infarct zone (TIMI Myocardial Perfusion Grade).

Thrombolytic therapy can reduce the relative risk of in-hospital death by up to 50% when administered within the first hour of the onset of symptoms of AMI, and much of this benefit is maintained for at least 10 years. Appropriately used thrombolytic therapy appears to reduce infarct size, limit LV dysfunction, and reduce the incidence of serious complications such as septal rupture, cardiogenic shock, and malignant ventricular arrhythmias. Since myocardium can be salvaged only before it has been irreversibly injured, the timing of reperfusion therapy, by thrombolysis or a catheter-based approach, is of extreme importance in achieving maximum benefit. While the upper time limit depends on specific factors in individual patients, it is clear that "every minute counts" and that patients treated within 1 to 3 h of the onset of symptoms generally benefit most. Although reduction of the mortality rate is more modest, the therapy remains of benefit for many patients seen 3 to 6 h after the onset of infarction, and some benefit appears to be possible up to 12 h, especially if chest discomfort is still present and ST segments remain elevated in ECG leads that do not yet demonstrate new Q waves. In addition to the possibility of early treatment, clinical factors that favor proceeding with thrombolytic therapy include anterior wall injury, hemodynamically complicated infarction, and widespread ECG evidence of myocardial jeopardy. Although patients (younger than 65 years) achieve a greater relative reduction in the mortality rate than elderly patients, the higher absolute mortality rate (15 to 25%) in elderly patients results in similar absolute reductions in the mortality rates for both age groups.

Intriguing data are accumulating to indicate that improved ventricular function and reduced mortality may also be achieved by late coronary reperfusion. The benefits of late reperfusion cannot be attributed to a reduction of infarct size but appear to result from improvement of tissue healing in the infarct zone with prevention of infarct expansion, enhancement of collateral flow, improvement of myocardial contractile performance, and reduction in the tendency to electrical instability. In addition, hibernating myocardium (i.e., poorly contractile myocardium in a zone that is supplied by a stenotic infarct-related coronary artery with slow antegrade perfusion, Chap. 244) may show improved contraction after angioplasty to increase coronary blood flow.

tPA is more effective than streptokinase at restoring full perfusion-i.e., TIMI grade 3 coronary flow-and has a small edge in improving survival as well. The current recommended regimen of tPA consists of a 15-mg bolus followed by 50 mg intravenously over the first 30 min, followed by 35 mg over the next 60 min. Streptokinase is administered as 1.5 million units (MU) intravenously over 1 h. Reteplase is administered in a double bolus regimen consisting of a 10-MU bolus given over 2 to 3 min followed by a second 10-MU bolus 30 min later.

Promising new pharmacologic regimens for reperfusion combine an intravenous glycoprotein IIb/IIIa inhibitor with a reduced dose of a thrombolytic agent. Such combination reperfusion regimens appear to facilitate the rate and extent of thrombolysis by inhibiting platelet aggregation, weakening the clot structure, and allowing penetration of the thrombolytic agent deeper into the clot.

Contraindications and Complications

Clear contraindications to the use of thrombolytic agents include a history of cerebrovascular hemorrhage at any time, a nonhemorrhagic stroke or other cerebrovascular event within the past year, marked hypertension (a reliably determined systolic arterial pressure >180 mmHg and/or a diastolic pressure >110 mmHg) at any time during the acute presentation, suspicion of aortic dissection, and active internal bleeding (excluding menses). While advanced age is associated with an increase in hemorrhagic complications, the benefit of thrombolytic therapy in the elderly appears to justify its use if no other contraindications are present and the amount of myocardium in jeopardy appears to be substantial.

Relative contraindications to thrombolytic therapy, which require careful assessment of the risk:benefit ratio, include current use of anticoagulants (international normalized ratio 0x0022652), a recent (<2 weeks) invasive or surgical procedure or prolonged (>10 min) cardiopulmonary resuscitation, known bleeding diasthesis, pregnancy, a hemorrhagic ophthalmic condition (e.g., hemorrhagic diabetic retinopathy), active peptic ulcer disease, and a history of severe hypertension that is currently adequately controlled. Because of the risk of an allergic reaction, patients should not receive streptokinase if that agent had been received within the preceding 5 days to 2 years.

Allergic reactions to streptokinase occur in approximately 2% of patients who receive it. While a minor degree of hypotension occurs in 4 to 10% of patients given this agent, marked hypotension occurs, although rarely, in association with severe allergic reactions.

Hemorrhage is the most frequent and potentially the most serious complication. Because bleeding episodes that require transfusion are more common when patients require invasive procedures, unnecessary venous or arterial interventions should be avoided in patients receiving thrombolytic agents. Hemorrhagic stroke is the most serious complication and occurs in approximately 0.5 to 0.9% of patients being treated with these agents. This rate increases with advancing age, with patients older than 70 years experiencing roughly twice the rate of intracranial hemorrhage as those younger than 65 years. Large-scale intervention trials have suggested that the rate of intracranial hemorrhage with tPA or rPA is slightly higher than that with streptokinase.

Routine angiography after thrombolysis with the intent of performing a PCI on underlying coronary artery stenoses in the culprit vessel is not recommended. Higher rates of abrupt closure of the infarct-related coronary artery with a need for urgent coronary artery bypass surgery as well as a trend toward an increase in mortality rate have been noted with this approach. Instead, after thrombolytic therapy, cardiac catheterization and coronary angiography should be carried out if there is evidence of either (1) failure of reperfusion (persistent chest pain and ST-segment elevation beyond 90 min) in which case a rescue PCI should be considered, or (2) coronary artery reocclusion (reelevation of ST segments and/or recurrent chest pain) or the development of recurrent ischemia (such as recurrent angina in the early hospital course or a positive exercise stress test before discharge), in which case an elective PCI should be considered. Coronary artery bypass surgery should be reserved for patients whose coronary anatomy is unsuited to angioplasty but in whom revascularization appears to be advisable because of extensive jeopardized myocardium or recurrent ischemia.

Primary Percutaneous Coronary Intervention

PCI, usually angioplasty and/or stenting without preceding thrombolysis, is also effective in restoring perfusion in AMI when carried out on an emergency basis in the first few hours of MI. It has the advantage of being applicable to patients who have contraindications to thrombolytic therapy but otherwise are considered appropriate candidates for reperfusion. It appears to be more effective than thrombolysis in opening occluded coronary arteries and, when performed by experienced operators in dedicated medical centers, is associated with better short-term and long-term clinical outcomes. It remains to be determined whether the advantages of primary PCI reported from organized research efforts can be replicated in routine clinical practice. However, PCI is expensive in terms of personnel and facilities, and its applicability is seriously limited by its availability, around the clock, in only a minority of hospitals.

Hospital Phase Management

Coronary Care Units

These units are routinely equipped with a system that permits continuous monitoring of the cardiac rhythm of each patient and hemodynamic monitoring in selected patients. Defibrillators, respirators, noninvasive transthoracic pacemakers, and facilities for introducing pacing catheters and flow-directed balloon-tipped catheters are also usually available. Equally important is the organization of a highly trained team of nurses who can recognize arrhythmias; adjust the dosage of antiarrhythmic, vasoactive, and anticoagulant drugs; and perform cardiac resuscitation, including electroshock, when necessary.

Patients should be admitted to a coronary care unit early in their illness when it is expected that they will derive benefit from the sophisticated and expensive care provided. The availability of electrocardiographic monitoring and trained personnel outside the coronary care unit has made it possible to admit lower-risk patients (e.g., those not hemodynamically compromised and without active arrhythmias) to "intermediate care units."

The duration of stay in the coronary care unit is dictated by the ongoing need for intensive care. If AMI has been ruled out (ideally within 8 to 12 h) and symptoms are controlled with oral therapy, patients may be transferred out of the coronary care unit. Also, patients who have a confirmed AMI but who are considered to be at low risk (no prior infarction and no persistent chest discomfort, congestive heart failure, hypotension, or cardiac arrhythmias) may be safely transferred out of the coronary care unit in 24 to 36 h.


Factors that increase the work of the heart during the initial hours of infarction may increase the size of the infarct. Therefore, patients with AMI should be kept at bed rest for the first 12 h. However, in the absence of complications, patients should be encouraged, under supervision, to resume an upright posture by dangling their feet over the side of the bed and sitting in a chair within the first 24 h. This practice is both psychologically beneficial and usually results in a reduction in the pulmonary capillary wedge pressure. In the absence of hypotension and other complications, by the second or third day patients typically are ambulating in their room with increasing duration and frequency, and they may shower or stand at the sink to bathe. By day 3 or 4 after infarction, patients should be increasing their ambulation progressively to a goal of 600 ft at least three times a day.


Because of the risk of emesis and aspiration soon after MI, patients should receive either nothing or only clear liquids by mouth for the first 4 to 12 h. The typical coronary care unit diet should provide 0x00226430% of total calories as fat and have a cholesterol content of 0x002264300 mg/d. Complex carbohydrates should make up 50 to 55% of total calories. Portions should not be unusually large, and the menu should be enriched with foods that are high in potassium, magnesium, and fiber but low in sodium. Diabetes mellitus and hypertriglyceridemia are managed by restriction of concentrated sweets in the diet.


Bed rest and the effect of the narcotics used for the relief of pain often lead to constipation. A bedside commode rather than a bedpan, a diet rich in bulk, and the routine use of a stool softener such as dioctyl sodium sulfosuccinate (200 mg/d) are recommended. If the patient remains constipated despite these measures, a laxative can be prescribed. Contrary to prior belief, it is safe to perform a gentle rectal examination on patients with AMI.


Many patients require sedation during hospitalization to withstand the period of enforced inactivity with tranquillity. Diazepam (5 mg), oxazepam (15 to 30 mg), or lorazepam (0.5 to 2 mg), given three or four times daily, is usually effective. An additional dose of any of the above medications may be given at night to ensure adequate sleep. Attention to this problem is especially important during the first few days in the coronary care unit, where the atmosphere of 24-h vigilance may interfere with the patient's sleep. However, sedation is no substitute for reassuring, quiet surroundings. Many drugs used in the coronary care unit, such as atropine, H2 blockers, and narcotics, can produce delirium, particularly in the elderly. This effect should not be confused with agitation, and it is wise to conduct a thorough review of the patient's medications before arbitrarily prescribing additional doses of anxiolytics.


Antithrombotic Agents

The use of antiplatelet and antithrombin therapy during the initial phase of AMI is based on extensive laboratory and clinical evidence that thrombosis plays an important role in the pathogenesis of this condition. The primary goal of treatment with antiplatelet and antithrombin agents is to establish and maintain patency of the infarct-related artery. A secondary goal is to reduce the patient's tendency to thrombosis and thus the likelihood of mural thrombus formation or deep venous thrombosis, either of which could result in pulmonary embolization. The degree to which antiplatelet and antithrombin therapy achieves these goals partly determines how effectively it reduces the risk of mortality from AMI.

As noted previously (see "Initial Management in the Emergency Department," above), aspirin is the standard antiplatelet agent for patients with AMI. The most compelling evidence for the benefits of antiplatelet therapy (mainly with aspirin) in AMI is found in the comprehensive overview by the Antiplatelet Trialists' Collaboration. Data from nearly 20,000 patients with AMI enrolled in nine randomized trials were pooled and revealed a reduction in the mortality rate from 11.7% in control patients to 9.3% in patients receiving antiplatelet agents. This difference corresponds to the prevention of 24 deaths for every 1000 patients treated. Similarly, 2 strokes and 12 recurrent infarctions are prevented for every 1000 patients treated with antiplatelet therapy.

The glycoprotein IIb/IIIa receptor is the focus of intense investigation by basic and clinical scientists (Fig. 243-10)(Chap. 116). Because platelet-rich thrombi are more resistant to thrombolytic agents than platelet-poor thrombi and because platelet aggregates appear to play a role in reocclusion after initially successful thrombolysis, glycoprotein IIb/IIIa inhibition may facilitate thrombolysis and reduce the rate of reocclusion of reperfused vessels. Compounds have been developed that block the glycoprotein IIb/IIIa receptor. These drugs appear useful for preventing thrombotic complications in patients with AMI undergoing PCI and reduce the rate of the composite endpoint of death and recurrent AMI in the medical management of patients without ST-segment elevation at presentation.

Figure 243-10

Figure 243-10: Despite its effectiveness, aspirin is a relatively weak platelet antagonist and does not effectively inhibit the platelet aggregation caused by many of the stimuli thought to be important in active ischemic heart disease (e. g., thrombin).

The standard antithrombin agent used in clinical practice is unfractionated heparin (UFH). Despite numerous clinical trials, the precise role of heparin in patients treated with thrombolytic agents remains uncertain. The available data fail to show any convincing benefit of UFH with respect to either coronary arterial patency or mortality rate when UFH is added to a regimen of aspirin and a non-fibrin-specific thrombolytic agent such as streptokinase. Although not conclusively proven, it appears that the immediate administration of intravenous UFH, in addition to a regimen of aspirin and tPA, helps to facilitate thrombolysis and to establish and maintain patency of the infarct-related artery. This effect is achieved at the cost of a small increased risk of bleeding. Most clinicians who use tPA also administer a bolus and infusion of UFH, which should be administered as a bolus of 60 U/kg followed by a maintenance infusion of 12 U/kg per hour. The activated partial thromboplastin time during maintenance therapy should be 1.5 to 2 times the control value.

An alternative to UFH for anticoagulation of patients with AMI that is being used with increased frequency are the low-molecular-weight heparin preparations (LMWHs), which are formed by enzymatic or chemical depolymerization to produce saccharide chains of varying length but with a mean molecular weight of about 5000 Da. The LMWHs have several advantages over UFH including an increased anti-factor Xa:IIa ratio, decreased sensitivity to platelet factor IV, a more stable reliable anticoagulant effect, and enhanced bioavailability, thereby permitting administration via the subcutaneous route. Because of the stable anticoagulant effect when LMWHs are used, routine monitoring of hematologic tests such as the activated partial thromboplastin time (aPTT) is not required. Although the LMWHs share many pharmacologic similarities, they also vary in a number of important features; and therefore these agents should be considered individually rather than as members of an interchangeable class of compounds. Of the LMWHs, nadroparin and dalteparin have been found to be similar to UFH in therapeutic effectiveness, while enoxaparin (1 mg/kg subcutaneously every 12 h) appears to be superior to UFH for reducing the mortality rate and cardiac ischemic events in patients with AMI who do not present with ST-segment elevation. Direct comparisons among the LMWHs have not been carried out.

Patients with an anterior location of the infarction, severe LV dysfunction, congestive heart failure, a history of embolism, two-dimensional echocardiographic evidence of mural thorombus, or atrial fibrillation are at increased risk of systemic or pulmonary thromboembolism. Such individuals should receive full therapeutic levels of antithrombin therapy (UFH or LMWHs) while hospitalized, followed by at least 3 months of warfarin therapy.

Beta-Adrenoceptor Blockers

The benefits of beta blockers in patients with AMI can be divided into those that occur immediately when the drug is given acutely and those that accrue over the long term when the drug is given for secondary prevention after an index infarction. Acute intravenous beta blockade improves the myocardial oxygen supply-demand relationship, decreases pain, reduces infarct size, and decreases the incidence of serious ventricular arrhythmias. An overview of the data from 27,000 patients enrolled in nine randomized trials in the prethrombolytic era indicates that intravenous followed by oral beta blockade is associated with a 15% relative reduction in mortality, nonfatal reinfarction, and nonfatal cardiac arrest. In patients who undergo thrombolysis soon after the onset of chest pain, no incremental reduction in mortality rate is seen with beta blockers, but recurrent ischemia and reinfarction are reduced.

Beta blocker therapy after AMI thus is useful for most patients except those in whom it is specifically contraindicated (patients with heart failure or severely compromised LV function, heart block, orthostatic hypotension, or a history of asthma) and perhaps those whose excellent long-term prognosis (defined as an expected mortality rate of <1% per year) markedly diminishes any potential benefit (patients younger than 55 years with normal ventricular function, no complex ventricular ectopy, and no angina).

Although the data supporting the use of beta blockers in patients with AMI who do not present with ST-segment elevation are limited, the available evidence suggests that even among such patients, the use of beta blockers decreases the rates of cardiovascular mortality and reinfarction, and increases the probability of long-term survival.

Angiotensin Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE) inhibitors reduce the mortality rate after AMI, and the mortality benefits are additive to those achieved with aspirin and beta blockers. The maximum benefit is seen in high-risk patients (those who are elderly or have an anterior infarction, a prior infarction, and/or globally depressed LV function), but evidence suggests that a short-term benefit occurs when ACE inhibitors are prescribed unselectively to all hemodynamically stable patients with AMI (i.e., those with a systolic pressure >100 mmHg). The mechanism involves a reduction in ventricular remodeling after infarction (see "Ventricular Dysfunction," below) with a subsequent reduction in the risk of congestive heart failure (CHF). The rate of recurrent infarction also may be lower in patients treated chronically with ACE inhibitors after infarction (Fig. 243-11).

Figure 243-11

Figure 243-11: Cardiac index versus pulmonary capillary wedge pressure (PCWP) in 200 patients after acute myocardial infarction (MI), demonstrating an inverse relationship between mortality and cardiac performance.

ACE inhibitors should be prescribed within 24 h to all patients with AMI and overt CHF as well as to hemodynamically stable patients with ST-segment elevation or left bundle branch block. There is little evidence to support the immediate use of ACE inhibitors in patients with AMI who present without ST-segment changes or only with ST-segment depression without CHF. Before hospital discharge, LV function should be assessed with an imaging study. ACE inhibitors should be continued indefinitely in patients who have clinically evident CHF, in patients whom an imaging study shows a reduction in global LV function or a large regional wall motion abnormality, or in those who are hypertensive.

Other Agents

Although the actual impact on the mortality rate is slight (three to four lives saved per 1000 patients treated), nitrates (intravenous or oral) may be useful in the relief of pain associated with AMI. Favorable effects on the ischemic process and ventricular remodeling (see below) have led many physicians to routinely use intravenous nitroglycerin (5 to 10 0x0003bcg/min initial dose and up to 200 0x0003bcg/min as long as hemodynamic stability is maintained) for the first 24 to 48 h after the onset of infarction.

Results of multiple trials of different calcium antagonists have failed to establish a role for these agents in the treatment of most patients with AMI, in contrast to the more consistent data that exist for other drugs (e.g., beta blockers, aspirin, thrombolytic agents). The routine use of calcium antagonists cannot be recommended.

A metabolic supportive measure that has shown promise in several small-scale trials of patients with AMI is the administration of a solution of glucose-insulin-potassium (GIK). A GIK infusion lowers the concentration of plasma free fatty acids and improves ventricular performance. Strict control of blood glucose in diabetic patients with AMI has been shown to reduce the mortality rate. It remains to be determined whether infusions of GIK should be administered to all patients with AMI.

Intracellular magnesium levels are frequently reduced in patients with AMI, but this deficit is not adequately reflected in serum measurements, as magnesium is predominantly an intracellular ion and <1% of its total body stores is intravascular. Whether giving routine empirical supplemental infusions of magnesium to high-risk patients with AMI is beneficial remains an open question. At present, serum magnesium should be measured in all patients on admission, and any demonstrated deficits should be corrected to minimize the risk of arrhythmias. There does not appear to be any benefit in the routine use of magnesium when it is administered relatively late (after more than 6 h) or to patients with an uncomplicated AMI who have a low mortality risk. Its role in high-risk patients is under investigation.

Complications and Their Treatment

Ventricular Dysfunction

After AMI, the LV undergoes a series of changes in shape, size, and thickness in both the infarcted and noninfarcted segments. This process is referred to as ventricular remodeling and generally precedes the development of clinically evident CHF in the months to years after infarction. Soon after AMI, the LV begins to dilate. Acutely, this results from expansion of the infarct (i.e., slippage of muscle bundles, disruption of normal myocardial cells, and tissue loss within the necrotic zone, resulting in disproportionate thinning and elongation of the infarct zone). Later, lengthening of the noninfarcted segments occurs as well. The overall chamber enlargement that occurs is related to the size and location of the infarct, with greater dilation following infarction of the apex of the LV and causing more marked hemodynamic impairment, more frequent heart failure, and a poorer prognosis. Progressive dilation and its clinical consequences may be ameliorated by therapy with ACE inhibitors and other vasodilators (e.g., nitrates) (Fig. 243-12). Thus, in patients with an ejection fraction <40%, regardless of whether or not heart failure is present, ACE inhibitors should be prescribed.

Figure 243-12

Figure 243-12: Left ventricular remodeling after myocardial infarction (MI).

Hemodynamic Assessment

Pump failure is now the primary cause of in-hospital death from AMI. The extent of ischemic necrosis correlates well with the degree of pump failure and with mortality, both early (within 10 days of infarction) and later. The most common clinical signs are pulmonary rales and S3 and S4 gallop rhythms. Pulmonary congestion is also frequently seen on the chest roentgenogram. Elevated LV filling pressure and elevated pulmonary artery pressure are the characteristic hemodynamic findings, but these findings may result from a reduction of ventricular compliance (diastolic failure) and/or a reduction of stroke volume with secondary cardiac dilation (systolic failure) (Chap. 231).

A classification originally proposed by Killip divides patients into four groups: class I, no signs of pulmonary or venous congestion; class II, moderate heart failure as evidenced by rales at the lung bases, S3 gallop, tachypnea, or signs of failure of the right side of the heart, including venous and hepatic congestion; class III, severe heart failure, pulmonary edema; and class IV, shock with systolic pressure <90 mmHg and evidence of peripheral vasoconstriction, peripheral cyanosis, mental confusion, and oliguria. When this classification was established in 1967, the expected hospital mortality rate of patients in these classes was as follows: class I, 0 to 5%; class II, 10 to 20%; class III, 35 to 45%; and class IV, 85 to 95%. With advances in management, the mortality rate in each class has fallen, perhaps by as much as one-third to one-half.

Hemodynamic evidence of abnormal LV function appears when contraction is seriously impaired in 20 to 25% of the LV. Infarction of 0x00226540% of the LV usually results in cardiogenic shock (see below). Positioning of a balloon flotation catheter in the pulmonary artery permits monitoring of LV filling pressure; this technique is useful in patients who exhibit hypotension and/or clinical evidence of CHF (Fig. 243-13). Cardiac output can also be determined with a pulmonary artery catheter. With the addition of intraarterial pressure monitoring, systemic vascular resistance can be calculated as a guide to adjusting vasopressor and vasodilator therapy. Some patients with AMI have markedly elevated LV filling pressures (>22 mmHg) and normal cardiac indexes [>2.6 and >3.6 L/(min/m2)], while others have relatively low LV filling pressures (<15 mmHg) and reduced cardiac indexes. The former patients usually benefit from diuresis, while the latter may respond to volume expansion by means of intravenous administration of colloid-containing solutions.

Figure 243-13

Figure 243-13: Shown with intersecting bars are sites at which an ACE inhibitor may interrupt an adverse consequence of myocardial infarction that would contribute to heart failure or death.


Hypovolemia is an easily corrected condition that may contribute to the hypotension and vascular collapse associated with AMI in some patients. It may be secondary to previous diuretic use, to reduced fluid intake during the early stages of the illness, and/or to vomiting associated with pain or medications. Consequently, hypovolemia should be identified and corrected in patients with AMI and hypotension before more vigorous forms of therapy are begun. Central venous pressure reflects RV rather than LV filling pressure and is an inadequate guide for adjustment of blood volume, since LV function is almost always affected much more adversely than RV function in patients with AMI. The optimal LV filling or pulmonary artery wedge pressure may vary considerably among patients. Each patient's ideal level (generally ~20 mmHg) is reached by cautious fluid administration during careful monitoring of oxygenation and cardiac output. Eventually, the cardiac output level plateaus, and further increases in LV filling pressure only increase congestive symptoms and decrease systemic oxygenation without raising arterial pressure.


The management of CHF in association with AMI is similar to that of acute heart failure secondary to other forms of heart disease (avoidance of hypoxemia, diuresis, afterload reduction, inotropic support) (Chap. 232), except that the benefits of digitalis administration to patients with AMI are unimpressive. By contrast, diuretic agents are extremely effective, as they diminish pulmonary congestion in the presence of systolic and/or diastolic heart failure. Left ventricular filling pressure falls and orthopnea and dyspnea improve after the intravenous administration of furosemide or other loop diuretics. These drugs should be used with caution, however, as they can result in a massive diuresis with associated decreases in plasma volume, cardiac output, systemic blood pressure, and hence coronary perfusion. Nitrates in various forms may be used to decrease preload and congestive symptoms. Oral isosorbide dinitrate, topical nitroglycerin ointment, or intravenous nitroglycerin all have the advantage over a diuretic of lowering preload through venodilation without decreasing the total plasma volume. In addition, nitrates may improve ventricular compliance if ischemia is present, as ischemia causes an elevation of LV filling pressure. The patient with pulmonary edema is treated as described in Chap. 232, but vasodilators must be used with caution to prevent serious hypotension. As noted earlier, ACE inhibitors are an ideal class of drugs for management of ventricular dysfunction after AMI, especially for the long term.

Cardiogenic Shock

In recent years, efforts to reduce infarct size and prompt treatment of ongoing ischemia and other complications of MI appear to have reduced the incidence of cardiogenic shock from 20% to about 7%. Only 10% of patients with this condition present with it on admission, while 90% develop it during hospitalization. Typically, patients who develop cardiogenic shock have severe multivessel coronary artery disease with evidence of "piecemeal" necrosis extending outward from the original infarct zone (Fig. 243-4).

Figure 243-4

Figure 243-4: Pathophysiology of cardiogenic shock: Systolic and diastolic myocardial dysfunction occurs after MI, resulting in pulmonary congestion and a reduction in cardiac output. Systemic and coronary hypoperfusion occur, resulting in progressive ischemia. Although a number of compensatory mechanisms are activated in an attempt to support the circulation, these compensatory mechanisms may become maladaptive and produce a worsening of hemodynamics. A vicious circle of progressive myocardial dysfunction occurs that ultimately results in death if it is not interrupted. LVEDP, left ventricular end-diastolic pressure.

Cardiogenic shock should be considered to be a form of severe LV failure. This syndrome is characterized by marked hypotension with systolic arterial pressure of <80 mmHg and a markedly reduced cardiac index [<1.8 L/(min/m2)] in the face of an elevated LV filling (pulmonary capillary wedge) pressure (>18 mmHg). Hypotension alone is not a basis for the diagnosis of cardiogenic shock, because many patients who make an uneventful recovery have serious hypotension (systolic pressure of <80 mmHg) for several hours. Such patients often have low LV filling pressures, and their hypotension usually resolves with the administration of intravenous fluids. In contrast to hypovolemic hypotension, cardiogenic shock is generally associated with a mortality rate of >70%; however, recent efforts to restore perfusion by coronary angioplasty or surgical revascularization suggest that this high mortality rate can be lowered by as much as one-half.

Risk factors for the in-hospital development of shock include advanced age, a depressed LV ejection fraction on admission, a large infarct, previous MI, and a history of diabetes mellitus. Patients with several of these risk factors should be considered for cardiac catheterization and mechanical reperfusion (by PCI or surgery) before the development of shock.

Pathophysiology of Severe Power Failure

A marked reduction in the quantity of contracting myocardium is the cause of cardiogenic shock in AMI. The initial insult reduces arterial pressure, and the reduction in coronary perfusion pressure and myocardial blood flow initiates a vicious cycle that impairs myocardial function further and may increase the size of the infarct (Fig. 243-4). Arrhythmias and metabolic acidosis also contribute to this deterioration, because they are the result of inadequate perfusion. This positive feedback loop accounts for the high mortality rate associated with the shock syndrome.

Right Ventricular Infarction

Approximately one-third of patients with inferoposterior infarction demonstrate at least a minor degree of RV necrosis. An occasional patient with inferoposterior LV infarction also has extensive RV infarction, and rare patients present with infarction limited primarily to the RV. Clinically significant RV infarction causes signs of severe RV failure [jugular venous distention, Kussmaul's sign (Chap. 225), hepatomegaly] with or without hypotension. ST-segment elevations of right-sided precordial ECG leads, particularly lead V4R, are frequently present in the first 24 h in patients with RV infarction. Two-dimensional echocardiography is helpful in determining the degree of RV dysfunction. Catheterization of the right side of the heart often reveals a distinctive hemodynamic pattern resembling cardiac tamponade or constrictive pericarditis (steep right atrial "y" descent and an early diastolic dip and plateau in right ventricular waveforms) (Chap. 239). Therapy consists of volume expansion to maintain adequate RV preload and efforts to improve LV performance with attendant reduction in pulmonary capillary wedge and pulmonary arterial pressures.

Mechanical Causes of Heart Failure

Free Wall Rupture

Myocardial rupture is a dramatic complication of AMI that is most likely to occur during the first week after the onset of symptoms; its frequency increases with the age of the patient. First infarction, a history of hypertension, no history of angina pectoris, and a relatively large Q-wave infarct are associated with a higher incidence of cardiac rupture. The clinical presentation typically is a sudden loss of pulse, blood pressure and consciousness while the ECG continues to show sinus rhythm (apparent electromechanical dissociation or pulseless electrical activity). The myocardium continues to contract, but forward flow is not maintained as blood escapes into the pericardium. Cardiac tamponade (Chap. 239) ensues, and closed-chest massage is ineffective. This condition is almost universally fatal, although dramatic cases of urgent pericardiotensis followed by successful surgical repair have been reported.

Ventricular Septal Defect

The pathogenesis of perforation of the ventricular septum is similar to that of free wall rupture, but the chance of successful therapy is greater. Patients with ventricular septal rupture present with sudden, severe LV failure in association with the appearance of a pansystolic murmur, often accompanied by a parasternal thrill. It is often impossible to differentiate this condition from rupture of a papillary muscle with resulting mitral regurgitation (MR), and the presence in both conditions of a tall "v" wave in the pulmonary capillary wedge pressure further complicates the differentiation. The diagnosis of ventricular septal defect can be established by the demonstration of a left-to-right shunt (i.e., an oxygen step-up at the level of the RV) by means of limited cardiac catheterization performed at the bedside with a flow-directed balloon catheter. Color flow Doppler echocardiography can also be extremely useful for making this diagnosis at the bedside (Fig. 243-14). A prolonged period of hemodynamic compromise may produce end-organ damage and other complications that can be avoided by early intervention, including nitroprusside infusion and intraaortic balloon counterpulsation.


Figure 243-14

Figure 243-14: Two-dimensional echocardiogram demonstrating ventricular septal (VS) rupture (VSR) following acute myocardial infarction.

The pathophysiology of acute MR is similar to that of acute ventricular septal perforation in that the level of aortic systolic pressure partly determines the regurgitant volume, the principal difference being the chamber into which the regurgitant fraction is ejected. In septal perforation, a fraction of LV output is ejected into the right ventricle. As in MR, lowering of the aortic systolic pressure by mechanical (intraaortic balloon counterpulsation) and/or pharmacologic (nitroglycerin or nitroprusside) means can decrease the hemodynamic compromise caused by perforation.

Mitral Regurgitation

The reported incidence of apical systolic murmurs of MR during the first few days after the onset of AMI varies widely (from 10 to 50% of patients) depending on the population studied and the acumen of the observers. While MR causes acute hemodynamic compromise in only a minority of these patients, it is a risk factor for late CHF and reduced survival.

The most common cause of MR after AMI is dysfunction of the mitral valve due to ischemia or infarction. Left ventricular dilatation or alteration in the size or shape of the LV due to impaired contractility or to aneurysm formation causes disordered contraction of the papillary muscles and failure of coaptation of the mitral valve leaflets. Rarely, a papillary muscle, or, more commonly, the head of a papillary muscle, may rupture. Then, LV function deteriorates dramatically, with superimposition of severe MR. The major element in the differential diagnosis is perforation of the ventricular septum as discussed above. Surgical repair or replacement of the mitral valve may lead to dramatic improvement in patients in whom acute heart failure results primarily from severe MR due to papillary muscle rupture or dysfunction and in whom global ventricular function is relatively good.

If aortic systolic pressure is lowered in patients with MR, a greater fraction of the LV output will be ejected antegrade, thus lessening the regurgitant fraction. To this end, both intraaortic balloon counterpulsation (IABC), which lowers the aortic systolic pressure mechanically, and the infusion of nitroglycerin or sodium nitroprusside, which reduce systemic vascular resistance, have been used with success in the interim management of patients with severe MR in the presence of AMI. Ideally, definitive operative treatment should be postponed until pulmonary congestion has cleared and the infarct has had time to heal. However, if the patient's hemodynamic and/or clinical condition does not improve or stabilize, surgical treatment should be undertaken, even in the acute stage.


The incidence of arrhythmias after AMI is higher in patients seen early after the onset of symptoms. The mechanisms responsible for infarction-related arrhythmias include autonomic nervous system imbalance, electrolyte disturbances, ischemia, and slowed conduction in zones of ischemic myocardium. An arrhythmia can usually be managed successfully if trained personnel and appropriate equipment are available when it develops. Since most deaths from arrhythmia occur during the first few hours after infarction, the effectiveness of treatment relates directly to the speed with which patients come under medical observation. The prompt management of arrhythmias constitutes a significant advance in the treatment of myocardial infarction.

Ventricular Premature Beats

Infrequent, sporadic ventricular premature depolarizations occur in almost all patients with AMI and do not require therapy. Whereas in the past, frequent, multifocal, or early diastolic ventricular extrasystoles (so-called warning arrhythmias) were routinely treated with antiarrhythmic drugs to reduce the risk of development of ventricular tachycardia and ventricular fibrillation, pharmacologic therapy is now reserved for patients with sustained ventricular arrhythmias. Prophylactic antiarrhythmic therapy (either intravenous lidocaine early or oral agents later) is contraindicated for ventricular premature beats in the absence of clinically important ventricular tachyarrhythmias, as such therapy may actually increase the mortality rate. 0x0003b2-Adrenoceptor blocking agents are effective in abolishing ventricular ectopic activity in patients with AMI and in the prevention of ventricular fibrillation. As described above (see "0x0003b2-Adrenoceptor Blockers"), they should be used routinely in patients without contraindications. In addition, hypokalemia and hypomagnesemia are risk factors for ventricular fibrillation in patients with AMI; the serum potassium concentration should be adjusted to approximately 4.5 mmol/L and magnesium to about 2.0 mmol/L.

Ventricular Tachycardia and Fibrillation

Within the first 24 h of AMI, ventricular tachycardia and fibrillation can occur without prior warning arrhythmias. The occurrence of ventricular fibrillation can be reduced by prophylactic administration of intravenous lidocaine. However, prophylactic use of lidocaine has not been shown to reduce overall mortality from AMI. In fact, in addition to causing possible noncardiac complications, lidocaine may predispose to an excess risk of bradycardia and asystole. For these reasons, and with earlier treatment of active ischemia, more frequent use of beta-blocking agents, and the nearly universal success of electrical cardioversion or defibrillation, routine prophylactic antiarrhythmic drug therapy is no longer recommended. It should be reserved for patients who cannot reach a hospital or for those treated in hospitals that lack the constant presence in the coronary care unit of a physician or nurse trained in the recognition and treatment of ventricular fibrillation.

Sustained ventricular tachycardia that is well tolerated hemodynamically should be treated with an intravenous regimen of lidocaine (bolus of 1.0 to 1.5 mg/kg; infusion of 20 to 50 0x0003bcg/kg per min), procainamide (bolus of 15 mg/kg over 20 to 30 min; infusion of 1 to 4 mg/min), or amiodarone (bolus of 75 to 150 mg over 10 to 15 min followed by infusion of 1.0 mg/min for 6 h and then 0.5 mg/min); if it does not stop promptly, electroversion should be used (Chap. 230). An unsynchronized discharge of 200 to 300 J (defibrillation) is used immediately in patients with ventricular fibrillation or when ventricular tachycardia causes hemodynamic deterioration. Ventricular tachycardia or fibrillation that is refractory to electroshock may be more responsive after the patient is treated with epinephrine (1 mg intravenously or 10 mL of a 1:10,000 solution via the intracardiac route), bretylium (a 5 mg/kg bolus), or amiodarone (a 75 to 150 mg bolus).

Ventricular arrhythmias, including the unusual form of ventricular tachycardia known as torsade de pointes (Chap. 230), may occur in patients with AMI as a consequence of other concurrent problems (such as hypoxia, hypokalemia, or other electrolyte disturbances) or of the toxic effects of an agent being administered to the patient (such as digoxin or quinidine). A search for such secondary causes should always be undertaken.

Although the in-hospital mortality rate is increased, the long-term survival is good in patients who survive to hospital discharge after primary ventricular fibrillation, i.e., ventricular fibrillation that is a primary response to acute ischemia and is not associated with predisposing factors such as CHF, shock, bundle branch block, or ventricular aneurysm. This result is in sharp contrast to the poor prognosis for patients who develop ventricular fibrillation secondary to severe pump failure. For patients who develop ventricular tachycardia or ventricular fibrillation late in their hospital course (i.e., after the first 48 h), the mortality rate is increased both in-hospital and during long-term follow-up. Such patients should be considered for electrophysiologic study (Chap. 230).

Accelerated Idioventricular Rhythm

Accelerated idioventricular rhythm (AIVR, "slow ventricular tachycardia"), a ventricular rhythm with a rate of 60 to 100 beats per minute, occurs in 25% of patients with AMI. It often occurs transiently during thrombolytic therapy at the time of reperfusion. The rate of AIVR is usually similar to that of the sinus rhythm that precedes and follows it, and this similarity of rate plus the relatively minor hemodynamic effects make this rhythm more difficult to detect except by electrocardiographic monitoring. For the most part, AIVR is benign and does not presage the development of classic ventricular tachycardia. Most episodes of AIVR do not require treatment if the patient is monitored carefully, as degeneration into a more serious arrhythmia is rare, and, if it occurs, AIVR can generally be readily treated with a drug that increases the sinus rate (atropine).

Supraventricular Arrhythmias

Sinus tachycardia is the most common supraventricular arrhythmia. If it occurs secondary to another cause (such as anemia, fever, heart failure, or a metabolic derangement), the primary problem should be treated first. However, if it appears to be due to sympathetic overstimulation, for example, as part of a hyperdynamic state, then treatment with a beta blocker is indicated. Other common arrhythmias in this group are atrial flutter and atrial fibrillation, which are often secondary to LV failure. Digoxin is usually the treatment of choice for supraventricular arrhythmias if heart failure is present. If heart failure is absent, beta blockers, verapamil, or diltiazem are suitable alternatives for controlling the ventricular rate, as they may also help to control ischemia. If the abnormal rhythm persists for >2 h with a ventricular rate in excess of 120 beats per minute, or if tachycardia induces heart failure, shock, or ischemia (as manifested by recurrent pain or ECG changes), a synchronized electroshock (100 to 200 J) should be used.

Accelerated junctional rhythms have diverse causes but may occur in patients with inferoposterior infarction. Digitalis excess must be ruled out. In some patients with severely compromised LV function, the loss of appropriately timed atrial systole results in a marked decrease in cardiac output. Right atrial or coronary sinus pacing is indicated in such instances.

Sinus Bradycardia

Treatment of sinus bradycardia is indicated if hemodynamic compromise results from the slow heart rate. Atropine is the most useful drug for increasing heart rate and should be given intravenously in doses of 0.5 mg initially. If the rate remains below 50 to 60 bpm, additional doses of 0.2 mg, up to a total of 2.0 mg, may be given. Persistent bradycardia (<40 bpm) despite atropine may be treated with electrical pacing. Isoproterenol should be avoided.

Atrioventricular and Intraventricular Conduction Disturbances

Both the in-hospital mortality rate and the post-discharge mortality rate of patients who have complete atrioventricular (AV) block in association with anterior infarction are markedly higher than those of patients who develop AV block with inferior infarction. This difference is related to the fact that heart block in inferior infarction is commonly a result of increased vagal tone and/or the release of adenosine and therefore is transient. In anterior wall infarction, heart block is usually related to ischemic malfunction of the conduction system, which commonly is associated with extensive myocardial necrosis.

Temporary electrical pacing provides an effective means of increasing the heart rate of patients with bradycardia due to AV block. However, acceleration of the heart rate may have only a limited impact on prognosis in patients with anterior wall infarction and complete heart block in whom the large size of the infarct is the major factor determining outcome. It should be carried out if it improves hemodynamics, however. Pacing does appear to be beneficial in patients with inferoposterior infarction who have complete heart block associated with heart failure, hypotension, marked bradycardia, or significant ventricular ectopic activity. A subgroup of these patients, those with RV infarction, often respond poorly to ventricular pacing because of the loss of the atrial contribution to ventricular filling. In such patients, dual-chamber AV sequential pacing may be required.

External noninvasive pacing electrodes should be positioned in a "demand" mode for patients with sinus bradycardia (rate <50 bpm) that is unresponsive to drug therapy, Mobitz II second-degree AV block, third-degree heart block, or bilateral bundle branch block (e.g., right bundle branch block plus left anterior fascicular block). Retrospective studies suggest that permanent pacing may reduce the long-term risk of sudden death due to bradyarrhythmias in the rare patient who develops combined persistent bifascicular and transient third-degree heart block during the acute phase of MI.

Other Complications

Recurrent Chest Discomfort

Recurrent angina develops in ~25% of patients hospitalized for AMI. This percentage is even higher in patients who undergo successful thrombolysis. Since recurrent or persistent ischemia often heralds extension of the original infarct or reinfarction in a new myocardial zone and is associated with a doubling of risk after AMI, patients with these symptoms should be considered for repeat thrombolysis or referred for prompt coronary arteriography and mechanical revascularization. Repeat administration of a thrombolytic agent is an alternative to early mechanical revascularization.


Pericardial friction rubs and/or pericardial pain are frequently encountered in patients with transmural AMI. This complication can usually be managed with aspirin (650 mg qid). It is important to diagnose the chest pain of pericarditis accurately, since failure to recognize it may lead to the erroneous diagnosis of recurrent ischemic pain and/or infarct extension, with resulting inappropriate use of anticoagulants, nitrates, beta blockers, or coronary arteriography. When it occurs, complaints of pain radiating to either trapezius muscle is helpful since such a pattern of discomfort is typical of pericarditis but rarely occurs with ischemic discomfort. Anticoagulants potentially could cause tamponade in the presence of acute pericarditis (as manifested by either pain or persistent rub) and therefore should not be used unless there is a compelling indication.


Clinically apparent thromboembolism complicates AMI in ~10% of cases, but embolic lesions are found in 20% of patients in necropsy series, suggesting that thromboembolism is often clinically silent. Thromboembolism is considered to be at least an important contributing cause of death in 25% of patients with AMI who die after admission to the hospital. Arterial emboli originate from LV mural thrombi, while most pulmonary emboli arise in the leg veins.

Thromboembolism typically occurs in association with large infarcts (especially anterior), CHF, and a LV thrombus detected by echocardiography. The incidence of arterial embolism from a clot originating in the ventricle at the site of an infarction is small but real. Two-dimensional echocardiography reveals LV thrombi in about one-third of patients with anterior wall infarction but in few patients with inferior or posterior infarction. Arterial embolism often presents as a major complication, such as hemiparesis when the cerebral circulation is involved or hypertension if the renal circulation is compromised. When a thrombus has been clearly demonstrated by echocardiographic or other techniques or when a large area of regional wall motion abnormality is seen even in the absence of a detectable mural thrombus, systemic anticoagulation should be undertaken (in the absence of contraindications), as the incidence of embolic complications appears to be markedly lowered by such therapy. The appropriate duration of therapy is unknown, but 3 to 6 months is probably prudent.

Left Ventricular Aneurysm

The term ventricular aneurysm is usually used to describe dyskinesis or local expansile paradoxical wall motion. Normally functioning myocardial fibers must shorten more if stroke volume and cardiac output are to be maintained in patients with ventricular aneurysm; if they cannot, overall ventricular function is impaired. True aneurysms are composed of scar tissue and neither predispose to nor are associated with cardiac rupture.

The complications of LV aneurysm do not usually occur for weeks to months after AMI; they include CHF, arterial embolism, and ventricular arrhythmias. Apical aneurysms are the most common and the most easily detected by clinical examination. The physical finding of greatest value is a double, diffuse, or displaced apical impulse. Ventricular aneurysms are readily detected by two-dimensional echocardiography, which may also reveal a mural thrombus in an aneurysm.

Rarely, myocardial rupture may be contained by a local area of pericardium, along with organizing thrombus and hematoma. Over time, this pseudoaneurysm enlarges, maintaining communication with the LV cavity through a narrow neck. Because a pseudoaneurysm often ruptures spontaneously, it should be surgically repaired if recognized.

Postinfarction Risk Stratification and Management

Many clinical factors have been identified that are associated with an increase in cardiovascular risk after initial recovery from AMI. Some of the most important factors include persistent ischemia (spontaneous or provoked), depressed LV ejection fraction (<40%), rales above the lung bases on physical examination or congestion on chest radiograph, and symptomatic ventricular arrhythmias. Other features associated with increased risk include a history of previous myocardial infarction, age over 70 years, diabetes, prolonged sinus tachycardia, hypotension, ST-segment changes at rest without angina ("silent ischemia"), an abnormal signal-averaged ECG, nonpatency of the infarct-related coronary artery (if angiography is undertaken), and persistent advanced heart block or a new intraventricular conduction abnormality on the ECG. Therapy must be individualized on the basis of the relative importance of the risk(s) present.

The goal of preventing reinfarction and death after recovery from AMI has led to strategies to evaluate risk after infarction. Early after AMI, this evaluation generally involves the use of noninvasive testing. In stable patients, submaximal exercise stress testing may be carried out before hospital discharge to detect residual ischemia and ventricular ectopy and to provide the patient with a guideline for exercise in the early recovery period. Alternatively, or in addition, a maximal (symptom-limited) exercise stress test may be carried out 4 to 6 weeks after infarction. Evaluation of LV function at rest and during exercise is usually warranted as well. Recognition of a depressed LV ejection fraction by echocardiography or radionuclide ventriculography identifies patients who should receive ACE inhibitors (see "Angiotensin-Converting Enzyme Inhibitors," above). Patients in whom angina is induced at relatively low workloads, those who have a large reversible defect on perfusion imaging or a depressed ejection fraction, those with demonstrable ischemia, and those in whom exercise provokes symptomatic ventricular arrhythmias should be considered at high risk for recurrent MI or death from arrhythmia; and cardiac catheterization with coronary angiography and/or invasive electrophysiologic evaluation is advised.

Exercise tests also aid in formulating an individualized exercise prescription, which can be much more vigorous in patients who tolerate exercise without any of the above-mentioned adverse signs. Additionally, predischarge stress testing may provide an important psychological benefit, building the patient's confidence by demonstrating a reasonable exercise tolerance. Furthermore, particularly when no arrhythmias or signs of ischemia are identified, the patient benefits by the physician's reassurance that objective evidence suggests no immediate jeopardy.

In many hospitals a cardiac rehabilitation program with progressive exercise is initiated in the hospital and continued after discharge. Ideally, such programs should include an educational component that informs patients about their disease and its risk factors.

The usual duration of hospitalization for an uncomplicated AMI is about 5 days. The remainder of the convalescent phase may be accomplished at home. During the first 2 weeks, the patient should be encouraged to increase activity by walking about the house and outdoors in good weather. Normal sexual activity may be resumed during this period. After 2 weeks, the physician must regulate the patient's activity on the basis of exercise tolerance. Most patients will be able to return to work within 2 to 4 weeks.

Secondary Prevention of Infarction

Various secondary preventive measures are at least partly responsible for the improvement in the long-term mortality and morbidity rates after AMI. Long-term treatment with an antiplatelet agent (usually aspirin) after AMI is associated with a 25% reduction in the risk of recurrent infarction, stroke, or cardiovascular mortality (36 fewer events for every 1000 patients treated). In addition, in patients taking aspirin chronically, AMIs tend to be smaller and are more likely to be non-Q-wave in nature. An alternative antiplatelet agent that may be used for secondary prevention in patients intolerant of aspirin is the ADP receptor antagonist clopidogrel (75 mg orally daily). ACE inhibitors should be used indefinitely by patients with clinically evident heart failure, a moderate decrease in global ejection fraction, or a large regional wall motion abnormality to prevent late ventricular remodeling and recurrent ischemic events.

The chronic routine use of oral 0x0003b2-adrenoceptor blockers for at least 2 years after AMI is supported by well-conducted, placebo-controlled trials that have convincingly demonstrated reductions in the rates of total mortality, sudden death, and, in some instances, reinfarction. In contrast, calcium antagonists are not recommended for routine secondary prevention.

Evidence suggests that warfarin lowers the risk of late mortality and the incidence of reinfarction after AMI. Since studies comparing aspirin and warfarin therapy separately or in combination have not yet been completed, most physicians prescribe aspirin routinely for all patients without contraindications and add warfarin for patients at increased risk of embolism (see "Thromboembolism," above).

Finally, risk factors for atherosclerosis (Chap. 241) should be discussed with the patient, and, when possible, favorably modified. In particular, efforts should be made to ensure the cessation of smoking and the control of hypertension and hyperlipidemia (the target low-density lipoprotein level is <100 mg/dL). In addition, regular physical exercise and reduction of emotional stress should be encouraged. The benefits of hormone replacement therapy in postmenopausal women recovering from MI remain controversial. The initiation of a combination of estrogen plus progestin is associated with an increased risk of cardiovascular events within the first year but may reduce events in later years (HERS Trial). Thus, hormone replacement therapy prevention of coronary events should not be given de novo to postmenopausal women after AMI. Postmenopausal women already taking estrogen plus progestin at the time of AMI may continue that therapy.