295: ST-Segment Elevation Myocardial Infarction

Acute myocardial infarction (AMI) is one of the most common diagnoses in hospitalized patients in industrialized countries. In the United States, approximately 525,000 patients experience a new AMI, and 190,000 experience a recurrent AMI each year. More than half of AMI-related deaths occur before the stricken individual reaches the hospital. The in-hospital mortality rate after admission for AMI has declined from 10% to about 6% over the past decade. The 1-year mortality rate after AMI is about 15%. Mortality is approximately fourfold higher in elderly patients (over age 75) as compared with younger patients.

When patients with prolonged ischemic discomfort at rest are first seen, the working clinical diagnosis is that they are suffering from an acute coronary syndrome (Fig. 295-1). The 12-lead electrocardiogram (ECG) is a pivotal diagnostic and triage tool because it is at the center of the decision pathway for management; it permits distinction of those patients presenting with ST-segment elevation from those presenting without ST-segment elevation. Serum cardiac biomarkers are obtained to distinguish unstable angina (UA) from non-ST-segment elevation myocardial infarction (NSTEMI) and to assess the magnitude of an ST-segment elevation myocardial infarction (STEMI). This chapter focuses on the evaluation and management of patients with STEMI, while Chap. 294 discusses UA/NSTEMI.

STEMI usually occurs when coronary blood flow decreases abruptly after a thrombotic occlusion of a coronary artery previously affected by atherosclerosis. Slowly developing, high-grade coronary artery stenoses do not typically precipitate STEMI because of the development of a rich collateral network over time. Instead, STEMI 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, STEMI occurs when the surface of an atherosclerotic plaque becomes disrupted (exposing its contents to the blood) and conditions (local or systemic) favor thrombogenesis. A mural thrombus forms at the site of plaque disruption, and the involved coronary artery becomes occluded. Histologic studies indicate that the coronary plaques prone to disruption are those with a rich lipid core and a thin fibrous cap (Chap. 291e). After an initial platelet monolayer forms at the site of the disrupted plaque, various agonists (collagen, ADP, epinephrine, serotonin) promote platelet activation. After agonist stimulation of platelets, thromboxane A₂ (a potent local vasoconstrictor) is released, further platelet activation occurs, and potential resistance to fibrinolysis develops.

In addition to the generation of thromboxane A₂, activation of platelets by agonists promotes a conformational change in the glycoprotein IIb/IIIa receptor (Chap. 140). Once converted to its functional state, this receptor develops a high affinity for soluble adhesive proteins (i.e., integrins) such as fibrinogen. Since fibrinogen is a multivalent molecule, it 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 disrupted plaque. Factors VII and X are activated, ultimately leading to the conversion of prothrombin to thrombin, which then converts fibrinogen to fibrin (Chap. 141). Fluid-phase and clot-bound thrombin participates in an autoamplification reaction leading 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, STEMI 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) endogenous 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 for developing STEMI include those with multiple coronary risk factors (Chap. 291e) and those with UA (Chap. 294). Less common underlying medical conditions predisposing patients to STEMI include hypercoagulability, collagen vascular disease, cocaine abuse, and intracardiac thrombi or masses that can produce coronary emboli.

There have been major advances in the management of STEMI with recognition that the “chain of survival” involves a highly integrated system starting with prehospital care and extending to early hospital management so as to provide expeditious implementation of a reperfusion strategy.

In up to one-half of cases, a precipitating factor appears to be present before STEMI, such as vigorous physical exercise, emotional stress, or a medical or surgical illness. Although STEMI 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.

Pain is the most common presenting complaint in patients with STEMI. 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. 19). It is similar in character to the discomfort of angina pectoris (Chap. 293) but commonly occurs at rest, is usually 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 epigastrium and the patients’ denial that they may be suffering a heart attack are chiefly responsible for the common mistaken impression of indigestion. The pain of STEMI 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, but when it begins during a period of exertion, it does not usually subside with cessation of activity, in contrast to angina pectoris.

The pain of STEMI can simulate pain from acute pericarditis (Chap. 288), pulmonary embolism (Chap. 300), acute aortic dissection (Chap. 301), costochondritis, and gastrointestinal disorders. These conditions should therefore be considered in the differential diagnosis. Radiation of discomfort to the trapezius is not seen in patients with STEMI and may be a useful distinguishing feature that suggests pericarditis is the correct diagnosis. However, pain is not uniformly present in patients with STEMI. The proportion of painless STEMIs is greater in patients with diabetes mellitus, and it increases with age. In the elderly, STEMI 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.

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 STEMI. Although many patients have a normal pulse rate and blood pressure within the first hour of STEMI, 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 include fourth and third heart sounds, decreased intensity of the first heart sound, and paradoxical splitting of the second heart sound (Chap. 267). A transient midsystolic or late systolic apical systolic murmur due to dysfunction of the mitral valve apparatus may be present. A pericardial friction rub may be heard in patients with transmural STEMI 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. Temperature elevations up to 38°C may be observed during the first week after STEMI. The arterial pressure is variable; in most patients with transmural infarction, systolic pressure declines by approximately 10–15 mmHg from the preinfarction state.

STEMI progresses through the following temporal stages: (1) acute (first few hours–7 days), (2) healing (7–28 days), and (3) healed (≥29 days). When evaluating the results of diagnostic tests for STEMI, the temporal phase of the infarction must be considered. The laboratory tests of value in confirming the diagnosis may be divided into four groups: (1) ECG, (2) serum cardiac biomarkers, (3) cardiac imaging, and (4) nonspecific indices of tissue necrosis and inflammation.

ELECTROCARDIOGRAM

The electrocardiographic manifestations of STEMI are described in Chap. 268. During the initial stage, total occlusion of an epicardial coronary artery produces ST-segment elevation. Most patients initially presenting with ST-segment elevation ultimately evolve Q waves on the ECG. However, Q waves in the leads overlying the infarct zone may vary in magnitude and even appear only transiently, depending on the reperfusion status of the ischemic myocardium and restoration of transmembrane potentials over time. A small proportion of patients initially presenting with ST-segment elevation will not develop Q waves when the obstructing thrombus is not totally occlusive, obstruction is transient, or if a rich collateral network is present. Among patients presenting with ischemic discomfort but without ST-segment elevation, if a serum cardiac biomarker of necrosis (see below) is detected, the diagnosis of NSTEMI is ultimately made (Fig. 295-1). A minority of patients who present initially without ST-segment elevation may develop a Q-wave MI. Previously, it was believed that transmural myocardial infarction (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 terms such as Q-wave MI, non-Q-wave MI, transmural MI, and nontransmural MI, have been replaced by STEMI and NSTEMI (Fig. 295-1). Contemporary studies using magnetic resonance imaging (MRI) suggest that the development of a Q wave on the ECG is more dependent on the volume of infarcted tissue rather than the transmurality of infarction.

SERUM CARDIAC BIOMARKERS

Certain proteins, called serum cardiac biomarkers, are released from necrotic heart muscle after STEMI. The rate of liberation of specific proteins differs depending on their intracellular location, their molecular weight, and the local blood and lymphatic flow. Cardiac biomarkers become detectable in the peripheral blood once the capacity of the cardiac lymphatics to clear the interstitium of the infarct zone is exceeded and spillover into the venous circulation occurs. The temporal pattern of protein release is of diagnostic importance. The criteria for AMI require a rise and/or fall in cardiac biomarker values with at least one value above the 99th percentile of the upper reference limit for normal individuals

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 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 STEMI to levels many times higher than the upper reference limit (the highest value seen in 99% of a reference population not suffering from MI), the measurement of cTnT or cTnI is of considerable diagnostic usefulness, and they are now the preferred biochemical markers for MI (Fig. 295-2). With improvements in the assays for the cardiac-specific troponins, it is now possible to detect concentrations <1 ng/L in patients without ischemic-type chest discomfort. 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 creatine phosphokinase (CK) and its MB isoenzyme (CK-MB) measurements, and they are, therefore, of particular value in distinguishing UA from NSTEMI. In practical terms, the high-sensitivity troponin assays are of less immediate value in patients with STEMI. 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 laboratory. Levels of cTnI and cTnT may remain elevated for 7–10 days after STEMI.

CK rises within 4–8 h and generally returns to normal by 48–72 h (Fig. 295-2). An important drawback of total CK measurement is its lack of specificity for STEMI, as CK may be elevated with skeletal muscle disease or trauma, including intramuscular injection. 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 CK-MB mass to CK activity ≥2.5 suggests but is not diagnostic of a myocardial rather than a skeletal muscle source for the CK-MB elevation.

Many hospitals are using cTnT or cTnI rather than CK-MB as the routine serum cardiac marker for diagnosis of STEMI, although any of these analytes remain clinically acceptable. It is not cost-effective to measure both a cardiac-specific troponin and CK-MB at all time points in every patient.

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 STEMI causes earlier peaking of biomarker measurements (Fig. 295-2) because of a rapid washout from the interstitium of the infarct zone, quickly overwhelming lymphatic clearance of the proteins.

The nonspecific reaction to myocardial injury is associated with polymorphonuclear leukocytosis, which appears within a few hours after the onset of pain and persists for 3–7 days; the white blood cell count often reaches levels of 12,000–15,000/μL. 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

Abnormalities of wall motion on two-dimensional echocardiography (Chap. 270e) are almost universally present. Although acute STEMI 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. When the ECG is not diagnostic of STEMI, 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., fibrinolysis 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 inhibitor of the renin-angiotensin-aldosterone system. 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 STEMI.

Several radionuclide imaging techniques (Chap. 270e) are available for evaluating patients with suspected STEMI. However, these imaging modalities are used less often than echocardiography because they are more cumbersome and 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. 293), reveals a defect (“cold spot”) in most patients during the first few hours after development of a transmural infarct. 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 STEMI. 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 nonspecific, as many cardiac abnormalities other than MI alter the radionuclide ventriculogram.

MI can be detected accurately with high-resolution cardiac MRI (Chap. 270e) using a technique referred to as late enhancement. A standard imaging agent (gadolinium) is administered and images are obtained after a 10-min delay. Since little gadolinium enters normal myocardium, where there are tightly packed myocytes, but does percolate into the expanded intercellular region of the infarct zone, there is a bright signal in areas of infarction that appears in stark contrast to the dark areas of normal myocardium.

An Expert Consensus Task Force for the Universal Definition of Myocardial Infarction has provided a comprehensive set of criteria for the definition of MI that integrates the clinical and laboratory findings discussed earlier (Table 295-1) as well as a classification of MI into five types that reflect the clinical circumstances in which it may occur (Table 295-2).

PREHOSPITAL CARE

The prognosis in STEMI is largely related to the occurrence of two general classes of complications: (1) electrical complications (arrhythmias) and (2) mechanical complications (“pump failure”). Most out-of-hospital deaths from STEMI 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 STEMI 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; (3) expeditious transportation of the patient to a hospital facility that is continuously staffed by physicians and nurses skilled in managing arrhythmias and providing advanced cardiac life support; and (4) expeditious implementation of reperfusion therapy (Fig. 295-3). The greatest 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 health care professionals educating the public concerning the significance of chest discomfort and the importance of seeking early medical attention. Regular office visits with patients having a history of or who are at risk for ischemic heart disease are important “teachable moments” for clinicians to review the symptoms of STEMI and the appropriate action plan.

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. General guidelines for initiation of fibrinolysis in the prehospital setting include the ability to transmit 12-lead ECGs to confirm the diagnosis, the presence of paramedics in the ambulance, training of paramedics in the interpretation of ECGs and management of STEMI, and online medical command and control that can authorize the initiation of treatment in the field.

In the Emergency Department, the goals for the management of patients with suspected STEMI include control of cardiac discomfort, 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 STEMI. Many aspects of the treatment of STEMI are initiated in the Emergency Department and then continued during the in-hospital phase of management (Fig. 295-4). The overarching goal is to minimize the time from first medical contact to initiation of reperfusion therapy. This may involve transfer from a non-PCI hospital to one that is PCI capable, with a goal of initiating PCI within 120 min of first medical contact (Fig. 295-4).

Aspirin is essential in the management of patients with suspected STEMI and is effective across the entire spectrum of acute coronary syndromes (Fig. 295-1). Rapid inhibition of cyclooxygenase-1 in platelets followed by a reduction of thromboxane A₂ levels is achieved by buccal absorption of a chewed 160–325-mg tablet in the Emergency Department. This measure should be followed by daily oral administration of aspirin in a dose of 75–162 mg.

In patients whose arterial O₂ saturation is normal, supplemental O₂ is of limited if any clinical benefit and therefore is not cost-effective. However, when hypoxemia is present, O₂ should be administered by nasal prongs or face mask (2–4 L/min) for the first 6–12 h after infarction; the patient should then be reassessed to determine if there is a continued need for such treatment.

Sublingual nitroglycerin can be given safely to most patients with STEMI. Up to three doses of 0.4 mg should be administered at about 5-min intervals. In addition to diminishing or abolishing chest discomfort, nitroglycerin 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 discomfort, 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 (<90 mmHg) or in whom there is clinical suspicion of RV infarction (inferior infarction on ECG, elevated jugular venous pressure, clear lungs, and hypotension). Nitrates should not be administered to patients who have taken a phosphodiesterase-5 inhibitor for erectile dysfunction within the preceding 24 h, because 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.

Morphine is a very effective analgesic for the pain associated with STEMI. However, it may reduce sympathetically mediated arteriolar and venous constriction, and the resulting venous pooling may reduce cardiac output and arterial pressure. These hemodynamic disturbances usually respond 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 inferior 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 (2–4 mg), rather than by the subcutaneous administration of a larger quantity, because absorption may be unpredictable by the latter route.

Intravenous beta blockers are also useful in the control of the pain of STEMI. These drugs control pain effectively in some patients, presumably by diminishing myocardial O₂ demand and hence ischemia. More important, there is evidence that intravenous beta blockers reduce the risks of reinfarction and ventricular fibrillation (see “Beta-Adrenoceptor Blockers” below). However, patient selection is important when considering beta blockers for STEMI. Oral beta blocker therapy should be initiated in the first 24 h for patients who do not have any of the following: (1) signs of heart failure, (2) evidence of a low-output state, (3) increased risk for cardiogenic shock, or (4) other relative contraindications to beta blockade (PR interval greater than 0.24 seconds, second- or third-degree heart block, active asthma, or reactive airway disease). A commonly employed regimen is metoprolol, 5 mg every 2–5 min for a total of three doses, provided the patient has a heart rate >60 beats/min, 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.

The primary tool for screening patients and making triage decisions is the initial 12-lead ECG. When ST-segment elevation of at least 2 mm in two contiguous precordial leads and 1 mm in two adjacent limb leads is present, a patient should be considered a candidate for reperfusion therapy (Fig. 295-4). The process of selecting patients for fibrinolysis versus primary PCI (angioplasty or stenting; Chap. 296e) is discussed below. In the absence of ST-segment elevation, fibrinolysis is not helpful, and evidence exists suggesting that it may be harmful.

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 (ischemic penumbra) may be improved by timely restoration of coronary perfusion, reduction of myocardial O₂ 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 STEMI may achieve spontaneous reperfusion of the infarct-related coronary artery within 24 h and experience improved healing of infarcted tissue. Reperfusion, either pharmacologically (by fibrinolysis) or by PCI, accelerates the opening of infarct-related arteries in those patients in whom spontaneous fibrinolysis 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 O₂ supply and demand through pain control, treatment of congestive heart failure (CHF), 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 patients with STEMI. 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.

Primary percutaneous coronary intervention

(See also Chap. 296e) PCI, usually angioplasty and/or stenting without preceding fibrinolysis, referred to as primary PCI, is effective in restoring perfusion in STEMI 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 fibrinolytic therapy (see below) but otherwise are considered appropriate candidates for reperfusion. It appears to be more effective than fibrinolysis 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. Compared with fibrinolysis, primary PCI is generally preferred when the diagnosis is in doubt, cardiogenic shock is present, bleeding risk is increased, or symptoms have been present for at least 2–3 h when the clot is more mature and less easily lysed by fibrinolytic drugs. However, PCI is expensive in terms of personnel and facilities, and its applicability is limited by its availability, around the clock, in only a minority of hospitals (Fig. 295-4).

Fibrinolysis

If no contraindications are present (see below), fibrinolytic therapy should ideally be initiated within 30 min of presentation (i.e., door-to-needle time ≤30 min). The principal goal of fibrinolysis is prompt restoration of full coronary arterial patency. The fibrinolytic agents tissue plasminogen activator (tPA), streptokinase, tenecteplase (TNK), and reteplase (rPA) have been approved by the U.S. Food and Drug Administration for intravenous use in patients with STEMI. 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 the former agents. TNK and rPA are referred to as bolus fibrinolytics since their administration does not require a prolonged intravenous infusion.

When assessed angiographically, flow in the culprit coronary artery is described by a simple qualitative scale called the Thrombolysis in Myocardial Infarction (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. The latter is the goal of reperfusion therapy, because full perfusion of the infarct-related coronary artery yields far better results in terms of limiting infarct size, maintenance of LV function, and reduction of both short- and long-term mortality rates. Additional methods of angiographic assessment of the efficacy of fibrinolysis include counting the number of frames on the cine film required 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). These methods have an even tighter correlation with outcomes after STEMI than the more commonly employed TIMI flow grade.

tPA and the other relatively fibrin-specific plasminogen activators, rPA and TNK, are more effective than streptokinase at restoring full perfusion—i.e., TIMI grade 3 coronary flow—and have 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. rPA is administered in a double-bolus regimen consisting of a 10-MU bolus given over 2–3 min, followed by a second 10-MU bolus 30 min later. TNK is given as a single weight-based intravenous bolus of 0.53 mg/kg over 10 s. In addition to the fibrinolytic agents discussed earlier, pharmacologic reperfusion typically involves adjunctive antiplatelet and antithrombotic drugs, as discussed subsequently.

Clear contraindications to the use of fibrinolytic 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 fibrinolytic 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 fibrinolytic therapy, which require assessment of the risk-to-benefit ratio, include current use of anti-coagulants (international normalized ratio ≥2), a recent (<2 weeks) invasive or surgical procedure or prolonged (>10 min) cardiopulmonary resuscitation, known bleeding diathesis, 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 ∼2% of patients who receive it. While a minor degree of hypotension occurs in 4–10% 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 fibrinolytic agents. Hemorrhagic stroke is the most serious complication and occurs in ∼0.5–0.9% of patients being treated with these agents. This rate increases with advancing age, with patients >70 years experiencing roughly twice the rate of intracranial hemorrhage as those <65 years. Large-scale trials have suggested that the rate of intracranial hemorrhage with tPA or rPA is slightly higher than with streptokinase.

Integrated reperfusion strategy

Evidence has emerged that suggests PCI plays an increasingly important role in the management of STEMI. Prior approaches that segregated the pharmacologic and catheter-based approaches to reperfusion have now been replaced with an integrated approach to triage and transfer of STEMI patients to receive PCI (Fig. 295-4). To achieve the degree of integration required to care for a patient with STEMI, all communities should create and maintain a regional system of STEMI care that includes assessment and continuous quality improvement of emergency medical services and hospital-based activities.

Cardiac catheterization and coronary angiography should be carried out after fibrinolytic therapy if there is evidence of either (1) failure of reperfusion (persistent chest pain and ST-segment elevation >90 min), in which case a rescue PCI should be considered; or (2) coronary artery reocclusion (re-elevation 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 urgent PCI should be considered. Routine angiography and elective PCI even in asymptomatic patients following administration of fibrinolytic therapy are used with less frequency, given the numerous technologic advances that have occurred in the catheterization laboratory and the increasing number of skilled interventionalists. Coronary artery bypass surgery should be reserved for patients whose coronary anatomy is unsuited to PCI but in whom revascularization appears to be advisable because of extensive jeopardized myocardium or recurrent ischemia.

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 symptoms are controlled with oral therapy, patients may be transferred out of the coronary care unit. Also, patients who have a confirmed STEMI but who are considered to be at low risk (no prior infarction and no persistent chest discomfort, CHF, hypotension, or cardiac arrhythmias) may be safely transferred out of the coronary care unit within 24 h.

Activity

Factors that increase the work of the heart during the initial hours of infarction may increase the size of the infarct. Therefore, patients with STEMI should be kept at bed rest for the first 6–12 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 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 after infarction, patients should be increasing their ambulation progressively to a goal of 185 m (600 ft) at least three times a day.

Diet

Because of the risk of emesis and aspiration soon after STEMI, patients should receive either nothing or only clear liquids by mouth for the first 4–12 h. The typical coronary care unit diet should provide ≤30% of total calories as fat and have a cholesterol content of ≤300 mg/d. Complex carbohydrates should make up 50–55% 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.

Bowel Management

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 STEMI.

Sedation

Many patients require sedation during hospitalization to withstand the period of enforced inactivity with tranquility. Diazepam (5 mg), oxazepam (15–30 mg), or lorazepam (0.5–2 mg), given three to 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 anticoagulant therapy during the initial phase of STEMI 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 anticoagulant agents is to maintain patency of the infarct-related artery, in conjunction with reperfusion strategies. 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 anticoagulant therapy achieves these goals partly determines how effectively it reduces the risk of mortality from STEMI.

As noted previously (see “Management in the Emergency Department” earlier), aspirin is the standard antiplatelet agent for patients with STEMI. The most compelling evidence for the benefits of antiplatelet therapy (mainly with aspirin) in STEMI is found in the comprehensive overview by the Antiplatelet Trialists’ Collaboration. Data from nearly 20,000 patients with MI enrolled in 15 randomized trials were pooled and revealed a relative reduction of 27% in the mortality rate, from 14.2% in control patients to 10.4% in patients receiving antiplatelet agents.

Inhibitors of the P2Y₁₂ ADP receptor prevent activation and aggregation of platelets. The addition of the P2Y₁₂ inhibitor clopidogrel to background treatment with aspirin to STEMI patients reduces the risk of clinical events (death, reinfarction, stroke) and, in patients receiving fibrinolytic therapy, has been shown to prevent reocclusion of a successfully reperfused infarct artery. New P2Y₁₂ ADP receptor antagonists, such as prasugrel and ticagrelor, are more effective than clopidogrel in preventing ischemic complications in STEMI patients undergoing PCI, but are associated with an increased risk of bleeding. Glycoprotein IIb/IIIa receptor inhibitors appear useful for preventing thrombotic complications in patients with STEMI undergoing PCI.

The standard anticoagulant agent used in clinical practice is unfractionated heparin (UFH). The available data suggest that when UFH is added to a regimen of aspirin and a non-fibrin-specific thrombolytic agent such as streptokinase, additional mortality benefit occurs (about 5 lives saved per 1000 patients treated). It appears that the immediate administration of intravenous UFH, in addition to a regimen of aspirin and relatively fibrin-specific fibrinolytic agents (tPA, rPA, or TNK), helps to maintain patency of the infarct-related artery. This effect is achieved at the cost of a small increased risk of bleeding. The recommended dose of UFH is an initial bolus of 60 U/kg (maximum 4000 U) followed by an initial infusion of 12 U/kg per hour (maximum 1000 U/h). The activated partial thromboplastin time during maintenance therapy should be 1.5–2 times the control value.

Alternatives to UFH for anticoagulation of patients with STEMI are the low-molecular-weight heparin (LMWH) preparations, a synthetic version of the critical pentasaccharide sequence (fondaparinux), and the direct antithrombin bivalirudin. Advantages of LMWHs include high bioavailability permitting administration subcutaneously, reliable anticoagulation without monitoring, and greater antiXa:IIa activity. Enoxaparin has been shown to reduce significantly the composite endpoints of death/nonfatal reinfarction and death/nonfatal reinfarction/urgent revascularization compared with UFH in STEMI patients who receive fibrinolysis. Treatment with enoxaparin is associated with higher rates of serious bleeding, but net clinical benefit—a composite endpoint that combines efficacy and safety—still favors enoxaparin over UFH. Interpretation of the data on fondaparinux is difficult because of the complex nature of the pivotal clinical trial evaluating it in STEMI (OASIS-6). Fondaparinux appears superior to placebo in STEMI patients not receiving reperfusion therapy, but its relative efficacy and safety compared with UFH is less certain. Due to the risk of catheter thrombosis, fondaparinux should not be used alone at the time of coronary angiography and PCI but should be combined with another anticoagulant with antithrombin activity such as UFH or bivalirudin. Contemporary trials of bivalirudin used an open-label design to evaluate its efficacy and safety compared with UFH plus a glycoprotein IIb/IIIa inhibitor. Bivalirudin was associated with a lower rate of bleeding, largely driven by reductions in vascular access site hematomas ≥5 cm or the administration of blood transfusions.

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

BETA-ADRENOCEPTOR BLOCKERS

The benefits of beta blockers in patients with STEMI 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 infarction. Acute intravenous beta blockade improves the myocardial O₂ supply-demand relationship, decreases pain, reduces infarct size, and decreases the incidence of serious ventricular arrhythmias. In patients who undergo fibrinolysis 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.

Thus, beta-blocker therapy after STEMI is useful for most patients (including those treated with an angiotensin-converting enzyme [ACE] inhibitor) 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, patients <55 years, no previous MI, with normal ventricular function, no complex ventricular ectopy, and no angina) markedly diminishes any potential benefit.

INHIBITION OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM

ACE inhibitors reduce the mortality rate after STEMI, 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 who 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 STEMI (i.e., those with a systolic pressure >100 mmHg). The mechanism involves a reduction in ventricular remodeling after infarction (see “Ventricular Dysfunction” later) with a subsequent reduction in the risk of CHF. The rate of recurrent infarction may also be lower in patients treated chronically with ACE inhibitors after infarction.

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 in whom an imaging study shows a reduction in global LV function or a large regional wall motion abnormality, or in those who are hypertensive.

Angiotensin receptor blockers (ARBs) should be administered to STEMI patients who are intolerant of ACE inhibitors and who have either clinical or radiologic signs of heart failure. Long-term aldosterone blockade should be prescribed for STEMI patients without significant renal dysfunction (creatinine ≥2.5 mg/dL in men and ≥2.0 mg/dL in women) or hyperkalemia (potassium ≥5.0 mEq/L) who are already receiving therapeutic doses of an ACE inhibitor, have an LV ejection fraction ≤40%, and have either symptomatic heart failure or diabetes mellitus. A multidrug regimen for inhibiting the renin-angiotensin-aldosterone system has been shown to reduce both heart failure–related and sudden cardiac death–related cardiovascular mortality after STEMI, but has not been as thoroughly explored as ACE inhibitors in STEMI patients.

OTHER AGENTS

Favorable effects on the ischemic process and ventricular remodeling (see below) previously led many physicians to routinely use intravenous nitroglycerin (5–10 μg/min initial dose and up to 200 μg/min as long as hemodynamic stability is maintained) for the first 24–48 h after the onset of infarction. However, the benefits of routine use of intravenous nitroglycerin are less in the contemporary era where beta-adrenoceptor blockers and ACE inhibitors are routinely prescribed for patients with STEMI.

Results of multiple trials of different calcium antagonists have failed to establish a role for these agents in the treatment of most patients with STEMI. Therefore, the routine use of calcium antagonists cannot be recommended. Strict control of blood glucose in diabetic patients with STEMI has been shown to reduce the mortality rate. Serum magnesium should be measured in all patients on admission, and any demonstrated deficits should be corrected to minimize the risk of arrhythmias.

VENTRICULAR DYSFUNCTION

After STEMI, the left ventricle 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 STEMI, the left ventricle 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 anterior wall and apex of the left ventricle 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). In patients with an ejection fraction <40%, regardless of whether or not heart failure is present, ACE inhibitors or ARBs should be prescribed (see “Inhibition of the Renin-Angiotensin-Aldosterone System” earlier).

HEMODYNAMIC ASSESSMENT

Pump failure is now the primary cause of in-hospital death from STEMI. The extent of infarction 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 sounds. 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. 279).

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, 0–5%; class II, 10–20%; class III, 35–45%; and class IV, 85–95%. 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 global LV function appears when contraction is seriously impaired in 20–25% of the left ventricle. Infarction of ≥40% of the left ventricle usually results in cardiogenic shock (Chap. 326). Positioning of a balloon flotation (Swan-Ganz) 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. Cardiac output can also be determined with a pulmonary artery catheter. With the addition of intra-arterial pressure monitoring, systemic vascular resistance can be calculated as a guide to adjusting vasopressor and vasodilator therapy. Some patients with STEMI have markedly elevated LV filling pressures (>22 mmHg) and normal cardiac indices (2.6–3.6 L/[min/m²]), while others have relatively low LV filling pressures (<15 mmHg) and reduced cardiac indices. The former patients usually benefit from diuresis, while the latter may respond to volume expansion.

HYPOVOLEMIA

This is an easily corrected condition that may contribute to the hypotension and vascular collapse associated with STEMI 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 STEMI 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, because LV function is almost always affected much more adversely than RV function in patients with STEMI. 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.

TREATMENT

CARDIOGENIC SHOCK

Prompt reperfusion, efforts to reduce infarct size and 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. The evaluation and management of cardiogenic shock and severe power failure after STEMI are discussed in detail in Chap. 326.

RIGHT VENTRICULAR INFARCTION

Approximately one-third of patients with inferior 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, hepatomegaly [Chap. 267]) 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 constrictive pericarditis (steep right atrial “y” descent and an early diastolic dip and plateau in RV waveforms) (Chap. 288). 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.

ARRHYTHMIAS

(See also Chaps. 274 and 276) The incidence of arrhythmias after STEMI 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 STEMI.

Ventricular Premature Beats

Infrequent, sporadic ventricular premature depolarizations occur in almost all patients with STEMI 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, because such therapy may actually increase the mortality rate. Beta-adrenoceptor blocking agents are effective in abolishing ventricular ectopic activity in patients with STEMI and in the prevention of ventricular fibrillation. As described earlier (see “Beta-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 STEMI; to reduce the risk, 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 STEMI, 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 STEMI. 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.

Sustained ventricular tachycardia that is well tolerated hemodynamically should be treated with an intravenous regimen of amiodarone (bolus of 150 mg over 10 min, followed by infusion of 1.0 mg/min for 6 h and then 0.5 mg/min) or procainamide (bolus of 15 mg/kg over 20–30 min; infusion of 1–4 mg/min); if it does not stop promptly, electroversion should be used (Chap. 276). An unsynchronized discharge of 200–300 J (monophasic waveform; approximately 50% of these energies with biphasic waveforms) 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) or amiodarone (a 75–150-mg bolus).

Ventricular arrhythmias, including the unusual form of ventricular tachycardia known as torsades des pointes (Chaps. 276 and 277), may occur in patients with STEMI 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 excellent in patients who survive to hospital discharge after primary ventricular fibrillation; i.e., ventricular fibrillation that is a primary response to acute ischemia that occurs during the first 48 h 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 and implantation of a cardioverter-defibrillator (ICD) (Chap. 276). A more challenging issue is the prevention of sudden cardiac death from ventricular fibrillation late after STEMI in patients who have not exhibited sustained ventricular tachyarrhythmias during their index hospitalization. An algorithm for selection of patients who warrant prophylactic implantation of an ICD is shown in Fig. 295-5.

Accelerated Idioventricular Rhythm

Accelerated idioventricular rhythm (AIVR, “slow ventricular tachycardia”), a ventricular rhythm with a rate of 60–100 beats/min, often occurs transiently during fibrinolytic therapy at the time of reperfusion. For the most part, AIVR, whether it occurs in association with fibrinolytic therapy or spontaneously, 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.

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 (e.g., 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 >120 beats/min, or if tachycardia induces heart failure, shock, or ischemia (as manifested by recurrent pain or ECG changes), a synchronized electroshock (100–200 J monophasic waveform) 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 reduction of 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 <50–60 beats/min, additional doses of 0.2 mg, up to a total of 2.0 mg, may be given. Persistent bradycardia (<40 beats/min) despite atropine may be treated with electrical pacing. Isoproterenol should be avoided.

Atrioventricular and Intraventricular Conduction Disturbances

(See also Chap. 274) Both the in-hospital mortality rate and the postdischarge 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, however, heart block is usually related to ischemic malfunction of the conduction system, which is commonly 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. 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 beats/min) 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

Because recurrent or persistent ischemia often heralds extension of the original infarct or reinfarction in a new myocardial zone and is associated with a near tripling of mortality after STEMI, patients with these symptoms should be referred for prompt coronary arteriography and mechanical revascularization. Administration of a fibrinolytic agent is an alternative to early mechanical revascularization.

Pericarditis

(See also Chap. 288) Pericardial friction rubs and/or pericardial pain are frequently encountered in patients with STEMI involving the epicardium. This complication can usually be managed with aspirin (650 mg four times daily). It is important to diagnose the chest pain of pericarditis accurately, because 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, because 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.

Thromboembolism

Clinically apparent thromboembolism complicates STEMI 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 an important contributing cause of death in 25% of patients with STEMI 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 an 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 3–6 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 STEMI; 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.

Many clinical and laboratory factors have been identified that are associated with an increase in cardiovascular risk after initial recovery from STEMI. 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 MI, age >75, diabetes mellitus, 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 STEMI has led to strategies to evaluate risk after infarction. 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 4–6 weeks after infarction. Evaluation of LV function is usually warranted as well. Recognition of a depressed LV ejection fraction by echocardiography or radionuclide ventriculography identifies patients who should receive medications to inhibit the renin-angiotensin-aldosterone system. 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 (Fig. 295-5). 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 previously mentioned adverse signs. In addition, predischarge stress testing may provide an important psychological benefit, building the patient’s confidence by demonstrating a reasonable exercise tolerance.

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 STEMI is about 5 days. The remainder of the convalescent phase may be accomplished at home. During the first 1–2 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 2–4 weeks.

Various secondary preventive measures are at least partly responsible for the improvement in the long-term mortality and morbidity rates after STEMI. Long-term treatment with an antiplatelet agent (usually aspirin) after STEMI is associated with a 25% reduction in the risk of recurrent infarction, stroke, or cardiovascular mortality (36 fewer events for every 1000 patients treated). An alternative antiplatelet agent that may be used for secondary prevention in patients intolerant of aspirin is clopidogrel (75 mg orally daily). ACE inhibitors or ARBs and, in appropriate patients, aldosterone antagonists 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 beta-adrenoceptor blockers for at least 2 years after STEMI is supported by well-conducted, placebo-controlled trials.

Evidence suggests that warfarin lowers the risk of late mortality and the incidence of reinfarction after STEMI. Most physicians prescribe aspirin routinely for all patients without contraindications and add warfarin for patients at increased risk of embolism (see “Thromboembolism” earlier). Several studies suggest that in patients <75 years old a low dose of aspirin (75–81 mg/d) in combination with warfarin administered to achieve an international normalized ratio >2.0 is more effective than aspirin alone for preventing recurrent MI and embolic cerebrovascular accident. However, there is an increased risk of bleeding and a high rate of discontinuation of warfarin that has limited clinical acceptance of combination antithrombotic therapy. There is increased risk of bleeding when warfarin is added to dual antiplatelet therapy (aspirin and clopidogrel). However, patients who have had a stent implanted and have an indication for anticoagulation should receive dual antiplatelet therapies in combination with warfarin. Such patients should also receive a proton pump inhibitor to minimize the risk of gastrointestinal bleeding and should have regular monitoring of their hemoglobin levels and stool hematest while on combination antithrombotic therapy.

Finally, risk factors for atherosclerosis (Chap. 265e) should be discussed with the patient and, when possible, favorably modified.