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MD Consult: Books: Goldman: Cecil Medicine: Chapter 72 – ST SEGMENT ELEVATION ACUTE MYOCARDIAL INFARCTION AND COMPLICATIONS OF MYOCARDIAL INFARCTION

Goldman: Cecil Medicine, 23rd ed.

Copyright © 2007 Saunders, An Imprint of Elsevier

Chapter 72 – ST SEGMENT ELEVATION ACUTE MYOCARDIAL INFARCTION AND COMPLICATIONS OF MYOCARDIAL INFARCTION

Jeffrey L. Anderson

Definition

Conceptually, myocardial infarction (MI) is myocardial necrosis caused by ischemia. Practically, MI can be diagnosed and evaluated by clinical, electrocardiographic, biochemical, radiologic, and pathologic methods. Technologic advances in detecting much smaller amounts of myocardial necrosis than previously possible (e.g., by troponin determinations) have required a redefinition of MI. Given these developments, the term MI now should be qualified with regard to size, precipitating circumstance, and timing. This chapter focuses on acute MI associated with ST segment elevation on the electrocardiogram (ECG). This category of acute MI is characterized by profound (“transmural”) acute myocardial ischemia affecting relatively large areas of myocardium. The underlying cause essentially always is complete interruption of regional myocardial blood flow (resulting from coronary occlusion, usually atherothrombotic) ( Chapter 69 ). This clinical syndrome should be distinguished from non–ST segment elevation MI, in which the blockage of coronary flow is incomplete and for which different acute therapies are appropriate ( Chapter 71 ).

Epidemiology

Cardiovascular disease is responsible for almost one half of all deaths in the United States and other developed countries and for one fourth of deaths in the developing world ( Chapter 49 ). By 2020, cardiovascular disease will cause one of every three deaths worldwide. Cardiovascular disease causes almost 1 million deaths in the United States each year; it accounts for 37% of all deaths and contributes to 58% of deaths. Annually, an estimated 1.2 million U.S. residents suffer a fatal or nonfatal acute MI. Coronary heart disease, the leading cause of cardiovascular death, underlies or is a contributing cause of 650,000 deaths annually. Half of coronary heart disease deaths (250,000/year) are directly related to acute MI, and at least half of these acute MI–related deaths occur within 1 hour of onset of symptoms and before patients reach a hospital emergency department.

More than 5 million people visit emergency departments in the United States each year for evaluation of chest pain and related symptoms, and almost 1.5 million are hospitalized for an acute coronary syndrome ( Chapter 48 ). The presence of ST segment elevation or new left bundle branch block (LBBB) on the ECG distinguishes patients with acute MI who require consideration of immediate recanalization therapy from other patients with an acute coronary syndrome (non–ST segment elevation MI/unstable angina; Chapter 71 ). Changing demographics, lifestyles, and medical therapies have led to a decrease in the ratio of ST segment elevation MI to non–ST segment elevation acute coronary syndromes over the past 10 to 15 years, so ST segment elevation MI now accounts for about 30% of all MIs. However, ST segment elevation MI is associated with greater in-hospital (but not post-hospital) mortality than non–ST segment elevation MI, and it remains an important contributor to total population mortality.

Pathobiology

Erosion, fissuring, or rupture of vulnerable atherosclerotic plaques has been determined to be the initiating mechanism of coronary thrombotic occlusion, thereby precipitating intraplaque hemorrhage, coronary spasm, and occlusive luminal thrombosis ( Chapter 70 ). Plaque rupture most frequently occurs in lipid-laden plaques with an endothelial cap weakened by internal collagenase (metalloproteinase) activity derived primarily from macrophages. These macrophages are recruited to the plaque from blood monocytes responding to inflammatory mediators and adhesion molecules.

With plaque rupture, elements of the blood stream are exposed to the highly thrombogenic plaque core and matrix containing lipid, tissue factor, and collagen. Platelets adhere, become activated, and aggregate; vasoconstrictive and thrombogenic mediators are secreted; vasospasm occurs; thrombin is generated and fibrin formed; and a partially or totally occlusive platelet- and fibrin-rich thrombus is generated. When coronary flow is occluded, electrocardiographic ST segment elevation occurs (ST segment elevation acute MI). Partial occlusion, occlusion in the presence of collateral circulation, and distal coronary embolization result in unstable angina or non–ST segment elevation MI ( Chapter 71 ). Ischemia from impaired myocardial perfusion causes myocardial cell injury or death, ventricular dysfunction, and cardiac arrhythmias.

Although most MIs are caused by atherosclerosis, occasional patients can develop complete coronary occlusions owing to coronary emboli, in situ thrombosis, vasculitis, primary vasospasm, infiltrative or degenerative diseases, diseases of the aorta, congenital anomalies of a coronary artery, or trauma ( Table 72-1 ). In a canine model of coronary occlusion and recanalization, myocardial cell death begins within 15 minutes of occlusion and proceeds rapidly in a wave front from endocardium to epicardium. Partial myocardial salvage can be achieved by releasing the occlusion within 3 to 6 hours; the degree of salvage is inversely proportional to the duration of ischemia and occurs in a reverse wavefront from epicardium to endocardium. The extent of myocardial necrosis can also be altered by modification of metabolic demands and collateral blood supply. The temporal dynamic of infarction in human disease, although more complex, is generally similar.


TABLE 72-1   — 
CONDITIONS OTHER THAN CORONARY ATHEROSCLEROSIS THAT CAN CAUSE ACUTE MYOCARDIAL INFARCTION

Coronary emboli Causes include aortic or mitral valve lesions, left atrial or ventricular thrombi, prosthetic valves, fat emboli, intracardiac neoplasms, infective endocarditis, and paradoxical emboli
Thrombotic coronary artery disease Can occur with oral contraceptive use, sickle cell anemia and other hemoglobinopathies, polycythemia vera, thrombocytosis, thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, antithrombin III deficiency and other hypercoagulable states, macroglobulinemia and other hyperviscosity states, multiple myeloma, leukemia, malaria, and fibrinolytic system shutdown secondary to impaired plasminogen activation or excessive inhibition
Coronary vasculitis Seen with Takayasu’s disease, Kawasaki’s disease, polyarteritis nodosa, lupus erythematosus, scleroderma, rheumatoid arthritis, and immune-mediated vascular degeneration in cardiac allografts
Coronary vasospasm Can be associated with variant angina, nitrate withdrawal, cocaine or amphetamine abuse, and angina with “normal” coronary arteries
Infiltrative and degenerative coronary vascular disease Can result from amyloidosis, connective tissue disorders (e.g., pseudoxanthoma elasticum), lipid storage disorders and mucopolysaccharidoses, homocystinuria, diabetes mellitus, collagen vascular disease, muscular dystrophies, and Friedreich’s ataxia
Coronary ostial occlusion Associated with aortic dissection, luetic aortitis, aortic stenosis, and ankylosing spondylitis syndromes
Congenital coronary anomalies Including Bland-White-Garland syndrome of anomalous origin of the left coronary artery from the pulmonary artery, left coronary artery origin from the anterior sinus of Valsalva, coronary arteriovenous fistula or aneurysms, and myocardial bridging with secondary vascular degeneration
Trauma Associated with and responsible for coronary dissection, laceration, or thrombosis (with endothelial cell secondary to trauma such as angioplasty) and with radiation and cardiac contusion
Augmented myocardial oxygen requirements exceeding oxygen delivery Encountered with aortic stenosis, aortic insufficiency, hypertension with severe left ventricular hypertrophy, pheochromocytoma, thyrotoxicosis, methemoglobinemia, carbon monoxide poisoning, shock, and hyperviscosity syndromes
Clinical Manifestations

Traditionally, the diagnosis of acute MI has rested on the triad of ischemic-type chest discomfort, ECG abnormalities, and elevated serum cardiac markers. Acute MI was considered present when at least two of the three were present. With their increasing sensitivity and specificity, serum cardiac markers (e.g., troponin I [TnI] or troponin T [TnT]) have assumed a dominant role in confirming the diagnosis of acute MI in patients with suggestive clinical and/or ECG features.

History

Ischemic-type chest discomfort is the most prominent clinical symptom in the majority of patients with acute MI (see Table 48-1 ). The discomfort is characterized by its quality, location, duration, radiation, and precipitating and relieving factors. The discomfort associated with acute MI is qualitatively similar to that of angina pectoris but more severe. It often is perceived as heavy, pressing, crushing, squeezing, bandlike, viselike, strangling, constricting, aching, or burning; it rarely is perceived as sharp pain and generally not as stabbing pain ( Chapters 48 and 70 ).

The primary location of typical ischemic pain is most consistently retrosternal, but it also can present left parasternally, left precordially, or across the anterior chest ( Chapter 48 ). Occasionally, discomfort is predominantly perceived in the anterior neck, jaw, arms, or epigastrium. It generally is somewhat diffuse; highly localized pain (finger point) is rarely angina or acute MI. The most characteristic pattern of radiation is to the left arm, but the right arm or both arms can be involved. The shoulders, neck, jaw, teeth, epigastrium, and interscapular areas also are sites of radiation. Discomfort above the jaws or below the umbilicus is not typical of acute MI. Associated symptoms often include nausea, vomiting, diaphoresis, weakness, dyspnea, restlessness, and apprehension.

The discomfort of acute MI is more severe and lasts longer (typically 20 minutes to several hours) than angina, and it is not reliably relieved by rest or nitroglycerin. The onset of acute MI usually is unrelated to exercise or other apparent precipitating factors. Nevertheless, acute MI begins during physical or emotional stress and within a few hours of arising more frequently than explained by chance.

It is estimated that at least 20% of acute MIs are painless (“silent”) or atypical (unrecognized). Elderly patients and patients with diabetes are particularly prone to painless or atypical MI, which occurs in as many as one third to one half of such patients. Because the prognosis is worse in elderly patients and in those patients with diabetes, diagnostic vigilance is required. In these patients, acute MI can present as sudden dyspnea (which can progress to pulmonary edema), weakness, lightheadedness, nausea, and/or vomiting. Confusional states, sudden loss of consciousness, a new rhythm disorder, or an unexplained fall in blood pressure are other uncommon presentations. The differential diagnosis of ischemic chest discomfort also should include gastrointestinal disorders (e.g., reflux esophagitis; Chapter 140 ), musculoskeletal pain (e.g., costochondritis), anxiety or panic attacks, pleurisy or pulmonary embolism ( Chapter 99 ), and acute aortic dissection ( Chapter 78 ; see Table 48-2 ).

Physical Examination

No physical findings are diagnostic or pathognomonic of acute MI. The physical examination can be entirely normal or may reveal only nonspecific abnormalities. An S4 gallop frequently is found if carefully sought. Blood pressure often is initially elevated, but it may be normal or low. Signs of sympathetic hyperactivity (tachycardia and/or hypertension) often accompany anterior wall MI, whereas parasympathetic hyperactivity (bradycardia and/or hypotension) is more common with inferior wall MI.

The examination is best focused on an overall assessment of cardiac function. Adequacy of vital signs and peripheral perfusion should be noted. Signs of cardiac failure, both left and right sided (e.g., S3 gallop, pulmonary congestion, elevated neck veins) should be sought, and observation for arrhythmias and mechanical complications (e.g., new murmurs) is essential. If hypoperfusion is present, determination of its primary cause (e.g., hypovolemia, right heart failure, left heart failure) is critical to management.

Diagnosis

Electrocardiogram

In patients with a possible acute MI, an ECG must be obtained immediately. Although the initial ECG is neither perfectly specific nor perfectly sensitive in all patients who develop acute ST segment elevation MI, it plays a critical role in initial stratification, triage, and management ( Chapter 48 ). In an appropriate clinical setting, a pattern of regional ECG ST segment elevation suggests coronary occlusion causing marked myocardial ischemia; hospital admission is indicated with triage to the coronary care unit (CCU). An emergency recanalization strategy (primary angioplasty or fibrinolysis) should be used unless it is contraindicated. Other ECG patterns (ST segment depression, T wave inversion, nonspecific changes, normal ECG) in association with ischemic chest discomfort are consistent with a non–ST segment elevation acute coronary syndrome (non–ST segment elevation MI or unstable angina) and are treated with different triage and initial management strategies ( Chapter 71 ).

Electrocardiographic Evolution

Serial ECG tracings improve the sensitivity and specificity of the ECG for the diagnosis of acute MI and assist in assessing the outcomes of therapy. When typical ST segment elevation persists for hours and is followed within hours to days by T wave inversions and Q waves, the diagnosis of acute MI can be made with virtual certainty. The ECG changes in ST segment elevation acute MI evolve through three overlapping phases: (1) hyperacute or early acute, (2) evolved acute, and (3) chronic (stabilized).

Early Acute Phase

This earliest phase begins within minutes, persists, and evolves over hours. T waves increase in amplitude and widen over the area of injury (hyperacute pattern). ST segments evolve from concave to a straightened to a convex upward pattern (acute pattern). When prominent, the acute injury pattern of blended ST-T waves can take on a “tombstone” appearance ( Fig. 72-1 ). ST segment depressions that occur in leads opposite those with ST segment elevation are known as “reciprocal changes” and are associated with larger areas of injury and a worse prognosis but also with greater benefits from recanalization therapy.

FIGURE 72-1  Electrocardiographic tracing shows an acute anterolateral myocardial infarction. Note ST segment elevation in leads I, L, and V1 to V6 with Q waves in V1 to V4.

Other causes of ST segment elevation must be considered and excluded. These conditions include pericarditis ( Chapter 77 ), left ventricular (LV) hypertrophy with J point elevation, and normal variant early repolarization ( Chapter 52 ). Pericarditis (or perimyocarditis) is of particular concern because it can mimic acute MI clinically, but fibrinolytic therapy is not indicated and can be hazardous.

Evolved Acute Phase

During the second phase, ST segment elevation begins to regress, T waves in leads with ST segment elevation become inverted, and pathologic Q or QS waves become fully developed (>0.03-second duration and/or depth >30% of R wave amplitude).

Chronic Phase

Resolution of ST segment elevation is quite variable. It is usually complete within 2 weeks of inferior MI, but it can be delayed further after anterior MI. Persistent ST segment elevation, often seen with a large anterior MI, is indicative of a large area of akinesis, dyskinesis, or ventricular aneurysm. Symmetrical T wave inversions can resolve over weeks to months or can persist for an indefinite period; hence, the age of an MI in the presence of T wave inversions is often termed indeterminate. Q waves usually do not resolve after anterior MI but often disappear after inferior wall MI.

Early recanalization therapy accelerates the time course of ECG changes so that, on coronary recanalization, the pattern can evolve from acute to chronic over minutes to hours instead of days to weeks. ST segments recede rapidly, T wave inversions and losses of R wave occur earlier, and Q waves may not develop or progress and occasionally may regress. Indeed, failure of ST segment elevation to resolve by more than 50 to 70% within 1 to 2 hours suggests failure of fibrinolysis and should prompt urgent angiography for “rescue angioplasty.”

True Posterior Myocardial Infarction and Left Circumflex Myocardial Infarction Patterns

“True posterior” MI presents a mirror-image pattern of ECG injury in leads V1 to V2 to V4 ( Fig. 72-2 ). The acute phase is characterized by ST segment depression, rather than ST segment elevation. The evolved and chronic phases show increased R wave amplitude and widening instead of Q waves. Recognition of a true posterior acute MI pattern should lead to an early recanalization strategy. Other causes of prominent upright anteroseptal forces include right ventricular (RV) hypertrophy, ventricular preexcitation variants (Wolff-Parkinson-White syndrome; Chapter 63 ), and normal variants with early R wave progression. New appearance of these changes or the association with an acute or evolving inferior MI usually allows the diagnosis to be made.

FIGURE 72-2  Electrocardiographic tracing shows an acute inferoposterior myocardial infarction.

Occlusion of the left circumflex artery, especially when it is nondominant, often is not associated with diagnostic ST segment elevation and is therefore more difficult to recognize, to prioritize by triage appropriately, and to manage. Extending the ECG to measure left posterior leads V7 to V9 increases sensitivity for detecting left circumflex–related posterior wall injury patterns with excellent specificity ( Chapter 52 ).

Right Ventricular Infarction

Proximal occlusion of the right coronary artery before the acute marginal branch can cause RV as well as inferior acute MI in about 30% of cases. Because the prognosis and treatment of inferior acute MI differ in the presence of RV infarction, it is important to make this diagnosis. The diagnosis is assisted by obtaining right precordial ECG leads, which are routinely indicated for inferior acute MI ( Chapter 52 ). Acute ST segment elevation of at least 1 mm (0.1 mV) in one or more of leads V4R to V6R is both sensitive and specific (>90%) for identifying acute RV injury, and Q or QS waves effectively identify RV infarction.

Diagnosis in the Presence of Bundle Branch Block

The presence of LBBB often obscures ST segment analysis in patients with suspected acute MI. The presence of a new (or presumed new) LBBB in association with clinical (and laboratory) findings suggesting acute MI is associated with high mortality; patients with new-onset LBBB benefit substantially from recanalization therapy and should undergo triage and treatment in the same way as patients with ST segment elevation MI. Certain ECG patterns, although relatively insensitive, suggest acute MI if present in the setting of LBBB: Q waves in two of leads I, aVL, V5, V6; R wave regression from V1 to V4; ST segment elevation of 1 mm or more in leads with a positive QRS complex; ST segment depression of 1 mm or more in leads V1, V2, or V3; and ST segment elevation of 5 mm or more associated with a negative QRS complex. The presence of right BBB (RBBB) usually does not mask typical ST-T wave or Q wave changes, except for rare cases of isolated true posterior acute MI, characterized by tall right precordial R waves and ST segment depressions.

Serum Cardiac Markers

The increasing sensitivity and specificity of serum cardiac markers have made them the “gold standard” for detection of myocardial necrosis. However, because of the 1- to 12-hour delay after the onset of symptoms before markers become detectable or diagnostic, and given laboratory delays even when markers are positive, the decision to proceed with an urgent recanalization strategy (primary angioplasty or fibrinolysis) must be based on the patient’s clinical history and initial ECG ( Chapter 48 ).

Serum cardiac markers of acute MI are macromolecules (proteins) released from myocytes undergoing necrosis. Ideal markers are not normally present in serum, become rapidly and markedly elevated during acute MI, and are not released from other injured tissues. In recent years, TnI and TnT have emerged as the best markers, although the MB isoenzyme of creatine kinase (CK) continues to be useful in selected settings ( Table 72-2 ).


TABLE 72-2   — 
FEATURES OF SERUM MARKERS OF ACUTE MYOCARDIAL INFARCTION

  Sensitivity at:
Marker Time to Appearance Duration of Elevation 6 hr 12 hr Specificity Comments
Troponin I 2–6 hr 5–10 days ∼75% 90–100% ∼98% Generally regarded as test of choice
Troponin T 2–6 hr 5–14 days ∼80% 95–100% ∼95% Test of choice; less specific than troponin I (elevated in renal insufficiency)
CK-MB 3–6 hr 2–4 days ∼65% ∼95% ∼95% Test of choice for recurrent angina once troponin is elevated
Troponins I and T

Cardiac-derived TnI (cTnI) and TnT (cTnT), proteins of the sarcomere, have amino acid sequences distinct from their skeletal muscle isoforms. These troponins are not normally present in the blood. With even small acute MIs, troponins increase to 20-fold or more above the lower limits of the assay, and elevations persist for several days. Troponins have replaced CK-MB because they are more specific in the setting of injuries to skeletal muscle or other organs that release CK and (to a lesser extent) CK-MB, and they also are more sensitive in the setting of minimal myocardial injury.

The troponins generally are first detectable 2 to 4 hours after the onset of acute MI, are maximally sensitive at 8 to 12 hours, peak at 10 to 24 hours, and persist for 5 to 14 days. Their long persistence has allowed them to replace lactate dehydrogenase and its isoenzymes for the diagnosis of acute MI in patients presenting late (>1 to 2 days) after symptoms. However, this persistence can obscure the diagnosis of recurrent MI, for which more rapidly cleared markers (i.e., CK-MB) are more useful. Clinically, cTnI and cTnT appear to be of approximately equivalent utility. However, renal failure is more likely to be associated with false-positive elevations of cTnT than of cTnI. Although qualitative point-of-service troponin tests can speed the diagnosis of acute MI in the emergency department, serum cardiac markers are often negative within the first few hours after the onset of symptoms.

CK-MB

Even though the MB isoenzyme of CK is present in lower concentrations than total CK, it is much more specific (although not entirely so) than total CK for cardiac injury. An increased ratio of CK-MB mass to total CK activity substantially improves the specificity of the diagnosis of acute MI with only a modest reduction in sensitivity. A problem in using the ratio occurs when total CK is markedly elevated (in the presence of skeletal muscle damage, including prolonged cardiac resuscitation) and CK-MB is elevated by units but not by ratio. Another clinical dilemma occurs when total CK is within the normal range but the ratio is elevated. Serial measurements of CK and CK-MB are more useful than single measurements in assessing diagnosis, timing, sizing, and success of therapy of acute MI. CK-MB increases within 3 to 4 hours after the onset of acute MI, is maximally sensitive within 8 to 12 hours, peaks at 12 to 24 hours, and returns to normal in 2 to 4 days.

The total quantity of CK/CK-MB protein released correlates with infarct size. Peak concentrations (e.g., for CK/CK-MB) correlate generally but less well with infarct size. Early reperfusion leads to higher and earlier peaks but similar or smaller integrated concentrations over time (consistent with myocardial salvage). The timing of the peak CK-MB can provide useful insight into the success (peak at 10 to 18 hours) or failure (peak at 18 to 30 hours) of recanalization therapy.

It does not appear to be cost-effective to measure both a cardiac-specific troponin and CK/CK-MB serially over time in every patient with suspected acute MI. However, CK/CK-MB still is useful for certain applications, such as to confirm the diagnosis when the troponin level is elevated in a confusing clinical setting, to evaluate possible reinfarction in patients with recurrent chest pain, and, in specific settings, to assess the success of recanalization noninvasively (using time to peak).

Other Laboratory Tests

On admission, routine assessment of complete blood count and platelet count, standard blood chemistry studies, a lipid panel, and coagulation tests (prothrombin time, partial thromboplastin time) are useful. Results assist in assessing comorbid conditions and prognosis and in guiding therapy. Hematologic tests provide a useful baseline before initiation of antiplatelet, antithrombin, and fibrinolytic therapy or coronary angiography or angioplasty. Myocardial injury precipitates polymorphonuclear leukocytosis, commonly resulting in an elevation of white blood cell count of up to 12,000 to 15,000/μL, which appears within a few hours and peaks at 2 to 4 days. The metabolic panel provides a useful check on electrolytes, glucose, and renal function. On hospital admission or the next morning, a fasting lipid panel is recommended to assist in decision making for inpatient lipid lowering (e.g., statin therapy if low-density lipoprotein is greater than 70 mg/dL; Chapter 217 ). Unless carbon dioxide retention is suspected, finger oximetry is adequate to titrate oxygen therapy. The C-reactive protein level increases with acute MI, but its incremental prognostic value in the acute setting is unknown. B-type natriuretic peptide, which increases with ventricular wall stress and relative circulatory fluid overload, may provide useful incremental prognostic information in the setting of acute MI.

Imaging

A chest radiograph is the only imaging test routinely obtained on admission for acute MI. Although the chest radiograph is often normal, findings of pulmonary venous congestion, cardiomegaly, or widened mediastinum can contribute importantly to diagnosis and management decisions. For example, a history of severe, “tearing” chest and back pain in association with a widened mediastinum should raise the question of a dissecting aortic aneurysm ( Chapter 78 ). In such cases, fibrinolytic therapy must be withheld pending more definitive diagnostic imaging of the aorta. Other noninvasive imaging (e.g., echocardiography [ Chapter 53 ], cardiac nuclear scanning [ Chapter 54 ], and other testing) is performed for evaluation of specific clinical issues, including suspected complications of acute MI. Coronary angiography ( Chapter 56 ) is performed urgently as part of an interventional strategy for acute MI or later for risk stratification in higher-risk patients who are managed medically.

Echocardiography

Two-dimensional transthoracic echocardiography with color-flow Doppler imaging is the most generally useful noninvasive test obtained on admission or early in the hospital course ( Chapter 53 ). Echocardiography efficiently assesses global and regional cardiac function and enables the clinician to evaluate suspected complications of acute MI. The sensitivity and specificity of echocardiography for regional wall motion assessment are high (>90%), although the age of the abnormality (new versus old) must be distinguished clinically or by ECG. Echocardiography is helpful in determining the cause of circulatory failure with hypotension (relative hypovolemia, LV failure, RV failure, or mechanical complication of acute MI). Echocardiography also can assist in differentiating pericarditis and perimyocarditis from acute MI. Doppler echocardiography is indicated to evaluate a new murmur and other suspected mechanical complications of acute MI (papillary muscle dysfunction or rupture, acute ventricular septal defect, LV free wall rupture with tamponade or pseudoaneurysm). Later in the course of acute MI, echocardiography may be used to assess the degree of recovery of stunned myocardium after recanalization therapy, the degree of residual cardiac dysfunction and indications for angiotensin-converting enzyme (ACE) inhibitors and other therapies for heart failure, and the presence of LV aneurysm and mural thrombus (requiring oral anticoagulants).

Radionuclide, Magnetic Resonance, and Other Imaging Studies

Radionuclide techniques generally are too time consuming and cumbersome for routine use in the acute setting. More commonly, they are used in risk stratification before or after hospital discharge to augment exercise or pharmacologic stress testing ( Chapter 54 ). Thallium-201 and technetium-99m-sestamibi alone or, more commonly, together (dual isotope imaging) are currently the most frequently used “cold spot” tracers to assess myocardial perfusion and viability, as well as infarct size. Infarct avid tracers to identify, locate, and size recent myocardial necrosis are available but are rarely required for ST segment elevation MI. Computed tomography ( Chapter 54 ) and magnetic resonance imaging ( Chapter 55 ) can be useful to evaluate patients with a suspected dissecting aortic aneurysm and, together with positron-emission tomography, for research purposes and in selected clinical applications such as for assessment of myocardial viability (infarct sizing). When the issue of a nonatherosclerotic cause of myocardial necrosis is raised (e.g., perimyocarditis simulating acute MI), contemporary multislice (e.g., 64-slice) coronary computed tomography ( Chapter 54 ) can assess coronary artery disease qualitatively and semiquantitatively, and it can also distinguish other causes of chest pain syndromes.

Treatment

Assessment and Management

Prehospital Phase

More than one half of deaths related to acute MI occur within 1 hour of onset of symptoms and before the patient reaches a hospital emergency department. Most of these deaths are caused by ischemia-related ventricular fibrillation (VF) and can be reversed by defibrillation ( Chapters 62 and 65 ). Rapid defibrillation allows resuscitation in 60% of patients when treatment is delivered by a bystander using an on-site automatic external defibrillator or by a first-responding medical rescuer ( Chapter 62 ). Moreover, the first hour represents the best opportunity for myocardial salvage with recanalization therapy. Thus, the three goals of prehospital care are as follows: (1) to recognize symptoms promptly and seek medical attention; (2) to deploy an emergency medical system team capable of cardiac monitoring, defibrillation and resuscitation, and emergency medical therapy (e.g., nitroglycerin, lidocaine, atropine); and (3) to transport the patient expeditiously to a medical care facility staffed with personnel capable of providing expert coronary care, including recanalization therapy (primary angioplasty or fibrinolysis).

The greatest time lag to recanalization therapy is the patient’s delay in calling for help. Public education efforts have yielded mixed results, and innovative approaches are needed. The feasibility of initiating fibrinolytic therapy by highly trained ambulance personnel in coordinated ambulance and emergency department systems has been shown. In coordinated systems and when transportation delays are substantial, initiation of fibrinolytic or other antithrombotic therapy in the field may be considered, thereby shortening the time to recanalization.

Hospital Phases

 

Emergency Department

The goals of emergency department care are to identify patients with acute myocardial ischemia rapidly, to stratify them into acute ST segment elevation MI as compared with other acute coronary syndromes (see Figs. 71-1 and 72-1 ), to initiate a recanalization strategy and other appropriate medical care in qualifying patients with acute ST segment elevation MI, and to prioritize by triage rapidly to inpatient (CCU, step-down unit, observation unit) or outpatient care (patients without suspected ischemia) (see Fig. 71-2 ).

The evaluation of patients with chest pain and other suspected acute coronary syndromes begins with a 12-lead ECG even as the physician is beginning a focused history, including contraindications to fibrinolysis, and a targeted physical examination. Continuous ECG monitoring should be started, an intravenous line should be established, and admission blood tests should be drawn (including cardiac markers such as cTnI or cTnT). As rapidly as possible, the patient should be stratified as having a probable ST segment elevation acute MI, a non–ST segment elevation acute MI, probable or possible unstable angina, or likely noncardiac chest pain.

In patients with ST segment elevation acute MI by clinical and ECG criteria, a recanalization strategy must be selected: alternative choices are primary percutaneous coronary intervention (primary PCI; the patient is transferred directly to the cardiac catheterization laboratory with a goal of door-to-balloon time of less than 90 minutes) or fibrinolysis (begun immediately in the emergency department with a goal of door-to-needle time of less than 30 minutes) ( Fig. 72-3 ).

Aspirin (162 to 325 mg) should be given to all patients unless it is contraindicated (see Fig. 72-3 ). Intravenous heparin (initial bolus 60 IU/kg, maximum, 4000 IU, then 12 IU/kg/hour, maximum 1000 IU/hour, for patients >70 kg, adjusted to maintain activated partial thromboplastin time 1.5 to 2 times the control value) or low-molecular-weight heparin (LMWH; e.g., enoxaparin, 30 mg intravenous bolus, then 1 mg/kg subcutaneously twice daily, for patients <75 years old without renal insufficiency) is appropriate in most patients. Patients with chest pain should be given sublingual nitroglycerin (0.4 mg every 5 minutes for a total of three doses) after which an assessment should be made of the need for intravenous nitroglycerin. Persistent ischemic pain may be treated with titrated to intravenous doses of morphine (i.e., 2 to 4 mg intravenously [IV], repeated every 5 to 15 minutes to relieve pain). Initiation of β-blocker therapy is usually indicated, especially in patients with hypertension, tachycardia, and ongoing pain; however, decompensated heart failure is a contraindication to the acute initiation of β-blocker therapy, particularly by the intravenous route. Oxygen should be used in doses sufficient to avoid hypoxemia (e.g., initially at 4 L/minute by nasal cannula; fingertip oximetry may be used to monitor effect). The ideal systolic blood pressure is 100 to 140 mm Hg. Excessive hypertension usually responds to titrated nitroglycerin, β-blocker therapy, and morphine (also given for pain). Relative hypotension could require discontinuation of these medications, fluid administration, or other measures as appropriate to the hemodynamic subset ( Table 72-3 ). Atropine (0.5 to 1.5 mg IV) should be available to treat symptomatic bradycardia and hypotension related to excessive vagotonia. Direct transfer to the catheterization laboratory or fibrinolysis followed by transfer to the CCU should occur as expeditiously as possible.

Early Hospital Phase: Coronary Care

Coronary care for early hospital management of acute MI has reduced in-hospital mortality by more than 50%. The goals of CCU care include (1) continuous ECG monitoring and antiarrhythmic therapy for serious arrhythmias (i.e., rapid defibrillation of VF), (2) initiation or continuation of a coronary recanalization strategy to achieve myocardial reperfusion, (3) initiation or continuation of other acute medical therapies, (4) hemodynamic monitoring and appropriate medical interventions for different hemodynamic subsets of patients, and (5) diagnosis and treatment of mechanical and physiologic complications of acute MI. General care and comfort measures also are instituted. A sample of CCU admission orders is given in Table 72-4 .

General care measures include attention to activity, diet and bowels, education, reassurance, and sedation. Bedrest is encouraged for the first 12 hours. In the absence of complications, dangling and bed-chair and self-care activities can begin within 24 hours. When stabilization has occurred, usually within 1 to 3 days, patients may be transferred to a step-down unit where progressive reambulation occurs. The risk of emesis and aspiration or the anticipation of angiography or other procedures usually dictates nothing by mouth or clear liquids for the first 4 to 12 hours. Thereafter, a heart-healthy diet in small portions is recommended. In patients at high risk for bleeding gastric stress ulcers, a proton pump inhibitor or an H2-antagonist is recommended for prophylaxis in patients receiving antithrombotic therapy. Many patients benefit from an analgesic (e.g., morphine sulfate, in 2- to 4-mg increments) to relieve ongoing pain and an anxiolytic or sedative during the CCU phase. A benzodiazepine is frequently selected. Sedatives should not be substituted for education and reassurance from concerned caregivers to relieve emotional distress and improve behavior; routine use of anxiolytics is neither necessary nor recommended. Constipation often occurs with bedrest and narcotics; stool softeners and a bedside commode are advised.

The ECG should be monitored continuously in the CCU (and usually in the step-down unit) to detect serious arrhythmias and to guide therapy. Measures to limit infarct size (i.e., coronary recanalization) and to optimize hemodynamics also stabilize the heart electrically. Routine antiarrhythmic prophylaxis (e.g., with lidocaine or amiodarone) is not indicated, but specific arrhythmias require treatment (see later text).

Hemodynamic evaluation is helpful in assessing prognosis and in guiding therapy (see Table 72-3 ). Clinical and noninvasive evaluation of vital signs is adequate for normotensive patients without pulmonary congestion. Patients with pulmonary venous congestion alone can usually be managed conservatively. Invasive monitoring is appropriate when the cause of circulatory failure is uncertain and when titration of intravenous therapies depends on hemodynamic measurements (e.g., pulmonary capillary wedge pressure and cardiac output). Similarly, an arterial line is not necessary in all patients and may be associated with local bleeding after fibrinolysis or potent antiplatelet and antithrombin therapy. Arterial catheters are appropriate and useful in clinically unstable, hypotensive patients who do not respond to intravenous fluids to replete or expand intravascular volume (see the later discussion of complications).

Later Hospital Phase

Transfer from the CCU to the step-down unit usually occurs within 1 to 3 days, when the cardiac rhythm and hemodynamics are stable. The duration of this late phase of hospital care is usually an additional 2 to 3 days in uncomplicated cases. Activity levels should be increased progressively under continuous ECG monitoring. Medical therapy should progress from parenteral and short-acting agents to oral medications appropriate and convenient for long-term outpatient use.

Risk stratification and functional evaluations are critical to assess prognosis and to guide therapy as the time for discharge approaches. Functional evaluation also can be extended to the early period after hospital discharge. Education must be provided about diet, activity, smoking, and other risk factors (e.g., lipids, hypertension, diabetes).

Specific Therapeutic Measures

Recanalization Therapy

Early reperfusion of ischemic, infarcting myocardium represents the most important conceptual and practical advance for ST segment elevation acute MI and is the primary therapeutic goal. Coronary recanalization is accomplished by using primary PCI with angioplasty and, commonly, stenting or with fibrinolytic (thrombolytic) therapy. With broad application of recanalization therapy, 30-day mortality rates from ST segment elevation acute MI have progressively declined over the past 3 decades (from 20 to 30% to 5 to 10%).

Fibrinolytic Therapy

Various fibrinolytic agents ( Table 72-5 ) are useful in patients with ST segment elevation or new or presumed-new LBBB who present for treatment within 12 hours of the onset of symptoms and who have no contraindications to the use of these agents ( Table 72-6 ). Compared with no recanalization therapy, older fibrinolytics such as streptokinase reduced mortality by 18% (from 11.5% to 9.8%) at 5 weeks.[1] Patients with anterior ST segment elevation benefit more (37 lives saved per 1000) than those with inferior ST segment elevation only (8 lives saved per 1000), and younger patients benefit more than the elderly (>75 years). No benefit or a slight adverse effect is seen in patients presenting with normal ECGs or ST depression alone. Benefit is time dependent; it declines from about 40 lives or more saved per 1000 within the first hour, to 20 to 30 lives saved per 1000 for hours 2 to 12, to a nonsignificant 7 lives saved per 1000 for hours 13 to 24. An accelerated regimen of tissue plasminogen activator (t-PA plus intravenous heparin) further reduces mortality at 30 days (by 14%, from 7.3 to 6.3%), compared with streptokinase,[2] because the patency rate of the infarct-related artery at 90 minutes is higher with t-PA (81%) than with streptokinase (53 to 60%). Longer-acting variants of t-PA, given by single-bolus (tenecteplase) or double-bolus (reteplase) injections are now in widespread clinical use because they are more convenient to give, but they have not improved survival further.

The major risk of fibrinolytic therapy is bleeding. Intracerebral hemorrhage is the most serious and frequently fatal complication; its incidence rate is 0.5 to 1% with currently approved regimens. Older age (>70 to 75 years), female gender, hypertension, and higher relative doses of t-PA and heparin increase the risk of intracranial hemorrhage. The risk-to-benefit ratio should be assessed in each patient when fibrinolysis is considered and specific regimens are selected.

Primary Percutaneous Coronary Intervention

PCI has emerged as an alternative, and usually the preferred, recanalization strategy ( Table 72-7 ). [3] [4] PCI achieves mechanical recanalization by inflation of a catheter-based balloon centered within the thrombotic occlusion ( Chapter 73 ). Percutaneous transluminal coronary angioplasty (PTCA) is generally augmented by placing a stent at the site of occlusion as a scaffold to enlarge the lumen and to retain optimal post-angioplasty expansion. Preference is often given to drug-eluting stents (e.g., sirolimus, paclitaxel), which markedly reduce the rates of restenosis but can increase the risk of late thrombosis.

The relative benefits of primary PTCA or PCI over fibrinolysis are confirmed by a meta-analysis that found a significantly lower mortality rate (4.4% versus 6.5%; odds ratio, 0.66) and lower rates of nonfatal reinfarction (2.9% versus 5.3%; odds ratio, 0.53) and intracerebral hemorrhage with primary PTCA compared with fibrinolysis.[3] PCI yields better outcomes than fibrinolysis across all age groups when it is performed within 1 to 2 hours of presentation to a health care facility.

Currently, a primary PCI strategy may begin with initiation of a glycoprotein (GP) IIb/IIIa inhibitor in the emergency department, together with aspirin and heparin, followed by rapid application of coronary angioplasty with stenting.[5] Whether the addition of a reduced dose of a plasminogen activator to GPIIb/IIIa therapy in the field or emergency department could further improve outcomes in selected patients who undergo early PCI without compromising safety is not conclusively resolved but appears doubtful (except possibly in selected patient subgroups), and this approach is not generally recommended. [6] [7]

Operator and institutional experience is an issue more important to outcomes with primary PCI than fibrinolysis and has been incorporated into current recommendations (see Table 72-7 ). Primary PCI is feasible in community hospitals without surgical capability, but concerns about timing and safety remain. Current guidelines allow that primary PCI “might be considered” in hospitals without on-site cardiac surgery, provided (1) there is a proven plan for rapid and safe transport to a nearby hospital with cardiac surgery capability and availability, and (2) the PCI is done by a skilled operator (≥75 PCIs/year) in a hospital with adequate experience (≥36 primary PCIs/year).

Mechanical reperfusion, primarily with stenting and abciximab, for patients presenting more than 12 but less than 48 hours after the onset of symptoms, also can reduce infarct size and perhaps adverse events.[8] Extending PCI to ST segment elevation MI beyond 12 hours deserves further testing in larger studies.

An additional important indication is cardiogenic shock occurring within 36 hours of the onset of acute MI and treated within 18 hours of the onset of shock.[9] However, benefit was not established for patients older than 75 years of age, and benefit was greater with earlier PCI.

Selecting a Recanalization Regimen

Whether to use PCI or fibrinolytic therapy depends on local resources and experience, as well as on patient factors. Outcomes appear to be determined both by timing and by institutional and operator experience. In general, in experienced facilities (≥200PCIs/center; surgical capability; ≥75PCIs/operator annually; frequent primary PCI, e.g., ≥36/year/center; ≥four/operator/year) that are able to mobilize and treat patients quickly (<90 minutes to balloon inflation), primary PCI is considered the preferred strategy, with stenting preferred over balloon PTCA. PCI is particularly preferred for patients at higher risk for mortality (including shock), for later presentations (>3 hours), and for patients with greater risk of intracerebral hemorrhage (age >70 years, female gender, therapy with hypertensive agents). Ancillary antithrombotic therapy with primary PCI includes aspirin, unfractionated heparin or LMWH, and a GPIIb/IIIa inhibitor (preferably initiated on admission before catheterization). Clopidogrel is begun directly after PCI and is continued after discharge.

For other situations, fibrinolytic therapy becomes the recommended recanalization strategy. If time since the onset of symptoms is within 3 hours and the difference between expected time to PCI and fibrinolytic administration is more than 1 hour, fibrinolysis is often the preferred strategy. Fibrinolysis also is preferred in centers without sufficient PCI experience or capability. In hospitals with long ambulance transport times (>60 to 90 minutes), a strategy for initiating prehospital fibrinolysis may be considered. Very early or prehospital fibrinolysis (followed by an invasive strategy on hospital arrival, i.e., “pharmacoinvasive therapy”), although an appealing concept, appears to cause a higher rate of in-hospital mortality, cardiac ischemic events, and strokes compared with primary PCI alone,[10] and its use cannot be recommended as a primary recanalization strategy. Whether fibrinolysis before PCI will be beneficial in selected subgroups with MI, such as patients seen within the first hour of symptoms and with an expected delay to PCI of 2 hours or more, deserves further testing. Currently, however, efforts should be made to provide primary PCI to a larger percentage of patients with acute MI.

The selection of a specific fibrinolytic regimen is based on the risk of complications of the acute MI, the risk of intracerebral hemorrhage, and a consideration of economic constraints. Using these factors, longer-acting variants of t-PA (i.e., tenecteplase and reteplase) have become dominant in the United States and other affluent medical markets; in other countries, less costly streptokinase is still widely used. A nonimmunogenic fibrinolytic agent is preferred for patients with a history of prior streptokinase use. Streptokinase has a lower risk of intracerebral hemorrhage than other regimens if excessive heparin is avoided. Tenecteplase combined with enoxaparin was more effective than tenecteplase with standard heparin or with a GPIIb/IIIa inhibitor (abciximab) and heparin in one but not another trial. Reteplase with abciximab showed no mortality advantage when combined (in half-dose) with abciximab than with heparin alone; ischemic events decreased, but intracerebral hemorrhage increased, especially in elderly patients. Over the past decade, the application of recanalization therapy has remained relatively constant in the United States and other Western countries at 70 to 75% of “eligible” patients with acute MI. Primary PCI use has increased (31% of time-eligible patients in one recent international study), although fibrinolytic therapy continues to be more commonly applied (45% of eligible patients).

Ancillary and Other Therapies

Antiplatelet Therapy

 

Aspirin

Platelets form a critical component of coronary thrombi. Aspirin inhibits platelet aggregation by irreversibly blocking cyclooxygenase 1 activity by selective acetylation of serine at position 530. Cyclooxygenase 1 catalyzes the conversion of arachidonic acid to thromboxane-A2, a potent platelet aggregator ( Chapter 34 ).

Aspirin has been extensively tested to prevent coronary heart disease ( Chapter 35 ). Aspirin trials in ST segment elevation acute MI have been more limited but positive. The most important trial of aspirin in ST segment elevation acute MI randomized more than 17,000 patients with “suspected acute MI” (representing mostly, but not entirely, ST segment elevation acute MI) to aspirin or control and to intravenous streptokinase or control. At 5 weeks, the relative risk of vascular death was reduced 21% by aspirin alone, 25% by streptokinase alone, and 40% by aspirin in combination with streptokinase. Since that time, aspirin has been included as standard therapy in most treatment regimens for ST segment elevation acute MI.

Current guidelines strongly recommend aspirin (class I indication) on admission in a dose of 162 to 325 mg, preferably chewed. Aspirin administration is continued throughout hospitalization and then indefinitely in a maintenance dose of 75 to 162 mg/day on an outpatient basis (enteric-coated forms are popular).

Adenosine Diphosphate Receptor Antagonists

The thienopyridine clopidogrel exerts potent antiplatelet effects by blocking the platelet membrane adenosine diphosphate receptor ( Chapter 35 ). For patients allergic to aspirin, clopidogrel has become the alternative of choice for short- and long-term therapy of ST segment elevation acute MI. A single loading dose of 300 mg is given (600 mg has been successfully tested in recent trials to achieve earlier onset of platelet inhibition, i.e., within 1 to 2 hours, if needed). The maintenance dose is 75 mg/day.

In patients who can take aspirin, the addition of clopidogrel (300 mg followed by 75 mg/day) to aspirin and fibrinolytic therapy in patients 75 years of age or younger reduces predischarge occlusion rates of infarct-related arteries (by 41%) and reduces ischemic complications at 30 days (by 20%) without increasing rates of intracerebral hemorrhage.[11] When given without a loading dose but also without an upper age restriction, clopidogrel reduces 15-day ischemic complications by 9% and death from any cause by 7%.[12] Hence, clopidogrel appears to represent a beneficial initial adjunctive therapy in patients with ST segment elevation MI who are treated with fibrinolytic agents. However, clopidogrel increases the risk of bleeding with coronary artery bypass grafting (CABG), so it is commonly initiated only after coronary angiography has been performed and early surgery has been excluded as a therapeutic choice; if CABG is planned, clopidogrel should be withheld for 5 to 7 days unless the urgency of surgery outweighs the risk of excessive bleeding.

Clopidogrel added to aspirin on admission for patients with non–ST segment elevation acute MI or unstable angina ( Chapter 71 ) or after a PCI reduces vascular events (by 22%) at 3 to 12 months compared with aspirin alone. Extrapolation of these findings led to the recommendations that clopidogrel be used for 3 to 12 months as an alternative antiplatelet agent in patients with ST segment elevation acute MI when aspirin is contraindicated and that it be considered routinely (in addition to aspirin) in patients after primary PCI.

Glycoprotein IIB/IIIA Inhibitors

Inhibitors of the platelet membrane GPIIb/IIIa receptor, a fibrinogen receptor, have been shown to benefit high-risk patients with non–ST segment elevation acute coronary syndrome ( Chapters 35 and 71 ) on admission or after PCI. The benefit in ST segment elevation MI is smaller when routine stenting is used and when GPIIb/IIIa therapy is administered only in the catheterization laboratory. Earlier (“upstream”) GP inhibition before hospital admission or in the emergency department (precatheterization) is effective in improving coronary patency by the time of emergency angiography and, possibly, clinical outcomes, although data from clinical trials are limited for ST segment elevation MI.[13] If early CABG is a possibility after angiography, a shorter-acting inhibitor (eptifibatide, tirofiban) may impart a lower perioperative risk of bleeding than abciximab. For patients with ST segment elevation acute MI who are treated with fibrinolysis, a GPIIb/IIIa inhibitor added to reduced-dose t-PA (e.g., half-dose t-PA) improves early coronary patency. However, improved survival has not been shown, and the risk of serious bleeding (including intracerebral hemorrhage) is increased. [6] [7]

Antithrombin Therapy

 

Unfractionated Heparin

On injection, heparin complexes with antithrombin III. The heparin–antithrombin III complex inactivates circulating thrombin and, less effectively, factor X. Clot-bound thrombin is resistant. Evidence for the contribution of heparin to antithrombotic regimens is mostly observational, indirect, or inferential ( Chapter 35 ).

Heparin is recommended for patients undergoing primary PCI and for those receiving fibrin-specific lytic agents (i.e., alteplase, reteplase, or tenecteplase; see Fig. 72-3 and Table 72-4 ). It is also recommended with intravenous streptokinase or anistreplase for patients at high risk for systemic emboli (e.g., large or anterior acute MI with LV thrombus, atrial fibrillation [AF]). Low-dose subcutaneous heparin (7500 to 12,500 U twice daily) was recommended in the past for patients with acute MI, to prevent deep vein thrombosis in the absence of intravenous heparin; however, current early reambulation after acute MI and routine use of aspirin have made the utility of routine subcutaneous heparin uncertain.

Excessive bleeding when heparin is used in combination with antithrombotic regimens has led to reductions in heparin doses, with improved safety. When given with a fibrinolytic, intravenous heparin is begun concurrently and is given for 48 hours. Currently recommended doses include a 60 U/kg bolus (maximum, 4000 U), followed initially by a 12 U/kg/hour infusion (maximum, 1000 U/hour), with adjustment after 3 hours based on activated partial thromboplastin time (target of 50 to 70 seconds, 1.5 to 2 times control). Experimental regimens including a GPIIb/IIIa inhibitor and a fibrinolytic agent have used even lower heparin doses. During primary PCI, high-dose heparin is used (activated clotting time, 300 to 350 seconds). Given together with a GPIIb/IIIa inhibitor during PCI, the dose of heparin is adjusted to a lower activated clotting time range (150 to 300 seconds).

Low-Molecular-Weight Heparins and Factor Xa Inhibitors

LMWHs have enhanced inhibitory activity for factor Xa ( Chapter 35 ). They also have more reliable bioavailability and longer durations of action, thus permitting subcutaneous administration once or twice daily in fixed (weight-adjusted) doses. LMWHs have been extensively tested for the non–ST segment elevation acute coronary syndromes and for prophylaxis of deep vein thrombosis. Evidence suggests that in patients with ST segment elevation acute MI who are treated with fibrinolytic therapy, LMWH can improve angiographic outcomes and can reduce reinfarction rates by 25% and mortality by about 10%. For example, in the largest trial of 20,506 patients, enoxaparin, given throughout the index hospitalization, reduced the composite outcome of death or nonfatal reinfarction at 30 days from 12.0 to 9.9%, compared with unfractionated heparin.[14] Enoxaparin may thus be preferred over unfractionated heparin as an antithrombotic agent for ST segment elevation acute MI in most patients treated with a fibrinolysis strategy. When used as ancillary therapy with a fibrinolytic agent, enoxaparin may be given to patients less than 75 years old who do not have renal insufficiency as a 30-mg intravenous bolus, followed by 1 mg/kg subcutaneously twice daily until hospital discharge, and to those 75 years and older as 0.75 mg/kg subcutaneously twice daily without a bolus.

Selective factor Xa inhibitors (e.g., fondaparinux, 2.5 mg once daily for up to 8 days during index hospitalization) reduce the end point of death or reinfarction at 30 days by 18 to 23% independent of heparin use in patients who receive fibrinolysis or no recanalization therapy but have no benefit in patients who have undergone PCI.[15] These results suggest that fondaparinux may be a preferred alternative to unfractionated heparin or no heparin (e.g., in patients who present later, in patients treated with streptokinase) in patients with ST segment elevation MI who are not undergoing a primary PCI strategy.

Direct Antithrombins

Direct-acting antithrombins, such as hirudin and its analogues (e.g., bivalirudin), do not require antithrombin III for activity; they inhibit clot-bound heparin and are not neutralized by plasma proteins ( Chapter 35 ). Unlike heparin, hirudins do not induce thrombocytopenia. Early studies using surrogate end points were promising. However, bleeding and optimal dose administration were problematic, and major clinical trials did not show a survival advantage. Bivalirudin is clinically available and is considered a useful alternative to unfractionated heparin for patients with known heparin-induced thrombocytopenia who are receiving streptokinase. Bivalirudin has had limited experience as an adjunct to primary PCI.

Other Pharmacologic Therapies

 

Nitrates

Nitroglycerin and other organic nitrates (isosorbide dinitrate and isosorbide mononitrate) induce vascular smooth muscle relaxation by generating vascular endothelial nitric oxide. The resulting vasodilation of veins and peripheral and coronary arteries can beneficially reduce excessive cardiac preload and afterload, increase coronary caliber in responsive areas of stenosis, reverse distal small coronary arterial vasoconstriction, improve coronary collateral flow to ischemic myocardium, and inhibit platelet aggregation in acute MI ( Chapter 70 ). The results are improved oxygen delivery and reduced oxygen consumption. Potential clinical benefits include relief of ischemia, limitation of infarct size, prevention of dilative remodeling, control of hypertension (afterload), and relief of congestion (preload).

In the era before reperfusion, nitrates appeared to confer a mortality benefit in acute MI. In the context of fibrinolytic therapy and aspirin, however, mortality benefits are modest, with a relative survival benefit of about four lives saved per 1000 treated.[16] Nitroglycerin is definitely recommended for the first 24 to 48 hours for patients with acute MI and pulmonary congestion, large anterior MI, persistent ischemia, or hypertension. For other patients without contraindications, nitrates are possibly useful.

When nitrates are clearly indicated early in acute MI, intravenous nitroglycerin is preferred. Intravenous nitroglycerin may begin with a bolus injection of 12.5 to 25 μg followed by an infusion of 10 to 20 μg/minute. The infusion dose is increased by 5 to 10 μg every 5 to 10 minutes up to about 200 μg/minute during hemodynamic monitoring until clinical symptoms are controlled or blood pressure targets are reached (blood pressure decreased by 10% in normotensive patients or by 30% in hypertensive patients but not less than 80 mm Hg mean or 90 mm Hg systolic).

β-Blockers

β-Adrenoceptor blockers reduce heart rate, blood pressure, and myocardial contractility, and they stabilize the heart electrically. These actions provide clinical benefit to most patients with acute MI by limiting myocardial oxygen consumption, relieving ischemia, reducing infarct size, and preventing serious arrhythmias.

In the era before fibrinolysis, a meta-analysis of 28 randomized trials involving 27,500 patients found a modest early benefit on mortality (14% odds reduction), cardiac arrest (16% reduction), and nonfatal reinfarction (19% reduction). In patients with acute MI who are receiving fibrinolytic therapy, immediate (intravenous then oral) metoprolol reduces recurrent ischemic events and reinfarction compared with deferred oral therapy. Further experience has shown that moderate to severe heart failure should preclude the early use of intravenous β-blockers, but not predischarge and outpatient oral therapy initiated in small doses and carefully adjusted once stability is achieved.

Early (first-day) initiation of oral β-blockade is generally recommended for patients with acute MI who have ongoing or recurrent ischemic pain or tachyarrhythmias if they do not have heart failure or other contraindications (asthma, hypotension, severe bradycardia), regardless of concomitant fibrinolysis or PCI. Intravenous initiation (e.g., metoprolol, 5 mg over 2 minutes to a total of 15 mg over 10 to 15 minutes, or atenolol, 2.5 to 5 mg over 2 minutes to a total of 10 mg over 10 to 15 minutes) is reasonable in the absence of contraindications if an indication for immediate therapy is present, such as a tachyarrhythmia or hypertension. However, the routine, short-term initiation of intravenous β-blockade should be avoided because it is not associated with benefit and, indeed, causes a small excess of early death from cardiogenic shock, primarily in patients with preexisting heart failure.[12] All patients without contraindications or intolerance to β-blocker therapy should receive oral doses, titrated to tolerance or goal (e.g., metoprolol, 25 to 100 mg twice daily, atenolol, 50 to 100 mg/day, or carvedilol, 6.25 to 25 mg twice daily). β-Blocker therapy should begin promptly, in the absence of heart failure and if not otherwise contraindicated, and should be continued during the in-hospital convalescent phase of ST segment elevation MI and beyond.

Renin-Angiotensin-Aldosterone System Inhibitors

The renin-angiotensin-aldosterone system is activated in acute MI and heart failure. Use of an ACE inhibitor has been shown to improve remodeling after acute MI (especially after large anterior MI). ACE inhibitors also have demonstrated efficacy in heart failure, wherein they prevent disease progression, hospitalization, and death ( Chapter 58 ). A meta-analysis of three major trials and 11 smaller ones involving more than 100,000 patients showed an overall mortality reduction of 6.5%, representing about five lives saved per 1000 patients treated. Benefit is concentrated and greater in higher-risk patients with large or anterior MI and with LV dysfunction or heart failure,[16] although patients with lesser degrees of LV dysfunction and only moderate cardiovascular risk can also benefit in the long term.[17]

Oral ACE inhibitor therapy should begin within the first 24 hours in patients with anterior infarction, pulmonary congestion, or low ejection fraction (<0.40) in the absence of hypotension (systolic pressure <100 mm Hg or >30 mm Hg less than usual baseline) or known contraindications. An angiotensin receptor blocker (ARB) should be given to otherwise qualifying patients who are intolerant of ACE inhibitors. An ACE inhibitor or an ARB also should be considered for other patients with ST segment elevation MI, especially those with a relative indication (e.g., hypertension, diabetes, or mild renal insufficiency), with the expectation of a smaller but worthwhile benefit. All patients without contraindications or intolerance to initial ACE inhibitor or ARB therapy also should receive these drugs during the in-hospital convalescent phase. ACE inhibitor therapy should begin with low oral doses and should be progressively adjusted to full dose as tolerated. For example, the short-acting agent captopril may be started in a dose of 6.25 mg or less and adjusted over 1 to 2 days to 50 mg twice daily. Before discharge, a transition may be made in graded dose schedules to longer-acting agents such as ramipril (2.5 mg titrated to 10 mg/day), lisinopril (2.5 to 5 mg titrated to 10 mg/day), or enalapril (2.5 mg, titrated to up to 20 mg twice daily). In patients who cannot tolerate ACE inhibitors (e.g., because of cough), graded doses of an ARB may be substituted (e.g., valsartan, 80 to 160 mg twice daily, or losartan, 50 to 100 mg/day).

Selective aldosterone receptor blockade with eplerenone (25 to 50 mg/day) reduces total and cardiovascular mortality (including sudden death) as well as cardiovascular hospitalizations in post-MI who have an ejection fraction of 0.40 or less and heart failure or diabetes and who are already receiving other optimal therapies, including ACE inhibitors.[18] Spironolactone also benefits patients with advanced heart failure, including those in whom it is caused by a remote MI. Hence, aldosterone receptor blockade should be added to other standard therapies during convalescence in patients with these characteristics. Hyperkalemia, which is the most common side effect, requires monitoring ( Chapter 58 ).

Antiarrhythmic Agents

Antiarrhythmic therapy is reserved for treatment of, or short-term prevention after, symptomatic or life-threatening ventricular arrhythmias, together with other appropriate measures (cardioversion, treatment of ischemia and metabolic disturbances). An implantable cardioverter-defibrillator (ICD) is indicated in patients with VF or hemodynamically significant sustained ventricular tachycardia (VT) occurring more than 2 days after ST segment elevation MI or in patients with inducible VT or VF at electrophysiologic study and a depressed ejection fraction (≤0.40) at least 1 month after ST segment elevation MI ( Chapter 64 ). An ICD also may be considered for patients with severe LV dysfunction (ejection fraction ≤0.30) at least 1 month after ST segment elevation MI and 3 months after CABG without spontaneous or induced VT or VF[21] ( Chapter 65 ).

Inotropes

Digitalis and intravenous inotropes can increase oxygen demand, provoke serious arrhythmias, and extend infarction. Current recommendations support the use of digoxin in selected patients recovering from acute MI who develop supraventricular tachyarrhythmias (e.g., AF) or heart failure refractory to ACE inhibitors and diuretics. Intravenous inotropes (e.g., dobutamine, dopamine, milrinone, and norepinephrine) are reserved for temporary support of patients with hypotension and circulatory failure that is unresponsive to volume replacement ( Chapters 58 and 108 ). Other treatment measures for these patients (e.g., intra-aortic balloon pump, early revascularization) are discussed herein.

Lipid-Lowering Therapy

Lipid lowering, particularly with hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins), reduces event rates in patients with coronary disease, and a more aggressive approach appears to provide superior benefits[19] ( Chapter 217 ). A fasting lipid profile should be obtained on admission, so a statin can be started promptly in the hospital with a low-density lipoprotein cholesterol goal of less than 70 mg/dL.

Other Medical Therapies

Calcium channel blockers, although anti-ischemic, also are negatively inotropic and have not been shown to reduce mortality after ST segment elevation acute MI. With certain agents and in specific groups of patient, harm has been suggested. For example, short-acting nifedipine has been reported to cause reflex sympathetic activation, tachycardia, hypotension, and increased mortality. Verapamil or diltiazem (heart rate–slowing drugs) may be given to patients in whom β-blockers are ineffective or contraindicated for control of rapid ventricular response with AF or relief of ongoing ischemia in the absence of heart failure, LV dysfunction, or atrioventricular (AV) block.

Magnesium is of no benefit in patients with acute MI who are treated with fibrinolysis. Supplementation is recommended if the magnesium level is lower than normal or in patients with torsades de pointes–type VT associated with a prolonged QT interval.

Glucose-insulin-potassium affords no benefit on mortality, cardiac arrest, or cardiogenic shock when this combination is added to usual care in patients with acute ST segment elevation MI.[20] However, glucose control, using an insulin infusion to normalize high blood glucose, is recommended for patients in the acute phase of ST segment elevation MI, especially for those with a complicated course. After the acute phase, individualized treatment is indicated using agents or combinations of agents that best achieve glycemic control and are well tolerated ( Chapters 247 and 248 ).

Management of Complications

Recurrent Chest Pain

When chest pain recurs after acute MI, the diagnostic possibilities include post-infarction ischemia, pericarditis, infarct extension, and infarct expansion. Characterization of the pain, physical examination, ECG, echocardiography, and cardiac marker determinations assist in differential diagnosis. CK-MB often discriminates reinfarction better than cTnI or cTnT.

Post-infarction angina developing spontaneously during hospitalization for acute MI despite medical therapy usually merits coronary angiography. β-blockers (IV, then orally) and nitroglycerin (IV, then orally or topically) are recommended medical therapies. Pain with recurrent ST segment elevation or recurrent elevation of cardiac markers may be treated with (re)administration of t-PA or, possibly, a GPIIb/IIIa inhibitor, together with nitroglycerin, β-blockade, and heparin. Streptokinase, which induces neutralizing antibodies, generally should not be reutilized after the first few days. If facilities for angiography, PCI, and surgery are available, an invasive approach is recommended to relieve discomfort occurring hours to days after an acute MI that is associated with objective signs of ischemia. Radionuclide testing (e.g., adenosine thallium) can be helpful in patients with discomfort that is transient or of uncertain ischemic origin.

Infarct expansion implies circumferential slippage with thinning of the infarcted myocardium. Infarct expansion can be associated with chest pain but without recurrent elevation of cardiac markers. Expansive remodeling can lead to an LV aneurysm. The risk of remodeling is reduced with early recanalization therapy and administration of ACE inhibitors.

Acute pericarditis most commonly manifests on days 2 to 4 in association with large, “transmural” infarctions causing pericardial inflammation. Occasionally, hemorrhagic effusion with tamponade develops; thus, excessive anticoagulation should be avoided. Pericarditis developing later (2 to 10 weeks) after acute MI could represent Dressler’s syndrome, which is believed to be immune mediated. The incidence of this post-MI syndrome has decreased dramatically in the modern reperfusion era. Pericardial pain is treated with aspirin (preferred, especially in the acute setting) or other nonsteroidal agents (e.g., indomethacin); patients with severe symptoms could require corticosteroids.

Rhythm Disturbances

 

Ventricular Arrhythmias

Acute MI is associated with a proarrhythmic environment that includes heterogeneous myocardial ischemia, heightened adrenergic tone, intracellular electrolyte disturbance, lipolysis and free fatty acid production, and oxygen free radical production on recanalization ( Chapters 62 and 64 ). Arrhythmias thus are common early during acute MI. Micro-re-entry is likely the most common electrophysiologic mechanism of early phase arrhythmias, although enhanced automaticity and triggered activity also are observed in experimental models.

Primary VF, the most serious MI-related arrhythmia, contributes importantly to mortality within the first 24 hours. It occurs with an incidence of 3 to 5% during the first 4 hours and then declines rapidly over 24 to 48 hours. Polymorphic VT and, less commonly, monomorphic VT are associated life-threatening arrhythmias that can occur in this setting. Clinical features (including warning arrhythmias) are not adequately specific or sensitive to identify patients at risk for sustained ventricular tachyarrhythmias, so all patients should be continuously monitored. Prophylactic lidocaine, which reduces primary VF but does not decrease (and may increase) mortality, is not recommended. Primary VF is associated with a higher rate of in-hospital mortality, but long-term prognosis is unaffected in survivors.

Accelerated idioventricular rhythm (60 to 100 beats per minute) frequently occurs within the first 12 hours and is generally benign (i.e., is not a risk factor for VF). Indeed, accelerated idioventricular rhythm frequently heralds recanalization after fibrinolytic therapy. Antiarrhythmic therapy is not indicated except for sustained, hemodynamically compromising accelerated idioventricular rhythm.

Late VF, which is defined as VF developing more than 48 hours after the onset of acute MI, often occurs in patients with larger MIs or heart failure, portends a worse prognosis for survival, and is an indication for aggressive measures (e.g., consideration of an ICD). Monomorphic VT resulting from re-entry in the context of a recent or old MI also can appear late after MI, and patients may require long-term therapy (e.g., an ICD).

Electrical cardioversion is required for VF and sustained polymorphic VT (unsynchronized shock) and for sustained monomorphic VT that causes hemodynamic compromise (synchronized shock) ( Chapters 62 and 65 ). Brief intravenous sedation is given to conscious, “stable” patients. For slower, stable VT and nonsustained VT requiring therapy, intravenous amiodarone or intravenous lidocaine is commonly recommended. After episodes of VT/VF, infusions of antiarrhythmic drugs may be given for 6 to 24 hours; the ongoing risk of arrhythmia then is reassessed. Electrolyte and acid-base imbalance and hypoxia should be corrected. β-Blockade is useful in patients with frequent polymorphic VT associated with adrenergic activation (“electrical storm”). Additional, aggressive measures should be considered to reduce cardiac ischemia (e.g., emergency PCI or CABG) and LV dysfunction (intra-aortic balloon pump) in patients with recurrent polymorphic VT despite the use of β-blockers and/or amiodarone.

Patients with sustained VT or VF occurring late in the hospital course should be considered for long-term prevention and therapy. An ICD provides greater survival benefit than antiarrhythmic drugs in patients with ventricular arrhythmias and can improve survival after acute MI for patients with an ejection fraction of 30% or less, regardless of their rhythm status.[21]

Atrial Fibrillation and other Supraventricular Tachyarrhythmias

AF occurs in up to 10 to 15% of patients after an acute MI, usually within the first 24 hours ( Chapter 63 ). The incidence of atrial flutter or another supraventricular tachycardia is much lower. The risk of AF increases with age, larger MIs, heart failure, pericarditis, atrial infarction, hypokalemia, hypomagnesemia, hypoxia, pulmonary disease, and hyperadrenergic states. The incidence of AF is reduced by effective early recanalization. Hemodynamic compromise with rapid rates and systemic embolism (in ∼2%) are adverse consequences of AF. Systemic embolism can occur on the first day, so prompt anticoagulation with heparin is indicated.

Recommendations for management of AF include the following: electrical cardioversion for patients with severe hemodynamic compromise or ischemia; rate control with intravenous digoxin for patients with ventricular dysfunction (i.e., give 1.0 mg, one half initially and one half in 4 hours), with an intravenous β-blocker (e.g., metoprolol, 5 mg over 2 minutes to a total of 15 mg over 10 to 15 minutes) in those without clinical ventricular dysfunction, or with intravenous diltiazem or verapamil in hemodynamically compensated patients with a contraindication to β-blockers; and anticoagulation with heparin (or LMWH). Amiodarone, which is generally reserved for patients with or at high risk for recurrence, may be continued for 6 weeks if sinus rhythm is restored and maintained.

Bradycardias, Conduction Delays, and Heart Block

Sinus and AV nodal dysfunction are common during acute MI. Sinus bradycardia, a result of increased parasympathetic tone often in association with inferior acute MI, occurs in 30 to 40% of patients. Sinus bradycardia is particularly common during the first hour of acute MI and with recanalization of the right coronary artery (Bezold-Jarisch reflex). Vagally mediated AV block also can occur in this setting. Anticholinergic therapy (atropine, 0.5 to 1.5 mg IV) is indicated for symptomatic sinus bradycardia (heart rate generally <50 beats per minute associated with hypotension, ischemia, or escape ventricular arrhythmia), including ventricular asystole, and symptomatic second-degree (Wenckebach) or third-degree block at the AV nodal level (narrow QRS complex escape rhythm). Atropine is not indicated and can worsen infranodal AV block (anterior MI, wide complex escape rhythm).

New-onset infranodal AV block and intraventricular conduction delays or BBBs predict substantially increased in-hospital mortality. Fortunately, their incidence has declined in the recanalization era (from 10 to 20% to ∼4%). Mortality is related more to extensive myocardial damage than to heart block itself, so cardiac pacing only modestly improves survival. Prophylactic placement of multifunctional patch electrodes, which allow for immediate transcutaneous pacing (and defibrillation) if needed, is indicated for symptomatic sinus bradycardia refractory to drug therapy, infranodal second-degree (Mobitz II) or third-degree AV block, and new or indeterminate-age bifascicular (LBBB; RBBB with left anterior or left posterior fascicular block) or trifascicular block (bilateral or alternating BBB [any age], BBB with first-degree AV block). Transcutaneous pacing is uncomfortable and is intended for prophylactic and temporary use only. In patients who require a pacemaker to maintain a rhythm or who are at very high risk (>30%) of requiring pacing (including patients with alternating, bilateral BBB, with new or indeterminate-age bifascicular block with first-degree AV block, and with infranodal second-degree AV block) should have a transvenous pacing electrode inserted as soon as possible.

Indications for permanent pacing after acute MI depend on the prognosis of the AV block and not solely on symptoms. Class I indications include even transient second- or third-degree AV block in association with BBB and symptomatic AV block at any level. Advanced block at the AV nodal level (Wenckebach) rarely is persistent or symptomatic enough to warrant permanent pacing.

Heart Failure and Other Low-Output States

Cardiac pump failure is the leading cause of circulatory failure and in-hospital death from acute MI. Manifestations of circulatory failure can include a weak pulse, low blood pressure, cool extremities, a third heart sound, pulmonary congestion, oliguria, and obtundation. However, several distinct mechanisms, hemodynamic patterns, and clinical syndromes characterize the spectrum of circulatory failure in acute MI. Each requires a specific approach to diagnosis, monitoring, and therapy (see Table 72-3 ).

Left Ventricular Dysfunction

The degree of LV dysfunction correlates well with the extent of acute ischemia or infarction. Hemodynamic compromise becomes evident when impairment involves 20 to 25% of the left ventricle, and cardiogenic shock or death occurs with involvement of 40% or more ( Chapter 108 ). Pulmonary congestion and S3 and S4 gallops are the most common physical findings. Early recanalization (with fibrinolytic agents, PCI, or CABG) is the most effective therapy to reduce infarct size, ventricular dysfunction, and associated heart failure. Medical treatment of heart failure related to the ventricular dysfunction of acute MI is otherwise generally similar to that of heart failure in other settings ( Chapter 58 ) and includes adequate oxygenation and diuresis (begun early, blood pressure permitting, and continued on a long-term basis if needed). Morphine sulfate (i.e., 2 to 4 mg IV, with increments as needed after 5 to 15 minutes or more) is useful for patients with pulmonary congestion. Nitroglycerin also reduces preload and effectively relieves congestive symptoms. Titrated oral ACE inhibitor therapy (e.g., captopril, incremented from 3.125 to 6.25 mg three times daily to 50 mg twice daily as tolerated) also is indicated for heart failure and pulmonary edema unless excessive hypotension (systolic blood pressure <100 mm Hg) is present. Treatment can be begun sublingually (0.4 mg every 5 minutes three times), and then the transition can be made to intravenous therapy (initially 5 to 10 μg/minute, incrementing by 5 to 20 μg/minute until symptoms are relieved or until mean arterial pressure falls by 10% in normotensive or 30% in hypertensive patients but not <90 mm Hg or >30 mm Hg lower than baseline). Intravenous vasodilator therapy to reduce preload and afterload, inotropic support, and intra-aortic balloon counterpulsation (IABP), together with urgent recanalization, are indicated in cardiogenic shock ( Chapter 108 ).

Volume Depletion

Relative or absolute hypovolemia is a frequent cause of hypotension and circulatory failure and is easily corrected if it is recognized and treated promptly. Poor hydration, vomiting, diuresis, and disease- or drug-induced peripheral vasodilation can contribute to this condition. Hypovolemia should be identified and corrected with intravenous fluids before more aggressive therapies are considered. An empirical fluid challenge may be tried in the appropriate clinical setting (e.g., for hypotension in the absence of congestion, for inferior or RV infarction, and for hypervagotonia). If filling pressures are measured, cautious fluid administration to a pulmonary capillary wedge pressure of up to about 18 mm Hg may optimize cardiac output and blood pressure without impairing oxygenation.

Right Ventricular Infarction

RV ischemia and infarction occur with proximal occlusion of the right coronary artery (before the take-off of the RV branches). Ten to 15% of inferior acute ST segment elevation MIs show classic hemodynamic features, and these patients form the highest risk subgroup for morbidity and mortality (25 to 30% versus <6% hospital mortality). Improvement in RV function commonly occurs over time, a finding suggesting reversal of ischemic stunning and other favorable accommodations, if short-term management is successful.

Hypotension in patients with clear lung fields and elevated jugular venous pressure in the setting of inferior or inferoposterior acute MI should raise the suspicion of RV infarction. Kussmaul’s sign (distention of the jugular vein on inspiration) is relatively specific and sensitive in this setting. Right-sided ECG leads show ST segment elevation, particularly in V4R ( Chapter 52 ), in the first 24 hours of RV infarction. Echocardiography is helpful in confirming the diagnosis (RV dilation and dysfunction are observed). When right-sided heart pressures are measured, a right atrial pressure of 10 mm Hg or greater and 80% or more of the pulmonary capillary wedge pressure are relatively sensitive and specific for RV ischemic dysfunction.

Management of RV infarction consists of early maintenance of RV preload with intravenous fluids, reduction of RV afterload (i.e., afterload-only reducing drugs as for LV dysfunction; consider intra-aortic balloon pump), early recanalization, short-term inotropic support if needed, and avoidance of venodilators (e.g., nitrates) and diuretics used for LV failure (they may cause marked hypotension). Volume loading with normal saline solution alone is often effective. If the cardiac output fails to improve after 0.5 to 1 L fluid, inotropic support with intravenous dobutamine (starting at 2 μg/kg/minute and titrating to hemodynamic effect or tolerance, up to 20 μg/kg/minute) is recommended. High-grade AV block is common, and restoration of AV synchrony with temporary AV sequential pacing can lead to substantial improvement in cardiac output. The onset of AF (in up to one third of RV infarcts) can cause severe hemodynamic compromise requiring prompt cardioversion. Early coronary recanalization with fibrinolysis or PCI markedly improves outcomes.

Cardiogenic Shock

Cardiogenic shock ( Chapter 108 ) is a form of severe LV failure characterized by marked hypotension (systolic pressures <80 mm Hg) and reductions in cardiac index (to <1.8 L/minute/m2) despite high LV filling pressure (pulmonary capillary wedge pressure >18 mm Hg). The cause is loss of a critical functional mass (>40%) of the left ventricle. Cardiogenic shock is associated with mortality rates of more than 70 to 80% despite aggressive medical therapy. Risk factors include age, large (usually anterior) acute MI, previous MI, and diabetes. In patients with suspected shock, hemodynamic monitoring and IABP are indicated. Intubation often is necessary. Vasopressors are often needed. Early urgent mechanical revascularization (PCI or CABG), if feasible, affords the best chance for survival, especially in patients less than 75 years old[9] ( Chapter 108 ).

IABP remains useful for patients with medically refractory unstable ischemic syndromes and for cardiogenic shock. The deflated balloon catheter is introduced into the femoral artery and is advanced into the aorta. The ECG triggers balloon inflation during early diastole, thereby augmenting coronary blood flow; deflation then occurs in early systole, thereby reducing LV afterload. Primary IABP therapy for cardiogenic shock associated with acute MI provides temporary stabilization but does not reduce mortality (>80%). IABP is currently recommended in the setting of acute MI as a stabilizing measure for patients undergoing angiography and subsequent PCI or surgery for (1) cardiogenic shock, (2) mechanical complications (acute mitral regurgitation, acute ventricular septal defect), (3) refractory post-MI ischemia, or (4) recurrent intractable VT or VF associated with hemodynamic instability. IABP is not useful in patients with significant aortic insufficiency or severe peripheral vascular disease.

Mechanical Complications

Mechanical complications usually occur within the first weeks and account for approximately 15% of MI-related deaths. Such complications include acute mitral valve regurgitation, ventricular septal defect, free wall rupture, and LV aneurysm. Suspicion and investigation of a mechanical defect should be prompted by a new murmur and/or sudden, progressive hemodynamic deterioration with pulmonary edema and/or a low output state. Transthoracic or transesophageal Doppler echocardiography usually establishes the diagnosis. A balloon flotation catheter can be helpful in confirming the diagnosis. Arteriography to identify correctable coronary artery disease is warranted in most cases. Surgical consultation should be requested promptly, and urgent repair is usually indicated.

Acute mitral valve regurgitation ( Chapter 75 ) results from infarct-related rupture or dysfunction of a papillary muscle. Total rupture leads to death in 75% of patients within 24 hours. Medical therapy is initiated with nitroprusside (beginning with 0.1 μg/kg/minute and titrating upward every 3 to 5 minutes to the desired effect, as tolerated by blood pressure response, up to 5 μg/kg/minute), to lower preload and to improve peripheral perfusion, and inotropic support (e.g., dobutamine, titrated from 2 up to 20 μg/kg/minute in normotensive patients; dopamine, titrated from 2 up to 20 μg/kg/minute in hypotensive patients; or combined dobutamine and dopamine). An IABP is used to maintain hemodynamic stability. Emergency surgical repair (if possible) or replacement is then undertaken. Surgery is associated with high mortality (≥25 to 50%), but it leads to better functional and survival outcomes than medical therapy alone.

Post-infarction septal rupture with ventricular septal defect, which occurs with increased frequency in elderly patients, in patients with hypertension, and possibly after fibrinolysis, also warrants urgent surgical repair. Because a small post-MI ventricular septal defect can suddenly enlarge and cause rapid hemodynamic collapse, all septal perforations should be repaired. On diagnosis, invasive monitoring is recommended, together with vasodilators (e.g., nitroprusside, initially 0.1 μg/kg/minute, titrated upward every 3 to 5 minutes to desired effect, as tolerated by blood pressure response, up to 5 μg/kg/minute) and, if needed, judicious use of inotropic agents (e.g., dobutamine, titrated from 2 up to 20 μg/kg/minute in normotensive patients; dopamine, titrated from 2 up to 20 μg/kg/minute in hypotensive patients; or combined dobutamine and dopamine). An IABP should be inserted, a surgical consultation promptly obtained, and surgical repair undertaken as soon as feasible.

LV free wall rupture usually causes acute cardiac tamponade with sudden death. In a small percentage of cases, however, resealing or localized containment (“pseudoaneurysm”) can allow medical stabilization, usually with inotropic support and/or an IABP, followed by emergency surgical repair.

An LV aneurysm can develop after a large, usually anterior, acute MI. If refractory heart failure, VT, or systemic embolization occurs despite medical therapy and PCI, aneurysmectomy with CABG is indicated.

Thromboembolic Complications

Thromboembolism has been described in approximately 10% of clinical series and 20% of autopsy series, a finding suggesting a high rate of undiagnosed events. Thromboembolism contributed to up to 25% of hospital deaths from acute MI in the past, but the incidence has declined in the recanalization era in association with greater use of antithrombotics, reductions of infarct size, and earlier ambulation. Systemic arterial emboli (including cerebrovascular emboli) typically arise from an LV mural thrombus, whereas pulmonary emboli commonly arise from thrombi in leg veins. Arterial embolism can cause dramatic clinical events, such as hemiparesis, loss of a pulse, ischemic bowel, or sudden hypertension, depending on the regional circulation involved.

Mural thrombosis with embolism typically occurs in the setting of a large (especially anterior) ST segment elevation acute MI and heart failure. The risk of embolism is particularly high when a mural thrombus is detected by echocardiography. Thus, in patients with anterior ST segment elevation acute MI and in other high-risk patients, echocardiography should be performed during hospitalization; if results are positive, anticoagulation should be started (with an antithrombin), if not already initiated, and continued (with warfarin) for 6 months.

Deep vein thrombosis can be prevented by lower extremity compression therapy, by limiting the duration of bedrest, and by the use of subcutaneous unfractionated heparin or LMWH (in patients at risk not receiving intravenous heparin) until patients are fully ambulatory ( Chapter 81 ). Patients with pulmonary embolism are treated with intravenous heparin, then oral anticoagulation for 6 months ( Chapter 99 ).

Risk Stratification after Myocardial Infarction

The goal of risk stratification before and early after discharge for acute MI is to assess ventricular and clinical function, latent ischemia, and arrhythmic risk, to use this information for patient education and prognostic assessment, and to guide therapeutic strategies (see Fig. 72-3 ).

Cardiac Catheterization and Noninvasive Stress Testing

Risk stratification generally involves functional assessment by one of three strategies: cardiac catheterization, submaximal exercise stress ECG before discharge (at 4 to 6 days), or symptom-limited stress testing at 2 to 6 weeks after discharge. Many or most patients with ST segment elevation acute MI undergo invasive evaluation for primary PCI or after fibrinolytic therapy. Catheterization generally is performed during hospitalization for patients at high risk. In others, predischarge submaximal exercise testing (to peak heart rate of 120 to 130 beats per minute or 70% of the predicted maximum) appears safe when it is performed in patients who are ambulating without symptoms; it should be avoided within 2 to 3 days of acute MI and in patients with unstable post-MI angina, uncompensated heart failure, or serious cardiac arrhythmias. Alternatively or in addition, patients may undergo symptom-limited stress testing at 2 to 6 weeks before they return to work or resume other increased physical activities. Abnormal test results include not only ST segment depression but also low functional capacity, exertional hypotension, and serious arrhythmias. Patients with positive test results should be considered for coronary angiography.

The sensitivity of stress testing can be augmented with radionuclide perfusion imaging (thallium-201 and/or technetium-99m-sestamibi; Chapter 54 ) or echocardiography ( Chapter 53 ). Supplemental imaging also can quantify the LV ejection fraction and size the area of infarction and/or ischemia (e.g., by cardiac magnetic resonance imaging; Chapter 55 ). For patients taking digoxin or for those with ST segment changes that preclude accurate ECG interpretation (e.g., baseline LBBB or LV hypertrophy), an imaging study is recommended with initial stress testing. In others, an imaging study may be performed selectively for those in whom the exercise ECG test result is positive or equivocal. For patients unable to exercise, pharmacologic stress testing can be performed using adenosine or dipyridamole scintigraphy or dobutamine echocardiography.

Electrocardiographic Monitoring

Modern telemetry systems capture complete rhythm information during hospital observations and allow for identification of patients with serious arrhythmias, so routine 24- to 48-hour ambulatory ECG (Holter) monitoring before or after hospital discharge is not recommended. Sustained VT or VF occurring late during hospitalization or provoked during electrophysiologic study in patients with nonsustained VT on monitoring are candidates for an ICD, especially if the ejection fraction is less than 40% ( Fig. 72-4 ) ( Chapters 64 and 65 ). Prophylactic ICD placement prevents sudden death after acute MI for patients with severely depressed function (ejection fraction ≤0.30) regardless of the rhythm status.[21]

Secondary Prevention, Patient Education, and Rehabilitation

Secondary Prevention

Advances in secondary prevention have resulted in increasingly effective measures to reduce recurrent MI and cardiovascular death. Secondary prevention should be conscientiously applied after acute MI ( Table 72-8 ).

A fasting lipid profile is recommended on admission, and lipid-lowering therapy, typically with a statin, is begun in the hospital, generally with an LDL cholesterol goal of less than 70 mg/dL ( Chapter 217 ). Continued smoking doubles the subsequent mortality risk after acute MI, and smoking cessation reduces the risk of reinfarction and death within 1 year ( Chapter 30 ). An individualized smoking cessation plan should be formulated, including pharmacologic aids (nicotine gum and patches, bupropion).

Antiplatelet therapy ( Chapter 35 ; Fig. 72-5 ) should consist of aspirin, given on a long-term basis to all patients without contraindications (maintenance dose, 75 to 162 mg/day). Clopidogrel (75 mg/day) is given to patients who received PCI with stenting and is also appropriate for others at higher risk for recurrent vascular events. Therapy is recommended for a minimum of 1 month after a bare metal stent, for at least 3 months for sirolimus-eluting stents, and for at least 6 months for paclitaxel-eluting stents. If patients are not at high risk of bleeding, therapy is continued for up to 1 year or more.

Anticoagulant therapy (i.e., warfarin, with an international normalized ratio goal of 2.0 to 3.0) is indicated after acute MI for patients unable to take antiplatelet therapy (aspirin or clopidogrel), for those with persistent or paroxysmal AF, for those with LV thrombus, and for those who have suffered a systemic or pulmonary embolism. Anticoagulants also may be considered for patients with extensive wall motion abnormalities and markedly depressed ejection fraction with or without heart failure. Data on the benefit of warfarin instead of or in addition to aspirin are inconclusive.

ACE inhibitor therapy can prevent adverse myocardial remodeling after acute MI and can reduce heart failure and death; it is clearly indicated for long-term use in patients with anterior acute MI or an LV ejection fraction less than 40%. ACE inhibitors also reduce recurrent MI in higher-risk patients with an ejection fraction greater than 40%. In contrast, ACE inhibition, when added to other contemporary therapies, provides little additional benefit in reducing cardiovascular events in patients who have stable coronary disease and a low risk (<5%/year) of a coronary event. These data suggest a rationale for the long-term use of ACE inhibitors (e.g., ramipril, 2.5 mg titrated to 10 mg/day, or lisinopril, 2.5 to 5 mg titrated to 10 mg/day) in all patients after MI, except perhaps those at lowest risk (i.e., without heart failure, hypertension, glucose intolerance, or reduced ejection fraction). An ARB (e.g., valsartan, 80 to 160 mg twice daily, or losartan, 50 to 100 mg/day) should be substituted in patients who cannot tolerate an ACE inhibitor; in patients with advanced heart failure, both an ACE inhibitor and an ARB may be complementary ( Chapter 58 ). An aldosterone receptor blocker (e.g., eplerenone, 25 mg/day orally, increased to 50 mg/day after 4 weeks if tolerated, with monitoring of serum potassium levels) also should be added to the ACE inhibitor or ARB (but not both) regimen on a long-term basis in patients with depressed ejection fraction (≤0.40) and clinical heart failure or diabetes, unless this approach is contraindicated.

Long-term β-blocker therapy is strongly recommended for all MI survivors without uncompensated heart failure or other contraindications. Long-term therapy in patients at low risk (normal ventricular function, successful recanalization, absence of arrhythmias) is reasonable but not mandatory.

Nitroglycerin (0.4 mg) is prescribed routinely for sublingual or buccal administration for acute anginal attacks. Longer-acting oral therapy (isosorbide mononitrate, 30 to 60 mg orally every morning, or dinitrate, 10 to 40 mg orally two to three times daily) or topical nitroglycerin (e.g., start 0.5 inch, can titrate up to 2 inches, every 6 hours for 2 days) may be added to treatment regimens for angina or heart failure in selected patients.

Calcium-channel blockers are negatively inotropic and are not routinely given on a long-term basis; however, they may be given to selected patients without LV dysfunction (ejection fraction >0.40) who are intolerant of β-blockers and who require these drugs for antianginal therapy (e.g., amlodipine, 5 to 10 mg/day orally, or diltiazem, 120 to 480 mg/day orally as sustained release or divided doses) or for control of heart rate in AF (e.g., diltiazem, 120 to 480 mg/day orally, or verapamil, 180 to 480 mg/day orally, as sustained release or in divided doses). Short-acting nifedipine should be avoided.

Hormone therapy with estrogen with or without progestin is not begun after an acute MI because it increases thromboembolic risk and does not prevent reinfarction. For women already receiving hormone replacement, therapy should be discontinued unless it is being given for another compelling indication.

Hypertension ( Chapter 66 ) and diabetes mellitus ( Chapter 247 ) must be assessed and tightly controlled in patients after acute MI. ACE inhibitors or β-blockers as described earlier are usually the first-choice therapies for hypertension, with ARBs indicated when ACE inhibitors are not tolerated. ACE inhibitors and ARBs also can reduce the long-term complications of diabetes.

Antioxidant supplementation (e.g., vitamin E, vitamin C) does not benefit patients after acute MI and is not recommended. Folate therapy reduces homocyst(e)ine levels, but it has not been effective in reducing clinical events in large secondary prevention trials. Evidence regarding fish oil supplements is insufficient to make recommendations for or against them.

Antiarrhythmic drugs are not generally recommended after acute MI, and class I antiarrhythmic agents can increase the risk of sudden death. Class III drugs (amiodarone, sotalol, dofetilide) may be used as part of the management strategy for specific arrhythmias (e.g., AF, VT) ( Chapters 63 and 64 ).

Patient Education and Rehabilitation

The hospital stay provides an important opportunity to educate patients about their MI and its treatment, coronary risk factors, and behavioral modification. Education should begin on admission and should continue after discharge. However, the time before hospital discharge is particularly opportune. Many hospitals use case managers and prevention specialists to augment physicians and nurses, to provide educational materials, to review important concepts, to assist in formulating and actualizing individual risk-reduction plans, and to ensure proper and timely outpatient follow-up. This follow-up should include early return appointments with the patient’s physician (within a few weeks). Instructions on activities also should be given before discharge. Many hospitals have cardiac rehabilitation programs that provide supervised, progressive exercise.

FIGURE 72-3  Evidence-based approach to need for catheterization (cath) and revascularization after ST segment elevation myocardial infarction (STEMI). This algorithm shows treatment paths for patients who initially undergo a primary invasive strategy, receive fibrinolytic therapy, or do not undergo reperfusion therapy for STEMI. Patients who have not undergone a primary invasive strategy and have no high-risk features should undergo functional evaluation with one of the noninvasive tests shown. When clinically significant ischemia is detected, patients should undergo catheterization and revascularization as indicated; if no clinically significant ischemia is detected, medical therapy is prescribed after STEMI.  (From Antman EM, Anbe DT, Armstrong PW, et al: 2004 Update: ACC/AHA Guidelines for the Managment of Patients with ST-Elevation Myocardial Infarction—Exective Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2004;110:588-636.) ECG = electrocardiography; Echo = echocardiography; EF = ejection fraction.


TABLE 72-3   — 
HEMODYNAMIC SUBSETS OF ACUTE MYOCARDIAL INFARCTION

  Blood Pressure (Relative) Typical Physical Findings Cardiac Index (L/min/m2) PA Wedge Pressure (mm Hg) Suggested Interventions
Normal Normal +/- S4 >2.5 ≤12 None required
Hyperdynamic Normal or high Anxious >3 <12 Control pain, anxiety; β-blocker; treat SBP to <140 mm Hg
Hypovolemia Low Dry ≤2.7 ≤9 Add fluids to maintain normal pressure; can develop pulmonary edema if hypotension caused by unrecognized LV failure
Mild LV failure Low to high Rales, +/- S3 2–2.5 >15 Diuresis; nitrates, ACE inhibitor; consider low-dose β-blocker
Severe LV failure Low to normal Above +S3, +/- ↑ JVP, +/- edema <2 >20 Diuresis; nitrates; low-dose ACE inhibitor; avoid β-blockers; consider inotropes, urgent revascularization
Cardiogenic shock Very low Above + cool, clammy; ↓ mental or renal function ≤1.5 >25 Avoid hypotensive agents; place intra-aortic balloon pump; urgent revascularization if possible
RV infarct Very low ↑ JVP with clear lungs <2.5 ≤12 Give IV fluids; avoid nitrates and hypotensive agents; dobutamine if refractory to fluids

Adapted from Forrester JS, Diamond G, Chatterjee K, Swan HJ: Medical therapy of acute myocardial infarction by application of hemodynamic subsets (second of two parts). N Engl J Med 1976;295:1404–1413.

↑ = increased; ↓ = decreased; ACE = angiotensin-converting enzyme; IV = intravenous; JVP = jugular venous pressure; LV = left ventricle; PA = pulmonary artery; RV = right ventricle; SBP = systolic blood pressure.


TABLE 72-4   — 
SAMPLE ADMISSION ORDERS FOR ST SEGMENT ELEVATION ACUTE MYOCARDIAL INFARCTION

Diagnosis: Acute ST segment elevation myocardial infarction
Admit: Coronary care unit with telemetry
Condition: Serious
Vital signs: q1/2h until stable, then q4h and prn; pulse oximetry × 24 hr; notify if heart rate <50 or >100; respiratory rate <8 or >20; SBP <90 or >150 mm Hg; O2 saturation <90%
Activity: Bedrest × 12 hr with bedside commode; thereafter, light activity if stable
Diet: NPO except for sips of water until pain-free and stable; then 2 g sodium, heart-healthy diet as tolerated, unless on call for catheterization (or other test requiring NPO)
Laboratory tests[*]: Troponin I or T and CK/CK-MB q8h × 3; comprehensive blood chemistry, magnesium, CBC with platelets; PT/INR, aPTT; BNP; lipid profile (fasting in morning); portable CXR
IV therapy: D5W or NS to keep vein open (increase fluids for relative hypovolemia); second IV if IV medication given
Recanalization therapy[*]: Emergency primary coronary angioplasty, or fibrinolysis (if appropriate)
 

   1.    Primary angioplasty (preferred if available within 90 min)
   2.    Tenecteplase, alteplase, reteplase, or streptokinase (see Table 72-5 for doses)
Medications:

   1.    Nasal O2 at 2 L/min × 6 hr, then by order (per O2 saturation)
   2.    Aspirin 325 mg chewed on admission, then 162 mg PO qd (enteric coated)
   3.    IV heparin, 60 U/kg bolus (maximum, 4000 U) and 12 U/kg/hr (maximum, 1000 U/hr) or enoxaparin 30 mg IV then 1 mg/kg SQ q12h (maximum SQ doses, 100 mg on day 1)
   4.    Metoprolol, 12.5 PO q6h, incremented to 25–50 mg q6h as tolerated (hold for SBP <100, pulse <50, asthma, heart failure); may consider IV metoprolol if immediate effect required (tachyarrhythmia, severe hypertension, unrelieved pain) in the absence of heart failure
   5.    Consider IV nitroglycerin drip × 24–48 hr (titrated to SBP 100–140 mm Hg)
   6.    Morphine sulfate, 2–4 mg IV and increment at 5–15 min prn for unrelieved pain
   7.    Stool softener
   8.    Anxiolytic or hypnotic if needed
   9.    ACE inhibitor for hypertension, anterior acute MI, or LV dysfunction, in low oral dose (e.g., captopril 6.25 mg q8h), begun within 24 hours or when stable (SBP >100 mm Hg) and adjusted upward
   10.  Consider: lipid-lowering agent (i.e., statin if LDL >70–100 mg/dL or, optionally, for all with total cholesterol >135 mg/dL), GPIIb/IIIa inhibitor (e.g., eptifibatide or tirofiban) “upstream” from planned PCI, and clopidogrel, 300 mg PO, then 75 mg PO qd immediately after PCI (if CABG not planned)
   11.  Specific treatments for hemodynamic subgroups (see Table 72-3 )

Adapted from Antman EM, Anbe DT, Armstrong PW, et al: 2004 Update: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction—executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2004;110:588–636.

ACE = angiotensin-converting enzyme; aPTT = activated partial thromboplastin time; BNP = brain natriuretic peptide; CABG = coronary artery bypass graft surgery; CBC = complete blood count; CK = creatine kinase; CXR = chest radiograph; D5W = 5% dextrose in water; GP = glycoprotein; INR = international normalized ratio; IV = intravenous; LDL = low density lipoprotein; LV = left ventricle; MI = myocardial infarction; NPO = nothing by mouth; NS = normal saline; PCI = percutaneous coronary intervention; PO = orally; prn = as needed; PT = prothrombin time; qd = once daily; SBP = systolic blood pressure; SQ = subcutaneous.

* If not ordered in the emergency department.


TABLE 72-5   — 
CHARACTERISTICS OF INTRAVENOUS FIBRINOLYTIC AGENTS APPROVED BY THE FOOD AND DRUG ADMINISTRATION

  Streptokinase (SK) Alteplase (t-PA) Reteplase (r-PA) Tenecteplase (TNK–t-PA)
Dose 1.5 MU in 30–60 min 100 mg in 90 min[*] 10 U +10 U, 30 min apart 30–50 mg[] over 5 sec
Circulating half-life (min) ≅20 ≅4 ≅18 ≅20
Antigenic Yes No No No
Allergic reactions Yes No No No
Systemic fibrinogen depletion Severe Mild to moderate Moderate Minimal
Intracerebral hemorrhage ≅0.4% ≅0.7% ≅0.8% ≅0.7%
Patency (TIMI-2/3) rate, 90 min[] ≅51% ≅73–84% ≅83% ≅77–88%
Lives saved per 100 treated ≅3[§] ≅4[] ≅4 ≅4
Cost per dose (approximate U.S. dollars) 300 1800 2200 2200

* Accelerated t-PA given as follows: 15-mg bolus, then 0.75 mg/kg over 30 min (maximum, 50 mg), then 0.50 mg/kg over 60 min (maximum, 35 mg).
TNK–t-PA is dosed by weight (supplied in 5 mg/mL vials): <60 kg = 6 mL; 61–70 kg = 7 mL; 71–80 kg = 8 mL; 81–90 kg = 9 mL; >90 kg = 10 mL.
TIMI = Thrombolysis in Myocardial Infarction. Data from Granger CB, Califf RM, Topol EJ: Thrombolytic therapy for acute myocardial infarction: A review. Drugs 1992;44:293–325; and Bode C, Smalling RW, Berg G, et al: Randomized comparison of coronary thrombolysis achieved with double-bolus reteplase (recombinant plasminogen activator) and front-loaded, accelerated alteplase (recombinant tissue plasminogen activator) in patients with acute myocardial infarction: The RAPID II Investigators. Circulation 1996;94:891–898.
§ Patients with ST segment elevation or bundle branch block, treated <6 hr.
Based on the finding from the GUSTO trial that t-PA saves one more additional life per 100 treated than does SK. Data from The GUSTO investigators: An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993;329:673–682; and Simes RJ, Topol EJ, Holmes DR Jr, et al: Link between the angiographic substudy and mortality outcomes in a large randomized trial of myocardial reperfusion: Importance of early and complete infarct artery reperfusion. GUSTO-I Investigators. Circulation 1995;91:1923–1928.


TABLE 72-6   — 
INDICATIONS AND CONTRAINDICATIONS TO FIBRINOLYTIC THERAPY

INDICATIONS

   Ischemic-type chest discomfort or equivalent for 30 min–12 hr with new or presumed new ST segment elevation in two contiguous leads of ≥2 mm (≥0.2 mV) in leads V1, V2, or V3 or ≥1 mm in other leads
   New or presumed-new left bundle branch block with symptoms consistent with myocardial infarction
   Absence of contraindications
CONTRAINDICATIONS, ABSOLUTE

   Active bleeding or bleeding diathesis (menses excluded)
   Prior hemorrhagic stroke, other strokes within 1 year
   Intracranial or spinal cord neoplasm or arteriovenous malformation
   Suspected or known aortic dissection
   Closed head or facial trauma within 3 months
CONTRAINDICATIONS, RELATIVE

   Severe, uncontrolled hypertension by history or on presentation (>180/110 mmHg)
   Anticoagulation with therapeutic or elevated international normalized ratio (>2–3)
   Old ischemic stroke (>3 mo ago); intracerebral disease other than above
   Recent (<3 wk) major trauma/surgery or prolonged (>10 min) cardiopulmonary resuscitation or internal bleeding
   Active peptic ulcer
   Recent noncompressible vascular punctures
   Pregnancy
   For streptokinase/anistreplase: prior exposure (especially if >5 day ago) or allergic reaction

Adapted from Antman EM, Anbe DT, Armstrong PW, et al: 2004 Update: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction—executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2004;110:588–636.


TABLE 72-7   — 
INDICATIONS FOR PRIMARY ANGIOPLASTY AND COMPARISON WITH FIBRINOLYTIC THERAPY

INDICATIONS

   Alternative recanalization strategy for ST segment elevation or LBBB acute MI within 12 hr of symptom onset (or >12 hr if symptoms persist)
   Cardiogenic shock developing within 36 hr of ST segment elevation/Q wave acute MI or LBBB acute MI in patients <75 yr old who can be revascularized within 18 hr of shock onset
   Recommended only at centers performing >200 PCI/yr with backup cardiac surgery and for operators performing >75 PCI/yr
ADVANTAGES OF PRIMARY PCI

   Higher initial recanalization rates
   Reduced risk of intracerebral hemorrhage
   Less residual stenosis; less recurrent ischemia or infarction
   Usefulness when fibrinolysis contraindicated
   Improvement in outcomes with cardiogenic shock
DISADVANTAGES OF PRIMARY PCI (COMPARED WITH FIBRINOLYTIC THERAPY)

   Access, advantages restricted to high-volume centers, operators
   Longer average time to treatment
   Greater dependence on operators for results
   Higher system complexity, costs

LBBB = left bundle branch block; MI = myocardial infarction; PCI = percutaneous coronary intervention (includes balloon angioplasty, stenting).

FIGURE 72-4  Algorithm to aid in selection of implantable cardioverter-defibrillator (ICD) in patients with ST segment elevation myocardial infarction (STEMI) and diminished ejection fraction (EF). The appropriate management path is selected based on left ventricular EF measured at least 1 month after STEMI. All patients, whether an ICD is implanted or not, should receive medical therapy.  (From Antman EM, Anbe DT, Armstrong PW, et al: 2004 Update: ACC/AHA Guidelines for the Managment of Patients with ST-Elevation Myocardial Infarction—Exective Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2004;110:588-536.) EPS = electrophysiologic studies; LOE = level of evidence; NSVT = nonsustained ventricular tachycardia; VF = ventricular fibrillation; VT = ventricular tachycardia.


TABLE 72-8   — 
DISCHARGE MEDICATION CHECKLIST AFTER MYOCARDIAL INFARCTION[*]

Medication Doses Reasons Not to Use Comments
Aspirin Initial: 162–325 mg High bleeding risk Reduces mortality, reinfarction, and stroke
Maintenance: 75–162 mg qd    
Clopidogrel Initial dose: 300 mg High bleeding risk Indicated after PCI for 3 mo–1 yr; also reduces vascular events when added to aspirin in non–ST segment elevation acute MI (also useful based on recent clinical trials after ST segment elevation acute MI)
Maintenance: 75 mg qd    
β-Blocker (e.g., metoprolol, carvedilol) Metoprolol: 25 to 200 mg qd Asthma, bradycardia, severe CHF Reduces mortality, reinfarction, sudden death, arrhythmia, hypertension, angina, atherosclerosis progression
Carvedilol: 6.25 to 25 mg bid    
ACE inhibitor (e.g., ramipril, lisinopril) or ARB (e.g., valsartan, losartan) Ramipril: 2.5–10 mg qd Hypotension, allergy, hyperkalemia Reduces mortality, reinfarction, stroke, heart failure, diabetes, atherosclerosis progression
Lisinopril: 5–10 mg qd    
Valsartan: 80–160 mg qd–bid    
Losartan: 50–100 mg qd    
Lipid-lowering agent (e.g., a statin) (e.g., atorvastatin, simvastatin) Atorvastatin: 10–80 mg qd Myopathy, rhabdomyolysis, hepatitis Goal = LDL <100 and preferably <70 (statins also can benefit patients with lower LDL[]); consider addition of niacin or fibrate for high non-HDL cholesterol, low HDL
Simvastatin: 20–40 mg qd    
Nitroglycerin sublingual 0.4 mg SL prn for angina Aortic stenosis; sildenafil (Viagra) use Instruct on prn use and appropriate need for medical attention

ARB = angiotensin receptor blocker; bid = twice daily; CHF = congestive heart failure; HDL = high-density lipoprotein; LDL = low-density lipoprotein; MI = myocar-dial infarction; PCI = percutaneous coronary intervention; prn = as needed; qd = once daily, SL = sublingual.

* Medications given at hospital discharge improve long-term compliance. See also Antman EM, Anbe DT, Armstrong PW, et al: 2004 Update: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction—executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2004;110:588–636.
Heart Protection Study (Lancet 2002;360:7); and PROVE-IT Study (N Engl J Med 2004;350:1495.)

FIGURE 72-5  Long-term antithrombotic therapy at hospital discharge after ST segment elevation myocardial infarction (STEMI). *Clopidogrel is preferred over warfarin because of increased risk of bleeding and low patient compliance in warfarin trials. †For 12 months. ‡Discontinue clopidogrel 1 month after implantation of a bare metal stent or several months after implantation of a drug-eluting stent (3 months after sirolimus and 6 months after paclitaxel) because of the potentially increased risk of bleeding with warfarin and two antiplatelet agents. Continue aspirin (ASA) and warfarin on a long-term basis if warfarin is indicated for other reasons such as atrial fibrillation, left ventricular thrombus, cerebral emboli or extensive regional wall motion abnormality. §An international normalized ratio (INR) of 2.0 to 3.0 is acceptable with tight control, but the lower end of this range is preferable. The combination of antiplatelet therapy and warfarin may be considered in patients less than 75 years old who have a low bleeding risk and who can be monitored reliably. LOE = level of evidence.  (Redrawn from Antman EM, Anbe DT, Armstrong PW, et al: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction—executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Circulation 2004;110:588-636.)

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