ST segment elevation acute myocardial infarction and complications of myocardial infarction - копия - копия.ppt

STEMI

1. ST SEGMENT ELEVATION ACUTE
MYOCARDIAL INFARCTION AND
COMPLICATIONS OF MYOCARDIAL
INFARCTION

2. 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 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). 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.

3. EPIDEMIOLOGY
Cardiovascular disease still has high mortality rate worldwide. 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; 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
posthospital) mortality than non–ST segment elevation MI, and it
remains an important contributor to total population mortality.

4. 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. 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

5. collateral circulation, and distal coronary embolization result in
unstable angina or non–ST segment elevation MI. 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.

6. CLINICAL MANIFESTATIONS
Traditionally, the diagnosis of acute MI has rested on the triad of
ischemictype 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 or ECG features.

History
Ischemic-type chest discomfort is the most prominent clinical
symptom in most patients with acute MI. 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

7. burning; it rarely is perceived as sharp pain and generally not as
stabbing pain. 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. 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

8. 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 vomiting.
Confusional states, sudden loss of consciousness, a new rhythm
disorder, and 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;), musculoskeletal pain (e.g., costochondritis),

9. anxiety or panic attacks, pleurisy or pulmonary embolism , and acute
aortic dissection.
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, hypertension, or
both) often accompany anterior wall MI, whereas parasympathetic
hyperactivity (bradycardia, hypotension, or both) 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

10. 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 myocardial infarction (STEMI), it plays a critical role in initial
stratification, triage, and management. 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

11. 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.
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).

12. 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. 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.
Other causes of ST segment elevation must be considered and
excluded. These conditions include pericarditis, left ventricular (LV)
hypertrophy with J point elevation, and normal variant early
repolarization. Pericarditis (or perimyocarditis) is of particular
concern because it can mimic acute MI clinically, but fibrinolytic
therapy is not indicated and can be hazardous.

14. 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 or depth >30% of R wave amplitude, or both).
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

15. 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. Anatomically, the location of injury of “true
posterior MI” by magnetic resonance imaging actually involves
portions of the lateral left ventricular wall and is typically caused by
occlusion of a nondominant left circumflex artery. The acute phase
is characterized by ST segment depression, rather than ST segment
elevation. The evolved and chronic phases show increased R wave

16. amplitude and widening instead of Q waves. Recognition of a true
posterior acute MI pattern is challenging but important because the
diagnosis should lead to an immediate recanalization strategy.
Extending the ECG to measure left posterior leads V7 to V9
increases sensitivity for detecting acute left circumflex–related injury
patterns (i.e., ST segment elevation) with excellent specificity. Other
causes of prominent upright anteroseptal forces include right
ventricular (RV) hypertrophy, ventricular preexcitation variants
(Wolff-Parkinson-White syndrome;), 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.

17. Right Ventricular Infarction

Proximal occlusion of the right coronary artery before the acute
marginal branch can cause RV as well as acute inferior MI in about
30% of cases. Because the prognosis and treatment of acute
inferior 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. 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.

18. 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 bundle branch block (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.

19. Differential Diagnosis
Although ST-segment elevation MI is often an easy diagnosis to
make based on the presentation and test results (see later), other
considerations include acute pericarditis, acute myocarditis,
stressinduced takotsubo syndrome, and early repolarization. All but
early repolarization can be associated with abnormal biomarkers,
but none is associated with a coronary occlusion. Early coronary
angiography is advised when any of these conditions is suggested
or when MI may be related to a cause other than atherosclerosis.

21. Serum Cardiac Markers
Ideal markers are not normally present in serum, become rapidly
and markedly elevated during acute MI, and are not released from
other injured tissues. The increasing sensitivity and specificity of
serum cardiac markers, which are macromolecules (proteins)
released from myocytes undergoing necrosis, 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.

Troponins I and T
Troponins have replaced other markers because they are more
specific in the setting of injuries to skeletal muscle or other organs

22. and also are more sensitive in the setting of minimal myocardial injury.
Cardiac-derived TnI (cTnI) and TnT (cTnT), proteins of the sarcomere,
are not normally present in the blood with standard sensitivity assays
and have amino acid sequences distinct from their skeletal muscle
isoforms. 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.
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 other markers for the diagnosis of acute MI in
patients presenting late (>1 to 2 days) after symptoms. However, this
persistence can obscure the diagnosis of an early 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, except renal failure is more likely to be associated with false-
positive elevations of cTnT than of cTnI.

23. Ultrasensitive troponin assays increase assay sensitivity and enable
even earlier diagnosis. However, because troponins also may be present
in low concentration in a number of nonischemic cardiovascular
conditions, specificity for MI remains an issue.

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,

24. 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 . 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”

25. chest and back pain in association with a widened mediastinum
should raise the question of a dissecting aortic aneurysm. In
such cases, fibrinolytic therapy must be withheld pending more
definitive diagnostic imaging of the aorta. Other noninvasive
imaging (e.g., echocardiography, cardiac nuclear scanning and
other testing) is performed for evaluation of specific clinical
issues, including suspected complications of acute MI. Coronary
angiography 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.
Echocardiography efficiently assesses global and regional
cardiac function and enables the clinician to evaluate suspected
complications of acute MI. The sensitivity and

26. 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).

27. 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. Thallium-201 and,
increasingly, technetium-99m sestamibi (alone or together—dual
isotope imaging) remain the most frequently used “cold spot” tracers
to assess myocardial perfusion and viability, as well as infarct size,
although additional tracers are becoming available. Infarct-avid
tracers to identify, locate, and size recent myocardial necrosis are
available but are rarely required for ST segment elevation MI.
Computed tomography and magnetic resonance
imaging 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),

28. contemporary multislice (e.g., 64-slice) coronary computed
tomography 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.
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

29. rescuer. 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. More recently, data indicate that high-dose prehospital
tirofiban (25 μg/kg bolus, then 0.15 μg/kg/minute for 18 hours) can

30. improve intermediate outcomes in patients with acute ST elevation
MI who undergo percutaneous coronary intervention and is
equivalent to abciximab. 1 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, 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
care (CCU, step-down unit, observation unit) or outpatient care
(patients without suspected ischemia).

31. 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-toballoon 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).

32. Aspirin (162 to 325 mg) should be given to all patients unless it is
contraindicated. A loading dose of a thienopyridine (e.g.,clopidogrel,
600 mg, or prasugrel, 60 mg) also is recommended for STEMI
patients for whom PCI is planned. In addition, it is reasonable to start
treatment with a glycoprotein IIb/IIIa (GPIIb-IIIa) receptor antagonist
(abciximab, 0.25 mg/kg IV bolus, then 0.125μg/kg/minute [maximum,
10 μg/minute] for up to 12 hours), tirofiban (25 μg/kg IV bolus, then
0.15 μg/kg/minute for 12 to 18 hours; reduce infusion rate by 50% for
estimated creatinine clearance less than 30 mL/
minute) or eptifibatide (180 μg/kg IV bolus, second bolus after 10
minutes, then 2.0 μg/kg/minute for up to 18 hours; reduce infusion by
50% for estimated creatinine clearance less than 50 mL/minute) at
the time of primary PCI for STEMI in selected patients, such as those
with a large burden of thrombus or those who have not received
adequate thienopyridine loading. It is uncertain whether there is any
incremental usefulness of starting GPIIb-IIIa receptor
antagonists “upstream,” before arrival in the catheterization
laboratory.

33. 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 lowmolecular- 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) or bivalirudin (for those undergoing a primary PCI
strategy— 0.75 mg/kg bolus, then 1.75 mg/kg/hour infusion) is
appropriate in most patients. In STEMI patients who are undergoing
PCI who are at higher risk for bleeding, evidence supports using
bivalirudin anticoagulation with a thienopyridine but without a GPIIb-
IIIa receptor antagonist.
Patients with chest pain should be given sublingual nitroglycerin
(0.4 mg every 5 minutes for up to three doses), after which an
assessment should be made of the need for intravenous
nitroglycerin. Persistent ischemic pain may be treated with titrated
intravenous doses of morphine (i.e., 2 to 4 mg intravenously,

34. 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 2 to 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. 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.

36. Early Hospital Phase: Coronary Care
Coronary care for early hospital management of acute MI has
reduced inhospital 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.
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, bed to 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

37. reambulation occurs. The risk for 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

38. 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.
Hemodynamic evaluation is helpful in assessing prognosis and in
guiding therapy. 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.

39. 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 longterm 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).

40. 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%). Each community should develop and follow a
multidisciplinary STEMI system of care that provides consistently
optimal STEMI care within the resources available.

41. Fibrinolytic Therapy
Various fibrinolytic agents 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. Compared with no
recanalization therapy, older fibrinolytics such as streptokinase
reduced mortality by 18% (from 11.5 to 9.8%) at 5 weeks. 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 elderly (>75
years) patients. 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

42. 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 for intracranial
hemorrhage. The risk-to-benefit ratio should be assessed in each
patient when fibrinolysis is considered and specific regimens are
selected.
For failed fibrinolysis, rescue PCI is more effective than repeat
fibrinolysis. After fibrinolysis, regardless of its apparent success, the
best strategy is to transfer all STEMI patients with high-risk features
rapidly to a hospital with PCI facilities to undergo angiography,

43. rather than to transfer only selected patients in whom fibrinolysis
failed or recurrent ischemia developed. This early transfer and
angiography strategy at a median of 3 hours after fibrinolysis
reduces the risk for recurrent ischemia, reinfarction, heart failure,
cardiogenic shock or death by 36%.

45. Primary Percutaneous Coronary Intervention
Prompt PCI is the preferred recanalization strategy. PCI achieves
mechanical recanalization by inflation of a catheter-based balloon
centered within the thrombotic occlusion. 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 postangioplasty 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.
Factors favoring a bare metal stent include inability to maintain at least
1 year of dual antiplatelet therapy because of an increased risk for
bleeding, need for concomitant anticoagulation, risk for poor
adherence or anticipated need for surgery requiring interruption of
thienopyridine.
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

46. intracerebral hemorrhage with primary PTCA compared with fibrinolysis.
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 begins with initiation of a
thienopyridine in the emergency department, together with aspirin and
an anticoagulant (e.g., heparin or bivalirudin), followed by rapid
application of coronary angioplasty with stenting. Augmented antiplatelet
therapy with a GPIIb-IIIa inhibitor may be added in selected patients,
generally at the time of catheterization. The addition of a reduced dose
of a plasminogen activator to GPIIb-IIIa therapy in the field or emergency
department may further improve outcomes only in selected patients who
undergo early PCI, but this approach is generally not recommended. 8
Facilitated PCI, whereby patients at hospitals without PCI capabilities
are given adjusted doses of fibrinolytic or GPIIb-IIIa inhibitors, or both,
and then are transferred to other hospitals for emergent (i.e., within 1 to
2 hours) PCI, overall appears to be no better than rapid transfer for
primary
PCI within 1 to 2 hours.

47. Operator and institutional experience is an issue more important to
outcomes with primary PCI than fibrinolysis and has been
incorporated into current recommendations. 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 a GPIIb-IIIa
receptor antagonist, for patients presenting more than 12 hours but
less than 48 hours after the onset of symptoms, also can reduce
infarct size and perhaps adverse events. Extending PCI to ST
segment elevation MI beyond 12 hours deserves further testing in
larger studies.
An additional important indication is cardiogenic shock occurring

48. within 36 hours of the onset of acute MI and treated within 18 hours
of the onset of shock. However, benefit was not established for
patients older than 75 years, and benefit was greater with earlier
PCI.
Increasing positive experience with PCI of the left main coronary
artery with stents, especially drug-eluting stents, suggests that it
may be an alternative to coronary artery bypass grafting (CABG) in
patients with an amenable anatomy, a low risk of PCI procedural
complications, and an increased risk of adverse surgical outcomes.
Mechanical thrombus aspiration at the time of angiography may
improve outcomes of patients with STEMI undergoing primary PCI.
To reduce the risk for contrast-induced nephropathy, an isosmolar
or a low-molecular-weight contrast medium together with
preprocedure hydration is recommended in patients undergoing
angiography.

50. Selecting a Recanalization Regimen
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 or bivalirudin, 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 a routine emergent (i.e., within 1

51. to 2 hours) invasive strategy on hospital arrival, that is,
“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 or by a more delayed invasive
approach after fibrinolysis in stabilized
patients, 4,5,12 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

52. with a history of prior streptokinase use. Streptokinase is associated
with a lower risk for 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 substantially over time, although fibrinolytic therapy
continues to be more commonly applied, particularly in developing
countries.

53. 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.
Aspirin has been extensively tested to prevent coronary heart disease.
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 for 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.

54. 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. 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 is given, usually 300 mg with fibrinolytic
therapy but 600 mg with PCI. 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 or younger reduces predischarge occlusion rates of infarct-
related arteries (by 41%) and reduces ischemic complications at 30

55. days (by 20%) without increasing rates of intracerebral hemorrhage.
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%. Hence, clopidogrel appears to
represent a beneficial initial adjunctive therapy in patients with STEMI
who are treated with fibrinolytic agents. However, clopidogrel
increases the risk for bleeding with 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.
Prasugrel, a new and more potent thienopyridine, may reduce
ischemic events at the cost of a small increase in bleeding compared
with clopidogrel after PCI in patients with acute STEMI. Prasugrel is
contraindicated in patients with a prior history of stroke or transient
ischemia attack and should be used with caution (or in reduced doses)
in older (≥75 years) and smaller (<60 kg) patients.
Clopidogrel added to aspirin on admission for patients with non–ST

56. Clopidogrel added to aspirin on admission for patients with non–ST
segment elevation acute MI or unstable angina 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 on admission or after PCI.
The benefit in STEMI is smaller when routine stenting is used and when
GPIIb- IIIa therapy is administered only in the catheterization laboratory.
Earlier (“upstream”) glycoprotein inhibition before hospital admission or
in the emergency (precatheterization) is effective in improving coronary
patency by the time of emergency angiography, but incremental benefit
on clinical outcomes has not

57. been established. If early CABG is a possibility after angiography, a
shorter-acting inhibitor (eptifibatide, tirofiban) may impart a lower
perioperative risk for bleeding than abciximab.
Antithrombin Therapy
Low-Molecular-Weight Heparins
Compared with unfractionated heparins, LMWHs have enhanced
inhibitory activity for factor Xa. They also have more reliable
bioavailability and longer durations of action, thus permitting
subcutaneous administration once or twice daily in fixed (weight-
adjusted) doses. 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% compared with unfractionated heparin.
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,

58. enoxaparin may be given to patients younger than 75 years 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.
Unfractionated Heparin
Unfractionated heparin can be used in patients undergoing primary PCI
and in those receiving fibrin-specific lytic agents (i.e., alteplase,
reteplase, or tenecteplase; ). It also can be used 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]). 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
agent, 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

59. (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).
Factor Xa Inhibitors
Selective factor Xa inhibitors (e.g., fondaparinux, 2.5 mg subcutaneously
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. 18
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 STEMI who are not undergoing a primary
PCI strategy.

62. Direct Antithrombins


Bivalirudin, a synthetic hirudin analogue with direct antithrombin
activity, compares favorably with heparin and a glycoprotein IIb/IIIa
inhibitor for ST segment elevation acute MI managed by primary
PCI, with better survival rates at 1 year. However, an increased risk
of ischemic events and stent thrombosis occurs in bivalirudin
patients who do not receive upstream therapy with a 600-mg
loading dose of clopidogrel. As a result, bivalirudin, together with
early administration of clopidogrel, has become a widely used
antithrombotic regimen in primary PCI for ST segment elevation
acute MI.

63. 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. 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

64. benefit of about 4 lives saved per 1000 patients treated.
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 rate 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).

65. 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

66. 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. 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 inhospital convalescent phase of STEMI and
beyond.

67. 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. 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 5 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, although patients with lesser degrees of LV
dysfunction and only moderate cardiovascular risk can also benefit in the
long term.
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

68. of ACE inhibitors. An ACE inhibitor or an ARB also should be
considered for other patients with STEMI, 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 longeracting
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

69. mg/day) reduces total and cardiovascular mortality (including sudden
death) as well as cardiovascular hospitalizations in post-MI patients
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. 19 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.
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

70. tachycardia (VT) occurring more than 2 days after STEMI or in
patients with inducible VT or VF at electrophysiologic study and a
depressed ejection fraction (≤0.40) at least 1 month after STEMI. An
ICD also may be considered for patients with severe LV dysfunction
(ejection fraction ≤0.30) at least 1 month after STEMI and 3 months
after CABG without spontaneous or induced VT or VF. These
differences reflect an apparent time dependence, in which the benefit
of an ICD appears to be delayed until the early post-MI and post-
revascularization periods. By comparison, early ICD implantation is
not beneficial in a broader group of patients because its usefulness in
preventing similar deaths is offset by the high rate of nonsudden
deaths.

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

71. 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. 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. 22 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.

72. 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 patients, 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 STEMI.

73. However, glucose control, using an insulin-based regimen to achieve
and maintain glucose levels less than 180 mg/dL while avoiding
hypoglycemia, is recommended in the acute phase of STEMI. After
the acute phase, individualized treatment is indicated using agents or
combinations of agents that best achieve glycemic control and are well
tolerated.

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
the 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

74. (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 readministered 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 perfusion stress testing can be helpful in patients with
discomfort that is transient or of uncertain
ischemic origin. For lesions with questionable degrees of stenosis at
angiography, coronary pressure (fractional flow reserve) or Doppler
velocimetry can determine whether PCI is warranted.
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 for remodeling is
reduced with early recanalization therapy and

75. 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

76. free fatty acid production, and oxygen free radical production on
recanalization. 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 lifethreatening 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.

77. 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 reentry 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). Brief intravenous
sedation is given to conscious, “stable” patients. For slower, stable VT
and nonsustained VT requiring therapy, intravenous amiodarone or
intravenous

78. amiodarone or intravenous lidocaine is commonly recommended.
After episodes of VT or VF, infusions of antiarrhythmic drugs may
be given for 6 to 24 hours; the ongoing risk for 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 or amiodarone, or
both.
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.

79. 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. The incidence of atrial flutter or another
supraventricular tachycardia is much lower. The risk for 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

80. 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 is 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

81. 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
bundle branch blocks (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

82. 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.

83. 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.
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.
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 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

84. 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.

85. 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 STEMIs show classic hemodynamic features, and

86. 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, 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.,

87. 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.

88. Cardiogenic Shock
Cardiogenic shock 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 younger than
75 years.
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;

89. 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

90. murmur or sudden, progressive hemodynamic deterioration with
pulmonary edema 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 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

91. 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.

92. 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 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

93. 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 for 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

94. ambulatory. Patients with pulmonary embolism are treated with
intravenous heparin, then oral anticoagulation for 6 months.

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.

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

95. 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 or technetium-99m sestamibi, or
both;) or echocardiography. Supplemental imaging also can quantify
the LV ejection fraction and size the area of infarction or ischemia

96. (e.g., by cardiac magnetic resonance imaging;). 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, a long-acting bolus analogue of adenosine
(e.g., regadenoson) or dipyridamole scintigraphy or using 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.
Patients with sustained VT or VF occurring late during hospitalization or
provoked during electrophysiologic study

97. with nonsustained VT on monitoring are candidates for an ICD,
especially if the ejection fraction is less than 40%. Prophylactic ICD
placement at least 1 month after acute MI prevents sudden death
for patients with severely depressed function (ejection fraction ≤
0.30) regardless of the rhythm status.
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. EPS = electrophysiologic studies; LOE = level of evidence; NSVT = nonsustained ventricular tachycardia;
VF = ventricular fibrillation; VT = ventricular tachycardia.

98. 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.
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.
Continued smoking doubles the subsequent mortality risk after
acute MI, and smoking cessation reduces the risk for reinfarction
and death within 1 year. An individualized smoking cessation plan
should be formulated, including pharmacologic aids (nicotine gum
and patches, bupropion, or varenicline).
Antiplatelet therapy 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) or prasugrel (10 mg/day) is

99. given to patients who received PCI with stenting, and clopidogrel 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 paclitaxeleluting stents. If patients are
not at high risk for 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 benefits
and risks of warfarin added to antiplatelet therapy are sparse.

100. 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 younger than 75 years who have a low bleeding risk and who can be monitored reliably. LOE = level
of evidence.

101. ACE inhibitor therapy can prevent adverse myocardial remodeling
after acute MI and can reduce heart failure and death; it is clearly
indicated for longterm use in patients with anterior acute MI or an LV
ejection fraction of 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) for 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. An aldosterone receptor blocker (e.g., eplerenone,

102. 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.
Options include metoprolol, 20 to 200 mg per day, or carvedilol, 6.25
to 25 mg twice daily. 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.

103. 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 and diabetes mellitus 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

104. 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. Fish
oil supplements showed no benefit in the best randomized trial.
Antiarrhythmic drugs are not generally recommended after acute
MI, and class I antiarrhythmic agents can increase the risk for
sudden death. Class III drugs (amiodarone, sotalol, dofetilide) may
be used as part of the management strategy for specific arrhythmias
(e.g., AF, VT).
The intracoronary infusion of stem cells has been proposed as a
mechanism to reduce infarct size. To date, however, trials have
been inconclusive.

105. 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.

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