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CURRENT Diagnosis & Treatment in Cardiology > Chapter 5. Acute Myocardial Infarction >

Essentials of Diagnosis

  • Chest discomfort, usually described as “pressure,” “dull,” “squeezing,” or “aching.”
  • Characteristic electrocardiographic changes.
  • Elevated biomarkers, such as troponin.
  • Imaging may show new regional wall motion abnormality with preserved wall thickness.
  • The elderly, women, and diabetics may have atypical presentation.

General Considerations

Acute myocardial infarction (MI) is a clinical syndrome that results from occlusion of a coronary artery, with resultant death of cardiac myocytes in the region supplied by that artery. Depending on the distribution of the affected coronary artery, acute MI can produce a wide range of clinical sequelae, varying from a small, clinically silent region of necrosis to a large overwhelming area of infarcted tissue resulting in cardiogenic shock and death. About 1.2 million people experience MI in the United States each year; every minute, one American will die of coronary artery disease.

The risk of having an acute MI increases with age, male gender, smoking, dyslipidemia, diabetes, hypertension, abdominal obesity, a lack of physical activity, low daily fruit and vegetable consumption, alcohol overconsumption, and psychosocial index. As much as 90% of the risk of acute MI has been attributed to the modifiable risk factors. The diagnostic criteria for acute MI are listed in Table 5–1.

Table 5–1. ESC/ACC Definition of Myocardial Infarction.

Criteria for acute MI


Typical rise and gradual fall (troponin) or more rapid rise and fall (CK-MB) of biochemical markers of myocardial necrosis with at least one of the following:


Ischemic symptoms


Development of pathologic Q waves on the ECG


ECG changes indicative of ischemia (ST segment elevation or depression)


Coronary artery intervention (eg, coronary angioplasty)


Pathologic findings of an AMI

Criteria for established MI

Any one of the following criteria satisfies the diagnosis for established MI:


Development of new pathologic Q waves on serial ECGs. The patient may or may not remember previous symptoms. Biochemical markers of myocardial necrosis may have normalized, depending on the length of time that has passed since the infarct developed.


Pathologic findings of a healed or healing MI

MI, myocardial infarction; CK-MB, myocardial muscle kinase isoenzyme; ECG, electrocardiogram.

Adapted, with permission, from Beller GA et al. J Am Coll Cardiol. 2000;36:957.

Pathophysiology & Etiology

A prolonged imbalance between myocardial oxygen supply and demand leads to the death of myocardial tissue. Coronary atherosclerosis is an essential part of the process in most patients. Ischemic heart disease seems to progress through stages of fatty-streak deposition in coronary arteries to development of fibro-fatty plaque, which then increases in size until it causes luminal obstruction, leading to exertional angina (see Chapter 3). However, at any stage in this process, the atherosclerotic lesion may erode, ulcerate, fissure, or rupture, thereby exposing subendothelial vessel wall substances to the circulating blood. Procoagulant factors (such as tissue factor) reside within the plaque itself and, in the absence of counterbalancing antithrombotic factors (eg, heparin, tissue-factor-inhibitor) and fibrinolytic activities (tissue plasminogen activator [t-PA] and single-chain urokinase-type plasminogen activator) within the endothelial cells of the coronary artery, can cause thrombosis. This potent procoagulant stimulus results in thrombus development in this region. In general, acute MI occurs when this thrombosis propagates and occludes flow within the artery, resulting in ischemia of cardiomyocytes distal to the obstruction. Recent work suggests that inflammation may play a pivotal role in the genesis of plaque rupture. Total thrombotic occlusion occurs most commonly in proximal coronary arteries; its presence has been documented during the first 4 hours after infarction in more than 85% of patients with ST-segment elevation (Figure 5–1).

Figure 5–1.

Incidence of total occlusion in patients with acute myocardial infarction.

(Reproduced, with permission, from DeWood MA et al. N Engl J Med. 1980;303:897.)

A similar type of myocardial insult occurs occasionally despite angiographically normal coronary arteries and may be caused by emboli (eg, in patients with prosthetic valves or those with endocarditis), dissection of the coronary artery (most commonly in pregnant women), or coronary vasospasm (on rare occasions). It can also be caused by thrombosis in situ, the probable mechanism by which patients who have variant angina or who abuse cocaine can suffer acute infarction. In these cases, vasoconstriction secondary to endothelial dysfunction and a propensity to thrombosis is of sufficient magnitude and duration to cause thrombus formation. Oxygen consumption and possibly direct myocyte toxicity also increase with cocaine use. In addition, thrombosis in situ can apparently cause infarction among women who take estrogens (especially if they smoke). An increasingly recognized differential diagnosis of acute MI is stress cardiomyopathy (also known as apical ballooning syndrome or tako-tsubo cardiomyopathy). This entity can present with a variety of symptoms and electrocardiographic (ECG) changes, including ST elevation, and there is akinesis of the anterior and inferior walls and apex of the left ventricle in the absence of coronary artery disease. It is often accompanied by severe emotional stress. The diagnosis is one of exclusion, after angiography demonstrates patent coronary arteries. The prognosis is good, and recovery of ventricular function is the norm.

In addition to blockage of coronary arteries (reduced “supply”), acute MI may be seen when myocardial oxygen requirements are elevated (increased “demand”). This often occurs when other medical illnesses coexist with ischemic heart disease. Pulmonary embolism, pneumonia, arrhythmia, septic shock, severe anemia, or great emotional distress can increase myocardial oxygen demand, reduce coronary perfusion pressure, or evoke paradoxical coronary artery responses and lead to MI. However, these tend to be smaller infarctions with no ECG ST elevation that are diagnosed by elevated biomarkers.

Libby P et al. Inflammation and atherosclerosis. Circulation. 2002 Mar 5;105(9):1135–43. [PMID: 11877368]

Rosamond W et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007 Feb 6;115(5):e69–171. [PMID: 17194875]

Wittstein IS et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med. 2005 Feb 10;352(6):539–48. [PMID: 15703419]

Clinical Findings

Symptoms and Signs

Chest discomfort is the most common symptom; it is usually described as “pressure,” “dull,” “squeezing,” or “aching,” although it may be described differently because of individual variability, differences in articulation or verbal abilities, or concomitant disease processes. The discomfort is usually in the center of the chest and commonly radiates to the left arm or the neck. However, it may also radiate to the right arm, epigastrium, jaw, teeth, or the back. The nature of the pain may lead patients to place a hand or fist over the sternum (Levine sign). These clinical signs and symptoms were originally defined in groups of males. It is now clear that women often have more atypical symptoms.

Associated symptoms may include dyspnea, nausea (particularly in inferior infarction), palpitations, and a sense of impending doom.

Patients, especially those with diabetes or hypertension, may have atypical presentations; for example, a diabetic person may have abdominal pain that mimics the discomfort commonly associated with gallstones. In elderly patients, heart failure is often the presenting symptom. By age 85, only 40% of patients will complain of chest discomfort as the initial symptom. The diagnosis of MI should be considered in patients in whom symptoms are atypical yet compatible with ischemia (paroxysms of dyspnea, for example) or in those with atypical chest discomfort. Patients can also have discomfort that is sharper or that radiates to the back. These patients can have pericarditis alone, pericarditis induced by infarction, or a dissecting aortic aneurysm—with or without concomitant infarction.

Physical Examination

The physical examination is a critical and underappreciated part of the initial assessment of patients with suspected acute MI. Findings may vary tremendously, from markedly abnormal, with signs of severe congestive heart failure (CHF), to totally normal.

On general inspection, most patients with a large MI appear pale or sweaty and may be agitated or restless. Heart rate should be measured for arrhythmia, heart block, or sinus tachycardia. This is crucial before administration of -blockers. Assessment of blood pressure is important because severe hypertension (which may be due to the pain) is a contraindication to fibrinolytic treatment and must be treated emergently. Conversely, hypotension in the setting of acute MI may be due to cardiogenic shock, which alters treatment strategy. Fibrinolytic treatments are not effective in cardiogenic shock, and the patient should be considered for an urgent intra-aortic balloon pump (IABP) and primary percutaneous coronary intervention (PCI).

The jugular venous pulse should be carefully examined. Its elevation in the setting of inferior MI without left heart failure suggests right ventricular MI. Detection of right ventricular MI is vital because it portends a much worse prognosis than isolated inferior MI, and the management strategy is different than isolated inferior MI. Whereas elevated jugular venous pulse in left ventricular MI with left ventricular failure may respond to diuresis, right ventricular MI may require intravenous fluid therapy to maintain left ventricular filling.

Cardiac auscultation should be specifically targeted to complications of MI (see later in this chapter) and detection of important comorbidities. Acute MI may result in ischemic mitral regurgitation with a soft S1 and a pansystolic murmur. Acquired ventricular septal defect (VSD) may also result in a pansystolic murmur, but it is usually loud and high-pitched and has a normal S1 and usually occurs later (see Complications of Myocardial Infarction section below). Both ischemic mitral regurgitation and acquired VSD may result in heart failure. The presence of a pericardial friction rub may indicate established infarction which has happened days earlier. Heart failure due to large infarctions may result in a third heart sound. Signs of left heart failure, such as rales and pulmonary hypertension, should also be sought. Important comorbidities, such as concomitant severe aortic stenosis, should also be documented because they may change the initial reperfusion strategy from fibrinolysis or PCI to cardiac surgery with coronary artery bypass graft (CABG) and aortic valve replacement simultaneously.

Alternative diagnoses may also be suggested by clinical examination. The presence of atrial fibrillation or prosthetic valve may suggest that thromboembolism to the coronary artery is the cause of the coronary occlusion. Furthermore, a brief assessment of pulse equality and blood pressure in both arms should be performed. Inequalities in perfusion between arms may indicate aortic dissection, causing compromised blood flow in the branch vessels of the aortic arch. Aortic dissection may also be responsible for occlusion of the ostium of the coronary artery causing the acute MI. This is a surgical emergency and should not be treated with anticoagulation or fibrinolysis. Therefore, a focused clinical examination is an essential part of the initial patient assessment and can be invaluable in guiding therapy.

Diagnostic Studies


The most rapid and helpful test in assessing patients with suspected acute MI is the 12-lead ECG. It should be performed as soon as possible, preferably within 10 minutes, after the patient’s arrival in the emergency department or clinician’s office, since the presence or absence of ST elevation determines the preferred management strategy. For a diagnosis of ST elevation MI (STEMI), ST elevation must be present in at least two contiguous leads. For anterior MI, the precordial (V) leads demonstrate ST elevation (Figure 5–2), and if there is lateral wall involvement, I and aVL may also show ST elevation. In inferior MI, leads II, III, and aVF are affected.

Figure 5–2.

ECG changes in anterolateral STEMI. A: Initial ECG on presentation shows ST segment elevation in the precordial leads, as well as I and aVL, indicative of acute anterolateral STEMI due to proximal left anterior descending (LAD) coronary artery occlusion. Note the reciprocal ST depression in the inferior leads. B: Following reperfusion, subsequent ECG 48 hours later demonstrates resolution of both the anterolateral ST elevation and the reciprocal changes. Note the Q wave in V2 and the development of T wave inversion.

In addition to standard ECG leads, right ventricular leads should be recorded in all patients with inferior MI. Inferior MI is usually caused by occlusion of the right coronary artery, which may also cause right ventricular infarction. Differentiating right ventricular infarction from left ventricular infarction is imperative because the management is different.

In posterior MI, usually due to circumflex artery occlusion, the only changes seen on a standard ECG may be reciprocal ST depression and R waves (reciprocal of Q waves) in the anterior leads. This ECG pattern should prompt the use of posterior ECG leads V7–9, which may show ST elevation. Even in the absence of ST elevation in posterior leads, true posterior infarction pattern on ECG in the presence of symptoms suggestive of MI should be treated like STEMI.

Non-ST elevation MI (NSTEMI) has a variable presentation on ECG. There may be no ECG changes, or patients may have ST depression, T wave flattening, or T wave inversion. Preexisting abnormalities like T wave inversion may also “pseudo-normalize” in NSTEMI, making it even more difficult to diagnose on ECG. Because determining whether ECG changes are new or old may be difficult, serial ECGs are necessary to diagnose dynamic changes. In patients with symptoms suggestive of MI and no evidence of ST elevation on ECG, the diagnosis of acute coronary syndrome is made. This encompasses unstable angina pectoris and NSTEMI. The distinction between these two entities is made on the presence or absence of elevated biomarkers of MI.

Cardiac Biomarkers

The diagnosis of infarction requires increases in molecular markers of myocardial injury (Figure 5–3). Myoglobin release from injured myocardium occurs quite early and is very sensitive for detecting infarction. Unfortunately, it is not very specific because minor skeletal muscle trauma also releases myoglobin. Myoglobin is cleared renally, so even minor decreases in glomerular filtration rate lead to elevation. The other early marker advocated by some are isoforms of creatine kinase (CK). This marker has comparable early sensitivity and specificity to myoglobin. The marker of choice in past years was the MB isoenzyme of creatine kinase (CK-MB). A typical rising-and-falling pattern of CKand CK-MB (in the proper clinical setting) was sufficient for the diagnosis of acute infarction. In the typical pattern of CK release after infarction, the enzyme marker level exceeds the upper bound of the reference range within 6–12 hours after the onset of infarction. Peak levels occur by 18–24 hours and generally return to baseline within no more than 48 hours. However, elevations can occur due to release of the enzyme from skeletal muscle. The lack of a rising-and-falling pattern should raise the suspicion that the release is from skeletal muscle, which is usually due to a chronic skeletal muscle myopathy. Elevations of CK in patients with hypothyroidism (where clearance of CK is slowed) and those with renal failure (where clearance is normal because CK is not cleared renally) are caused, in part, by myopathy.

Figure 5–3.

Biomarkers in acute MI. Plot of the appearance of cardiac markers in blood versus time after onset of symptoms. Peak A, early release of myoglobin or CK-MB isoforms after acute MI. Peak B, cardiac troponin after acute MI. Peak C, CK-MB after acute MI. Peak D, cardiac troponin after unstable angina. Data are plotted on a relative scale, where 1.0 is set at the acute MI cutoff concentration.

(Reprinted, with permission, from Wu AH et al. Clin Chem. 1999;45:1104.)

Cardiac troponins I and T are proteins found in cardiac muscle cells and released into the circulation from damaged cardiac myocytes during acute MI. Troponin levels (either I or T) are significantly more sensitive and specific for myocardial damage than CK. Troponin becomes detectable in serum between 4 hours and 6 hours after onset of an acute MI, peaks and then falls to lower levels, and remains elevated at these low levels for 5–7 days (Figure 5–3). Thus, the late or retrospective diagnosis of acute MI can be made with this marker, making the use of lactate dehydrogenase isoenzymes superfluous. Therefore, because of its sensitivity and specificity for cardiac muscle damage as well as its early rise and continued low level detectability, troponin is the preferred biomarker for diagnosis of acute MI. Furthermore, it has been shown to correlate with prognosis even in the absence of CK or CK-MB elevation (Figure 5–4).

Figure 5–4.

Troponin I and mortality. Relationship between cardiac troponin levels and risk of mortality in patients with acute coronary syndromes.

(Used with permission from Antman EM et al. N Engl J Med. 1996;335:1342.)

Coronary recanalization, whether spontaneous or induced pharmacologically or mechanically, alters the timing of all markers’ appearance in the circulation. Because it increases the rapidity with which the marker is washed out from the heart, leading to rapid increases in plasma, the diagnosis of infarction can be made much earlier—generally within 2 hours of coronary recanalization. Although patency can be approximated from the marker rise, distinguishing between thrombolysis in myocardial infarction (TIMI) II and TIMI III flow is not highly accurate. It should also be understood that peak elevations are accentuated, which must be taken into account if the clinician wants to use peak values as a surrogate for infarct size.


In the emergency setting, most diagnoses of acute MI are made on history, physical examination, and ECG. However, when the history is atypical and the ECG is equivocal or uninterpretable, performance of a rapid bedside echocardiogram may demonstrate a new regional wall motion abnormality with preserved wall thickness, suggestive of acute MI. In most cases of STEMI, however, echocardiography is not warranted because it delays reperfusion therapy. Echocardiography is also helpful in diagnosing complications of MI, such as VSD, papillary muscle rupture or free wall rupture, and tamponade.

In NSTEMI that is diagnosed on elevated plasma levels of cardiac biomarkers, nuclear scintigraphy or echocardiography may help determine the region of the heart affected by the MI, but these are not standard diagnostic tools.

Alpert JS et al. Myocardial infarction redefined—a consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol. 2000 Sep;36(3):959–69. [PMID: 10987628]

Menown IB et al. Early diagnosis of right ventricular or posterior infarction associated with inferior wall left ventricular acute myocardial infarction. Am J Cardiol. 2000 Apr 15;85(8):934–8. [PMID: 10760329]

Ottani F et al. Elevated cardiac troponin levels predict the risk of adverse outcome in patients with acute coronary syndromes. Am Heart J. 2000 Dec;140(6):917–27. [PMID: 11099996]


The goals of treatment in acute MI are stabilization of the patient and salvage of as much myocardium as possible. A number of general measures should be performed in all patients. In patients with ST elevation—who are at highest risk for complications and have ongoing cardiomyocyte necrosis—immediate reperfusion of the infarct artery should be attempted. The management of acute MI is summarized in Table 5–2.

Table 5–2. Overview of Management of Acute MI.

Pre-hospital management

  Call 911
  Continuous cardiac monitoring
  Consider pre-hospital 12-lead ECG
Emergency department treatment
  Intravenous access
  Continuous cardiac monitoring
  12-lead ECG
Reperfusion strategies
  Primary PCI vs fibrinolysis for STEMI
  Glycoprotein IIb/IIIa for NSTEMI, followed by elective PCI
In-hospital management
  Initial bedrest
  Continuous cardiac monitoring
   Oxygen for hypoxemia
   Nitroglycerin for ongoing pain
   ACE inhibitor, -blocker, aspirin, clopidogrel, statin
  Prognostic indicators
  Cardiac rehabilitation
  Aggressive secondary prevention with smoking cessation, therapeutic lifestyle changes, and medications

ACE, angiotensin-converting enzyme; ECG, electrocardiogram; NSTEMI, non-ST elevation myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST elevation myocardial infarction.

Early recognition of symptoms of myocardial ischemia may lead to faster treatment and salvage of myocardium. Therefore, it is recommended that patients at risk for MI be educated about the symptoms suggestive of acute MI and call for emergency help immediately if they have these symptoms.

Pre-Hospital Management

Aspirin, 162–325 mg, should be given immediately. Continuous cardiac monitoring, oxygen, and sublingual nitroglycerin should be administered to all patients with suspected acute MI. Communities usually have organized protocols for ambulance personnel regarding (1) whether or not they should obtain a 12-lead ECG, (2) whether there are designated hospitals that receive patients in whom an acute MI is suspected, or (3) whether the patient should be taken to the nearest emergency department. In some regions of the world, fibrinolytic treatment is initiated in the ambulance, based on a 12-lead ECG.

Emergency Department Therapy

On arrival, all patients with suspected acute MI should have a 12-lead ECG performed immediately. If aspirin has not been given, then 162–325 mg of aspirin should be administered immediately. All patients with suspected MI should have continuous cardiac ECG monitoring, and intravenous access (two separate intravenous lines) should be gained in all patients. Sublingual nitroglycerin and intravenous morphine should be administered if patients have active chest pain. Oxygen saturations should be monitored noninvasively, rather than by arterial blood gas measurement. Supplemental oxygen, 2–4 L/min, should be given to all patients, particularly if they are hypoxemic. A portable chest radiograph should be ordered but should not delay reperfusion, unless a diagnosis of aortic dissection is strongly considered. Echocardiography may be considered if the diagnosis of MI remains in doubt (eg, equivocal history, uninterpretable ECG). Oral -blockers should be administered to all patients with acute MI, unless there is a contraindication, such as hypotension, bradycardia, or asthma. This has been shown to improve outcomes and limit the size of infarction. Intravenous -blockers could be considered when there is hypertension or tachyarrhythmia, for example (Table 5–3). However, they should be avoided in patients with signs of heart failure, in those with contraindications to -blockers, and in those at high risk for cardiogenic shock (age > 70 years, heart rate > 110/min or < 60/min, systolic blood pressure < 120 mm Hg, or prolonged time since the onset of symptoms).

Table 5–3. Standard Intravenous Doses of Commonly Used Agents in Patients with Acute Myocardial Infarction.

Agents Dosage Comments
   Lidocaine Initial bolus of 1 mg/kg and 2 mg/min infusion; additional bolus doses to 3 mg/kg may be necessary. For symptomatic arrhythmias and sustained ventricular tachycardia and ventricular fibrillation, not arrest
   Procainamide 20 mg/min–1 g, then 2–4 mg/min drip May cause hypotension, QRS or QT lengthening, or toxicity
  Magnesium 1–2 g over 1–2 min or infusion of 8 g over 24 h Observe for changes in heart rate, blood pressure
   Amiodarone 15 mg/min x 10 min, then 1 mg/min x 6 h and 0.5 mg/min x 24 h For refractory ventricular tachycardia, ventricular fibrillation and arres
   Esmolol 250 mcg/kg IV loading dose, then 25–50 mcg/kg/min to maximum dose of 300 mcg/kg/min Very short half-life
   Metoprolol 5 mg q 5 min IV x 3 then 25–50 mg q12h orally Long duration of action; may exacerbate heart failure
   Propranolol 0.1 mg/kg over 5 mm IV, followed by 20–40 mg q6h orally Long duration of action; may exacerbate heart failure
Calcium channel blockers  
   Diltiazem 20–25 mg IV test dose, then 10–15 mg/h as needed; 90–120 mg three times daily orally May exacerbate heart failure
Inotropes and Pressors  
  Amrinone Initial bolus of 0.75 mg/kg, then 5–10 mg/kg/min May exacerbate ischemia
   Dobutamine Begin at 2.5 mcg/kg/min and titrate to effect Increases in heart rate > 10% may exacerbate ischemia
   Dopamine Start at 2 mcg/kg/min, titrate to effect May exacerbate pulmonary congestion and ischemia
   Norepinephrine Start at 2 mcg/min, titrate to effect Temporizing treatment only
   Nitroglycerin Begin at 10 mcg/min IV, titrate to effect Avoid reducing blood pressure by > 10% if normotensive, > 30% if hypertensive
   Nitroprusside Begin at 0.1 mcg/kg/min, titrate to effect Mean dose 50–80 mcg/kg/min
   Nesiritide 2 mcg/kg bolus followed by 0.01 mcg/kg/min infusion, can increase by 0.005 to maximum infusion 0.03 mcg/kg/min Hold diuretics and other vasodilators. Keep systolic blood pressure > 100 mm Hg
  Unfractionated heparin 5000 unit bolus followed by 1000 units/h adjusted by a PTT Less efficacious than LMWH
   Enoxaparin 1 mg/kg SQ q12h, can give immediate 30 mg bolus intravenously if necessary Hard to reverse effects; avoid in patients with renal failure
   Dalteparin 120 international units/kg q12h Avoid in patients with renal failure
   Abciximab 0.25 mg/kg followed by 0.125 mcg/kg/min x 12 h, maximum time-24 h Care necessary if renal failure; thrombocytopenia greater with repeated use
   Eptifibatide 180 mcg/kg bolus x 2 (30 min later) followed by 2 mcg/kg/min for as long as 96 h for ACS, 24 h post PCI Care necessary if renal failure
   Tirofiban 0.4 mcg/kg/min x 30 min followed by 0.1 mcg/kg/min for up to 108 h for ACS, 12–19 h for PCI Care necessary if renal failure
   Clopidogrel 300 mg loading dose, then 75 mg/day x at least 1 month TTP possible

ACS, acute coronary syndromes; LMWH, low-molecular-weight heparin; PCI, percutaneous coronary intervention; PTT, partial thromboplastin time.

Heparin should be administered to all patients with acute MI, unless a contraindication exists. The choice between unfractionated heparin (UFH) infusion and low-molecular-weight heparin (LMWH) should be based on the likelihood of invasive therapy. Unfractionated heparin is preferred in most institutions for invasive therapy (primary PCI) because it has a short half-life, it can be turned off rapidly if there is a complication during invasive therapy, and because it can be monitored during procedures with a bedside activated clotting time test. In contrast, LMWHs have a long half-life, and there is no bedside test of their anticoagulant efficiency. In STEMI, patients undergoing fibrinolysis can have adjunctive UFH or LMWH, with both having evidence of benefit as adjunctive therapy.

Reperfusion Therapy

Patients with STEMI

All patients with STEMI who seek medical care within the first 12 hours after symptom onset should be considered for urgent reperfusion of the infarct-related artery, but the earlier therapy is begun, the greater the benefit. In addition, those patients who seek medical care within 12–24 hours of symptom onset may be considered for reperfusion, particularly if chest pain is ongoing or heart failure or shock has developed, but the benefit of reperfusion therapies after more than 12 hours is less well established. The definitive therapies for reperfusion in STEMI are fibrinolysis or PCI. Both these strategies improve patency of the infarct-related artery, reduce infarct size, and lower mortality rates. Therefore, one or the other method should be performed as quickly as possible. The goal of reperfusion therapies in the United States is a door-to-needle time of 30 minutes (for fibrinolysis) and a door-to-balloon inflation time of less than 90 minutes (for PCI). Percutaneous coronary intervention has been shown to be superior to fibrinolysis when it is performed without significant delay by experienced clinicians in experienced centers (Figure 5–5). However, significant delays in performing PCI reduce its benefit over fibrinolytic therapy. There are special cases where primary PCI is always preferred over fibrinolysis: cardiogenic shock, severe CHF or pulmonary edema (Killip class III), or if there are contraindications to fibrinolysis (Table 5–4). These patients may require insertion of an IABP and may benefit from mechanical reperfusion with primary PCI. The different management of patients with these high-risk clinical features underscores the need for careful clinical examination of all patients with chest pain.

Figure 5–5.

PCI vs fibrinolysis for STEMI. Short-term (4 to 6 weeks; A) and long-term (B) outcomes for various end points shown are plotted for STEMI patIents randomized to PCI or fibrinolysis for reperfusion in 23 trials (n = 7739). Primary angioplasty for acute STEMI improves both short- and long-term outcomes. (CVA, cerebrovascular accident; Hem. Stroke, hemorrhagic stroke; Rec. Isch, recurrent ischemia; ReMI, recurrent myocardial infarction; STEMI, ST elevation myocardial infarction.)

(Modified, with permission, from Keeley et al. The Lancet. 2003;361:13 and Antman et al. J Am Coll Cardiol. 2004;44:671.)

Table 5–4. Contraindications for Fibrinolysis Use in STEMI.

Absolute contraindications


Any prior ICH


Known structural cerebral vascular lesion (eg, AVM)


Known malignant intracranial neoplasm (primary or metastatic)


Ischemic stroke within previous 3 months


Suspected aortic dissection


Active bleeding or bleeding diathesis (excluding menses)


Significant closed head or facial trauma within 3 months


Severe uncontrolled hypertension (SBP > 180 mm Hg and/or DBP > 110 mm Hg)

Relative contraindications


History of prior ischemic stroke greater than 3 months, dementia, or known intracranial pathology not covered in contraindications


Traumatic or prolonged (greater than 10 minutes) CPR or major surgery in previous 3 weeks


Recent internal bleeding (within 4 weeks)


Noncompressible vascular punctures


For streptokinase/anistreplase: prior exposure (more than 5 days ago) or prior allergic reaction to these agents




Active peptic ulcer


Current use of anticoagulants: the higher the INR, the higher the risk of bleeding

AVM, arteriovenous malformation; CPR, cardiopulmonary resuscitation; DBP, diastolic blood pressure; ICH, intracranial hemorrhage; INR, international normalized ratio; SBP, systolic blood pressure; STEMI, ST elevation myocardial infarction.

Recent data suggest that all patients with STEMI, whether they undergo primary PCI or fibrinolytic therapy, benefit from early administration of clopidogrel. However, this may cause an increase in bleeding complications if the patient undergoes CABG surgery. Therefore, administration of a clopidogrel 300 mg loading dose followed by 75 mg daily should be considered in all STEMI patients, whether they receive fibrinolysis or primary PCI.

Patients with NSTEMI

These patients should not be treated with fibrinolytics. The definitive management of NSTEMI involves anticoagulation, platelet inhibition, and an early invasive strategy (ie, routine coronary angiography with or without PCI during the index hospitalization).

All patients should receive aspirin and general acute MI treatment as discussed above. Anticoagulation with heparin, either UFH or LMWH, should be given to all patients. Unless CABG surgery is anticipated, all patients should receive clopidogrel, since it reduces recurrent ischemia in NSTEMI. Clopidogrel should be continued for 9–12 months. In addition to aspirin, heparin, and clopidogrel, all NSTEMI patients should be treated with a glycoprotein IIb/IIIa inhibitor (eptifibatide, abciximab, or tirofiban) immediately after the diagnosis is made and continued until after coronary angiography with or without PCI. Most NSTEMI patients treated with all the above will experience recovery from their ischemic symptoms and therefore do not need to be taken to the cardiac catheterization laboratory emergently. However, if there is ongoing ischemia that cannot be controlled by the above measures, or if there is cardiogenic shock or pulmonary edema, the patient should be taken emergently to the cardiac catheterization laboratory for insertion of IABP and coronary angiography with or without PCI.

In-Hospital Management

All patients with acute MI should be admitted for continuous cardiac monitoring. Patients should have bed rest for the first 12–24 hours following MI and reperfusion, but in the absence of ongoing ischemia, should be mobilized after this time. All patients should receive the appropriate cardiac diet, adhering to the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) dietary guidelines, as well as education regarding the necessary dietary changes they should make after discharge.

Within the first 24 hours of presentation, the long-term medical management of patients with both STEMI and NSTEMI should be commenced (Table 5–5). Angiotensin-converting enzyme (ACE) inhibitors should be given on day 1, if the patient’s blood pressure allows, particularly in those with anterior MI or impaired left ventricular function. ACE inhibitors reduce left ventricular remodeling and heart failure and should be continued long-term. -Blockade should have already been started in the emergency department and should be continued orally in all patients, unless there are absolute contraindications, and should also be continued long-term. Aspirin, 162–325 mg daily, should be administered initially, then 81 mg daily for life. Clopidogrel, 75 mg daily, should be administered for at least 1 month in all patients, and longer-term therapy should be considered. Patients who receive bare metal stents should receive at least 1 month of aspirin 325 mg daily, and clopidogrel 75 mg daily, then aspirin 81 mg daily for life. Patients receiving drug-eluting stents should receive clopidogrel 75 mg daily for at least 1 year, and aspirin for life. Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statin therapy) should be given soon after MI and should be continued at high dose long-term.

Table 5–5. Meta–Analysis of Randomized Trials of Drug Therapy Administered during and after Acute Myocardial Infarction.

Drug Class and Time Administered Number of Trials Number of Patients Relative Risk of Death (95% CI) P Value 
–Adrenergic antagonists          
During MI 29 28,970 0.87 (0.77–0.98) 0.02
After MI 26 24,298 0.77 (0.70–0.84) < 0.001
ACE inhibitors          
During MI 15 100,963 0.94 (0.89–0.98) 0.006
After MI, patients with left ventricular dysfunction 3 5,986 0.78 (0.70–0.86) < 0.001
Nitrates (during MI) 22 81,908 0.94 (0.90–0.99) 0.03
Calcium channel blockers (during and after MI) 24 20,342 1.04 (0.95–1.14) 0.41
Antiarrhythmic drugs          
Lidocaine (during MI) 14 9,155 1.38 (0.98–1.95) > 0.05
Class I drugs (after MI) 18 6,300 1.21 (1.01–1.44) 0.04
Amiodarone (after MI) 9 1,557 0.71 (0.51–0.97) 0.03
Magnesium (during MI) 11 61,860 1.02 (0.96–1.08) > 0.05

ACE, angiotensin-converting enzyme; MI, myocardial infarction.

Reproduced, with permission, from Hennekens CH et al. N Engl J Med. 1996;335:1660.

During hospitalization, all patients should be educated about adhering to therapeutic lifestyle changes, including dietary and lifestyle measures, smoking cessation, and medication compliance. Selected patients should be referred to a cardiac rehabilitation program to consolidate these messages and develop an appropriate exercise regimen.

Primary PCI versus Fibrinolysis

The goal of reperfusion is to rapidly restore blood flow to the myocardium to prevent ongoing ischemic cell death. Therefore, whichever means can achieve reperfusion most quickly should be used. Primary PCI results in improved patency rates of the infarct-related artery, as well as improved TIMI flow grade, compared with fibrinolysis. In general, the patency rate with primary PCI is 90% or higher, whereas with thrombolysis, the rate is about 65% and recurrent events are more common. With modern advances, coronary stenting has further improved long-term outcomes over balloon angioplasty alone. Percutaneous coronary intervention has therefore been widely accepted as the treatment of choice for STEMI in centers that can perform primary PCI rapidly and effectively (Figure 5–6). However, very early after the onset of symptoms, when the thrombus in the infarct-related artery is still soft, fibrinolysis may recanalize the artery as quickly as, if not more so than, primary PCI. This is true in the first hour and possibly the first 3 hours after symptom onset. Therefore, fibrinolysis is an acceptable treatment in these early time-points. However, after 3 hours, primary PCI has a clear benefit over fibrinolysis and should be considered the preferred therapy. It bears re-stating that primary PCI should only be performed in centers skilled in the treatment of STEMI that can achieve rapid reperfusion, with a goal door-to-balloon inflation time of 90 minutes.

Figure 5–6.

Primary PCI for acute MI. A:  Initial angiography of a patient presenting with acute anterior STEMI shows an occluded left anterior descending (LAD) coronary artery (arrow). B: Following angioplasty and stenting, patency of the LAD is restored.

In deciding whether elderly patients with acute STEMI should undergo PCI or fibrinolytic therapy, the risks and benefits must be weighed carefully. Elderly patients with STEMI are at high risk for increased morbidity and mortality with thrombolytic agents. Indeed, some studies suggest that these agents have no benefit in this group. On the other hand, PCI is clearly beneficial. However, if PCI cannot be accomplished, individual decisions concerning the risk (which is substantial, especially in regard to intracranial bleeding) and the potential benefits must be balanced. Given the high (20–30%) mortality rate from STEMI in the elderly, some increased risk may be reasonable.

Fibrinolytic Agents

There are a number of fibrinolytic agents that have been successfully used in acute MI. Table 5–6 shows the currently approved agents for use in the United States. A brief discussion of each is warranted before deciding on the most appropriate agent. Plasmin, the key ingredient in the fibrinolytic system, degrades fibrin, fibrinogen, prothrombin, and a variety of other factors in the clotting and complement systems. This effect inhibits clot formation and can lead to bleeding. Patients with acute MI and ST-segment elevation have little evidence of spontaneous or intrinsic fibrinolysis, despite the intense thrombotic stimulus present. This may be due in part to increased levels of circulating plasminogen activator inhibitor (PAI-1) in plasma or PAI-1 that is elaborated locally from platelets. The pharmacologic administration of fibrinolytic agents (Table 5–6) to such patients seems reasonable. Plasminogen activators can be administered intravenously or directly into the coronary artery. Although more rapid patency occurs with local administration, and lower doses can be used, given the need for early treatment, plasminogen activators are generally administered intravenously.

Table 5–6. Fibrinolytic Agents.

Agent Dosage Adjunctive Treatments
Streptokinase 1,500,000 units over 1 h Aspirin, ± heparin
Tissue plasminogen activator    
  Standard 15 mg bolus, then 50 mg over 30 min and 35 mg over next 60 min Aspirin, heparin, essential
  Patients weighing less than 65 kg 1.25 mg/kg over 3 h, 10% of dose as initial bolus  
Urokinase 3,000,000 units over 1 h Aspirin, ± heparin
Reteplase 10 mg initial bolus, second 10-mg bolus after 30 min Aspirin, heparin, essential
Tenecteplase < 60 kg: 30-mg bolus  
  60–70 kg: 35-mg bolus  
  71–80 kg: 40-mg bolus  
  81–90 kg: 45-mg bolus  
  > 90 kg: 50-mg bolus Aspirin, heparin essential

In addition to invoking fibrinolysis and inhibiting clotting by degrading clotting factors, all plasminogen activators enhance clot formation. These effects seem greater with nonspecific plasminogen activators such as streptokinase and urokinase and could partly explain why fibrin-specific activators such as t-PA open arteries more rapidly. The enhancement of coagulation by plasminogen activators suggests an important role for the concomitant use of antithrombotic agents.

All fibrinolytic agents increase the risk of bleeding and therefore patients at high risk for life-threatening bleeding should not be given fibrinolysis (Table 5–4).


Streptokinase is derived from streptococcal bacteria and activates plasminogen indirectly, forming an activator complex with a slightly longer half-life than streptokinase alone (23 minutes versus 18 minutes after a bolus). Because it activates both circulating plasminogen and plasminogen bound to fibrin, both local and systemic effects occur; that is, circulating fibrinogen degrades substantially (fibrinogenolysis as well as fibrinolysis occurs).

Because antibodies to the streptococci exist in many patients, allergic reactions can occur; anaphylaxis is rare, however, and the use of corticosteroids to avoid allergic reactions is no longer recommended. When streptokinase is administered intravenously, a large dose is necessary to overcome antibody resistance. Because a dose of 250,000 units will suffice in 90% of patients, the recommended dose of 1.5 million units over a 1-hour period is generally more than adequate to overcome resistance. Patients who are known to have had a severe streptococcal infection or to have been treated with streptokinase within the preceding 5 or 6 months (or longer) should not receive the agent.

Rapid administration of streptokinase, even at the recommended dose, can cause a substantial reduction in blood pressure. Although this might be considered a potential benefit of the agent, it may also be detrimental. The rate of the infusion should therefore be reduced in response to significant hypotension, and the blood pressure should be monitored closely. Because streptokinase is more procoagulant than other thrombolytic agents, it should not be surprising that patients benefit to a greater extent from the concomitant use of potent antithrombins such as hirudin. However, in combination with glycoprotein IIB/IIIA inhibitors, streptokinase seems to be associated with markedly increased bleeding rates.


Urokinase is a direct activator of plasminogen. It has a shorter half-life than streptokinase (14 ± 6 minutes) and is not antigenic. Its effects on both circulating and bound-to-fibrin plasminogen are similar to those from streptokinase. It is therefore difficult to understand why intravenous doses of urokinase (2.0 million units as bolus or 3 million over 90 minutes) seem to induce coronary artery patency more rapidly than does streptokinase. There is substantial synergism between urokinase and t-PA.

Tissue Plasminogen Activator

The initial human t-PA was made by recombinant DNA technology. The half-life in plasma was short (4 minutes) as a bolus but longer (46 minutes) with prolonged infusions. Despite the short half-life, lytic activity persisted for many hours after clearance of the activator. Although t-PAs are considered “fibrin-specific,” no activator is totally fibrin-specific, and fibrin specificity is lost at higher doses. At clinical doses, however, less fibrinogen degradation took place than with nonspecific activators. Tissue plasminogen activator clearly opened coronary arteries more rapidly than nonspecific activators and this is likely why its use improved mortality rates. Bleeding was not less and there was a slight increase in the number of intracranial bleeds, which was in part due to the need for dosage adjustment for lighter-weight patients.

The original regimen for the use of t-PA was 100 mg over 3 hours: 10 mg as a bolus, followed by 50 mg over the first hour and 40 mg over the next 2 hours. Patients who weighed less than 65 kg received 1.25 mg/kg over 3 hours with 10% of the total dose given as a bolus. An alternative front-loaded regimen was found to be more effective and included an initial bolus of 15 mg, followed by 50 mg over 30 minutes and 35 mg over the next 60 minutes. Doses higher than 100 mg are associated with a higher incidence of intracranial bleeding.


Reteplase, a mutant form of t-PA, lacks several of the structural areas of the parent molecule (the finger domain, kringle 1, and the epidermal growth factor domain). It is less fibrin-specific (causes more systemic degradation of fibrinogen) than the parent molecule and has a longer half-life. Accordingly, it is used as a double bolus of 10 units initially followed by a second bolus 30 minutes later, and this requires no adjustment for patient weight. Although not shown to be superior to t-PA, many clinicians have elected to use reteplase because of the convenience of the double bolus administration.


Tenecteplase is also a mutant form of t-PA. It has substitutions in the kringle 1 and protease domains to increase its half-life, increase its fibrin specificity, and reduce its sensitivity to its native inhibitor (PAI-1). Although not shown to be superior to t-PA, tenecteplase is generally being used in preference to the parent molecule because of the convenience of a single bolus dose.

Regardless of the fibrinolytic agent used, all patients should receive aspirin and heparin (either UFH or LMWH) to counteract the procoagulant effect of the fibrinolytic agent.

Intravenous heparin, used with plasminogen activators, improves the rapidity with which patency is induced; it is essential for maintaining coronary patency, especially with t-PA type agents. Its use is less necessary after treatment with streptokinase, probably because of the anticoagulant effects of fibrinogen depletion and degradation products.

The standard dose of UFH is usually a bolus of 5000 units, followed by a 1000-unit-per-hour infusion until the partial thromboplastin time can be used to titrate a dose between 1.5 and 2 times the normal range. It has become clear that optimal titration of UFH is problematic and that if the activated partial thromboplastin time is either too high or too low, some benefit is lost. For this reason, the use of LMWH has been recommended. With the exception of patients with renal failure, a dose of 1 mg/kg of enoxaparin and 120 unit/kg of dalteparin provide consistent reduction in anti-Xa levels and thus consistent anticoagulation. This is probably the reason that recent studies suggest LMWH is more effective for the treatment of patients with acute MI. In addition, because LMWH inhibits Xa activity predominantly, there is some suggestion that discontinuing it may be less problematic than is the case for UFH, which has fewer effects on Xa and more direct effects (when combined with antithrombin 3) on thrombin itself. The ability to use LMWH intravenously in the catheterization laboratory has not been a problem in regions where this strategy has been embraced.

Adverse Effects of Fibrinolytic Therapy

The most serious complication of treatment with thrombolytic agents is bleeding, particularly intracranial hemorrhage; however, catheter-based interventions substantially reduce this complication. The mechanism of bleeding with thrombolytic agents is unclear but has been related to the efficacy of the agent; the concomitant use of antithrombotic agents, such as heparin and aspirin; and the degree of hemostatic perturbation induced by the plasminogen activators. In most studies, the incidence of stroke and intracranial bleeding has been slightly higher with t-PA type activators. This may be in keeping with the greater efficacy and rapidity of their effects. Although most bleeding occurs early during treatment, bleeding can occur 24–48 hours later, and vigilance even after the first few hours is important.

Intracranial bleeding is by far the most dangerous bleeding complication because it is often fatal. For most plasminogen activators, the incidence of intracranial hemorrhage is less than 1%, but it may be as high as 2–3% in elderly patients. Risk factors for intracranial bleeding include a history of cerebrovascular disease, hypertension, and age. These factors must be taken into account when determining whether a thrombolytic agent has an appropriate benefit-to-risk relationship. Changes in mental status require an immediate evaluation—clinical and computed tomography or magnetic resonance imaging. If bleeding is strongly suspected, heparin should be discontinued or neutralized with protamine.

There also is a substantial incidence of nonhemorrhagic, probably thrombotic, stroke that may be partly due to dissolution of thrombus within the heart, followed by migration. The exact mechanisms of this phenomenon are unclear. In some studies, the excess of strokes with t-PA has been found to be related to this phenomenon, and in other studies, it has been due to an apparent increase in intracranial bleeding.

Bleeding outside the brain can occur in any organ bed and should be prevented whenever possible. The puncture of noncompressible arterial or venous vessels is relatively contraindicated in all cardiovascular patients: those with unstable angina one day may be candidates for thrombolytic treatment on the next. Blood gas determinations should therefore be avoided if possible and oximeters used instead in cardiovascular patients. It should be understood that central lines placed in cardiovascular patients pose a substantial risk should there be a subsequent need for a lytic agent. Foley catheters and endotracheal (especially nasotracheal) intubation can also predispose to significant hemorrhage. Bleeding should be watched for assiduously. If severe bleeding occurs while heparin is in use, it should be antagonized with protamine. In general, this and supportive measures are all that can be done. In some studies, there appears to be a slightly higher incidence of extracranial bleeding with nonspecific activators than with t-PA; this finding has not been consistent. In an occasional patient, who begins to bleed shortly after receiving the plasminogen activator, aminocaproic acid, which changes the activation of plasminogen, may be useful. Otherwise, discontinuation of the drug and conservative local measures are all that can be done. If volume repletion is necessary, red blood cells are preferred to whole blood, and cryoprecipitate is preferred to fresh frozen plasma because it does not replenish plasminogen.

Allergic reactions related to the use of streptokinase are unusual but should be identified when they occur. Mild reactions, such as urticaria, can be treated with antihistamines; more severe reactions, such as bronchospasm, may require corticosteroids or epinephrine.

Bleeding after primary PCI can also be substantial, particularly if glycoprotein IIB/IIIA agents are administered. The use of newer closure devices are touted by some clinicians, but close observation is the key to minimizing bleeding from the catheter site. On occasion, platelet transfusions may be necessary.

Antman EM et al; American College of Cardiology; American Heart Association; Canadian Cardiovascular Society. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction—executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1999 guidelines for the management of patients with acute myocardial infarction). J Am Coll Cardiol. 2004 Aug 4;44(3):671–719. [PMID: 15358045]

Braunwald E et al; American College of Cardiology; American Heart Association. Committee on the Management of Patients with Unstable Angina. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non–ST-segment elevation myocardial infarction—summary article: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee on the Management of Patients with Unstable Angina). J Am Coll Cardiol. 2002 Oct 2;40(7):1366–74. [PMID: 12383588]

Sabatine MS et al; CLARITY-TIMI 28 Investigators. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med. 2005 Mar 24;352(12):1179–89. [PMID: 15758000]

Stone GW et al; Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Investigators. Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction. N Engl J Med. 2002 Mar 28;346(13):957–66. [PMID: 11919304]

Yusuf S et al; Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001 Aug 16;345(7):494–502. [PMID: 11519503]

Complications of Myocardial Infarction

The complications of acute MI are listed in Table 5–7.

Table 5–7. Complications of Acute MI.

Cardiogenic shock
Congestive heart failure (CHF)
Ischemic mitral regurgitation
Ventricular septal defect (VSD)
Free wall rupture
Recurrent ischemia
Conduction disturbances
Mural thrombus
Aneurysm or pseudoaneurysm of the left ventricle
Right ventricular infarction

Cardiogenic Shock

Cardiogenic shock is characterized by peripheral hypoperfusion and hypotension refractory to volume repletion. This occurs secondary to inadequate cardiac output resulting from severe left ventricular dysfunction.

Goals of therapy for cardiogenic shock include hemodynamic stabilization to ensure adequate oxygenation of perfused tissue and prompt assessment for reversible causes of the cardiogenic shock. If reversible causes are not found, immediate reperfusion, especially with PCI, is indicated (see Chapter 6).

Congestive Heart Failure

In general, there is greater urgency in treating patients with CHF during the early phases of acute MI because such patients often have multivessel disease and are at increased risk for recurrent infarction and increased infarct size. A high degree of suspicion and close monitoring are key to anticipating this complication of acute MI.

Echocardiography has been the technique of choice in evaluating such patients from a perspective of both valvular and myocardial function. Swan-Ganz pulmonary artery catheterization can also be used to aid diagnosis and to assess ongoing management. Management strategies depend on the clinical history of the patient. Patients with new-onset acute CHF are typically euvolemic and benefit from nitrate therapy for ischemia. These patients in general should not receive diuretics initially because diuretic therapy often complicates the clinical course with the development of hypotension. In addition, reduced respiratory effort, reduced heart rate, and normalization of oxygen saturation are central to early clinical management.

Nitroglycerin is often the best agent to use for ischemia in patients with CHF. In some instances, the hemodynamic profile provided by nitroprusside may be desirable. However, nitroprusside may exacerbate ischemia by inducing a coronary steal phenomenon; in this setting, nitroprusside would be a second-line therapy.

Continuous positive airway pressure can reduce the work of breathing in patients with pulmonary edema and should be considered early in these patients.

Nesiritide (recombinant b-type natriuretic peptide) infusion has demonstrated hemodynamic and neurohormonal benefits in the management of acute heart failure.

Intravenous ACE inhibitor therapy should not be used in this setting until hemodynamic stability is achieved. Hypotension is a complicating factor because it reduces coronary perfusion and may lead to further ischemia. Low-dose dobutamine, starting at 2.5 mcg/kg/min, can be used to achieve hemodynamic benefit. Also, phosphodiesterase inhibitors can be considered although their vasodilating effects may limit their inotropic benefit in patients with significant hypotension.

The use of Swan-Ganz catheterization monitoring is controversial, and no randomized controlled data support their use as a first-line recommendation in the management of CHF with acute MI. However, Swan-Ganz monitoring can be beneficial in verifying diagnosis, and its use in the early phases of management may allow rapid titration of parenteral therapy.

Once hemodynamic stabilization has been achieved, which is generally within the first 6–12 hours, initiation of oral agents is appropriate. Drugs of choice in this setting are ACE inhibitors, which improve cardiac performance, have beneficial effects on ventricular remodeling, and have been demonstrated not only to reduce morbidity but also to reduce mortality rates in patients with CHF. Oral -blocker therapy should also be initiated early in the treatment of these patients; however, this should be done in a stepwise fashion in relation to ACE inhibitor therapy to avoid hypotensive effects.

Aldosterone blockade with spironolactone or eplerenone should be given to patients with left ventricular impairment (left ventricular ejection fraction less than 40%) or clinical heart failure or both following MI. Aldosterone blockade should be started, in addition to ACE inhibitors, in patients who do not have significant renal impairment or hyperkalemia. The serum potassium level should be monitored closely, since both eplerenone and spironolactone can cause hyperkalemia.

Acute Mitral Valve Regurgitation

The development of acute severe mitral valve regurgitation occurs in approximately 1% of patients with acute MI and contributes to 5% of deaths. Mitral regurgitation occurs as a result of papillary muscle rupture most commonly involving the posterior medial papillary muscle because its singular blood vessel supply is derived from the posterior descending coronary artery. In contrast, the anterior lateral papillary muscle much less commonly ruptures because it has a dual blood supply derived from the left anterior descending and circumflex coronary arteries. Rupture of the papillary muscle may be complete or partial with the development of a flail mitral valve leaflet. Pulmonary edema usually ensues rapidly and occurs within 2–7 days after inferior infarction. The intensity of associated murmur varies depending on the extent of unobstructed flow back into the left atrium. If severe regurgitation is present, no murmur may be audible. As a result, a high degree of suspicion is needed to promptly diagnose acute mitral regurgitation. Two-dimensional echocardiography can be used to demonstrate the partial or completely ruptured papillary muscle head and the flail segment of the mitral valve. Typically, hyperdynamic left ventricular function is demonstrated, and its occurrence in severe CHF should prompt the diagnosis. The treatment of choice is to stabilize the patient hemodynamically with the use of intravenous vasodilators and possibly intra-aortic balloon counterpulsation. The basis of a successful outcome, however, is prompt emergency surgery. The operative mortality rate in this setting can be up to 10%, but this affords most opportunity for survival. Mitral valve repair with reimplantation of the severed papillary muscle is the preferred technique as an alternative to mitral valve replacement. The mortality rate is unacceptably high in the absence of prompt surgery.

Ischemic mitral regurgitation without papillary muscle rupture occurs in up to 50% of patients with acute inferior wall MI. In those patients in whom severe CHF symptoms develop, hemodynamic compensation needs to be undertaken and could include the use of IABP for adequate afterload reduction. Treatment of ischemia in this setting may include reperfusion therapy with PCI, intravenous vasodilator therapy, and mechanical support. Once the acute phase of the infarction is past, resolution of the severe mitral regurgitation may occur, which then avoids the need for surgery.

Acute Ventricular Septal Rupture

Rupture of the ventricular septum has been reported to occur in up to 3% of acute MIs and contributes to about 5% of deaths. Typically, half of VSDs occur in anterior wall MIs, often in patients with their first infarction, with peak incidence occurring 3–7 days after initial infarction. Findings associated with VSD can be confused with acute mitral regurgitation because both can result in hypotension, severe heart failure, and prominent murmur. However, the diagnosis of VSD should be suspected clinically when a new pansystolic murmur is noted. Generally, the murmur is most prominent along the left sternal border and may have an associated thrill. Prompt surgical intervention is recommended, which, if successful, can reduce the mortality rate from nearly 100% to below 50%.

Although percutaneous repair of postinfarction VSDs in the catheterization laboratory using septal occluding devices has been reported, surgical repair remains the gold standard.

Cardiac Rupture

Rupture of the free wall of the left ventricle occurs in approximately 1–3% of patients with acute infarction and accounts for up to 15% of peri-infarction deaths. Free wall rupture may occur as early as within the first 48 hours of infarction. Fifty percent of ruptures occur within the first 5 days of infarction and 90% within the first 2 weeks. Rupture may be due to expansion of the peri-infarct zone, with thinning of the infarcted wall occurring in response to increased stress. The paradoxical motion of the infarcted segment at the margin of the infarcted zone may also contribute stress, resulting in muscle rupture. Patients may complain of recurrence of chest pain, and an ECG may show persistent ST elevation with Q waves. Prompt intervention at that time may include echocardiography with pericardiocentesis, IABP placement, and urgent cardiac catheterization with anticipation of immediate surgery. Unfortunately, all too often signs of cardiac rupture are not present until acute hemodynamic decompensation occurs with cardiac arrest due to electromechanical dissociation. Successful treatment of cardiac rupture requires the clinician to have a high index of suspicion and undertake immediate intervention if there is to be any possibility of preventing death.

Recurrent Ischemia

Episodes of chest pain recur in up to 60% of patients after infarction. When chest discomfort recurs early (within 24 hours of MI), the discomfort usually reflects the process of completing the infarction. Chest discomfort may reflect the effects of ongoing ischemia or recurrent infarction. In this situation prompt reassessment and treatment is critical. Patients with hemodynamic compromise in association with new ECG changes in the distribution other than that of the infarct-related artery are at significant risk and require prompt attention, often including coronary angiography with catheter-based intervention.

In those patients who were treated initially with reperfusion therapy and have recurrent chest pain, prompt evaluation is needed to assess the adequacy of anticoagulation and the possibility of reocclusion of the culprit coronary artery. Adequacy of adjunctive therapy in the setting of recurrent chest pain is necessary, and often adjustments in drug doses are required. Occasionally short-term use of intravenous nitroglycerin and intravenous -blockers are required to quiet the ischemic episode. In this setting, glycoprotein IIb/IIIa inhibitors should be considered if no contraindications are present. In patients who have had coronary angiography and PCI, correlation between angiographic findings and the 12-lead ECG should be made. Acute stent thrombosis will usually be seen on the ECG as recurrence of ST elevation. This requires emergent repeat catheterization. Conversely, patients with diffuse coronary artery disease may have ischemia due to narrowings in the non-culprit coronary arteries, precipitated by stress or tachycardia, for example. The treatment of this is anticoagulation, glycoprotein IIb/IIIa inhibitors, and -blockers.

In patients with NSTEMI, recurrent chest pain is a marker of significant risk for reinfarction, especially if transient ST segment and T wave changes are noted or if persistent ST segment depression is associated with the initial presentation. Prompt coronary angiography and PCI is often required in this setting.


Pericarditis is common in patients with acute MI, particularly in the course of transmural infarctions. In general, the larger the area of infarction, the more likely pericarditis will develop. Pericarditis may be clinically silent or may be associated with a pericardial rub, pleuritic chest pain, or pericardial effusion as suggested by chest radiograph or two-dimensional echocardiography. The associated chest discomfort, classically described as being relieved by sitting up, may also be associated with a description of shortness of breath and epigastric discomfort with inflammation of the contiguous diaphragm. Pericardial rubs are most commonly heard when the patient is seated with held inspiration. Late pericardial inflammation occurring 2 weeks to 3 months after MI is termed “Dressler syndrome” and most likely reflects an autoimmune mechanism. Dressler syndrome is often associated with large serosanguinous pleural and pericardial effusions, and tamponade develops in persons who die of this syndrome. The treatment of choice for Dressler syndrome is aspirin, or colchicine, and in some instances corticosteroids may be necessary. The use of corticosteroids, however, is not generally advocated because of the high frequency of relapse when corticosteroid therapy is discontinued. Echocardiographic assessment is appropriate as a follow-up tool in these patients to determine the extent of effusion if present and to exclude tamponade or the possibility of partial myocardial rupture. Nonsteroidal antiinflammatory drugs (NSAIDs) should be avoided in patients with ischemic heart disease, particularly those with evidence of acute infarction. Agents such as indomethacin inhibit new collagen deposition and, therefore, may impair the healing process necessary for stabilization of the infarcted region. This may, in a small number of patients, contribute to the development of myocardial rupture. When used in cases refractory to aspirin, NSAIDs should be used for the shortest time possible and tapered as rapidly as possible. In addition, recent data have linked the use of NSAIDs and cyclooxygenase-2 (COX-2) inhibitors to increased rates of cardiac events. Therefore, the use of NSAIDs and COX-2 inhibitors should be minimized or discouraged. Heparin use early in acute MI should not be stopped if pericarditis is present. However, the presence of Dressler syndrome is a contraindication to heparin use, because of its high incidence of hemorrhage into the pericardial fluid with resulting tamponade.

Conduction Disturbances

The presence of a conduction disturbance is associated with increased in-hospital and long-term mortality rates. The prognostic significance and management of these disturbances may vary with the location of the infarction, the type of conduction disturbance, associated clinical findings, and the extent of hemodynamic compromise. Patients whose conduction disturbances result in bradycardias and produce hemodynamic compromise generally require transvenous pacing. Bradycardias, especially those associated with inferior infarction, can often be treated with atropine. Recurrent episodes, however, warrant insertion of a pacemaker. Often ventricular pacing to provide a back-up rate is all that is required. A need for improved hemodynamics may be a reason to consider atrioventricular (AV) sequential pacing.

Anterior STEMI

The highest risk conduction disturbances occur in these patients. Abnormalities are present early after the onset of infarction and are usually the result of extensive infarction producing pump failure; treatment with a pacemaker may not improve the prognosis. Conduction disturbances in this circumstance are generally right bundle branch block (RBBB), with or without concomitant fascicular block. RBBB without fascicular block may have the same incidence of progression to complete heart block (20–40%) as does an RBBB with fascicular block. Patients with RBBB and a fascicular block with anterior MI should be considered for placement of temporary transvenous pacing and be observed for evidence of progression to complete heart block, warranting permanent transvenous pacing.

Left bundle branch block (LBBB) is most often a chronic manifestation of hypertension and myocardial dysfunction rather than an acute abnormality. In a setting of acute MI, however, it is often difficult to determine whether the LBBB is new. Recommendations have been to use pacemakers for patients with LBBB known to be new; this approach has also been advocated for patients with RBBB. Given the present availability of external pacemakers, these issues appear to be less critical.

In the absence of the signs and symptoms of hemodynamic instability or evidence of the progression to heart block, it is reasonable to observe patients with RBBBs or LBBBs and to use external pacing if conduction disturbances develop. Once such a disturbance develops, a transvenous pacemaker is indicated, and it is likely that AV sequential devices would be of benefit.

Inferior MI

Conduction disturbances with acute inferior MI are often less critical, but they do suggest a poorer prognosis. The conduction disturbances that commonly occur represent involvement of the AV node and usually include first-degree AV block, Mobitz I (Wenckebach) or Mobitz II second-degree AV block with narrow QRS complexes, and complete heart block with a junctional rhythm. Conduction disturbances are more common in patients with right ventricular infarction. If hemodynamic stability is maintained, patients with these conduction disturbances do not require pacemakers, and they often respond to the administration of atropine (0.5 mg intravenously). If hemodynamic compromise occurs in association with either Wenckebach block or a junctional rhythm, however, or if any arrhythmia requires treatment with more than one dose of atropine, a transvenous pacemaker is warranted. Large initial or total doses of atropine can lead to tachycardia with exacerbation of ischemia and, at times, ventricular tachycardia (VT) or ventricular fibrillation (VF). For patients with right ventricular infarction and hemodynamic compromise associated with the loss of atrial kick, an AV sequential pacemaker is recommended. In general, hemodynamically significant conduction disturbances occur in patients with inferior infarction early during the evolution of infarction; late conduction disturbances are usually well tolerated. Some of these conduction disturbances respond to an intravenous infusion of 250 mg of aminophylline.

Mobitz II Second-Degree AV Block

Mobitz II second-degree AV block or complete heart block with a wide QRS complex are both absolute indications for transvenous pacemaker insertion. Such disturbances can occur from electrolyte abnormalities or conduction system disease, but they are most often associated with hemodynamic abnormalities caused by bradycardia. The use of temporary AV sequential pacing may benefit patients who have hemodynamic abnormalities; these patients are also likely to require permanent pacing (see the section, Prognosis, Risk Stratification, & Management).

Other Arrhythmias

Sinus Tachycardia

Sinus tachycardia occurs in up to 25% of patients with acute MI. It is a marker of physiologic stress (pain, anxiety, hypovolemia) and often indicates the presence of CHF. In some patients, such as those with right ventricular infarction, it may represent relative or absolute volume depletion. In general, although tachycardia increases myocardial oxygen consumption and can exacerbate ischemia, it should not be treated as a discrete entity. The proper approach is to treat the underlying physiologic drive. It may be unwise to block a tachycardia that is compensating for the increased cardiac work required, for example, by sepsis. Accordingly, -blockers should only be used once it is clear that no underlying abnormality is inducing the tachycardia or that the underlying abnormality (eg, hyperthyroidism) is amenable to such treatment. Making this determination may require hemodynamic monitoring.

Supraventricular Tachycardia

Paroxysmal supraventricular tachycardia (PSVT), atrial flutter, and atrial fibrillation can all occur with acute MI. Atrial fibrillation is by far the most common arrhythmia and is often associated with the presence of high atrial filling pressures. The presence of supraventricular tachycardia should lead to consideration of CHF as a cause. A complete differential diagnosis, including conditions such as hyperthyroidism, pulmonary embolism, pericarditis, and drug-induced arrhythmias, is appropriate. Paroxysmal supraventricular tachycardia should be treated immediately because of the high likelihood in this setting that the tachycardia will induce ischemia. Adenosine in bolus doses of 6–12 mg intravenously is the initial approach of choice and often terminates the tachycardia. If it does not, cardioversion should be considered prior to other treatment, unless the PSVT terminates and restarts recurrently. Prolonged pharmacologic management before cardioversion may complicate the procedure, and the delay may induce toxicity if the heart rate is rapid, even in the absence of overt hemodynamic compromise. For recurrent or once-terminated PSVT (depending on the mechanisms of the tachycardia; see Chapter 20), small doses of digitalis, diltiazem, verapamil, or a class I antiarrhythmic agent are reasonable choices for maintenance, as long as the indications and contraindications for each of these agents are kept in mind.

Atrial flutter and atrial fibrillation are generally markers of CHF. Frequently the diagnosis of flutter or fibrillation is made after administration of adenosine; once diagnosed, control of the ventricular response is critical. This can generally be accomplished with digitalis, verapamil, or diltiazem in conventional doses (see Chapter 21) once the CHF is treated. Intravenous diltiazem is effective in an emergency situation, usually with an initial test dose of 20–25 mg. If the response is favorable, a titrated dose of 10–15 mg/h should be used. Intravenous diltiazem should be used cautiously in patients with acute MI and CHF. Cardioversion is indicated if a rapid ventricular response persists; the ventricular rate is difficult to control; or there are signs of hypotension, CHF, or recurrent ischemia. In general, PSVT and atrial flutter require 100 J as the initial shock energy; atrial fibrillation requires 200 J.

Arrhythmias that recur after transient reversion in response to pharmacologic maneuvers or cardioversion require additional treatment. Treatment of the underlying initiating stimulus is critical. -Blockers can also be used to control the ventricular response acutely or for maintenance.

Ventricular Arrhythmias

The incidence of postinfarct malignant ventricular arrhythmias in patients with acute MI appears to be diminishing, perhaps because of the use of reperfusion therapy. It also is conceivable that interventions such as intravenous -blockers have also contributed to this decline. Because of the diminishing incidence of VT and fibrillation in patients with acute infarction, as well as an unfavorable benefit-risk ratio, the use of prophylactic lidocaine is not recommended. Although prophylactic lidocaine reduces the incidence of VF, it is associated in many series with an increase in cardiac death, possibly because it abolishes ventricular escape rhythms in patients who may also be prone to bradycardia. Because warning arrhythmias, once considered progenitors of VF, do not appear to be highly predictive, it is recommended that only symptomatic arrhythmias and VT be indications for treatment.

VT with hemodynamic compromise, angina or pulmonary edema, and VF should be treated with immediate electric shock. Sustained monomorphic VT without hemodynamic compromise, angina, or pulmonary edema can be treated with amiodarone. Amiodarone should be administered as an initial bolus of 150 mg over 10 minutes. If arrhythmias persist, additional boluses of 150 mg every 10–15 minutes can be given; however, the total dose should never exceed 2.2 g in 24 hours. Hypotension and CHF can be induced during the acute administration of amiodarone as a result of its negative inotropic effects. If amiodarone does not relieve the symptoms or the arrhythmias, patients can be treated with intravenous procainamide. The initial loading dose is 1 g, at no more than 50 mg/min, followed by a 2–6 mg/min drip. The infusion rate should be reduced if hypotension occurs; this effect is due to procainamide’s -adrenergic effects. If successful, the drug is continued until the patient is hemodynamically stable; it can then be tapered after initiation of treatment with secondary-prevention agents and an assessment made in terms of long-term risk stratification. On rare occasions, a pacemaker may need to be placed in the right ventricle to compete with or overdrive-suppress malignant ventricular arrhythmias. This is usually reserved for rhythms refractory to pharmacologic therapy and can, on occasion, be life-saving. The ventricular pacemaker is generally set at 90–110 bpm, or whatever rate is necessary to suppress the ventricular arrhythmias.

Accelerated idioventricular rhythm occurs in up to 40% of patients and can in some instances be a marker of reperfusion. This rhythm is generally thought to be benign and is usually not treated.

Mural Thrombi

Patients with acute MI are at risk for the development of endocardial thrombi for a variety of reasons. Left ventricular thrombus develops in up to 40% of patients with anterior wall infarction but uncommonly in inferior infarcts. Large areas of dyskinesis with poor flow are prone to develop clots. Because there may be a return in contractility in the borders of the infarcted zone during the remodeling process, it could paradoxically be that clots develop more readily in patients with larger infarctions, but those with somewhat smaller infarctions tend to have them result in emboli more frequently. It has been recommended that all patients with an anterior wall MI be considered for anticoagulation during hospitalization and for 3–6 months thereafter. If anticoagulation is not used routinely, echocardiographic evaluation for the presence of mural thrombi is recommended. Because short-term anticoagulation until the ventricle is remodeled might well be adequate for most patients, the value of long-term (3 months or more) anticoagulation is unclear. In the absence of contraindications, it is probably worthwhile to use heparin during hospitalization and subsequently to use warfarin for 3 months for patients with anterior infarction. Because it has not been established whether low doses of warfarin are as effective as larger doses in inhibiting left ventricular mural thrombi, only a full dose (an INR 2.0–2.5) is recommended. Anticoagulation may be valuable for some patients for other reasons, such as atrial fibrillation. Patients with inferior or non-Q wave infarctions do not require routine anticoagulation following MI but should receive warfarin if mural thrombi are detected by echocardiography. Some clinicians use echocardiographic criteria to select patients who should be treated; others would treat any thrombus detected.

In the current era of routine aspirin and clopidogrel use after MI, there is little data on which patients should receive warfarin. It is prudent to fully anticoagulate patients with established mural thrombi, and those with other reasons for warfarin therapy, such as atrial fibrillation or aspirin allergy. Other cases, including anterior MI, should be judged individually with the risk of thromboembolism from mural thrombus balanced against the risk of bleeding from warfarin.

Mural thrombi can form in the atrium as well as in the ventricle. Atrial fibrillation is common in patients with CHF; in the setting of atrial fibrillation, stagnation of blood in the atrial appendage leads to a high incidence of clots. This condition can be established only with transesophageal echocardiography, but it may explain the high incidence of emboli in patients with paroxysmal atrial fibrillation. Accordingly, patients with atrial fibrillation should receive anticoagulation, not only because of their increased incidence of thrombus but because it appears that emboli can be prevented in this group with reasonably modest doses of anticoagulants (goal INR 2.0–2.5). Anticoagulation is discussed in depth in Chapter 29.

Patients with CHF and acute MI are at increased risk for pulmonary emboli because of deep venous thrombosis in the calf and thigh. This may be prevented by the use of warfarin. An argument can be made to consider the use of warfarin in any patient with acute infarction who has had no contraindications for several months. Because aspirin was withheld in some studies, it is unclear whether it offers similar benefits, which would allow it to be substituted for warfarin. In the current era of aspirin and clopidogrel following MI, warfarin should be considered for MI with extensive wall motion abnormality, including anterior MI, and any MI with established mural thrombus on echocardiography. However, it is probably not necessary in other patients.

Aneurysm and Pseudo-Aneurysms

Large areas of infarction tend to thin and bulge paradoxically. These large dyskinetic areas eventually form discrete aneurysms with defined borders. In general, treatment involves the same principles as those for patients with heart failure: vasodilatation and adequate control of filling pressures to reduce pulmonary congestion. Often patients with large dyskinetic areas will have a component of heart failure. If severe heart failure can be managed over time, an aneurysm may form that will then be amenable to surgical resection.

Occasionally, while aneurysms are forming, a myocardial rupture will occur. A small amount of rupture can become tamponaded by the pericardium, leading to what is known as a pseudo-aneurysm. Pseudo-aneurysms, which tend to have narrow necks and are not lined with endocardium, function like aneurysms in that they fill with blood during ejection, reducing systolic performance. In addition to reducing stroke volume and leading to increases in ventricular volume as a compensatory response with concomitant increases in pulmonary congestion, pseudo-aneurysms are prone to rupture. The larger the pseudo-aneurysm, the greater the possibility of rupture. Accordingly, the diagnosis of pseudo-aneurysm usually leads to relatively prompt surgery. Although pseudo-aneurysms can occur with both anterior and inferior MIs, true aneurysms are unusual in the inferior-posterior distribution. A large aneurysmal dilatation is therefore more apt to be a pseudo-aneurysm in an inferior-posterior location.

Right Ventricular Infarction

Right ventricular involvement in acute inferior wall MI is common. Hemodynamically significant right ventricular dysfunction, however, is uncommon, occurring in relatively few patients with right ventricular infarction. Substantial right ventricular infarction contributing to hemodynamic compromise occurs in up to 20% of patients with inferior and posterior infarction. These patients often clinically demonstrate hypotension and elevated jugular venous pressure but clear lung fields in the setting of acute inferior wall infarction. ST segment elevation in right-sided leads (V3R or V4R), right ventricular wall motion abnormalities on echocardiography help confirm the diagnosis of right ventricular involvement. With right ventricular infarction, the right ventricle becomes noncontractile, and cardiac output is maintained by increased excursion of the septum into the right ventricle and by elevated right-sided filling pressures. The incidence of high-grade AV block is also increased in patients with right ventricular infarction.

If reperfusion is not possible, the stunned right ventricle tends to resolve its dysfunction. Support entails intravenous fluid administration if left ventricular filling pressures are reduced, and occasionally the use of positive inotropic therapy or AV sequential pacing, or both are required. Early treatment with intravenous diuretics may lead to hypotension and confound patient presentation; therefore, focused clinical examination on presentation is paramount. Patients who display the development of shock despite supportive treatment may benefit from catheter-based intervention (angioplasty and stenting) of the occluded right coronary artery. The balance between the extent of right ventricular and left ventricular dysfunction, however, determines long-term outcome.

Crenshaw BS et al. Risk factors, angiographic patterns, and outcomes in patients with ventricular septal defect complicating acute myocardial infarction. GUSTO-I (Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries) Trial Investigators. Circulation. 2000 Jan 4–11;101(1):27–32. [PMID: 10618300]

Hochman JS et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock. N Engl J Med. 1999 Aug 26;341(9):625–32. [PMID: 10460813]

Welch PJ et al. Management of ventricular arrhythmias: a trial-based approach. J Am Coll Cardiol. 1999 Sep;34(3):621–30. [PMID: 10483940]

Yeo TC et al. Clinical characteristics and outcome in postinfarction pseudoaneurysm. Am J Cardiol. 1999 Sep 1;84(5):592–5, A8. [PMID: 10482162]

Prognosis, Risk Stratification, & Management

Risk Predictors

Infarct Size

Infarct size is an important determinant of long-term risk: the larger the infarction, the poorer the long-term prognosis. This association is easy to demonstrate in patients with first infarctions. In patients with multiple infarctions, the cumulative amount of damage is predictive. Measures that estimate cumulative infarct size (eg, ejection fraction; sestamibi scanning) provide important prognostic information. Nonetheless, the presence of an adverse prognosis does not, in and of itself, mandate a more aggressive therapeutic approach. However, ACE inhibitors and -blockers are important adjunctive therapies.

Infarct Type

Patients with NSTEMI are more prone to recurrent episodes of chest discomfort and infarction than are patients with STEMI. Patients with STEMI have an adverse short-term prognosis and should be considered for immediate reperfusion therapy; they often manifest arrhythmias that, especially in association with a low left ventricular ejection fraction, are an important marker of an adverse prognosis. Often these are the patients who have CHF during hospitalization for acute infarction. Their prognosis is worse than that of patients without heart failure, even if the left ventricular ejection fraction appears reasonably well preserved.

Malignant Arrhythmias

Many patients who suffer malignant arrhythmias during evolution of the infarction are also at increased risk. The one exception appears to be patients with primary VF (ie, VF with no complication of infarction).

Risk Assessment

Advanced age (> 65 years), prior MI, anterior location of infarction, postinfarction angina, NSTEMI, mechanical complications of infarction, CHF, and the presence of diabetes all suggest higher risk for reinfarction or death in the 6 months following infarction. These patients require aggressive risk stratification prior to hospital discharge after infarction.

Myocardial Ischemia

Patients with recurrent ischemia during hospitalization are generally considered unstable because of the adverse prognosis associated with recurrent angina following MI. For patients with multiple episodes of recurrent chest discomfort, or ischemia in a distribution distant from the current infarction, cardiac catheterization is recommended to permit consideration of PCI.

In patients without complications, who are not receiving reperfusion therapy, ECG treadmill stress tests provide additional prognostic information. Thallium or sestamibi scintigraphy add to the sensitivity and specificity of this analysis. Nuclear or echocardiographic imaging can be used in patients whose ECGs cannot be interpreted because of drug effects, resting ST-T wave changes, or conduction disturbances. Patients who are unable to exercise may benefit from pharmacologic stress tests, such as dobutamine echocardiography or dipyridamole or adenosine nuclear stress imaging. The inability to exercise is in itself a marker of poor prognosis.

Patients who have received thrombolytics or PCI and have not had recurrent episodes of chest discomfort constitute a very low-risk group for which the ability of any stress testing method to predict events is significantly reduced. Generally, however, patients who have been treated with thrombolytic agents and have evidence of ischemia undergo invasive investigation with cardiac catheterization.

The evidence that the prognosis of patients with NSTEMI is adequately determined by stress testing is controversial and in part depends on the nature of the stress procedure, perhaps including whether patients exercise rigorously enough. There is some suggestion that because most stress tests during acute hospitalization tend to be submaximal, a maximal stress test 6–8 weeks after the infarction is most appropriate for thorough risk stratification.

Ventricular Function

Patients with complications of infarction or any findings of CHF should have a noninvasive evaluation of ventricular function during their acute hospitalization. Assuming the absence of intercurrent events, one evaluation of ventricular function generally suffices.

In the absence of such an assessment, a stress echocardiogram can provide information concerning both ischemia and ventricular performance. Advocates believe that the combination of these parameters is important; detractors argue that the evaluation of ischemia is less complete than can be accomplished with radionuclide scintigraphy.

The evaluation of some patients with poor ventricular function may also require determining the presence of viable but dysfunctional myocardium (stunned or hibernating regions). Sophisticated metabolic studies using positron emission tomography seem to have the most promise for delineating the regions apt to improve with revascularization; however, they are not widely available for routine use. The response of dysfunctional regions may also be evaluated with dobutamine echocardiography (improved function is thought to be predictive of viable myocardium) or delayed thallium imaging (delayed uptake suggests viability).


Patients who have VT or recurrent episodes of VF after the first day require further evaluation. Evaluation is mandatory for patients who have recurrent arrhythmias without easily remediable causes, especially sustained VT, which generally requires invasive electrophysiological studies. Although treadmill- and ambulatory ECG-guided therapy are equivalent in some studies, the use of invasive electrophysiological studies to select and titrate antiarrhythmic agents or choose a mechanical device provide one approach. Recent data suggest that if the ejection fraction is < 0.35 and VT is present that implantable cardioverter defibrillators (ICDs) save lives.

At present, it is unclear how to manage less severe arrhythmias, which may include frequent ectopy or nonsustained VT. Signal-averaged ECG can be used in such patients; although a negative study is reassuring, the sensitivity of the procedure for detecting risk is inadequate. Recent data suggest that prophylactic ICDs in the 6 weeks following MI for ejection fraction < 35% do not reduce mortality. Therefore, depressed ejection fraction alone, in the absence of life-threatening arrhythmias, following MI is not an indication for ICD therapy. Patients should have optimal medical therapy and left ventricular ejection fraction should be reassessed after 6 weeks.

Patients who have had bradycardias often require pacemakers. Long-term pacemakers improve the prognosis for patients in whom complete heart block has developed via a mechanism involving bundle branch block. Some clinicians advocate pacing for patients who had transient complete heart block without the development of bundle branch blocks (those with inferior MI and narrow QRS complexes), but supportive data are not conclusive. There also is controversy concerning the use of pacemakers in patients with conduction disturbance such as RBBB and anterior fascicular block, who may (or may not) have had transient Mobitz II second-degree AV block; the benefits of pacing have yet to be established.

Risk Management

Patients with recurrent ischemia, severe ventricular arrhythmias, reduced ejection fraction (< 0.40), or evidence of severe ischemia during stress testing require cardiac catheterization. Although, in general, treatment is guided by anatomic considerations and their relationship to a long-term prognosis, the ability to predict—from the anatomy—which vessels are apt to be involved in subsequent events is poor. Furthermore, it is unclear that mechanical interventions will reduce the incidence of infarction or death except in well-defined subsets of patients (eg, those with left main disease, proximal three-vessel disease, and a reduced ejection fraction).

Risk Factor Modification

Central to the patient’s in-hospital treatment is the identification of factors that increase the risk for progression of coronary artery disease. These include the traditional risk factors for atherosclerosis: hypertension, diabetes, smoking, cholesterol abnormalities, family history, and a sedentary lifestyle. Attempts to modify the diet, stop smoking, and increase exercise should begin once the patient has left the intensive care unit. Although such efforts will vary with each patient, a structured program with active follow-up of patients to ensure some level of success may be helpful.

Recent statin therapy trials support aggressive reduction in cholesterol for the stabilization, and possibly regression, of atherosclerosis. Therefore, a very aggressive approach toward the reduction of LDL cholesterol and increases in high-density lipoprotein is justified early (within the first 24–48 hours) in postinfarction management. All post-MI patients should receive a statin, and aim to achieve an LDL of < 70 mg/dL.

Secondary Prevention

-Blockers should be given to all patients who have had acute ST and non–ST elevation MIs with or without reperfusion therapy. Patients with CHF tend to benefit most with gradual titration of dose.

Although secondary-prevention trials with aspirin have not indicated statistically significant benefits, most studies do show a trend toward improvement, and meta-analysis supports the concept that aspirin improves prognosis after acute infarction. Whether this benefit is synergistic with the effects of -blockers is unclear. Nonetheless, it appears reasonable for patients to start taking low doses of aspirin (81–325 mg/day) after acute MI and to continue it long-term.

Long-term treatment with ACE inhibitors is recommended for patients at risk for ventricular remodeling and the sequelae associated with that process. In general, this includes patients with left ventricular ejection fractions of < 45%. Given the results of recent trials, even patients with a low normal ejection fraction after infarction should be considered for ACE inhibitor treatment, particularly with an anterior MI.


Studies of exercise rehabilitation have been confounded by the fact that individuals who participate in such programs generally have favorable risk factor and psychological profiles that lessen their risk of recurrent events. It has been argued that the improved prognosis of such patients is related to these initial characteristics—and not to the effects of exercise training. Nonetheless, exercise training clearly improves peripheral muscle efficiency, and intense long-term physical training (5 days a week for at least 9 months) has been shown to reduce the development of cardiac ischemia. Therefore, exercise rehabilitation programs are recommended whenever possible for postinfarction patients.

The amount of exercise prescribed must obviously be based on the patient’s heart rate and blood pressure. These should be monitored as the patients start to walk during the convalescent phase in the hospital, and marked increases (eg, blood pressure more than 140/90 mm Hg) should be avoided. The patient’s rehabilitation activity schedule should be reduced if this level of hypertension occurs. This may also indicate the need for treatment with -blockers or ACE inhibitors to reduce the labile hypertensive response. In any event, the response of blood pressure and heart rate to exercise must be monitored. Phase II of the program begins at hospital dismissal and generally continues for 8–12 weeks. Objectives should include further patient education, risk factor modification, and gradual resumption of normal work and recreational activities.

Psychological Factors

It is now clear that as many as 20–25% of patients with acute MI meet formal clinical criteria for depression. It also appears that this is an adverse prognostic feature and that such patients have increased morbidity and mortality rates. Although there is some argument that this is so because these patients have more severe disease, this hypothesis has not been supported by recent studies. It may well be that whatever leads to depression is negatively synergistic with underlying coronary artery disease, as suggested by the increase in catecholamines in such patients. Regardless of the mechanism, however, careful consideration of the presence or absence of depression in patients is recommended. Psychological consultation should be sought for patients in whom depression is suspected, and treatment should be initiated to improve both the quality of the individual’s life and—to the extent that there is an interaction with ischemic heart disease—the prognosis. Because tricyclic antidepressants initially liberate catecholamines and may thereby induce adverse effects, drug treatment has previously been thought to be problematic in cardiovascular patients. On the other hand, these agents have membrane-stabilizing effects that may reduce the propensity to arrhythmias and it is believed that the potential for risk has been exaggerated. Newer agents that antagonize serotonin as their primary mode of action may be safer, but cognitive therapy has also been shown to be effective.

Ades PA. Cardiac rehabilitation and secondary prevention of coronary heart disease. N Engl J Med. 2001 Sep 20;345(12)892–902. [PMID: 11565523]

Antman EM et al. The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making. JAMA. 2000 Aug 16;284(7):835–42. [PMID: 10938172]

Hohnloser SH et al; DINAMIT Investigators. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med. 2004 Dec 9;351(24):2481–88.

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