Regardless of whether ACS is due to UA, NSTEMI, or STEMI, the goal is to minimize ischemic time and, when appropriate, initiate reperfusion therapy with thrombolysis, PCI, or CABG.

1. The history should attempt to differentiate between UA and MI. Symptoms are often indistinguishable (see Section II.A). Primary presentations that distinguish ACS from stable or exertional angina are rest angina (often >20 minutes in duration), new-onset angina that markedly limits physical activity, or angina that is more frequent, longer in duration, or occurs with less exertion than before. However, among patients with acute MI, one-third may not have any chest pain on presentation. They are likely to be older, diabetic, and female.
2. The physical examination is unlikely to distinguish UA from an acute MI (see Section II.B).
3. As for angina, noninvasive studies include the ECG and cardiac enzymes.
1. A 12-lead ECG should be obtained as soon as possible to determine whether a STEMI is occurring and whether immediate revascularization is needed. Although not often captured, the earliest change in a STEMI is hyperacute or peaked T waves reflecting localized hyperkalemia. The ECG evolves through a typical sequence: initial elevation of the J point with preservation of a concave ST segment, followed by a more pronounced ST elevation where it becomes convex, and eventually the ST segment may become indistinguishable from the T wave. Transient ST-segment elevations (>0.05 mV) that resolve with rest likely indicate true ischemia and severe underlying CAD. Elevation of less than 0.05 mV, ST-segment depression, or T-wave inversion is more often associated with NSTEMI or UA. A normal ECG does not rule out MI because up to 6% of patients later confirmed to have had MIs may present as such. Serial ECGs are more accurate than an isolated study. The ECG continues to evolve over the next 2 weeks: the ST segment returns to isoelectric baseline, the R-wave amplitude is reduced, the Q wave deepens and the T wave inverts. In patients with an NSTEMI, ST-segment depressions often do not form pathologic Q waves. In patients with UA, ST-segment and T-wave changes usually resolve completely.
2. The best biomarker confirmation is a rise in cTnI or cTnT (>99th percentile. If not initially elevated, these should be repeated at 3 to 6 hours, and if still negative but clinical suspicion for MI is high, serial troponins should be drawn again up to 12 to 24 hours. With a high clinical suspicion, appropriate care should not be delayed even if the cTn is not elevated. cTnI and cTnT are highly specific for myocardial damage but do not indicate the mechanism of damage. CK-MB is less sensitive but may be substituted if troponin measurement is not available.
3. The chest x-ray can detect MI complications such as pulmonary venous congestion and can rule out aortic dissection, pneumonia, pleural effusion, and pneumothorax.
4. Transthoracic echocardiography (TTE) is not an initial diagnostic study in most presentations of ACS. If biomarkers and ECG analysis are equivocal, TTE may help identify new regional wall motion abnormalities or elucidate complications of ischemia or MI such as thromboembolic events, valve morphologies, and changes in global ventricular function. If TTE is available and the echocardiographer is experienced, this modality offers a convenient method by which a more complete clinical picture of myocardial function can be gained while awaiting the return of biomarker labs.
4. Management of Acute Myocardial Infarction
1. The general approach to acute MI focuses on minimizing total ischemic time, which is the time between onset of symptoms and start of reperfusion therapy. Ideally, this time should be less than 120 minutes. Initiation of thrombolysis in less than 30 minutes is the system goal for STEMI when PCI is not available.
2. Supportive measures: Supplemental O₂, IV access, routine vitals, and continuous ECG monitoring should be initiated. Supplemental O₂ is most useful in patients with an arterial saturation less than 90%, patients in respiratory distress, HF, or high-risk features for hypoxia. In patients without hypoxia, supplemental oxygen has not been associated with benefit or harm. Patients with severe HF or cardiogenic shock may need intubation and mechanical ventilation. Laboratory studies include electrolytes with magnesium, lipid profile, and complete blood count to detect anemia. Continuous pulse oximetry is critical to evaluate oxygenation, especially in patients with HF or cardiogenic shock.
3. Medical treatment: Unless contraindicated, a β-blocker, ASA, anticoagulation, a glycoprotein IIb/IIIa inhibitor, and a thienopyridine (ticlopidine, clopidogrel) should be administered.
1. β-Blockers: If no contraindications (significant heart block, bradycardia, reactive airway disease, HF, evidence of low output state, high risk for cardiogenic shock, refer toTable 15.2) exist, β-blockers should be administered to all patients with an acute STEMI. β-Blockade appears to reduce myocardial O₂ consumption by slowing the HR and reducing cardiac contractility. By slowing the HR and lengthening diastole, β-blockade increases the period of reduced wall pressures, augmenting myocardial O₂ delivery. Initially, metoprolol 5 mg IV every 5 minutes to a total of 15 mg may be given. If tolerated, metoprolol 25 to 50 mg orally every 6 hours can be administered for 2 days and then increased up to 100 mg orally twice daily. Carvedilol 6.25 mg administered orally tid, titrated up to a maximum of 25 mg tid, may reduce mortality in patients with an acute MI and LV dysfunction.
2. Nitrates: Nitrates dilate epicardial coronary arteries and collateral circulation and also inhibit platelet function. They may also increase venous capacitance, thus decreasing preload and cardiac work. Evidence does not support routine long-term nitrate therapy in MI unless pain persists. Patients with acute MI or HF, large anterior infarcts, persistent pain after 3 sublingual nitroglycerin (NTG) tablets, or HTN may benefit from IV NTG for the first 24 to 48 hours. IV NTG is started at 10 μg per minute and titrated until symptom relief or BP response. Those with continuing pulmonary edema or recurrent ischemia or angina may benefit from even more prolonged use of NTG. NTG should be avoided in hypotension, or when hypotension could lead to hemodynamic decompensation such as in severe aortic stenosis or a right ventricular infarct.
3. Statin therapy: Intensive statin therapy should be initiated as early as possible in all patients with a STEMI.
4. Analgesia:Morphine sulfate (1-5 mg IV) for analgesia and anxiolysis is reasonable if there is an unacceptable level of pain but should otherwise be avoided because of an association with adverse outcomes. It is also contraindicated in the presence of hypotension or in patients with a history of morphine intolerance. Modest reductions in HR and BP decrease O₂ consumption. Side effects include hypotension, respiratory depression, bradycardia, or nausea. Recently, concerns have been raised about an increased risk of death in patients receiving morphine but data from a large clinical trial is lacking.
5. Antiplatelet therapy should be considered in any patient presenting with ACS. Agents are chosen depending on whether the proposed management will be conservative or invasive (eg, CABG or PCI, which yields an increased risk of hemorrhage).
1. Aspirin 325 mg po should be given to all patients, unless contraindicated by hypersensitivity or a history of major gastrointestinal (GI) bleeding. By irreversibly inhibiting cyclooxygenase-1 in platelets, ASA prevents the formation of thromboxane A₂ and decreases platelet aggregation.
2. If a contraindication exists to aspirin, a 300-mg oral loading dose of clopidogrel followed by 75 mg once a day can be started. Clopidogrel and ASA are given together if invasive management is planned.
3. Glycoprotein IIb/IIIa inhibitors improve outcomes in patients undergoing a primary PCI.
6. Further anticoagulation depends on the choice of reperfusion strategy. Unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), a direct thrombin inhibitor (bivalirudin), or a factor Xa inhibitor (fondaparinux) may be chosen.
1. UFH is most commonly used and readily reversible by protamine but has the risk of heparin-induced thrombocytopenia (HIT). Initial dosing is to target an activated partial thromboplastin time (APTT) of 1.5 to 2 times normal. A normal dose is 60 U/kg as a bolus followed by 12 U/kg per hour.
2. LMWH has a lower risk of HIT and is easier to administer. Concerns about the ability to monitor the effectiveness of LMWH compared to UFH and less effective reversal with protamine have limited its use when PCI is planned.
3. Direct thrombin inhibitors have no risk of HIT but are associated with more bleeding complications and cannot be reversed with protamine or fresh frozen plasma (FFP). Bivalirudin is a direct-acting synthetic antithrombin that acts against clot-bound thrombin with a very short half-life (25 minutes). Its major advantages may be a lower rate of bleeding when compared to UFH plus a GP IIb/IIIa inhibitor.
4. Fondaparinux is a factor Xa inhibitor that confers a lower risk of bleeding when compared to UFH and GP IIb/IIIa inhibitors.
7. Potassium and magnesium: Although there is a lack of evidence documenting the effects of electrolyte repletion in acute MI, AHA guidelines recommend maintaining serum K above 4.0 mEq/L and Mg above 2.0 mEq/L. Magnesium dilates coronary arteries, inhibits platelet activity, suppresses automaticity, and may protect against reperfusion injury. Supplemental magnesium is indicated for hypomagnesemia and torsades de pointes. Hypomagnesemia is corrected with magnesium sulfate 2 g IV over 30 to 60 minutes, whereas torsades de pointes is treated with 1 to 2 g IV over 5 minutes. Because most magnesium in the body is intracellular, patients with hypomagnesemia may require multiple replacement doses to achieve normal levels. Prophylactic administration in acute MI is not indicated.
8. The utility of a glucose-insulin-potassium infusion, which was thought to limit the extent of myocardial injury and decrease potentially lethal arrhythmias after MI has been recently called into question. Although frank hyperglycemia should be treated with insulin, the use of glucose- insulin-potassium has not been found to confer a benefit in recent trials.
9. Transfusions: Evolving thresholds for red blood cell transfusion in MI ultimately take into account balancing the risks of transfusions (transfusion reactions, transfusion-transmitted infections, costs) with a clinical judgment of whether transfusion is likely to improve oxygen delivery (in severe or symptomatic anemia such as Hgb <8 g/dL, or 8-10 g/dL with hemodynamic instability or ongoing ischemia) or if there are other considerations such as active bleeding or trauma.
10. Prompt pharmacologic or mechanical reperfusion therapy is critical to optimize the salvage of viable myocardium. Reperfusion reduces infarct size, improves function, and decreases mortality. Temporary myocardial impairment (“stunned myocardium”) may exist even after perfusion is restored. Factors to consider when selecting a reperfusion strategy include (i) the timing of presentation and (ii) anticipated PCI availability. Primary PCI is preferred when it can be performed within 120 minutes of first medical contact, and ideally within 90 minutes. It is also preferred over fibrinolytic therapy in some patients even when delayed beyond this time window: those at high bleeding risk and those at high risk of death such as ongoing cardiogenic shock. Otherwise, fibrinolytic therapy should be considered and may be appropriate in patients with up to 12 hours of symptoms. Reperfusion is assessed noninvasively through relief of symptoms, restoration of hemodynamic or respiratory stability, or a 50% or better reduction in initial ST-segment elevation.
1. Thrombolysis is only indicated in the presence of ST-segment elevation greater than 0.1 mV in at least two contiguous leads. Thrombolysis yields the greatest benefit when initiated within 6 hours of symptom onset, although definite benefit exists even at 12 hours. Patients presenting within 12 to 24 hours but with continuing symptoms may also benefit. Response to therapy results in improvement in ST-segment elevation and resolution of chest discomfort. Persistent symptoms and ST-segment elevation 60 to 90 minutes after thrombolysis are indications for urgent angiography and possible PCI. Thrombolysis offers no benefit in patients without ST-segment elevation or new BBB, or in those with MI complicated by HF or cardiogenic shock. Table 15.3 compares the commonly used thrombolytic agents. Absolute contraindications are any prior intracranial hemorrhage, a cerebral vascular malformation or neoplasm, suspected aortic dissection, active bleeding, or significant head trauma or ischemic stroke within 3 months (except an acute cerebrovascular accident [CVA] within 3 hours). Relative contraindications include known bleeding diathesis, concurrent anticoagulation, recent trauma (2-4 weeks), prolonged cardiopulmonary resuscitation (>10 minutes), recent major surgery (<3 weeks), recent internal bleeding (2-4 weeks), severe HTN (systolic BP >180/110 mm Hg), other intracranial pathology, noncompressible vascular puncture sites, pregnancy, active peptic ulcer disease, or prior exposure (5 days to 2 years) to streptokinase or anisoylated plasminogen streptokinase activator complex (APSAC). Patients requiring retreatment, having failed streptokinase or APSAC, should receive tissue plasminogen activator (tPA). Those with contraindications to thrombolysis should be considered for PCI.
1. Streptokinase is a bacterial protein produced by α-hemolytic streptococci. It induces activation of free and clot-associated plasminogen, eliciting a nonspecific systemic fibrinolytic state. It may decrease mortality by 18%. Side effects are hypotension and allergic-type reactions.
2. Tissue plasminogen activator (tPA) is a recombinant natural protein. By increasing plasmin binding to fibrin, it provides relative clot-selective fibrinolysis without inducing a systemic lytic state. When given with heparin, its early reperfusion rate is slightly better than that of other agents. Compared to streptokinase, it is less likely to cause hemorrhage requiring transfusion and has greater survival benefit (10 additional lives in 1000 treated). It has a modest increase in the incidence of hemorrhagic stroke (0.7% as compared to 0.5%). The global utilization of streptokinase and tPA for occluded arteries (GUSTO) trial showed evidence of higher vessel patency with tPA compared to streptokinase. Reteplase is a deletion mutein of tPA but does not appear to have any benefits over tPA. Tenecteplase is a genetically engineered tPA mutant with a higher specificity for fibrin and a similar mortality rate.
3. Anisoylated plasminogen streptokinase activator complex (APSAC) (anistreplase) has clinical characteristics between those of tPA and streptokinase (see Table 15.3).
2. PCI and stenting: The term PCI has replaced percutaneous transluminal coronary angioplasty (PTCA) because atherectomy and stenting have improved patency rates above that of angioplasty alone. Primary PCI refers to PCI without prior administration of thrombolysis. Facilitated PCI refers to PCI after administration of a medical regimen to improve coronary patency. Rescue PCI refers to PCI within 12 hours of a failed fibrinolysis (continuing or recurrent ischemia) but is no longer recommended. All patients who undergo primary PCI should be pretreated at diagnosis with anticoagulant and antiplatelet therapy. In addition to the absence of a thoracotomy and associated complications, there are fewer neurologic sequelae with PCI compared to CABG. The primary constraint of PCI is the availability of personnel and support facilities that are only available in about 20% of hospitals in the United States. Adjuncts to PCI that reduce coronary reocclusion include IV heparin, ASA, ticlopidine, and GP IIb/IIIa inhibitors. The benefit of LMWH compared to UFH in PCI is unclear at this time. A glycoprotein IIb/IIIa inhibitor (eg, abciximab) may decrease mortality, MI recurrence, and the need for urgent revascularization.
3. Acute surgical reperfusion (CABG) may be emergently indicated for patients with operable coronary anatomy who have failed medical management but are not candidates for PCI; have failed PCI; have persistent ischemia, hemodynamic instability, or cardiogenic shock; have surgically correctable complications of MI (eg, severe MR or ventricular septal defect [VSD]); or have life-threatening arrhythmias in the presence of severe left main or three-vessel disease. Mortality from emergent CABG and CABG in the first 3 to 7 days after STEMI is high.
11. Intra-aortic balloon counterpulsation with an intra-aortic balloon pump (IABP) may be indicated in patients awaiting PCI or CABG who have low CO unresponsive to inotropic support or who demonstrate refractory pulmonary congestion. The effects of IABP counterpulsation include diastolic BP augmentation, thus increasing coronary perfusion, and systolic BP reduction, thus decreasing the impedance to ejection. Although IABP continues to be widely used in this setting, its overall benefit has been questioned in various studies.