In the Emergency Department, the goals for the management of patients with suspected STEMI include control of cardiac discomfort, rapid identification of patients who are candidates for urgent reperfusion therapy, triage of lower-risk patients to the appropriate location in the hospital, and avoidance of inappropriate discharge of patients with STEMI. Many aspects of the treatment of STEMI are initiated in the Emergency Department and then continued during the in-hospital phase of management.
Aspirin is essential in the management of patients with suspected STEMI and is effective across the entire spectrum of acute coronary syndromes (Fig. 245-1). Rapid inhibition of cyclooxygenase-1 in platelets followed by a reduction of thromboxane A2 levels is achieved by buccal absorption of a chewed 160–325-mg tablet in the Emergency Department. This measure should be followed by daily oral administration of aspirin in a dose of 75–162 mg.
In patients whose arterial O2 saturation is normal, supplemental O2 is of limited if any clinical benefit and therefore is not cost-effective. However, when hypoxemia is present, O2 should be administered by nasal prongs or face mask (2–4 L/min) for the first 6–12 h after infarction; the patient should then be reassessed to determine if there is a continued need for such treatment.
Sublingual nitroglycerin can be given safely to most patients with STEMI. Up to three doses of 0.4 mg should be administered at about 5-min intervals. In addition to diminishing or abolishing chest discomfort, nitroglycerin may be capable of both decreasing myocardial oxygen demand (by lowering preload) and increasing myocardial oxygen supply (by dilating infarct-related coronary vessels or collateral vessels). In patients whose initially favorable response to sublingual nitroglycerin is followed by the return of chest discomfort, particularly if accompanied by other evidence of ongoing ischemia such as further ST-segment or T-wave shifts, the use of intravenous nitroglycerin should be considered. Therapy with nitrates should be avoided in patients who present with low systolic arterial pressure (<90 mmHg) or in whom there is clinical suspicion of right ventricular infarction (inferior infarction on ECG, elevated jugular venous pressure, clear lungs, and hypotension). Nitrates should not be administered to patients who have taken the phosphodiesterase-5 inhibitor sildenafil for erectile dysfunction within the preceding 24 h, because it may potentiate the hypotensive effects of nitrates. An idiosyncratic reaction to nitrates, consisting of sudden marked hypotension, sometimes occurs but can usually be reversed promptly by the rapid administration of intravenous atropine.
Morphine is a very effective analgesic for the pain associated with STEMI. However, it may reduce sympathetically mediated arteriolar and venous constriction, and the resulting venous pooling may reduce cardiac output and arterial pressure. These hemodynamic disturbances usually respond promptly to elevation of the legs, but in some patients volume expansion with intravenous saline is required. The patient may experience diaphoresis and nausea, but these events usually pass and are replaced by a feeling of well-being associated with the relief of pain. Morphine also has a vagotonic effect and may cause bradycardia or advanced degrees of heart block, particularly in patients with inferior infarction. These side effects usually respond to atropine (0.5 mg intravenously). Morphine is routinely administered by repetitive (every 5 min) intravenous injection of small doses (2–4 mg), rather than by the subcutaneous administration of a larger quantity, because absorption may be unpredictable by the latter route.
Intravenous beta blockers are also useful in the control of the pain of STEMI. These drugs control pain effectively in some patients, presumably by diminishing myocardial O2 demand and hence ischemia. More important, there is evidence that intravenous beta blockers reduce the risks of reinfarction and ventricular fibrillation (see "Beta-Adrenoceptor Blockers" below). However, patient selection is important when considering beta blockers for STEMI. Oral beta-blocker therapy should be initiated in the first 24 h for patients who do not have any of the following: 1) signs of heart failure, 2) evidence of a low-output state, 3) increased risk for cardiogenic shock, or 4) other relative contraindications to beta blockade (PR interval greater than 0.24 seconds, second- or third-degree heart block, active asthma, or reactive airway disease). A commonly employed regimen is metoprolol, 5 mg every 2–5 min for a total of 3 doses, provided the patient has a heart rate >60 beats per minute (bpm), systolic pressure >100 mmHg, a PR interval <0.24 s, and rales that are no higher than 10 cm up from the diaphragm. Fifteen minutes after the last intravenous dose, an oral regimen is initiated of 50 mg every 6 h for 48 h, followed by 100 mg every 12 h.
Unlike beta blockers, calcium antagonists are of little value in the acute setting, and there is evidence that short-acting dihydropyridines may be associated with an increased mortality risk.
The primary tool for screening patients and making triage decisions is the initial 12-lead ECG. When ST-segment elevation of at least 2 mm in 2 contiguous precordial leads and 1 mm in 2 adjacent limb leads is present, a patient should be considered a candidate for reperfusion therapy(Fig. 245-4). The process of selecting patients for fibrinolysis versus primary PCI (angioplasty, or stenting; Chap. 246) is discussed below. In the absence of ST-segment elevation, fibrinolysis is not helpful, and evidence exists suggesting that it may be harmful.
Options for transportation of patients with STEMI and initial reperfusion treatment. Patient transported by EMS after calling 911: Reperfusion in patients with STEMI can be accomplished by the pharmacologic (fibrinolysis) or catheter-based (primary PCI) approaches. Implementation of these strategies varies based on the mode of transportation of the patient and capabilities at the receiving hospital. Transport time to the hospital is variable from case to case, but the goal is to keep total ischemic time within 120 min. There are three possible scenarios: (1) If EMS has fibrinolytic capability and the patient qualifies for therapy, prehospital fibrinolysis should be started within 30 min of EMS arrival on scene. (2) If EMS is not capable of administering prehospital fibrinolysis and the patient is transported to a non-PCI-capable hospital, the hospital door-to-needle time should be within 30 min for patients in whom fibrinolysis is indicated. (3) If EMS is not capable of administering prehospital fibrinolysis and the patient is transported to a PCI-capable hospital, the hospital door-to-balloon time should be within 90 min. Interhospital transfer: It is also appropriate to consider emergency interhospital transfer of the patient to a PCI-capable hospital for mechanical revascularization if: (1) there is a contraindication to fibrinolysis, (2) PCI can be initiated promptly (within 90 minutes after the patient presented to the initial receiving hospital or within 60 min compared to when fibrinolysis with a fibrin-specific agent could be initiated at the initial receiving hospital), (3) fibrinolysis is administered and is unsuccessful (i.e., "rescue PCI"). Secondary nonemergency interhospital transfer can be considered for recurrent ischemia. Patient self-transport: Patient self-transportation is discouraged. If the patient arrives at a non-PCI-capable hospital, the door-to-needle time should be within 30 min. If the patient arrives at a PCI-capable hospital, the door-to-balloon time should be within 90 min. The treatment options and time recommended after first hospital arrival are the same. [Adapted with permission from Antman et al: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Circulation 110:e82, 2004.]
Limitation of Infarct Size
The quantity of myocardium that becomes necrotic as a consequence of a coronary artery occlusion is determined by factors other than just the site of occlusion. While the central zone of the infarct contains necrotic tissue that is irretrievably lost, the fate of the surrounding ischemic myocardium (ischemic penumbra) may be improved by timely restoration of coronary perfusion, reduction of myocardial O2 demands, prevention of the accumulation of noxious metabolites, and blunting of the impact of mediators of reperfusion injury (e.g., calcium overload and oxygen-derived free radicals). Up to one-third of patients with STEMI may achieve spontaneous reperfusion of the infarct-related coronary artery within 24 h and experience improved healing of infarcted tissue. Reperfusion, either pharmacologically (by fibrinolysis) or by PCI, accelerates the opening of infarct-related arteries in those patients in whom spontaneous fibrinolysis ultimately would have occurred and also greatly increases the number of patients in whom restoration of flow in the infarct-related artery is accomplished. Timely restoration of flow in the epicardial infarct–related artery combined with improved perfusion of the downstream zone of infarcted myocardium results in a limitation of infarct size. Protection of the ischemic myocardium by the maintenance of an optimal balance between myocardial O2 supply and demand through pain control, treatment of congestive heart failure (CHF), and minimization of tachycardia and hypertension extends the "window" of time for the salvage of myocardium by reperfusion strategies.
Glucocorticoids and nonsteroidal anti-inflammatory agents, with the exception of aspirin, should be avoided in patients with STEMI. They can impair infarct healing and increase the risk of myocardial rupture, and their use may result in a larger infarct scar. In addition, they can increase coronary vascular resistance, thereby potentially reducing flow to ischemic myocardium.
Primary Percutaneous Coronary Intervention
(See also Chap. 246) PCI, usually angioplasty and/or stenting without preceding fibrinolysis, referred to as primary PCI, is effective in restoring perfusion in STEMI when carried out on an emergency basis in the first few hours of MI. It has the advantage of being applicable to patients who have contraindications to fibrinolytic therapy (see below) but otherwise are considered appropriate candidates for reperfusion. It appears to be more effective than fibrinolysis in opening occluded coronary arteries and, when performed by experienced operators [≥75 PCI cases (not necessarily primary) per year] in dedicated medical centers (≥36 primary PCI cases per year), is associated with better short-term and long-term clinical outcomes. Compared with fibrinolysis, primary PCI is generally preferred when the diagnosis is in doubt, cardiogenic shock is present, bleeding risk is increased, or symptoms have been present for at least 2–3 h when the clot is more mature and less easily lysed by fibrinolytic drugs. However, PCI is expensive in terms of personnel and facilities, and its applicability is limited by its availability, around the clock, in only a minority of hospitals.
If no contraindications are present (see below), fibrinolytic therapy should ideally be initiated within 30 min of presentation (i.e., door-to-needle time ≤30 min). The principal goal of fibrinolysis is prompt restoration of full coronary arterial patency. The fibrinolytic agents tissue plasminogen activator (tPA), streptokinase, tenecteplase (TNK), and reteplase (rPA) have been approved by the U.S. Food and Drug Administration for intravenous use in patients with STEMI. These drugs all act by promoting the conversion of plasminogen to plasmin, which subsequently lyses fibrinthrombi. Although considerable emphasis was first placed on a distinction between more fibrin-specific agents, such as tPA, and non-fibrin-specific agents, such as streptokinase, it is now recognized that these differences are only relative, as some degree of systemic fibrinolysis occurs with the former agents. TNK and rPA are referred to as bolus fibrinolytics since their administration does not require a prolonged intravenous infusion.
When assessed angiographically, flow in the culprit coronary artery is described by a simple qualitative scale called the thrombolysis in myocardial infarction (TIMI)grading system: grade 0 indicates complete occlusion of the infarct-related artery; grade 1 indicates some penetration of the contrast material beyond the point of obstruction but without perfusion of the distal coronary bed; grade 2 indicates perfusion of the entire infarct vessel into the distal bed, but with flow that is delayed compared with that of a normal artery; and grade 3 indicates full perfusion of the infarct vessel with normal flow. The latter is the goal of reperfusion therapy, because full perfusion of the infarct-related coronary artery yields far better results in terms of limiting infarct size, maintenance of LV function, and reduction of both short- and long-term mortality rates. Additional methods of angiographic assessment of the efficacy of fibrinolysis include counting the number of frames on the cine film required for dye to flow from the origin of the infarct-related artery to a landmark in the distal vascular bed (TIMI frame count) and determining the rate of entry and exit of contrast dye from the microvasculature in the myocardial infarct zone (TIMI myocardial perfusion grade). These methods have an even tighter correlation with outcomes after STEMI than the more commonly employed TIMI flow grade.
Fibrinolytic therapy can reduce the relative risk of in-hospital death by up to 50% when administered within the first hour of the onset of symptoms of STEMI, and much of this benefit is maintained for at least 10 years. When appropriately used, fibrinolytic therapy appears to reduce infarct size, limit LV dysfunction, and reduce the incidence of serious complications such as septal rupture, cardiogenic shock, and malignant ventricular arrhythmias. Since myocardium can be salvaged only before it has been irreversibly injured, the timing of reperfusion therapy, by fibrinolysis or a catheter-based approach, is of extreme importance in achieving maximum benefit. While the upper time limit depends on specific factors in individual patients, it is clear that every minute counts and that patients treated within 1–3 h of the onset of symptoms generally benefit most. Although reduction of the mortality rate is more modest, the therapy remains of benefit for many patients seen 3–6 h after the onset of infarction, and some benefit appears to be possible up to 12 h, especially if chest discomfort is still present and ST segments remain elevated. Compared with PCI for STEMI (primary PCI), fibrinolysis is generally the preferred reperfusion strategy for patients presenting in the first hour of symptoms, if there are logistical concerns about transportation of the patient to a suitable PCI center (experienced operator and team with a track record for a "door-to-balloon" time of <2 h), or there is an anticipated delay of at least 1 h between the time that fibrinolysis could be started versus implementation of PCI. Although patients <75 years achieve a greater relative reduction in the mortality rate with fibrinolytic therapy than do older patients, the higher absolute mortality rate (15–25%) in the latter results in similar absolute reductions in the mortality rates for both age groups.
tPA and the other relatively fibrin-specific plasminogen activators, rPA and TNK, are more effective than streptokinase at restoring full perfusion—i.e., TIMI grade 3 coronary flow—and have a small edge in improving survival as well. The current recommended regimen of tPA consists of a 15-mg bolus followed by 50 mg intravenously over the first 30 min, followed by 35 mg over the next 60 min. Streptokinase is administered as 1.5 million units (MU) intravenously over 1 h. rPA is administered in a double-bolus regimen consisting of a 10-MU bolus given over 2–3 min, followed by a second 10-MU bolus 30 min later. TNK is given as a single weight-based intravenous bolus of 0.53 mg/kg over 10 s. In addition to the fibrinolytic agents discussed above, pharmacologic reperfusion typically involves adjunctive antiplatelet and antithrombotic drugs, as discussed subsequently.
Alternative pharmacologic regimens for reperfusion combine an intravenous glycoprotein IIb/IIIa inhibitor with a reduced dose of a fibrinolytic agent. Compared with fibrinolytic agents that involve a prolonged infusion (e.g., tPA), such combination reperfusion regimens facilitate the rate and extent of fibrinolysis by inhibiting platelet aggregation, weakening the clot structure, and allowing penetration of the fibrinolytic agent deeper into the clot. However, combination reperfusion regimens have similar efficacy as compared with bolus fibrinolytics and are associated with an increased risk of bleeding, especially in patients >75 years. Therefore, combination reperfusion regimens are not recommended for routine use. Glycoprotein IIb/IIIa inhibitors, given alone or in combination with a reduced dose of a fibrinolytic agent as part of a preparatory regimen before planned immediate PCI (facilitated PCI), have not been shown to reduce infarct size or improve outcomes and, furthermore, are associated with increased bleeding. Facilitated PCI is, therefore, also not a strategy that is recommended for routine use.
Integrated Reperfusion Strategy
Evidence has emerged that suggests PCI plays an increasingly important role in the management of STEMI. Prior approaches that segregated the pharmacologic and catheter-based approaches to reperfusion have now been replaced with an integrated approach to triage and transfer of STEMI patients to receive PCI (Fig. 245-5).
Each community and each facility in that community should have an agreed-upon plan for how STEMI patients are to be treated that includes which hospitals should receive STEMI patients from EMS units capable of obtaining diagnostic ECGs, management at the initial receiving hospital, and written criteria and agreements for expeditious transfer of patients from non-PCI-capable facilities. Patients initially seen at a PCI-capable facility (left side of diagram) should be sent promptly to the cardiac catheterization laboratory with the intent to perform primary PCI. Patients initially seen at a non-PCI-capable facility (right side of diagram) should rapidly be assessed for the optimum reperfusion therapy (see box in top right corner for assessment criteria). This may include transfer for primary PCI or initial treatment with a fibrinolytic. Following administration of a fibrinolytic, management is dictated by the patient's overall risk for death/serious complications of STEMI, and whether or not they experience recurrent ischemic symptoms or left-ventricular failure (see the two boxes at the bottom right of diagram). [Adapted from Kushner FG et al: 2009 focused update of the ACC/AHA Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction (updating the 2004 guideline and 2007 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 120:2271, 2009.]
Contraindications and Complications
Clear contraindications to the use of fibrinolytic agents include a history of cerebrovascular hemorrhage at any time, a nonhemorrhagic stroke or other cerebrovascular event within the past year, marked hypertension (a reliably determined systolic arterial pressure >180 mmHg and/or a diastolic pressure >110 mmHg) at any time during the acute presentation, suspicion of aortic dissection, and active internal bleeding (excluding menses). While advanced age is associated with an increase in hemorrhagic complications, the benefit of fibrinolytic therapy in the elderly appears to justify its use if no other contraindications are present and the amount of myocardium in jeopardy appears to be substantial.
Relative contraindications to fibrinolytic therapy, which require assessment of the risk:benefit ratio, include current use of anticoagulants (international normalized ratio ≥2), a recent (<2 weeks) invasive or surgical procedure or prolonged (>10 min) cardiopulmonary resuscitation, known bleeding diathesis, pregnancy, a hemorrhagic ophthalmic condition (e.g., hemorrhagic diabetic retinopathy), active peptic ulcer disease, and a history of severe hypertension that is currently adequately controlled. Because of the risk of an allergic reaction, patients should not receive streptokinase if that agent had been received within the preceding five days to two years.
Allergic reactions to streptokinase occur in ∼2% of patients who receive it. While a minor degree of hypotension occurs in 4–10% of patients given this agent, marked hypotension occurs, although rarely, in association with severe allergic reactions.
Hemorrhage is the most frequent and potentially the most serious complication. Because bleeding episodes that require transfusion are more common when patients require invasive procedures, unnecessary venous or arterial interventions should be avoided in patients receiving fibrinolytic agents. Hemorrhagic stroke is the most serious complication and occurs in ∼0.5–0.9% of patients being treated with these agents. This rate increases with advancing age, with patients >70 years experiencing roughly twice the rate of intracranial hemorrhage as those <65 years. Large-scale trials have suggested that the rate of intracranial hemorrhage with tPA or rPA is slightly higher than with streptokinase.
Cardiac catheterization and coronary angiography should be carried out after fibrinolytic therapy if there is evidence of either (1) failure of reperfusion (persistent chest pain and ST-segment elevation >90 min), in which case a rescue PCI should be considered; or (2) coronary artery reocclusion (re-elevation of ST segments and/or recurrent chest pain) or the development of recurrent ischemia (such as recurrent angina in the early hospital course or a positive exercise stress test before discharge), in which case an urgent PCI should be considered. The potential benefits of routine angiography and elective PCI even in asymptomatic patients following administration of fibrinolytic therapy are controversial, but such an approach may have merit given the numerous technological advances that have occurred in the catheterization laboratory and the increasing number of skilled interventionalists. Coronary artery bypass surgery should be reserved for patients whose coronary anatomy is unsuited to PCI but in whom revascularization appears to be advisable because of extensive jeopardized myocardium or recurrent ischemia.