Chapter 13. Acute Coronary Syndrome

Acute coronary syndrome (ACS) is not a single diagnosis but a spectrum of disease. It encompasses ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and unstable angina (UA). It is a disease process that, if unrecognized, imparts upon the patient profound morbidity, if not mortality. In fact, acute myocardial infarction is the leading cause of death in the United States, if not the entire developed world.1 For these reasons, ACS should be respected and treated expeditiously and aggressively.

In the United States, coronary heart disease (CHD) affected approximately 16 million people in 2005, and in 2008 an estimated 770,000 Americans had a new coronary event while 430,000 had a recurrent one.2 CHD includes ACS as well as UA. While stable angina is an important condition, it is not a focus of this discussion because on its own, it is not directly responsible for mortality statistics (although a small number of deaths due to CHD are coded as being from angina pectoris). With respect to mortality, one in every five deaths in the United States in 2004 was due to CHD with an American suffering a coronary event once every 26 seconds and one American dying every minute as a result of a myocardial infarction.2 The 2008 estimated cost of caring for these patients was $156.4 billion.2 The prevalence of ACS is expected to continue to climb as increasing numbers of patients are being diagnosed with NSTEMI and UA. This is not solely due to the aging of the population but also due to utilization of more sensitive diagnostic tests, increased availability of early invasive therapies, and treatment of comorbid conditions early and aggressively that delay the progression of disease to STEMI.3–5

With a heightened level of concern and recognition of these clinical entities, fewer patients have gone unrecognized. Consequently, mortality related to ACS has declined dramatically, particularly for STEMI. Unfortunately, the rate of decline has not been as great for NSTEMI and UA. This is likely due to a delay in the implementation of treatment guidelines for patients with these conditions.6,7

Understanding acute myocardial infarction requires understanding the pathophysiology of coronary artery thrombosis. While ACS can be caused by an embolic obstruction, this is much less common than ACS caused by atherosclerotic disease. There are two general types of atherosclerotic plaque, stable and unstable, and each produces a different presentation of ACS. The stable plaque has a thick fibrous cap that slowly thickens and produces the symptoms of classic angina such as progressively worsening exertional chest tightness. In this situation, oxygen delivery to the myocardium is gradually diminished, producing decreased tolerance of myocardial stress. Unstable plaques, however, have a thin fibrous cap suffused with inflammatory cells that make the plaques vulnerable to rupture. ACS associated with acute plaque rupture produces a spectrum of findings based on the location and degree of associated thrombosis and consequent impairment of oxygen delivery. A small thrombus can produce anginal symptoms while a higher-degree occlusion produces similar symptoms with non-ST-segment elevation myocardial infarction (NSTEMI). Complete occlusion can produce frank STEMI of differing severity depending on the amount and location of myocardium affected. Many of the treatments for ACS focus on maximizing oxygen delivery while minimizing platelet activation, aggregation, and clotting.8

With respect to ACS, certain risk factors have been associated with the probability of developing cardiac disease over a lifetime but have been shown to be of very little utility in the acute setting.9 Age, sex, family history, hypertension, diabetes mellitus, elevated cholesterol, obesity, smoking, and physical inactivity, while important, are not predictive of acute disease. One of the more common tools for risk stratifying patients with suspected ACS is the Thrombolysis In Myocardial Infarction (TIMI) score (Table 13-1). Associated with each score is a specific risk of poor outcome defined as death, myocardial infarction, or need for acute percutaneous coronary intervention (PCI). In a 2006 study by Pollack et al, a score of 3 or higher equates to a high risk with one study showing 5% mortality at 14 days and an 8% chance of needing PCI10 (Table 13-2).

As with most diagnoses, an accurate history and thorough physical examination are necessary to generate a broad and appropriate differential as well as an accurate diagnosis. Unfortunately, there is no way to effectively rule out ACS by history and physical examination alone. Some patients present in a way classically referred to as “typical”: poorly localized chest pain or pressure radiating to the left jaw, both shoulders, or left upper extremity; intermittent in nature; lasting 15–20 minutes at a time; exacerbated or precipitated by physical activity; relieved by rest or nitroglycerin; and associated with diaphoresis and shortness of breath. Unfortunately, most patients do not present in such a typical manner. Furthermore, certain patient populations, most notably women, the elderly, and diabetics, present with what has been termed “anginal equivalent.” These symptoms may include isolated jaw, neck, shoulder, back, arm, or epigastric discomfort, as well as nausea, vomiting, dizziness, generalized fatigue, or weakness. Even more subtle, a patient may simply describe an increasing difficulty with performing his or her activities of daily living. Those with cognitive impairment, diabetics, and substance abusers may present with altered mental status. It is absolutely critical to remember that the diagnosis of UA may be based on history and physical examination alone, despite a normal electrocardiogram (ECG) or negative cardiac enzyme testing.

Physical examination for patients with ACS is most useful for evaluating other potential etiologies of the patient's complaint, although the exam has utility in predicting patients who may be at risk for a poorer outcome or who have developed a complication related to their myocardial infarction. For example, patients with unstable vital signs, jugular venous distention, pulmonary edema, and/or an S3 gallop are indicative of heart failure. A new murmur is suggestive of papillary muscle rupture. Hemiparesis can indicate aortic dissection. Each of these is associated with worse prognosis than those without these complications. Caution must be exhibited, though, when it comes to physical examination and the possibility of ascribing a patient's symptoms to a process more benign than ACS. For example, a significant proportion of ACS patients may in fact have pleuritic, positional, or reproducible chest pain on examination.11 Simply stated, there is no single feature of physical examination that safely rules out ACS.

The most crucial diagnostic study in any patient suspected of having ACS is the ECG that should be obtained within 10 minutes of the patient's arrival to the emergency department (ED) or similarly within minutes after the development of chest pain if the patient is already hospitalized. It is vital to the patient's outcome that the ECG be completed and accurately interpreted in a timely manner. Also, if not already on one, the patient should be placed on a monitor as soon as possible. For the inpatient who develops chest pain in a nonmonitored setting, this may require transfer to a telemetry unit or ICU depending on the result of the ECG. If a STEMI is identified, appropriate resources should be immediately mobilized and interventions undertaken.12,13 STEMI diagnostic criteria, as described by the American College of Cardiology (ACC) and American Heart Association (AHA), are outlined in Table 13-3.14 Reciprocal ST-segment changes, such as depressions in opposite leads or findings on right-sided or posterior ECGs, make the diagnosis of STEMI more specific. While these criteria have been established and accepted, an ECG with these findings is still only 75% sensitive and 69% specific for STEMI.15 Of course, there are several other conditions that may cause ST-segment elevations such as pericarditis, early repolarization, left ventricular hypertrophy, prior myocardial infarction with resultant ventricular aneurysm, etc.

As it relates to NSTEMI, the ECG is perhaps of equal importance but 1–5% of patients with a myocardial infarction will have a completely normal ECG at the time of presentation.16 Therefore, serial ECGs are of tremendous value when considering a diagnosis of ACS and should be obtained with subsequent episodes of chest pain and with repeat cardiac enzyme testing. In fact, dynamic ECG changes associated with intermittent episodes of chest pain are most predictive of ACS. According to the ACC and AHA, ST-segment depressions greater than 0.05 mV with or without T-wave inversions are the most concerning findings associated with a poor outcome. Thirty-day mortality of patients with isolated ST-segment depressions is equivalent to those with ST-segment elevations. T-wave inversions ≥0.2 mV were next most concerning. Finally, ST-segment depressions and T-wave inversions of lesser magnitude or T waves newly upright (pseudonormalized) were found to be less concerning, but still clinically significant with regard to outcome.16

The necessity of accurate ECG interpretation cannot be overstated. A retrospective study of 1,684 patients with an acute myocardial infarction revealed that 12% of those patients presenting to the ED with active, ongoing ischemia, identifiable by ECG analysis, were missed.17 While not statistically significant, there was a trend toward increased in-hospital mortality as a result.

In certain instances, the ECG may be more difficult to interpret. One such example is in the setting of a preexisting left bundle branch block (LBBB). The Sgarbossa criteria have been validated as being highly specific for a patient having an STEMI who at baseline has a LBBB (see Table 13-4).18 The more criteria met, the more likely a STEMI is occurring. A score of 5–10 indicates an 88–99% probability of an acute STEMI. But even with 0 points, there still exists a 16% chance of an acute STEMI. Because of the low sensitivity of the Sgarbossa criteria when there are <10 points, the ECG cannot be used alone in the diagnostic evaluation of a patient with chest pain. In the right setting, however, the ECG along with the patient's history of present illness and a focused physical examination may be all that is necessary to accurately diagnose the patient and allow for swift, life-saving intervention.

In addition to electrocardiography, serum biomarker analysis is an essential tool in the setting of NSTEMI. While useful in STEMI as well, biomarkers play a less important role as treatment should be started based on the ECG alone. As mentioned earlier, UA is a diagnosis made by history, physical examination, and a consideration of alternative diagnoses by generating an appropriate differential and perhaps ruling out other etiologies. One may expect an unremarkable ECG and negative serum cardiac biomarker analysis in the setting of UA. Like STEMI and NSTEMI, UA is a diagnosis one cannot afford to miss. These patients still require aggressive management as they may unpredictably progress to NSTEMI or STEMI.

Serum cardiac biomarker analysis allows for diagnostic confirmation as well as risk stratification, as patients with positive results have a higher complication rate.19,20 The most commonly used biomarkers include creatine kinase-myocardial band (CK-MB), myoglobin, and troponin T or I. The ACC and AHA guidelines no longer recommend the use of myoglobin in the evaluation of patients suspected of having NSTEMI. The marker is sensitive early in the course of the disease process, rising within 1 hour of the ischemic event, but is not at all specific. LDH, which was used as a marker for many years, is similarly not recommended due to its lack of specificity. In contrast, CK-MB and troponin are both sensitive and specific when it comes to myocardial infarction, although CK-MB is less specific than troponin as it is also found in skeletal muscle. Both enzymes rise later than myoglobin, and may reach abnormal values within 3–4 hours after an ischemic event with peak levels seen 15–20 hours after the event. CK-MB levels should decrease to a normal range within 48 hours while troponin levels remain elevated for up to 10 days. Due to their high degree of specificity, the ability of diagnostic equipment to measure even the smallest of elevated values (compared with earlier thresholds) and the current definition of acute myocardial infarction at the slightest of troponin elevations, both the prevalence and incidence of the disease have increased dramatically.14 Of course, even small elevations identify patients at greater risk who may benefit from more aggressive intervention. There are other reasons a patient may have an elevated troponin, such as renal failure (which affects troponin I less than T), trauma, congestive heart failure (CHF), and sepsis, but each of these patients, as a consequence of his or her comorbidity, is at even greater risk and possesses a higher mortality.21

With all of the biomarkers, serial measurements are more useful than any one single measurement. For patients with an initially negative measurement, a second CK-MB value 2 hours later yielded a sensitivity of 93% and specificity of 94% for acute myocardial infarction.22 Still, CK-MB is a second-line biomarker for myocardial infarction as patients with an elevated CK-MB but negative troponin have the same outcome as patients with a both a normal CK-MB and negative troponin.19

There have been several other novel biomarkers studied including BNP, CRP, ischemia-modified albumin, and homocysteine, but none are recommended by the AHA or ACC for the evaluation of ACS in the acute setting.

In addition to ECG and cardiac biomarker analysis, various other modalities may be utilized for evaluating the cardiac patient. In the appropriate setting, provocative testing via exercise stress testing with or without myocardial perfusion imaging and stress echocardiography is being utilized in an effort to evaluate patients for ACS with higher certainty to allow for safer discharge. Similarly, echocardiography during an acute episode of ACS can evaluate the myocardium for wall motion abnormalities. An experienced cardiac sonographer can detect changes from the normal symmetric contraction of the myocardium that may indicate cardiac stunning associated with acute ischemia.

Computed tomography (CT) has been and is still currently being investigated as an alternative to coronary angiography with the benefit of being less invasive and perhaps more readily available. Cardiac computed tomography (CCT) is a modality by which the degree of calcification of coronary arteries is measured without the need for intravenous contrast and with greater degrees of calcification indicative of a higher likelihood of a future coronary event.23 It does not evaluate the true cardiac lumen. The greater the degree of calcification, the higher is the chance of an obstructive lesion in need of intervention being identified during coronary angiography. However, the score generated by such measurement reflects only relative or overall risk and not absolute risk or the certainty of an obstructing lesion being present.24

Unlike CCT, cardiac CT angiography (CCTA) evaluates the true cardiac lumen by utilizing intravenous contrast and has been shown to correlate well with findings derived from PCI. Less invasive and more readily available than PCI, CCTA is not without risk. Compared with CCT, CCTA adds the risk of exposure to intravenous contrast and involves significantly more radiation than cardiac catheterization. Furthermore, both CCTA and CCT are purely diagnostic tools. So while they may be utilized to safely discharge a certain subgroup of ED patients without need for admission and/or coronary angiography, patients who require intervention will end up receiving significantly more radiation and contrast than if they initially had a traditional cardiac angiogram. The same is true when CCTA is utilized for ED or ICU patients to determine the need for transfer to PCI-capable facilities. Furthermore, to date, published data derived from multiple, randomized, multicenter clinical trials are lacking.

Cardiac magnetic resonance imaging (CMR) with or without contrast is another novel diagnostic tool under investigation that has been shown to have a high positive predictive value and specificity for myocardial infarction.25 Images obtained can be synchronized with the cardiac cycle and can combine both angiographic evaluation of the patient's coronary arteries and wall motion abnormalities. Like CT, CMR is also in need of additional study and validation before it can be deemed appropriate for routine clinical use.

The mainstay of treatment of the critical patient with ACS is focused on improving oxygen delivery to the myocardium. This is accomplished in four ways: anti-ischemic therapy, antiplatelet therapy, anticoagulation therapy, and reperfusion therapy. Anti-ischemic therapies, such as oxygen, nitroglycerin, and β-blockers, work by matching oxygen delivery and demand and therefore by increasing oxygen delivery or decreasing oxygen demand. Antiplatelet medications, such as aspirin, prevent further thrombosis by minimizing platelet activation and adhesion. Anticoagulants such as heparin inhibit clot formation via the clotting cascade or by direct thrombin inhibition. Reperfusion of ischemic myocardium is accomplished via thrombolytics or PCI, both of which are used to directly restore cardiac circulation. In some cases, these treatments will fail and the patient will require coronary artery bypass grafting (CABG) or, in the case of frank cardiogenic shock, invasive mechanical support such as intra-aortic balloon pump or left ventricular assist device placement, both of which are covered in Chapter 17.

Anti-Ischemic Therapy

Supplemental oxygen delivery has been a standard treatment for ACS for nearly a century, although the data on its effectiveness are quite thin and inconclusive.26,27 The recommendations from the most recent ACC/AHA guidelines strongly endorse the use of oxygen in all patients with ACS and hypoxia and less strongly endorse oxygen for all ACS patients (although they clearly indicate this is based on opinion rather than settled evidence).28 Oxygen should be used with caution in patients with a history of COPD.

Nitrates, like oxygen, are nearly ubiquitous in the treatment of ACS, although the research on their utility is limited. The largest effect was noted in a meta-analysis of more than 80,000 patients that demonstrated that nearly 300 patients would need to be treated with nitrates to prevent one additional death.29 Nitrates produce arterial and venous dilatation resulting in decreased cardiac preload and afterload, and subsequently decreased myocardial oxygen demand. Simultaneously, nitrate-induced coronary artery dilation can improve oxygen delivery to the myocardium. Nitrates should be administered initially via a sublingual route at doses of 0.4 mg for a total of three doses, 5 minutes apart. If anginal symptoms persist after these doses, an intravenous infusion should be started, typically at 200 mcg/min and titrated up every 3–4 minutes until the resolution of ischemia or the development of hypotension.28 Nitrates should generally not be administered to patients who are markedly bradycardic, tachycardic, or hypotensive (systolic blood pressure below 90 mm Hg or a drop in blood pressure of greater than 30 mm Hg from their baseline).28 Other contraindications include suspected right ventricular infarction, in which patients depend on their preload to maintain adequate blood pressure, and patients who have taken a phosphodiesterase inhibitor within 24 hours.28 While the use of transdermal nitrates is commonplace, these preparations are of limited use in a patient with ACS due to the passive nature of administration. Active ACS in the ED or the ICU requires close monitoring and should be managed actively with periodic sublingual or continuous intravenous nitrates.

For many years, β-adrenergic blocking agents were commonly used in ACS patients to directly decrease cardiac work and oxygen demand based on early studies that showed a mortality benefit to patients who received intravenous agents on the day of their presentation.30 Some recent studies, however, have demonstrated increased morbidity with early β-blockade. The most dramatic results came from the COMMIT study that demonstrated increased risk of cardiogenic shock in patients receiving IV β-blockers within 24 hours of myocardial infarction.31 Based on this and similar studies, current treatment guidelines have limited their use to younger patients who do not have contraindications such as CHF, bronchospasm, cocaine abuse, low output states, heart block, and increased risk of cardiogenic shock.28 Another recent review concluded that no evidence supports intravenous use of these agents over the oral route.32

Morphine has frequently been used to provide analgesia for patients with anginal pain that is refractory to nitrates. It is known to block catecholamine surge, resulting in decreased blood pressure, heart rate, and, consequently, oxygen demand.28 It is also postulated to play a role in preventing further plaque rupture.28 This potentially beneficial action has not been demonstrated in the literature, however. In fact, a recent observational study demonstrated an increased likelihood of death in ACS patients receiving morphine, possibly related to masking of ongoing cardiac ischemia.33 Despite this concern, the ACC and AHA have continued to support the judicious use of morphine as the analgesic agent of choice for refractory pain associated with ACS.

Antiplatelet Therapy

Aspirin is an irreversible COX-1 inhibitor that minimizes platelet activation and aggregation by blocking arachidonic acid. This prevents further clotting in ACS and was shown to reduce mortality in the ISIS-2 study that used doses of 162 mg.34 The utility of aspirin was further confirmed in two subsequent meta-analyses.35,36 The common practice of chewing aspirin, rather than swallowing the pills whole, has been demonstrated to deactivate platelets more quickly.37,38 Current recommendations are for 162–325 mg of aspirin to be given immediately after the onset of symptoms, in the prehospital setting if possible, or on arrival to the hospital.28 Aspirin should be avoided in patients with allergy or significant active bleeding or bleeding risk.28

Clopidogrel is a thienopyridine that also inhibits platelets irreversibly by antagonizing the adenosine diphosphate receptor. It has been shown to be equally effective for ACS in patients who cannot receive aspirin and should be given to these patients in place of aspirin for suspected ACS.39 Some papers have recommended a 600-mg loading dose in these patients, as opposed to a 300-mg loading dose for patients who will also receive aspirin.40 Its utility in ACS, when combined with aspirin, was demonstrated in the CRUSADE and CURE trials that both showed modest improvements in survival with dual antiplatelet therapy despite a small increase in bleeding complications.41,42 Other studies demonstrated dual antiplatelet benefit for patients less than 75 years old with STEMI who undergo thrombolysis or for whom no revascularization treatment is planned.43,44 Based on these findings, ACS patients who do not have PCI planned within 48 hours should receive clopidogrel 300 mg orally early in their hospital course in addition to aspirin.28

For patients with STEMI or planned early PCI, the use of thienopyridines is less well established. It may still be used as an aspirin substitute as described above, but there is some controversy regarding dual antiplatelet therapy in these patients. The only supporting literature on this treatment strategy demonstrated some benefit but was a somewhat flawed subgroup analysis of a larger study.45 To date, no direct comparison exists. The use in PCI patients is further complicated by the fact that both the CURE and CRUSADE trials demonstrated additional bleeding complications for patients with dual antiplatelet therapy who underwent CABG within 5 days of administration of clopidogrel.41,42 However, neither of these studies demonstrated an increased mortality in these patients. Since most patients do not undergo CABG within 5 days of PCI, despite the controversy, the most recent recommendation is to administer 300–600 mg of clopidogrel to all STEMI patients undergoing PCI.46

It should be noted that there is a newer thienopyridine, prasugrel, which is given as a 60-mg loading dose. It is also recommended for patients undergoing primary PCI but has some caveats when compared with clopidogrel: if possible, CABG should be delayed for 7 days after the last prasugrel dose and it should not be used in patients who have a history of stroke or transient ischemic attack.46

The final category of antiplatelet agents are glycoprotein IIb/IIIa inhibitors (GPI) that block fibrinogen cross-linking of activated platelets and consequently prevent platelet aggregation. There are two general types of GPIs: large molecule such as abciximab and small molecule such as eptifibatide and tirofiban. The largest body of data is on abciximab that has been shown to be beneficial in patients undergoing PCI for STEMI or as part of an early invasive strategy for ACS without STEMI when given in addition to aspirin with or without clopidogrel.47,48 Similar evidence exists for small molecule GPIs for both of these categories of patients.49,50 The evidence for abciximab in patients with ACS who undergo a conservative management strategy without planned PCI demonstrated increased complications without significant benefit.51 No randomized studies of small molecule GPIs exist for this patient population. Therefore, the current recommendation restricts GPI use to patients at the time of catheterization as part of a double or triple antiplatelet strategy.46 These agents are typically continued in the ICU for up to 24 hours after the time of presentation.

Anticoagulant Therapy

The commonly used anticoagulants, unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and the newer fondaparinux, function by activating the enzyme antithrombin III that in turn inactivates thrombin and factor Xa, thereby inhibiting the clotting cascade. UFH is a naturally occurring substance that contains molecules of a variety of lengths. This is relevant because the longer heparin molecules inactivate both factor Xa and thrombin, while the shorter molecules inactivate only factor Xa. LMWHs, such as enoxaparin or daltoparin, are formulations of heparin containing primarily short-chain heparin molecules and consequently inhibit factor Xa to a much greater degree than thrombin. Fondaparinux is a short-chain synthetic heparin-like molecule that functions like LMWH but only inhibits factor Xa. Because their activity is more focused, these three can be dosed subcutaneously in a more predictable manner and do not require monitoring, unlike UFH that requires a continuous infusion and monitoring of partial thromboplastin time (PTT). Because LMWH and fondaparinux do not affect thrombin, neither medication results in alteration of PTT. Similarly, LMWH is much less likely to produce heparin-induced thrombocytopenia (HIT) and fondaparinux has no risk of HIT. Consequently, both can be used for an extended period without significant risk of developing HIT, although patients with a history of HIT should preferentially receive fondaparinux.

The data on these medications in ACS are complex, with multiple competing studies producing somewhat conflicted results. Trials of UFH added to aspirin failed to show significant benefit in multiple small studies, but showed some benefit when analyzed together.52 In contrast, the LMWHs have been shown to be directly beneficial in ACS when added to aspirin.53 Comparisons between LMWH and UFH have been mixed with some showing benefit for LMWH and others showing no difference between LMWH or UFH.54–56 These studies have been performed in patients receiving both conservative management and early invasive management with PCI.57 Of note, some of these studies demonstrated an apparent increased risk of bleeding associated with LMWH, although some analysis indicates this may have been due to switching between the two medications.58 A rational regimen should ensure that the initial anticoagulant given for ACS be continued throughout the patient's hospital stay, assuming no contraindication develops (such as HIT).

In contrast, fondaparinux has a lower rate of bleeding complications than either UFH or LMWH and has been demonstrated to be equivalent to LMWH when directly compared.59 As a result of these data, it is currently considered a first-line option for anticoagulation in ACS patients.28,46

The bottom line, however, is that these medications are essentially equivalent and local culture, rather than empiric evidence, will likely play a larger role in medication selection. LMWH may carry a slightly higher bleeding risk. LMWH and fondaparinux may provide some benefit over UFH when patients are treated for longer than 48 hours due to the increased incidence of HIT after 2 days of UFH. UFH is preferred when CABG is planned within 24 hours due to its more rapid clearance.

Bivalirudin is a newer anticoagulant and functions by direct thrombin inhibition without any anti–factor Xa activity. It is derived from hirudin, a natural anticoagulant produced by leeches. It is administered as a drip, has a very rapid onset of action, and reverses very quickly when stopped. Bivalirudin also carries no risk of HIT and has produced the lowest rates of bleeding complications of any of the anticoagulants, although the literature is limited in its use for ACS. One large study demonstrated benefit in patients undergoing PCI, but was complicated by the use of other medications.60 Bivalirudin is currently recommended as a treatment adjunct in ACS patients undergoing PCI but is best administered in consultation with the treating cardiology service.46

Reperfusion Therapy

The initial decision to reperfuse a patient with ACS should be based on the ECG. Frank STEMI indicates complete occlusion of a coronary artery and requires acute intervention. The choice of reperfusion strategies for STEMI patients is highly dependent on local resources. The general rule is that the timeliness of reperfusion is more important than the manner in which it is achieved. Assuming equivalent availability of both approaches, PCI provides superior outcome compared with intravenous thrombolysis.61,62 However, for patients who cannot receive PCI within 2 hours, there is no difference between the two modalities. Therefore, thrombolytics should not be delayed for PCI unless the PCI can be accomplished within 90 minutes of presentation.46

Thrombolytics are more widely available than PCI and have been demonstrated to produce good outcomes in STEMI patients when administered in a timely fashion. However, the quality of the outcomes worsens as time to treatment lengthens. Whenever possible, the “door to needle time,” the interval between ED arrival and initiation of IV thrombolytics, should be less than 30 minutes for any STEMI patient with less than 12 hours of symptoms.63 The currently used medications for thrombolysis are alteplase, reteplase, and tenecteplase which are all tissue plasminogen activators. While the dosing of these medications differs widely, the reperfusion and complication rates are similar and most institutions have only one of the three available. Streptokinase, which is an older thrombolytic, has generally fallen out of common use given its worse side effect profile. There are clearly defined contraindications to the administration of thrombolytics and these are listed in Table 13-5.46

Primary PCI is the treatment of choice for STEMI if it can be accomplished in a timely fashion. The goal for PCI in the STEMI patient is to achieve a “door to balloon” time—the time between arrival and the inflation of the balloon during angioplasty—of 90 minutes or less. Systems of care in the ED should be designed to minimize the amount of time to diagnose STEMI, activate the cardiology team, and transfer the patient to the catheterization lab. For STEMI patients presenting to facilities without PCI availability, transfer to a PCI-capable institution should be initiated immediately if the patient can be transferred and treated within the 90-minute window.64

There are three additional, nonprimary forms of PCI that can be considered in the STEMI patient. Rescue PCI should be considered within 24 hours if a patient does not have an acceptable response to primary thrombolytic therapy as evidenced by less than 50% resolution of ST-segment elevation within 90 minutes, persistent unstable arrhythmias, persistent ischemic symptoms, or development or worsening of cardiogenic shock. Facilitated PCI is a strategy involving planned PCI after less than full-dose thrombolytics in a patient with high mortality risk when PCI is not available within 90 minutes. Follow-up PCI is common after primary fibrinolysis and considered after primary PCI if there is evidence of persistent narrowing of coronary arteries that may be amenable to further intervention.64

Patients with NSTEMI or ACS patients without myocardial infarction generally have only partial occlusion of the coronary vessels and the benefits of early reperfusion therapy are less clear. Classically these patients have been managed conservatively with medication followed by risk stratification, such as treadmill testing, but without reperfusion therapy. Some of these patients may also undergo diagnostic PCI, with the opportunity for stenting concerning lesions, as part of their initial hospitalization. Investigations of thrombolysis in these patients have demonstrated no benefit and a trend toward harm.65 PCI within 48 hours, however, may confer some benefit to the ACS patient as demonstrated in a Cochrane systematic review of the literature and a meta-analysis, both of which were published in 2006.66,67 A different meta-analysis showed a benefit for early PCI in patients with positive biomarkers, but no benefit in men with negative biomarkers, and a detrimental effect in women with negative biomarkers. Regardless of the initial choice of management, patients with high-risk features as described above or those with refractory or recurrent ischemia should receive early PCI and dual antiplatelet therapy assuming the patient does not have substantial comorbidities.46

The complications associated with ACS are clearly not just related to those of the cardiovascular system, but for the purpose of this discussion we will mention only those deemed most significant and related directly to the cardiovascular tree. A few of those mentioned are discussed in other sections of this book.

All types of derangements in electrical conduction may be encountered: those that have little to no effect on prognosis, such as sinus bradycardia, first-degree AV block, second-degree AV block type I, premature atrial contractions, and premature ventricular contractions, and those that have a significant impact on patient outcome, such as persistent sinus tachycardia, supraventricular tachycardia, atrial fibrillation, atrial flutter, and both right and left bundle branch blocks. With respect to ventricular tachycardia and fibrillation, the presence of either of these rhythm disturbances does not portend a poor prognosis early in the course of an acute myocardial infarction. In contrast, ventricular tachycardia or fibrillation that is delayed in its onset and encountered later in the course of disease is typically due to transmural infarction and severe ventricular dysfunction and is therefore associated with a much more grave prognosis.

As mentioned earlier, BNP as a cardiac biomarker is utilized in such a way so as to risk stratify a patient with ACS. Patients with CHF have a poorer prognosis than those without CHF. The clinical status of patients with CHF as defined by their Killip classification (Table 13-6) correlates with their percent mortality, with a higher classification indicative of a worse prognosis. For example, cardiogenic shock by itself or as a consequence of right ventricular infarction is defined as Killip Class IV and is associated with an approximate 80% likelihood of mortality, as opposed to those patients with no evidence of CHF—Killip Class I—who have an approximate 5% mortality.

A particularly lethal complication of myocardial infarction is ventricular free wall rupture that results in cardiac tamponade and death. Interventricular septum rupture may also occur, but the patient's ultimate prognosis depends on the size of the defect and the resultant degree of shunt created. Acute valvular insufficiency as a sign of papillary muscle rupture may be encountered and requires surgical correction.

Acute ascending aortic dissection, not as a consequence of but associated with acute myocardial infarction, is a rare occurrence but, when present, carries a high mortality. If unrecognized, 50% of patients will die within 48 hours. Most of these dissections involve the right coronary artery with coronary artery occlusion due to mural dissection or extravasation of blood into the pericardial space or perivascular tissues.

Other complications such as pericarditis with or without a pericardial effusion, ventricular thrombus formation with embolization, and postinfarct angina and extension are also possibilities.

Ascertaining the correct disposition for patients with ACS can be difficult. The disposition of patients with definitive evidence of disease is fairly easy. Patients who have undergone PCI or thrombolysis or with evidence of ongoing cardiac ischemia should be admitted to a cardiac intensive care unit. Many ACS patients, however, present with vague symptoms without electrocardiographic or laboratory evidence of disease. The disposition of this set of patients presents a challenge and can be highly dependent on local resources. Some EDs can provide early stress testing after repeat EKG and enzyme testing that may obviate the need for admission. Other EDs offer chest pain units (CPU) with standardized pathways for monitoring and testing patients. After repeat lab testing, patients in CPUs frequently undergo risk stratification with stress testing, CT angiography, or catheterization depending on their findings and available resources.

In the ED, CPU, or on admission to the hospital, patients with suspected ACS should be observed with cardiac telemetry.28 Given the volume of patients admitted for possible ACS and the relative paucity of telemetry beds, some researchers have attempted to develop decision rules regarding the need for telemetry monitoring. While these findings have yet to be included in the current guidelines, there have been some impressive results. One study evaluated the Goldman score, which was developed to assess perioperative cardiac risk, and found that it could reliably predict which patients could be safely admitted to an inpatient bed without telemetry monitoring.68

Regardless of the ultimate disposition of ACS patients, current guidelines recommend that every patient undergo an evaluation of cardiac risk. This can be accomplished via exercise or chemical stress testing, radioisotope scanning, CT angiography, or cardiac catheterization. This should be accomplished during the initial ED visit or hospitalization. Low-risk patients can have this done as an outpatient, but arrangements should be made to ensure that it is accomplished within 72 hours of discharge.28