Chapter 20. Low Probability Acute Coronary Syndromes

Patients with chest pain or other symptoms suggesting coronary ischemia require stratification based upon the probability of acute coronary syndrome (ACS) for proper treatment and disposition. This chapter discusses the features of low probability ACS, or possible ACS. By definition, patients classified into this group have no objective evidence of acute coronary ischemia or infarction—no characteristic electrocardiogram (ECG) ST-segment elevation or depression, and normal levels of cardiac markers.

A key determination by the emergency physician is whether to pursue further evaluation for possible ACS. Currently 3% to 6% of patients thought to have noncardiac chest pain or a clear-cut alternative diagnosis will have a short-term adverse cardiac event.

The clinical features of patients with possible ACS are the same as discussed in Chapter 17 “Chest Pain: Cardiac or Not.” High-risk historical features include chest pain with any of the following descriptors: radiating, occurs with exertion, described as pressure, similar to prior cardiac pain, or is accompanied by nausea or diaphoresis. However, even patients without high-risk features have some risk of ACS. Therefore absence of high-risk features should not solely be used to exclude ACS. Significant coronary disease is rare in patients <30 years old but youth does not completely eliminate ACS as a cause of acute chest pain. The physical exam should focus on excluding alternative diagnoses and detecting signs of cardiac failure.

A previous negative cardiac test should not prevent an appropriate evaluation for ACS in a patient with a concerning history or ischemic ECG findings. Plaque rupture is a major cause of ACS and commonly occurs in lesions that were previously nonobstructive. Previous stress testing results cannot determine whether the patient's current symptoms represent new ischemia from a recent plaque rupture. In contrast, previous cardiac catheterization results can be of benefit in determining whether a patient should undergo stress testing after exclusion of myocardial infarction. It is unlikely that a patient with previously normal or near-normal coronary arteries has developed significant epicardial stenosis within 2 years of the procedure.

The evaluation of patients with possible ACS can be conceptualized into a primary and secondary assessment. The primary evaluation must detect patients with ST-segment elevation that require emergent revascularization and distinguish between patients with definite ACS, possible ACS, and those with symptoms that are definitely not ACS. Alternative causes of chest pain should be considered (see Chapter 17).

The primary evaluation should include a history, physical examination, ECG, chest radiography, and cardiac biomarkers if ACS remains in the differential diagnosis. Serial ECGs should be obtained in patients with ongoing symptoms. All available data should be used to create a composite picture for decision making. Some have calculated that when the pretest probability of ACS is ≤2%, further testing is not indicated. Others have suggested a threshold of <1%.

At the conclusion of the primary evaluation, patients should be classified as having acute myocardial infarction (AMI), possible acute ischemia, or definitely not ischemia. Patients with possible acute ischemia are further stratified into high, intermediate, and low risk for adverse events based on the pattern of symptoms, clinical features, and ECG findings. (Table 20-1) The TIMI risk score may also assist with this assessment of risk, but should not be used to determine if a patient is above or below the testing threshold.

The secondary assessment can be conducted in an observation unit or in the inpatient arena. This assessment should exclude both components of ACS, myocardial infarction and unstable angina. Myocardial infarction is excluded through the use of serial troponin measurements to detect myocardial necrosis. Serum troponin levels can take as long as 8 hours from the time of infarction to become elevated. Therefore, a cardiac biomarker approach should take into account the time from symptom onset and generally should include multiple measurements. A traditional approach is to obtain troponin measurements at the time of arrival and 6 to 8 hours after arrival. An interim 3 to 4 hours measurement may be added if desired.

Normal serial myocardial marker measurements reduce the likelihood of AMI but do not exclude unstable angina, which still puts the patient at high risk for a subsequent adverse cardiac event. Therefore, patients with possible ACS should undergo some form of objective cardiac testing. Objective cardiac testing defines either the patient's coronary anatomy, cardiac function, or both. Common modalities used include stress electrocardiography, stress echocardiography, resting and/or stress nuclear imaging, stress cardiac magnetic resonance imaging (MRI), and computed tomography coronary angiography (CTCA). Most patients undergo testing during the initial encounter. However, outpatient testing is an option for low-risk patients in whom AMI has been excluded. This option is most useful in reliable patients presenting to a facility where a mechanism exists to arrange this testing.

Selection of an objective cardiac testing approach should be guided by general principles discussed below and will also need to take into account the modalities available at each institution.

1. The first determination is whether stress testing or coronary imaging with CTCA is desired. The most promising application of CTCA is the exclusion of coronary disease in low-risk patients, and its use in this population is supported in the 2007 ACC/AHA Guidelines. Upcoming data will further define the role of this modality. At present, a functional assessment with stress testing is preferable in patients likely or known to have coronary atherosclerosis.

2. If a stress testing approach is desired, the method of stress (exercise or pharmacologic) should be determined next. In general, patients able to exercise should undergo an exercise-based testing modality. Those unable to exercise should receive a pharmacologic stress strategy.

3. Finally, the method of cardiac assessment during stress testing should be selected. Options include electrocardiography, nuclear imaging, echocardiography, or magnetic resonance imaging-based strategies. Selection from these strategies is often based on local expertise at the study institution, testing availability, matching pretest probability of disease with sensitivity of the imaging modality, and minimizing radiation exposure. ECG-based exercise treadmill testing is the least costly and is widely available, but has the lowest sensitivity (68%) of the imaging options and therefore should not be used in patients with high pretest probability for disease. Further, ECG-based exercise treadmill testing should not be used in patients with abnormal baseline ECGs due to difficulties in interpretation. Stress echocardiography has the advantages of no radiation exposure, improved sensitivity (80%), and wide availability. Nuclear imaging is also widely available, allows assessment of myocardial perfusion, and has high accuracy, but is associated with radiation exposure and radio-isotope related delays. Cardiac MRI is also highly accurate and does not expose patients to radiation, but is less available.

The treatment of patients with possible ACS is confined to the short period during which the care provider is uncertain whether the patient has ACS or some alternative diagnosis. Once the diagnosis of ACS is confirmed, treatment is started for that disease process (Chapter 18). When an alternative diagnosis is confirmed and ACS is excluded, treatment should begin for the alternative diagnosis. While testing is ongoing for possible ACS, patients should receive supplemental oxygen plus the following treatment:

1. Aspirin 160 to 325 milligrams po.

2. Nitroglycerin 0.4 milligram spray or sublingual.

3. If symptoms continue, administer anti-ischemic therapy using β-blockers (metoprolol 25 to 50 milligrams PO in the first 24 hours) and/or morphine sulfate 1 to 5 milligrams IV. There are several contraindications to β-blockade including heart failure, low cardiac output, heart blocks, active reactive airway disease, tachycardia, and hypotension. (See Chapter 18 “Acute Coronary Syndrome,” for further details.)

4. In addition to the core therapy above, there are other adjunctive treatment options for patients at intermediate risk. The decision to administer these medications should be institution specific, balanced with the patient's bleeding risk and potential benefit, and determined through multidisciplinary discussions. These options include (a) dual antiplatelet therapy: a common regimen is clopidogrel 300 to 600 milligrams PO in addition to aspirin, (b) anti-thrombin therapy: common regimens are heparin 60 units/kilogram IV bolus (maximum bolus 4000 units) 12 units/kilogram/h IV infusion (maximum infusion 1000 units/h) or enoxaparin 1 milligram/kilogram SC every 12 hours.

5. Patients with negative serial cardiac markers, without diagnostic ECG changes, and who have normal objective cardiac testing are unlikely to have ACS as a cause of their symptoms. Consideration should be given to alternative life-threatening causes with further evaluation conducted as appropriate. Those with positive cardiac markers, diagnostic ECG changes, or diagnostic testing supporting ACS are admitted to the hospital for cardiology care. Those with nondiagnostic testing should be handled on a case-by-case basis and most should be discussed with a cardiologist.