The three primary symptom characteristics:

• Substernal chest or arm discomfort with a characteristic quality and duration
  
• Provoked by exertion or emotional stress
  
• Relieved by rest or nitroglycerin

• Pleuritic pain (i.e., sharp or knife-like pain brought on by respiratory movements or cough)
  
• Primary or sole location of discomfort in the middle or lower abdominal regions
  
• Pain that may be localized at the tip of one finger, particularly over costochondral junctions or the
  LV apex
  
• Pain reproduced with movement or palpation of the chest wall or arms
  
• Constant pain that lasts for many hours
  
• Very brief episodes of pain that last a few seconds or less
  
• Pain that radiates into the lower extremities

(Modified from the ACC/AHA Stable Angina Guideline [1999], Table 5 and ACC/AHA UA - NSTEMI guideline [2002], pages 11-12).

DISCUSSION

Table 5 provides the basis for deciding that a patient has an ACS. The table has been formulated using the following assumptions and is derived principally from the ACC/AHA UA - NSTEMI (2002) guideline.

The major criteria section lists ECG and laboratory findings for either AMI or unstable angina, which alone are sufficiently strong enough to warrant a tentative diagnosis of ACS and immediate evaluation and treatment. When these findings are present, the diagnosis of ACS should be considered irrespective of the patient's age, gender, character of the symptoms, or the presence of other indicators of CAD.

The minor criteria in Column I include the three principal presentations of unstable angina (e.g., prolonged, new onset, or worsening of discomfort), adapted from Table 3 of the ACC/AHA UA - NSTEMI (2002) guideline. When any one of these clinical findings is present in the absence of definite ECG or cardiac marker evidence of ACS, it should raise an initial suspicion of ACS. None of these clinical findings alone are sufficient evidence of ACS and should be considered within the context of the likelihood that the patient has an underlying CAD.

Therefore, a diagnosis of ACS in the absence of diagnostic ECG or cardiac markers (major criteria) requires patients with one or more of the principal presentations of unstable angina (minor criteria - Column I), to have additional evidence indicating at least an intermediate likelihood (i.e., greater than 10%) of CAD (minor criteria – Column II).

The minor criteria listed in Column II are adapted from two sources: the ACC/AHA UA - NSTEMI (2002) guideline (Table 5: Likelihood That Signs and Symptoms Represent an ACS Secondary to CAD) and Table 7: Pretest Likelihood of CAD in Symptomatic Patients According to Age and Sex). The presence of any item in Column II is considered to constitute sufficient evidence that the likelihood of CAD is greater than 10%.

H.  Is There ST-Segment Elevation Or New or Presumably New Left Bundle Branch Block (LBBB) With Ongoing/Recent Symptoms?

OBJECTIVE

Determine whether emergent reperfusion therapy may be appropriate.

ANNOTATION

Patients with ST-segment elevation, true posterior MI, or a new or presumably new LBBB, and with symptoms consistent with myocardial ischemia or infarction should be considered for emergent reperfusion therapy. These patients should receive urgent therapy for AMI as delineated in Module A. Patients with NSTE-ACS should be admitted and receive urgent therapy for NSTEMI/UA that is covered in Module B.

DISCUSSION

STEMI - Acute Myocardial Infarction (ST-Segment Elevation), true posterior MI, or New or Presumably New LBBB

Patients with symptoms suggestive of myocardial ischemia or infarction and ongoing ST-segment elevations in two or more contiguous leads have been shown to benefit from reperfusion therapies, either through the use of fibrinolytic agents or by direct percutaneous revascularization (ACC/AHA AMI, 1999). Per the Joint European Society of Cardiology/American College of Cardiology (ESC/ACC) recommendations, the electrocardiographic criterion for ST-segment elevation MI is “new or presumed new ST-segment elevation at the J point in two or more contiguous leads with the cut-off points > 0.2 mV in leads V1, V2, or V3 and > 0.1 mV in other leads (contiguity in the frontal plane is defined by the lead sequence I, aVL (lateral) or II, III, aVF (inferior).

Patients presenting with symptoms and ST-segment depression, on the other hand, have not been shown to benefit from the fibrinolytic therapy, though early percutaneous revascularization may be of benefit in patients with a high-risk presentation and ongoing symptoms unrelieved by medical therapy.

Patients presenting with LBBB which is new or presumably new, and ongoing symptoms suggestive of an AMI should be referred for emergent reperfusion therapy because LBBB morphology on ECG obscures ST-segment interpretation and because of the association of LBBB with underlying CAD (ACC/AHA AMI, 1999). True posterior MI is best recognized in leads V1 to V3 as an inverse of the electrical event occurring in the posterior wall. Classically this is described as ST-depression with terminally upright T-waves or can be seen directly with the application of posterior leads.

Patients who meet STEMI criteria should receive early revascularization unless there are contraindications. Both pharmacologic and mechanical revascularization are efficacious, but the effectiveness of each is clearly impacted by the time it rakes to initiate this therapy.

NSTE-ACS: Unstable Angina (UA) and Non-ST-Elevation Myocardial Infarction (NSTEMI)

Patients with NSTE-ACS commonly considered having three presentations: (1) rest angina; (2) new onset of severe angina, defined as at least Class III severity by the Canadian Cardiovascular Society (CCS) classification; and (3) increasing angina to at least CCS Class III severity. The hallmark of NSTE-ACS is an elevation of cardiac biomarkers in the blood stream (e.g., troponin I, troponin T, or CK-MB). Because the pathogenesis and treatment of UA and NSTEMI are similar, they are considered together here.

The distinction between STEMI and NSTE-ACS is important, because immediate reperfusion, with fibrinolytic agents, has been shown to reduce mortality in patients with STEMI, whereas it may be potentially harmful in patient with NSTE-ACS. Patients with STEMI clearly may benefit from early angioplasty, however there is insufficient evidence regarding the urgency of angioplasty in NSTE-ACS.

EVIDENCE

I.   Continue to Monitor Patients at Low-Risk for Death or MI

OBJECTIVE

Monitor low risk patients who may subsequently develop ACS

ANNOTATIO N

Unstable Angina with Low Risk

For patients with suspected ACS who, at initial presentation, do not have clinical features suggesting intermediate- or high-risk for death or MI, the following are recommended:

• Initial treatment with 160 mg to 325 mg of chewable aspirin
• Initial treatment with sublingual NTG for angina or suspected anginal equivalents
• Continuous ECG monitoring and continued surveillance of vital signs and for recurrent symptoms, for at least 6 to 12 hours, in an appropriate facility-specific unit
• A 12-lead ECG at the time of admission and at least 6 hours from the onset of symptoms, or as needed at change of symptoms or clinical status
• Assessment of serum cardiac biomarkers (troponin, CK-MB) at the time of presentation. For patients with normal cardiac markers within 6 hours of symptom onset, another sample should be obtained over the subsequent 6-12 hours.
• Early stress testing for patients who do not develop clinical indicators of intermediate- or high-risk by the end of the monitoring period
• Hospital admission and intensification of medical therapy for patients who develop clinical indicators of intermediate- or high-risk by the end of the monitoring period

DISCUSSION

Not all patients who meet the broad criteria for ACS are at intermediate- or high-risk for death or MI. Many such patients may have a non-ACS etiology for their symptoms and therefore are less likely to benefit from initial treatment with intravenous anti-thrombotic and anti-ischemic therapy, such as heparin and nitroglycerin.

Some patients initially deemed to be at low-risk for death or MI will subsequently develop recurrent symptoms, new ECG findings, or elevated cardiac markers and, therefore, will be reassessed as intermediate- or high-risk. Therefore, all patients with suspected ACS warrant continuous ECG monitoring and continued surveillance of vital signs and for recurrent symptoms. The optimum monitoring period for such patients has not been determined, but the current ACC/AHA guidelines for UA and NSTEMI suggest a minimum of 6 to 12 hours from presentation (ACC/AHA UA - NSTEMI, 2002).

Low-risk patients may be monitored either in an inpatient cardiac monitoring unit or in a specialized “chest pain unit.” Many institutions have developed specialized outpatient monitoring units for the evaluation of low risk patients with suspected ACS. While the exact physical location of such units is not critical, at a minimum, they should provide for continuous monitoring of the ECG and the rapid availability of emergency medical care (e.g., ACLS) and be adequately staffed by personnel trained in the recognition and management of cardiac arrhythmias. Several studies have documented the potential safety and cost-effectiveness of such units (Gaspoz, 1994; Gibler 1995; Graff 1995; Gomez 1996; Roberts, 1997; Farkouh, 1998). The effectiveness of such units may be enhanced via the use of validated decision tools and critical pathways (Lee, 2000).

A standardized protocol for repeat 12-lead ECG and serum cardiac markers during the monitoring phase of patients with ACS who are not at intermediate- or high-risk for death or MI has not been established. However, the current ACC/AHA guidelines for UA - NSTEMI (ACC/AHA UA - NSTEMI, 2002) suggest that if the patient has not developed recurrent symptoms, and if the follow-up ECG and cardiac markers obtained after 6 to 8 hours are normal, the patient may proceed to stress testing, either immediately before discharge from the hospital or chest pain unit, or after discharge and within 72 hours.

J. Are There Recurrent Symptoms Suggestive of Ischemia, or Diagnostic ECG and/or Elevated Cardiac Markers?

OBJECTIVE

Identify patients with ACS

ANNOTATION

Patients with recurrent symptoms, positive cardiac specific markers, or evolutionary or dynamic ECG changes during the monitoring period are now demonstrated to have probable or definite ACS and considered at intermediate- or high-risk for death or MI. These patients should receive urgent therapy for ACS as delineated in Module A (STEMI) or B (NSTEMI/Unstable Angina), as appropriate.

Patients who do not develop these features, remain at low risk, and may proceed to stress testing, either immediately before discharge from the hospital or chest pain unit, or after discharge and within 72 hours.

K.  Non-Invasive Cardiac Stress Test

OBJECTIVE

Determine the presence or absence of ischemia in patients with a low likelihood of CAD

ANNOTATION

Patients who are pain-free, have a normal/unchanged ECG and a normal initial cardiac marker measurement should have a follow-up ECG and repeat cardiac marker measurement after 6 – 8 hours. Those patients, who remain pain-free with no ECG changes and negative cardiac marker measurements, should undergo a cardiac stress test either before discharge or within 72 hours to separate patients with nonischemic discomfort from those with low risk ACS. This information is key for the development of further diagnostic steps and therapeutic measures

Patients with NSTE-ACS who have been stabilized on medical therapy, but who are found to have LV dysfunction, may benefit from further risk stratification using coronary angiography to assess their hemodynamic status and to determine their likelihood of benefit from revascularization.

A detailed discussion of noninvasive stress testing in CAD is presented in Module F.

L.  Stress Test Results Indicate Diagnosis of CAD with High/Intermediate Risk Features

OBJECTIVE

Refer patients who may benefit from coronary angiography or revascularization.

ANNOTATION

Patients with high or intermediate risk features on noninvasive stress testing may benefit from coronary angiography and subsequent coronary revascularization and should be referred to a specialist in cardiovascular diseases.

The following list includes examples of non-invasive test results that indicate high or intermediate risk, for which cardiology referral for coronary angiography should be considered (adapted from ACC/AHA Guidelines for Coronary Angiography: Executive Summary and Recommendations, 1999).

High-Risk

• Severe resting LV dysfunction (LVEF<0.35)
• High-risk Duke treadmill score (score < -11) (estimated annual mortality rate >3%)
• Severe exercise LV dysfunction (exercise LVEF<0.35)
• Stress-induced large perfusion defect (particularly if anterior)
• Stress-induced moderate-size multiple perfusion defects
• Large, fixed perfusion defect with LV dilatation or increased lung uptake (thallium - 201)
• Stress-induced moderate-size perfusion defect with LV dilatation or increased lung uptake (thallium - 201)
• Echocardiographic wall motion abnormality (involving >2 segments) developing at low dose of dobutamine ( < 10 mg/kg/min) or at a low heart rate (<120 bpm)
• Stress echocardiographic evidence of extensive ischemia.

Intermediate-Risk:

• Mild/moderate resting left ventricular dysfunction (LVEF = 35% to 49%)
• Intermediate-risk treadmill score (greater than –11 and less than 5) (1%-3% annual mortality rate)
• Stress-induced moderate perfusion defect without LV dilation or increased lung intake (thallium-201)
• Limited stress echocardiographic ischemia with a wall motion abnormality only at higher doses of dobutamine involving less than or equal to two segments.

Patients with high or intermediate risk features on stress testing may benefit from further risk stratification using coronary angiography to determine their likelihood of benefit from revascularization. The decision about coronary revascularization resides with a specialist in cardiovascular diseases, since this specialist is in the best position to discuss the relative risks and benefits of bypass surgery versus medical therapy or percutaneous coronary revascularization.

The survival benefits of myocardial revascularization are most pronounced among patients with LV dysfunction. Therefore, all patients with NSTEMI/UA who are found to have a reduced EF (<0.40) on non-invasive testing should be considered for referral to cardiology for possible coronary angiography and subsequent revascularization (AHA/ACC UA – NSTEMI, 2002). This recommendation applies even to patients who do not have clinical signs and symptoms of heart failure and to those whose ischemic symptoms have been stabilized.

M.   Does The Patient Have Documented IHD Or A High Probability Of CAD?

OBJECTIVE

For patients who do not meet criteria for an ACS, identify those who have CAD or a high probability of CAD.

ANNOTATION

Known CAD

For purposes of this guideline, a patient may be considered to have a “known” CAD if any of the following exist:

• Prior coronary revascularization procedure (PCI or CABG)
• Prior documented MI
• Prior coronary angiogram demonstrating an obstructive CAD (>50% left main stenosis and/or >70% stenosis of a major epicardial artery)
• Prior non-invasive test indicating a high probability of CAD (see also Module F):
  • Pathologic Q-waves (>0.04 seconds duration and >25% of the height of the R-wave) on a standard resting ECG (except leads III, aVR, and V 1 )
  • Greater than 1mm horizontal or down sloping ST-segment depression on exercise electrocardiography—Medium- or large-sized fixed or reversible defect on myocardial perfusion imaging (e.g., thallium)
  • Segmental wall motion abnormalities by cardiac ultrasound examination or LV angiography
  • Inducible, segmental wall motion abnormalities on stress echocardiography
• Silent ischemia, defined as reversible ST-segment depression by ambulatory ECG monitoring

Probability of CAD

For patients who do not have documented CAD, the likelihood that a patient's symptoms are due to CAD is estimated using only age, gender and the character of the symptoms. For instance, typical angina in a male older than 50 years indicates high probability of CAD. The pretest likelihood of CAD is presented in Table 7. It should be reemphasized that Table 7 applies only to patients who do not have ACS . The table is based on data from the ACC/AHA Stable Angina (2003) guideline, Table 9: Pretest Likelihood of CAD in Symptomatic Patients According to Age and Sex. The ECG and serum markers of myocardial necrosis are not considered.

*Each value represents the percent with significant CAD on catheterization.

(a) No data exist for patients less than 30 years or greater than 69 years, but it can be assumed that prevalence of CAD increases with age. In a few cases, patients with ages at the extremes of the decades listed may have probabilities slightly outside the high or low range.

(b) Definitions Used In The Classification Of Symptoms Into Typical/Definite Angina, Atypical/Probable Angina, And Non-Anginal Chest Pain:

N. Does The Patient Have Intermediate Probability Of CAD?

OBJECTIVE

Identify patients who have symptoms with an intermediate likelihood of CAD.

ANNOTATION

Patients who do not have a documented CAD, but the likelihood that the symptoms are due to CAD is intermediate (using age, gender and the character of the symptoms in Table 7), should be referred for noninvasive evaluation to rule out or confirm the diagnosis of CAD (see Module F).

O. Does The Patient Have A Low Probability of CAD but Abnormal Cardiac Screening Tests?

OBJECTIVE

Consider evaluating specific asymptomatic patients who have abnormal cardiac screening tests.

ANNOTATION

In general, asymptomatic patients with normal ECGs do not warrant further evaluation for IHD. However, patients may seek guidance from their primary physician regarding abnormalities in cardiac tests performed elsewhere. Non-invasive testing for CAD is being performed with increasing regularity in asymptomatic individuals—both because of the concern of an association between subclinical (“silent”) CAD and an increased risk of coronary events, and of advances in techniques used to detect occult CAD. The testing may be done as part of a routine physical examination, an exercise program, a preoperative evaluation, an evaluation performed for peripheral or cerebral vascular disease, or by patient request. Patients with a low probability of CAD (e.g., asymptomatic or atypical/probably non-cardiac chest pain) but abnormal cardiac screening tests may warrant cardiology evaluation for need for further testing (Module D).

P. Consider Other Causes For The Symptoms

OBJECTIVE

Consider both cardiac (non-ischemic) and non-cardiac causes of the patient's chest discomfort.

ANNOTATION

Although the primary goal of the Core Module is to evaluate for ischemic sources of chest discomfort, the patient's complaints deserve investigation even if ischemia is ruled out. In many instances, the source of non-cardiac chest discomfort will be obvious from the history (e.g., ascending midline pain associated with reflux of acid into the mouth and relieved entirely by antacids) or physical examination (e.g., the presence of dermatomal blisters in herpes zoster). Also, the physician must keep in mind that other cardiac diseases (such as pericarditis or valvular heart disease) can present with chest pain.