What non-invasive risk stratification methods are recommended for patients with acute coronary syndrome (ACS)?

Non-Invasive Risk Stratification for Acute Coronary Syndrome

For patients with acute coronary syndrome, non-invasive risk stratification should be performed using stress testing (exercise or pharmacologic with imaging) in low- and intermediate-risk patients who have been clinically stable and free of ischemia for at least 12-24 hours, while high-risk patients with recurrent ischemia, hemodynamic instability, or severe LV dysfunction should proceed directly to coronary angiography without non-invasive testing. 1

Initial Clinical Risk Assessment

Before considering non-invasive testing, patients must be stratified using validated clinical scoring systems and baseline assessments:

• Calculate TIMI, GRACE, or PURSUIT risk scores to identify high-risk patients (TIMI ≥3 indicates 13-41% risk of adverse events at 14 days) who will benefit most from early invasive strategy rather than non-invasive testing 1, 2

• Evaluate baseline ECG findings as ST-segment depression, transient ST elevation, or T-wave inversions provide critical prognostic information across the ACS spectrum 1, 2

• Assess cardiac biomarkers (preferably high-sensitivity troponin) as elevated levels identify higher-risk patients who derive greater benefit from invasive approaches 1

• Determine LV function using echocardiography or radionuclide angiography in all ACS patients not scheduled for coronary angiography 1

Patient Selection for Non-Invasive Testing

Appropriate Candidates (Class I Recommendation)

Low- and intermediate-risk patients who meet ALL of the following criteria should undergo non-invasive stress testing 1, 3:

• Free of ischemia at rest or with low-level activity for minimum 12-24 hours 1, 3
• No heart failure symptoms for minimum 12-24 hours 1
• Clinically stable without recurrent angina 1, 3
• Normal cardiac biomarkers or diagnosis of ACS is questioned 1

Patients Who Should Bypass Non-Invasive Testing

Proceed directly to coronary angiography (without non-invasive risk stratification) in patients with 1, 3:

• Recurrent rest angina despite intensive medical therapy 1
• Hemodynamic instability or electrical instability 1, 3
• Acute pulmonary edema or heart failure 1
• Severe LV dysfunction (LVEF ≤0.40) 1
• Worsening mitral regurgitation 1
• Refractory or recurrent ischemic symptoms 1, 3

Selection of Specific Non-Invasive Test

Exercise Treadmill Testing (First-Line for Appropriate Patients)

Standard exercise ECG is recommended for patients who meet ALL criteria 1:

• Able to perform adequate exercise 1
• Resting ECG free of baseline ST-segment abnormalities 1
• No bundle-branch block, LV hypertrophy with ST-T changes, intraventricular conduction defect, paced rhythm, pre-excitation, or digoxin effect 1

Stress Testing With Imaging (When Exercise ECG Inadequate)

Add imaging modality (echocardiography, myocardial perfusion imaging, or cardiac MRI) in the following scenarios 1:

• Resting ST-segment depression ≥0.10 mV 1
• LV hypertrophy with ST-T changes 1
• Bundle-branch block or intraventricular conduction defect 1
• Pre-excitation or paced rhythm 1
• Digoxin use 1
• Low-level exercise test where imaging adds prognostic sensitivity 1

Note: Exercise stress testing provides superior prognostic information in women compared to diagnostic accuracy, though imaging studies have better diagnostic performance 1

Pharmacologic Stress Testing With Imaging

Pharmacologic stress with imaging is recommended when physical limitations preclude adequate exercise 1:

• Severe arthritis or amputation 1
• Severe peripheral vascular disease 1
• Severe chronic obstructive pulmonary disease 1
• General debility or deconditioning 1

Alternative: Coronary CT Angiography

Coronary CTA may be considered for non-invasive risk stratification in lower-risk patients prior to hospital discharge, particularly when stress testing is not available or contraindicated 1

• If CCTA shows uncertain functional significance, functional imaging for myocardial ischemia is recommended 4
• CCTA is NOT recommended as routine follow-up in patients with established CAD 1, 4

Timing Considerations

For low-risk unstable angina patients, stress testing can be performed when stabilized and free of active ischemic or heart failure symptoms for minimum 8-12 hours 3

For NSTEMI patients at similar risk, wait 2-5 days before stress testing if clinically stable 1

Symptom-limited stress testing is appropriate (not submaximal) for stabilized low- and intermediate-risk patients 1

Common Pitfalls to Avoid

• Do not perform stress testing in high-risk patients with ongoing ischemia, as this delays necessary angiography and increases risk 1, 3
• Do not use exercise ECG alone in patients with baseline ECG abnormalities that interfere with ST-segment interpretation, as this reduces diagnostic accuracy 1
• Do not assume all women need imaging for risk stratification—exercise treadmill testing provides comparable prognostic information in women despite lower diagnostic accuracy 1
• Do not perform non-invasive testing in patients unwilling to consider revascularization or with severe comorbidities precluding revascularization 1
• Do not use ICA solely for risk stratification in stable patients—non-invasive testing should guide the decision for angiography 1, 4

Integration With Management Strategy

Selective invasive approach (non-invasive testing before angiography) is appropriate for lower-risk patients, while routine invasive approach (early angiography within 24-48 hours) is preferred for high-risk patients with elevated biomarkers 1, 5

High-risk findings on non-invasive testing that warrant subsequent coronary angiography include 1:

• Significant LV dysfunction (LVEF <0.40) 1
• Large anterior or multiple perfusion defects 1
• Multiple wall motion abnormalities on echocardiography 1
• High-risk Duke treadmill score ≤-11 1