What is the recommended diagnostic work‑up and acute management for an adult presenting with symptoms suggestive of a non‑ST‑segment‑elevation myocardial infarction (NSTEMI) or unstable angina (UA) (acute coronary syndrome, ACS)?

Diagnosis and Management of NSTEMI/Unstable Angina

Initial Diagnostic Workup

Obtain a 12-lead ECG within 10 minutes of presentation in all patients with suspected acute coronary syndrome. 1, 2 This is the single most critical initial test to distinguish STEMI (requiring immediate reperfusion) from NSTE-ACS.

ECG Findings in NSTE-ACS

• ST-segment depression ≥0.5 mm in multiple leads indicates high-risk NSTE-ACS 1
• Transient ST-segment elevation (resolves spontaneously or with nitrates) signifies very high risk 1
• T-wave inversions >1 mm in leads with dominant R waves suggest ischemia 1
• Dynamic ST-T changes during chest pain episodes that normalize when pain resolves are highly specific 1
• Normal ECG does not exclude ACS—approximately 41% of NSTE-ACS patients have non-diagnostic ECGs 2

Cardiac Biomarker Strategy

Measure high-sensitivity troponin at presentation (0 hours) and repeat at 3-6 hours. 1, 3 With high-sensitivity assays, measurements at 0h and 1h (or 2h) are acceptable. 3

A rising and/or falling pattern with at least one value above the 99th percentile distinguishes NSTEMI from unstable angina. 1, 3, 4 Key diagnostic features:

• Dynamic change ≥20% between serial measurements strongly suggests acute MI rather than chronic troponin elevation from other causes 4
• Troponin elevation >5-fold the upper reference limit has >90% positive predictive value for type 1 MI 3, 4
• If initial troponins are normal but clinical suspicion remains high, obtain additional measurements at 12-24 hours 3, 4

Critical Pitfall: Troponin Elevation Without ACS

Multiple conditions cause troponin elevation without coronary occlusion 3, 4:

• Acute heart failure exacerbation
• Tachyarrhythmias
• Hypertensive emergencies
• Pulmonary embolism
• Myocarditis
• Takotsubo syndrome
• Renal dysfunction
• Critical illness

To differentiate true NSTEMI from non-ischemic troponin elevation, look for the combination of: (1) dynamic rise/fall pattern, (2) typical ischemic symptoms, and (3) ischemic ECG changes. 4

Additional Diagnostic Tests

• Emergency echocardiography to assess left ventricular function, regional wall motion abnormalities, right ventricular function, valvular disease, and exclude mechanical complications 1, 4
• Hemoglobin to detect anemia as a precipitant 1
• Estimated GFR to assess renal function for medication dosing 1
• Blood glucose to screen for diabetes 1

Risk Stratification

Use the GRACE risk score to guide management decisions—scores >140 indicate very high risk requiring early invasive strategy. 1

Very High-Risk Features (Require Emergency Angiography)

• Hemodynamic instability or cardiogenic shock 1
• Recurrent or ongoing chest pain refractory to medical therapy 1
• Life-threatening arrhythmias (ventricular tachycardia, ventricular fibrillation) 1
• Mechanical complications (acute mitral regurgitation, ventricular septal defect) 1
• Acute heart failure complicating ACS 1

High-Risk Features (Require Invasive Strategy Within 24 Hours)

• Elevated troponin confirming NSTEMI 1
• Dynamic ST-segment changes suggesting ongoing ischemia 1
• Transient ST-segment elevation 1
• GRACE score >140 1

Intermediate-Risk Features

• Prior MI, peripheral vascular disease, or prior CABG 1
• Age >70 years 1
• Diabetes mellitus 1
• Prolonged rest pain (>20 minutes) now resolved 1

Low-Risk Features

• Normal troponin with non-diagnostic ECG 1
• New-onset angina within 2 weeks to 2 months 1
• No high-risk clinical features 1

Acute Medical Management

Antiplatelet Therapy

Administer aspirin 150-300 mg loading dose (or 75-100 mg if already on aspirin) immediately unless contraindicated. 1 Continue aspirin 75-100 mg daily indefinitely. 1

Add a P2Y12 inhibitor at presentation for all patients without contraindications: 1

• Ticagrelor 180 mg loading dose (preferred in most patients) 1
• Prasugrel 60 mg loading dose (if proceeding to PCI and no prior stroke/TIA, age <75, weight >60 kg) 1
• Clopidogrel 300-600 mg loading dose (if ticagrelor/prasugrel contraindicated or unavailable) 1

Continue dual antiplatelet therapy for 12 months after PCI unless excessive bleeding risk. 1, 5

Anticoagulation

Initiate anticoagulation immediately in all NSTE-ACS patients: 1

• Fondaparinux 2.5 mg subcutaneous daily (preferred for conservative strategy, lowest bleeding risk) 1
• Enoxaparin 1 mg/kg subcutaneous twice daily (alternative, dose-adjust for renal dysfunction) 1
• Unfractionated heparin IV (if high bleeding risk, severe renal dysfunction, or proceeding immediately to angiography) 1

Continue anticoagulation until revascularization or hospital discharge. 1

Anti-Ischemic Therapy

Beta-blockers: Initiate oral beta-blocker within 24 hours in hemodynamically stable patients without heart failure, hypotension, or AV block. 1, 5 Avoid IV beta-blockers acutely due to increased risk of cardiogenic shock. 5

Nitrates: Sublingual nitroglycerin 0.4 mg every 5 minutes for up to 3 doses for ongoing chest pain, followed by IV nitroglycerin if pain persists. 1 Contraindicated if systolic BP <90 mmHg or recent phosphodiesterase inhibitor use. 1

ACE inhibitors: Start within 24 hours in patients with heart failure, LV dysfunction (EF <40%), diabetes, or anterior MI. 5 Continue indefinitely. 5

High-intensity statin: Initiate immediately (atorvastatin 80 mg or rosuvastatin 40 mg daily) regardless of baseline cholesterol. 5

Invasive Strategy Timing

Emergency Angiography (<2 Hours)

Perform immediate coronary angiography for: 1

• Cardiogenic shock
• Severe ongoing ischemia despite medical therapy
• Life-threatening arrhythmias
• Hemodynamic instability
• Mechanical complications

Early Invasive Strategy (<24 Hours)

Perform coronary angiography within 24 hours for patients with any high-risk feature: 1

• Elevated troponin (NSTEMI diagnosis)
• Dynamic or new ST-segment changes
• Transient ST-elevation
• GRACE score >140

Selective Invasive Strategy (24-72 Hours)

For intermediate-risk patients without high-risk features, perform angiography within 72 hours after appropriate ischemia testing. 1

Conservative Strategy

For low-risk patients (normal troponin, non-diagnostic ECG, GRACE score <140), perform non-invasive ischemia testing before discharge. 1 Proceed to angiography only if ischemia is detected. 1

Revascularization Strategy

Radial artery access is the standard approach for coronary angiography. 1 This reduces bleeding complications compared to femoral access.

For patients proceeding to PCI: 1

• Use drug-eluting stents (not bare-metal stents) regardless of clinical presentation or anticipated DAPT duration 1
• Treat the culprit lesion first 1
• In stable patients with multivessel disease, complete revascularization can be performed during the index procedure or staged 1

In cardiogenic shock, treat only the culprit lesion immediately—do NOT perform immediate multivessel PCI. 1 The CULPRIT-SHOCK trial demonstrated that culprit-lesion-only PCI with possible staged revascularization reduces 30-day mortality compared to immediate multivessel PCI. 1

CABG is indicated for: 5

• Left main disease >50% stenosis
• Three-vessel disease
• Two-vessel disease with proximal LAD involvement and either EF <50% or demonstrable ischemia
• Coronary anatomy unsuitable for PCI in patients with cardiogenic shock 1

Special Populations

Cardiogenic Shock

• Emergency coronary angiography is mandatory 1
• Emergency PCI of culprit lesion if anatomy amenable 1
• Emergency CABG if anatomy not suitable for PCI 1
• Routine IABP is NOT recommended 1
• Short-term mechanical circulatory support may be considered in selected patients 1

MINOCA (MI with Non-Obstructive Coronary Arteries)

• Follow diagnostic algorithm to differentiate true MINOCA from alternative diagnoses 1
• Perform cardiac MRI in all MINOCA patients without obvious cause 1
• Manage according to disease-specific guidelines once underlying cause established 1

Chronic Kidney Disease

• Apply same diagnostic and therapeutic strategies with dose adjustments 1
• Use low- or iso-osmolar contrast at lowest possible volume 1

Older Patients (>75 Years)

• Apply same diagnostic and invasive strategies as younger patients 1
• Adjust antithrombotic dosing for renal function 1

Key Contraindications

Fibrinolytic therapy is absolutely contraindicated in NSTE-ACS and may cause harm. 1 Unlike STEMI, these patients have partial or intermittent occlusion, not complete thrombotic occlusion requiring immediate reperfusion.