What labs should be ordered to rule out acute coronary syndrome (ACS) and other causes of chest pain?

Laboratory Testing for Chest Pain Rule Out

For patients presenting with chest pain, order a 12-lead ECG within 10 minutes and high-sensitivity cardiac troponin (hs-cTn) immediately, with serial measurements at 1-3 hours if the initial value is detectable or if symptoms began less than 3 hours prior to presentation. 1

Essential Initial Laboratory Tests

Cardiac Troponin Testing

• High-sensitivity cardiac troponin (hs-cTn) is the primary and preferred biomarker for ruling out acute coronary syndrome (ACS) and should be measured immediately upon presentation 1, 2
• Results must be available within 60 minutes of blood sampling 1
• Institutions should use the 99th percentile upper reference limit as the diagnostic threshold for myocardial injury 1

ECG Requirements

• Obtain a 12-lead ECG within 10 minutes of presentation 1, 3
• Repeat ECG if symptoms recur or if initial findings are nondiagnostic 1
• Consider additional leads (V3R, V4R, V7-V9) if ongoing ischemia is suspected with inconclusive standard leads 1

Additional Baseline Testing

• Chest radiograph to evaluate for cardiac, pulmonary, and thoracic causes of chest pain 2
• Do not routinely measure other cardiac biomarkers (CK-MB, myoglobin, copeptin, h-FABP) when hs-cTn is available, as they do not add diagnostic value 1, 2

Serial Troponin Measurement Protocols

High-Sensitivity Troponin Assays

• Repeat measurement at 1-3 hours after initial sample for patients requiring serial testing 1, 4, 2
• For patients with symptom onset ≥3 hours before presentation and initial hs-cTn below the limit of detection, a single measurement may be sufficient to rule out myocardial injury 1, 4
• Specific thresholds for single-measurement rule-out: hs-cTnI <5 ng/L or hs-cTnT <6 ng/L 1, 4

Conventional Troponin Assays

• Repeat measurement at 3-6 hours after initial sample when using conventional (non-high-sensitivity) assays 1, 4
• Serial measurements remain necessary regardless of symptom duration with conventional assays 4

When Serial Testing is Required

• Symptoms began <3 hours before initial troponin measurement 4
• Initial hs-cTn is in the "observational zone" (detectable but below 99th percentile) 1, 4
• Clinical suspicion remains high despite initial negative results 2
• ECG findings are nondiagnostic and symptoms persist 1

Risk-Stratified Testing Approach

Low-Risk Patients (<1% 30-day MACE risk)

• Single hs-cTn below detection limit at presentation (if symptoms ≥3 hours) allows safe discharge without repeat testing 1, 4
• Modified HEART score ≤3 or EDACS <16 supports low-risk classification 1
• Recent normal testing (stress test <1 year or coronary angiogram <2 years) may obviate need for additional testing 1, 4

Intermediate-Risk Patients

• Serial hs-cTn measurements at 0 and 1-3 hours using validated clinical decision pathways 1
• Additional measurement at 3-6 hours if first two measurements are inconclusive and clinical suspicion persists 1
• Consider observation unit management to facilitate serial testing 4

High-Risk Patients

• Immediate hs-cTn measurement with rapid turnaround 1
• Serial measurements regardless of initial values 1
• Continuous cardiac monitoring is mandatory 1

Implementation of Clinical Decision Pathways

Recommended Algorithms

• ESC 0/1-hour algorithm: Blood sampling at 0 and 1 hour with validated hs-cTn assay 1
• ESC 0/2-hour algorithm: Alternative approach with sampling at 0 and 2 hours 1
• 0/3-hour protocol: For high-sensitivity or sensitive troponin assays with validated 0/3-hour algorithms 1

Pathway Requirements

• Institutions must implement standardized protocols based on their specific troponin assay 1, 2
• Incorporate previous testing results when available 1, 2
• Use validated risk scores (HEART, TIMI, EDACS) to guide disposition decisions 1, 5

Critical Pitfalls to Avoid

Timing Errors

• A normal troponin at presentation does not exclude MI if symptoms began within 6 hours, particularly with conventional assays 4
• Do not discharge patients with symptoms <3 hours duration based on single hs-cTn measurement alone 4

Interpretation Errors

• Elevated troponin indicates cardiac injury but not necessarily ischemic injury—consider alternative diagnoses (myocarditis, pulmonary embolism, heart failure, chronic kidney disease) 4
• Any detectable troponin elevation identifies high-risk patients, with risk proportional to the absolute level 4, 6

System Errors

• Avoid delayed transfer from office settings to ED for troponin testing 2
• Ensure familiarity with your institution's specific assay characteristics and 99th percentile cutoffs 1, 2
• Do not use outdated CK-MB or myoglobin testing when hs-cTn is available 2

Prognostic Value Beyond Diagnosis

• Elevated troponin identifies patients who benefit most from glycoprotein IIb/IIIa inhibitors, low-molecular-weight heparin, and early percutaneous coronary intervention 4, 6
• hs-cTn provides superior prognostic information for death and heart failure compared to conventional assays 7
• Dynamic changes in hs-cTn >30% indicate highest risk for adverse outcomes 8