What is the differential diagnosis of acute chest pain, categorized by urgency, and what initial investigations should be performed?

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Differential Diagnosis of Acute Chest Pain

Life-Threatening Causes Requiring Immediate Exclusion (First 10 Minutes)

Obtain a 12-lead ECG within 10 minutes and measure high-sensitivity cardiac troponin immediately in every patient presenting with acute chest pain. 1, 2

Acute Coronary Syndrome (ACS)

  • Presentation: Retrosternal pressure, squeezing, or heaviness building gradually over minutes (not instantaneously), often radiating to left arm, jaw, or neck; associated with diaphoresis, dyspnea, nausea, or lightheadedness. 1, 2
  • Critical pitfall: A normal physical examination does NOT exclude myocardial infarction—uncomplicated MI can present with entirely normal findings. 2, 3
  • Another pitfall: Sharp or pleuritic pain does NOT rule out ACS—approximately 13% of patients with pleuritic-type chest pain have acute myocardial ischemia. 2, 3
  • Serial troponin strategy: Repeat high-sensitivity troponin at 1–3 hours (or conventional troponin at 3–6 hours) after initial sample; a single normal troponin does NOT exclude ACS. 1, 2
  • ECG caveat: 30–40% of acute myocardial infarctions present with a normal or nondiagnostic initial ECG. 2, 3

Acute Aortic Dissection

  • Presentation: Sudden-onset "ripping" or "tearing" chest or back pain that is maximal at onset, radiating to upper or lower back. 1, 2, 3
  • Physical findings: Pulse differential between extremities (~30% of cases), systolic blood pressure difference >20 mmHg between arms, new aortic regurgitation murmur (40–75% of type A dissections). 2, 3
  • High-probability triad: Severe abrupt pain + pulse differential + widened mediastinum on chest X-ray = >80% probability of dissection. 2, 3

Pulmonary Embolism (PE)

  • Presentation: Sudden dyspnea with pleuritic chest pain worsening on inspiration. 1, 2, 4
  • Physical findings: Tachycardia in >90% of patients, tachypnea in ~70%. 2, 4, 3
  • Risk stratification: Apply Wells criteria; obtain age- and sex-specific D-dimer in low-to-intermediate probability patients—negative D-dimer effectively rules out PE. 2, 4
  • Imaging: Proceed directly to CT pulmonary angiography when clinical suspicion is high or D-dimer is positive. 2, 4

Tension Pneumothorax

  • Presentation: Dyspnea and sharp chest pain intensifying with inspiration. 2, 3
  • Physical findings: Unilateral absent breath sounds, hyperresonant percussion, tracheal deviation, hypotension. 2, 3

Cardiac Tamponade

  • Presentation: Pleuritic chest pain worsening supine. 2
  • Physical findings: Jugular venous distension, hemodynamic compromise (SBP <100 mmHg, HR >100 or <50 bpm), pericardial friction rub. 2

Esophageal Rupture (Boerhaave Syndrome)

  • Presentation: Severe chest pain following forceful vomiting. 2, 3
  • Physical findings: Subcutaneous emphysema, pneumothorax in ~20% of cases, painful tympanic abdomen. 2, 3

Serious But Non-Immediately Fatal Cardiac Causes

Acute Pericarditis

  • Presentation: Sharp, pleuritic chest pain that worsens when lying supine and improves when sitting forward or leaning forward. 1, 2, 4, 3
  • Physical findings: Pericardial friction rub (absence does NOT exclude disease), fever. 2, 4, 3
  • ECG findings: Diffuse concave ST-elevation with PR-segment depression. 2, 4, 3
  • Management: High-dose aspirin (500 mg–1 g every 6–8 hours) plus colchicine (0.5–0.6 mg once or twice daily for ~3 months). 4
  • Avoid: Glucocorticoids and non-aspirin NSAIDs—they increase risk of recurrent MI and impair myocardial healing. 4

Myocarditis

  • Presentation: Chest pain with fever, signs of heart failure (S3 gallop), mimics ACS. 2, 3
  • Diagnosis: Requires cardiac troponin measurement and cardiac MRI with gadolinium contrast to differentiate from other causes. 2, 4

Valvular Heart Disease

  • Aortic stenosis: Systolic murmur with delayed/diminished carotid pulse (pulsus tardus-parvus). 3
  • Aortic regurgitation: Early diastolic murmur at right sternal border with rapid carotid upstroke. 3
  • Hypertrophic cardiomyopathy: Displaced LV impulse, prominent "a" wave in JVP, systolic murmur increasing with Valsalva. 3

Pulmonary Causes (Non-PE)

Pneumonia

  • Presentation: Fever with localized pleuritic chest pain, productive cough. 2, 4, 3
  • Physical findings: Regional dullness to percussion, egophony, pleural friction rub. 2, 4, 3

Non-Tension Pneumothorax

  • Presentation: Dyspnea and pleuritic pain worsening with inspiration. 4, 3
  • Physical findings: Unilateral absent breath sounds, hyperresonant percussion. 4, 3

Gastrointestinal Causes

Gastroesophageal Reflux Disease (GERD) / Esophagitis

  • Presentation: Burning retrosternal pain related to meals or occurring at night, relieved by antacids. 2, 3
  • Critical pitfall: Esophageal spasm may respond to nitroglycerin—do NOT use nitroglycerin response to differentiate cardiac from esophageal pain. 2, 4, 3

Peptic Ulcer Disease

  • Presentation: Epigastric tenderness with possible radiation to chest. 2, 3

Gallbladder Disease

  • Presentation: Right-upper-quadrant tenderness with positive Murphy sign. 3

Musculoskeletal Causes

Costochondritis / Tietze Syndrome

  • Presentation: Chest wall pain reproducible with palpation, breathing, turning, twisting, or bending; tenderness over costochondral joints. 2, 4, 3
  • Prevalence: Accounts for ~43% of chest pain presentations in primary care after cardiac causes are excluded. 2, 3
  • Critical pitfall: Reproducible chest wall tenderness does NOT fully exclude ACS—up to 7% of patients with palpable tenderness still have ACS. 2, 4, 3

Dermatologic Causes

Herpes Zoster

  • Presentation: Unilateral dermatomal pain triggered by touch (burning/tingling), followed by vesicular rash that does not cross midline. 2, 3

Initial Investigations (First 10 Minutes)

Mandatory Tests

  • 12-lead ECG within 10 minutes: Identify STEMI (≥1 mm ST-elevation in contiguous leads), ST-depression, T-wave inversions, or pericarditis patterns. 1, 2, 3
  • High-sensitivity cardiac troponin immediately: Most sensitive and specific biomarker for myocardial injury. 1, 2, 3
  • Vital signs: Heart rate, blood pressure in both arms (to detect pulse/BP differentials), respiratory rate, oxygen saturation. 2, 3

Focused Physical Examination

  • Cardiovascular: Diaphoresis, tachycardia, hypotension, pulmonary crackles, S3 gallop, new murmurs, pericardial friction rub. 2, 3
  • Pulmonary: Unilateral absent breath sounds, hyperresonant percussion, tracheal deviation. 2, 3
  • Vascular: Pulse differentials between extremities, blood pressure differentials between arms. 2, 3
  • Abdominal: Epigastric tenderness, right-upper-quadrant tenderness, subcutaneous emphysema. 2, 3

Additional Testing When Indicated

  • Chest X-ray: Evaluate for pneumothorax, pneumonia, pleural effusion, widened mediastinum (aortic dissection). 2, 4, 3
  • D-dimer (age- and sex-adjusted): In low-to-intermediate probability PE patients—negative result rules out PE. 2, 4
  • CT pulmonary angiography: For high clinical suspicion of PE or positive D-dimer. 2, 4
  • Transthoracic echocardiography: Evaluate for pericardial effusion, wall motion abnormalities, valvular disease. 2, 4
  • Cardiac MRI with gadolinium: Differentiate myopericarditis from other causes when diagnostic uncertainty persists. 2, 4

Risk Stratification After Initial Assessment

High-Risk Features (Immediate Coronary Care Unit Admission)

  • Ongoing rest pain >20 minutes. 2
  • Hemodynamic instability (SBP <100 mmHg, HR >100 or <50 bpm). 2
  • Troponin above 99th percentile. 2
  • Evidence of heart failure (crackles, S3 gallop, new murmurs). 2
  • ST-elevation or new ischemic changes on ECG. 2, 3

Low-Risk Criteria (Chest Pain Unit Observation or Early Discharge)

  • Normal or nondiagnostic ECG. 2
  • Negative troponin at presentation and at 6–12 hours. 2
  • Stable vital signs, no ongoing pain, no heart failure signs. 2
  • Management: Observe in chest pain unit for 10–12 hours OR discharge with outpatient stress testing within 72 hours. 2

Special Populations

Women

  • Higher risk of underdiagnosis: More likely to present with accompanying symptoms (jaw/neck pain, nausea, fatigue, dyspnea, epigastric discomfort) rather than classic chest pain. 1, 2, 3
  • Use sex-specific troponin thresholds: >16 ng/L for women vs >34 ng/L for men—reclassifies ~30% of women as having STEMI who would be missed with universal cutoff. 2

Older Adults (≥75 Years)

  • Atypical presentations: Isolated dyspnea, syncope, acute delirium, unexplained falls without classic chest pain. 1, 2, 3

Patients with Diabetes

  • Atypical symptoms: Vague abdominal symptoms, confusion, isolated dyspnea; higher risk for silent ischemia. 2

Critical Pitfalls to Avoid

  • Do NOT rely on nitroglycerin response to differentiate cardiac from non-cardiac pain—esophageal spasm also responds. 2, 4, 3
  • Do NOT assume young age excludes ACS—it can occur in adolescents without risk factors. 2
  • Do NOT delay EMS transport for troponin testing in office settings when ACS is suspected. 1, 2, 3
  • Do NOT use the term "atypical chest pain"—describe as "cardiac," "possibly cardiac," or "non-cardiac" to prevent misinterpretation. 1, 2, 3
  • Do NOT assume a normal ECG rules out ACS—30–40% of MIs present with normal/nondiagnostic ECG. 2, 3

Transport and Pre-Hospital Management

  • Activate EMS immediately for suspected life-threatening causes—do NOT transport by personal automobile. 2, 3
  • Pre-hospital ECG reduces mortality by ~17% and enables rapid STEMI activation. 2
  • Chew aspirin 162–325 mg immediately unless contraindicated (allergy, active GI bleeding). 2, 3
  • Sublingual nitroglycerin unless SBP <90 mmHg or HR <50 or >100 bpm. 2
  • Intravenous morphine 4–8 mg for pain relief (repeat 2 mg every 5 minutes as needed). 2
  • Supplemental oxygen 2–4 L/min only if breathless, heart failure features, or low oxygen saturation—routine oxygen in normoxemic patients may be harmful. 2

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

2
Guideline

Initial Evaluation of Chest Pain

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

3
Guideline

Differential Diagnosis for Chest Pain

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

4
Guideline

Pleuritic Chest Pain Diagnosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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