What are the differential diagnoses and initial evaluation steps for a patient presenting with chest pain, including how to rule out life‑threatening causes?

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Differential Diagnosis of Chest Pain

Life-Threatening Causes That Must Be Excluded First (Within 10 Minutes)

Obtain a 12-lead ECG within 10 minutes and draw high-sensitivity cardiac troponin immediately in every patient with chest pain, regardless of age or presentation, because these two tests form the foundation for excluding the six conditions that can cause death within minutes to hours. 1, 2

The six immediately life-threatening diagnoses are:

  • Acute Coronary Syndrome (ACS) – retrosternal pressure, squeezing, or heaviness building gradually over minutes (not instantaneous), often radiating to left arm, jaw, or neck, accompanied by diaphoresis, dyspnea, nausea, or syncope. 1, 2 Critically, 30–40% of acute myocardial infarctions present with a normal or nondiagnostic initial ECG, and approximately 13% of patients with sharp, pleuritic chest pain still have acute myocardial ischemia—so atypical features do not exclude ACS. 1, 2

  • Acute Aortic Dissection – sudden-onset "ripping" or "tearing" chest or back pain maximal at onset, radiating to the back. 1, 2 Look for pulse differential between extremities (~30% of cases), systolic blood-pressure difference >20 mmHg between arms, or new aortic regurgitation murmur (present in 40–75% of type A dissections). 1, 2 The combination of severe abrupt pain, pulse differential, and widened mediastinum on chest X-ray predicts >80% probability of dissection. 1, 2

  • Pulmonary Embolism (PE) – sudden dyspnea with pleuritic chest pain worsening on inspiration; tachycardia occurs in >90% of patients and tachypnea in ~70%. 1, 2 Apply Wells criteria; obtain age- and sex-adjusted D-dimer for low-to-intermediate probability or proceed directly to CT pulmonary angiography for high probability. 1

  • Tension Pneumothorax – dyspnea and sharp chest pain intensifying with inspiration, unilateral absent breath sounds, hyperresonant percussion, tracheal deviation, and hemodynamic instability. 1, 2

  • Cardiac Tamponade – pleuritic chest pain worsening supine, Beck's triad (jugular venous distension, hypotension, muffled heart sounds), and pulsus paradoxus >10 mmHg. 1, 2 Bedside transthoracic echocardiography is the preferred initial test. 1, 2

  • Esophageal Rupture (Boerhaave Syndrome) – severe chest pain following forceful vomiting, subcutaneous emphysema of neck or chest, and concurrent pneumothorax in ~20% of cases. 1, 2

Mandatory Initial Evaluation (First 10 Minutes)

Interpret the ECG immediately for ST-elevation ≥1 mm in contiguous leads (STEMI), ST-depression, T-wave inversions, or diffuse ST-elevation with PR-depression (pericarditis). 1, 2 If STEMI is identified, activate the STEMI protocol targeting door-to-balloon <90 minutes for primary PCI or door-to-needle <30 minutes for fibrinolysis. 1

Measure high-sensitivity cardiac troponin on arrival; it is the most sensitive and specific biomarker for myocardial injury, outperforming CK and CK-MB. 1, 2 A single normal troponin does not exclude ACS—repeat at 1–3 hours (or 3–6 hours with conventional assay). 1, 2

Perform a focused cardiovascular examination for diaphoresis, tachypnea, tachycardia, hypotension, pulmonary crackles, S3 gallop, new murmurs (mitral or aortic regurgitation), pericardial friction rub, unilateral absent breath sounds, pulse differentials, jugular venous distension, and subcutaneous emphysema. 1, 2 A completely normal physical examination does not exclude uncomplicated myocardial infarction. 1, 2

Measure vital signs in both arms; a systolic blood-pressure difference >20 mmHg suggests aortic dissection, and tachycardia >100 bpm is present in >90% of PE. 1, 2

Serious Cardiac Causes (Non-ACS)

  • Acute Pericarditis – sharp, pleuritic chest pain worsening supine and improving when sitting or leaning forward, often with fever and pericardial friction rub (absence does not exclude disease). 1, 2 ECG shows diffuse concave ST-elevation with PR-depression. 1, 2 First-line therapy: ibuprofen 600–800 mg three times daily for 1–2 weeks or colchicine 0.6 mg twice daily for 3 months. 1, 2

  • Myocarditis – chest pain with fever and signs of heart failure (S3 gallop, crackles); clinical presentation mimics ACS, requiring troponin measurement for differentiation. 1, 2, 3

  • Valvular Disease – aortic stenosis (systolic murmur with delayed carotid pulse), aortic regurgitation (early diastolic murmur with rapid carotid upstroke), hypertrophic cardiomyopathy (systolic murmur increasing with Valsalva). 1, 2

Pulmonary Causes

  • Pneumonia – fever with localized pleuritic chest pain, regional dullness, egophony, or pleural friction rub. 1, 2

  • Non-Tension Pneumothorax – dyspnea and chest pain worsening with inspiration, unilateral absent breath sounds, hyperresonant percussion. 1, 2

Gastrointestinal Causes

  • Gastroesophageal Reflux Disease (GERD) / Esophagitis – burning retrosternal pain related to meals or at night, often relieved by antacids. 1, 2 Do not rely on nitroglycerin response to differentiate cardiac from esophageal pain, as esophageal spasm may also respond. 1, 2

  • Peptic Ulcer Disease – epigastric tenderness with possible radiation to chest. 1, 2

  • Esophageal Motility Disorders – squeezing retrosternal pain or spasm, often with dysphagia. 1, 2

Musculoskeletal Causes

  • Costochondritis / Tietze Syndrome – tenderness over costochondral joints reproducible with palpation, breathing, turning, or twisting; accounts for ~43% of chest-pain presentations after cardiac causes are excluded. 1, 2 However, up to 7% of patients with reproducible chest-wall tenderness still have ACS, so tenderness does not fully exclude cardiac disease. 1, 2

Other Causes

  • Herpes Zoster – unilateral dermatomal pain triggered by touch, described as burning or tingling, followed by a vesicular rash that does not cross the midline. 1, 2

  • Panic Disorder / Anxiety – chest pain with dyspnea, palpitations, and diaphoresis; this is a diagnosis of exclusion after full cardiac work-up. 1, 2

Special Populations at High Risk for Underdiagnosis

  • Women – higher risk of underdiagnosis; more frequently present with jaw/neck pain, nausea, fatigue, dyspnea, epigastric discomfort, or back pain rather than classic chest pressure. 1, 2 Use sex-specific high-sensitivity troponin thresholds (>16 ng/L for women vs >34 ng/L for men); universal cut-offs miss ~30% of women with STEMI. 1, 2

  • Older Adults (≥75 years) – may present atypically with isolated dyspnea, syncope, acute delirium, or unexplained falls without classic chest pain. 1, 2

  • Patients with Diabetes – more likely to present with atypical symptoms including vague abdominal symptoms, confusion, or isolated dyspnea, and have higher risk for silent ischemia. 1, 2

Risk Stratification After Initial Assessment

High-risk features mandating immediate coronary-care-unit admission: 1, 2

  • Ongoing rest pain >20 minutes with ischemic ECG changes
  • Hemodynamic instability (SBP <100 mmHg, HR >100 or <50 bpm)
  • Troponin above 99th percentile
  • Evidence of left-ventricular failure (crackles, S3 gallop, new murmurs)

Low-risk criteria for chest-pain-unit observation or early discharge: 1, 2

  • Normal or nondiagnostic ECG
  • Negative troponin at presentation and at 6–12 hours
  • Stable vital signs, no ongoing pain, no heart-failure signs

Low-risk patients can be observed in a chest-pain unit for 10–12 hours or discharged for outpatient stress testing within 72 hours. 1, 2

Critical Pitfalls to Avoid

  • Do not dismiss ACS in women, older adults, or patients with diabetes based on atypical presentations; they frequently present with sharp, stabbing, or pleuritic pain. 1, 2

  • Do not assume a normal physical examination excludes ACS; uncomplicated myocardial infarction can present with entirely normal findings. 1, 2

  • Do not delay EMS transport for troponin testing in office or outpatient settings when ACS is suspected; immediate transport is essential. 1, 2

  • Avoid the term "atypical chest pain"; describe presentations as "cardiac," "possibly cardiac," or "non-cardiac" to prevent misinterpretation as benign. 1, 2

  • A normal initial ECG does not rule out ACS; 30–40% of acute myocardial infarctions present with a normal or nondiagnostic ECG. 1, 2

  • Sharp, pleuritic pain does not exclude ACS; approximately 13% of patients with pleuritic pain have acute myocardial ischemia. 1, 2

Pre-Hospital Management

  • Activate EMS immediately for any suspected life-threatening chest pain; personal-vehicle transport carries a 1.5% risk of cardiac arrest en route. 1, 2

  • Administer chewed aspirin 162–325 mg to alert adults without allergy or active gastrointestinal bleeding while awaiting EMS. 1, 2

  • Give sublingual nitroglycerin unless systolic BP <90 mmHg or HR <50 or >100 bpm. 1, 2

  • Provide intravenous morphine 4–8 mg (repeat 2 mg every 5 minutes as needed) for pain relief; uncontrolled pain increases sympathetic drive and myocardial workload. 1, 2

  • Supply supplemental oxygen 2–4 L/min only if the patient is breathless, shows heart-failure features, or has low oxygen saturation; routine oxygen in normoxemic patients may be harmful. 1, 2

References

1
Guideline

Initial Evaluation of Chest Pain

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

2
Guideline

Differential Diagnosis for Chest Pain

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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Professional Medical Disclaimer

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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