What are the differential diagnoses for chest pain, including emergent and non‑urgent causes?

Differential Diagnoses for Chest Pain

Chest pain evaluation must immediately focus on identifying life-threatening emergencies—acute coronary syndrome (ACS), acute aortic syndromes, and pulmonary embolism (PE)—before considering non-urgent causes. 1

Emergent (Life-Threatening) Causes

The "Big Three" Emergency Diagnoses

• Acute Coronary Syndrome (ACS): Includes unstable angina and myocardial infarction; may present with diaphoresis, tachypnea, tachycardia, hypotension, crackles, S3 gallop, or new mitral regurgitation murmur, though examination may be entirely normal in uncomplicated cases 2
• Acute Aortic Syndromes: Aortic dissection presents with severe, abrupt-onset pain plus pulse differential in 30% of patients (more common in Type A than Type B); when combined with widened mediastinum on chest x-ray, probability exceeds 80% 2
• Pulmonary Embolism: Tachycardia plus dyspnea occurs in over 90% of patients; pain with inspiration is characteristic 2

Additional Life-Threatening Causes

• Esophageal rupture: Presents with severe pain, abrupt onset, emesis, subcutaneous emphysema, and pneumothorax in 20% of patients; unilateral decreased or absent breath sounds may be present 2
• Tension pneumothorax: Dyspnea and pain on inspiration with unilateral absence of breath sounds 2
• Cardiac tamponade: Requires immediate recognition and intervention 3

Critical pitfall: In women, ACS may present with atypical accompanying symptoms rather than classic chest pain, creating risk for underdiagnosis; obtain history emphasizing symptoms more common in women with ACS 2. In patients over 75 years, consider ACS when shortness of breath, syncope, acute delirium, or unexplained falls occur even without typical chest pain 2.

Non-Emergent Cardiac Causes

Structural Heart Disease

• Aortic stenosis: Characteristic systolic murmur with tardus or parvus carotid pulse 2
• Aortic regurgitation: Diastolic murmur at right of sternum with rapid carotid upstroke; occurs in 40-75% of Type A dissections 2
• Hypertrophic cardiomyopathy: Increased or displaced left ventricular impulse, prominent a wave in jugular venous pressure, systolic murmur 2

Inflammatory Cardiac Conditions

• Pericarditis: Fever, pleuritic chest pain increased in supine position, friction rub 2
• Myocarditis: Fever, chest pain, heart failure signs including S3; can progress to fulminant myocarditis with high mortality 1, 2

Non-Cardiac Causes

Gastrointestinal

• Gastroesophageal reflux disease (GERD): Most prevalent cause of non-cardiac chest pain; effectively diagnosed and treated with proton-pump inhibitors 4
• Esophagitis and peptic ulcer disease: Epigastric tenderness on examination 2
• Gallbladder disease: Right upper quadrant tenderness with positive Murphy sign 2

Pulmonary (Non-PE)

• Pneumonia: Fever, localized chest pain (may be pleuritic), friction rub, regional dullness to percussion, egophony 2
• Pneumothorax (non-tension): Dyspnea and pain on inspiration with unilateral absence of breath sounds 2

Musculoskeletal

• Costochondritis/Tietze syndrome: Tenderness of costochondral joints on palpation 2
• Thoracic wall pain: Somatic pain differentiated from visceral organ pain by history and careful physical examination 5

Dermatologic

• Herpes zoster: Pain in dermatomal distribution triggered by touch; characteristic unilateral dermatomal rash 2

Diagnostic Approach Algorithm

Immediate actions (within 10 minutes of arrival):

1. Obtain ECG to evaluate for STEMI 2
2. Perform focused cardiovascular examination to identify ACS, aortic dissection, PE, or esophageal rupture complications 2

Key diagnostic principle: No single feature of history, physical examination, or diagnostic test can diagnose ACS to the exclusion of other causes; serial evaluations are frequently required 6. Approximately half of chest pain cases are cardiac in origin (ischemic or non-ischemic cardiac disease), while the other half are primarily due to esophageal disorders 4.

Office setting considerations: Unless a non-cardiac cause is evident, perform ECG for patients with stable chest pain; if ECG is unavailable, refer to emergency department 2. Patients with clinical evidence of ACS or other life-threatening causes should be transported urgently to the emergency department, ideally by emergency medical services 2.

Complicating factor: Psychological and psychiatric conditions such as depression or panic disorder commonly coexist and may cause or worsen chest pain regardless of underlying etiology, though they are not easily detected 4.