What is the best differential diagnosis for chest pain?

Differential Diagnosis for Chest Pain

The differential diagnosis for chest pain must prioritize immediate identification of life-threatening conditions—acute coronary syndrome (ACS), aortic dissection, pulmonary embolism, tension pneumothorax, and esophageal rupture—before considering more benign etiologies. 1

Life-Threatening Causes (Immediate Exclusion Required)

Cardiovascular Emergencies

• Acute Coronary Syndrome (STEMI/NSTEMI/Unstable Angina): Retrosternal pressure-type discomfort building gradually over minutes, radiating to left arm/jaw/neck, associated with diaphoresis, dyspnea, nausea, or syncope; may occur at rest or with minimal exertion 1
• Aortic Dissection: Sudden-onset "ripping" or "tearing" chest pain (often described as "worst pain of my life"), radiating to upper or lower back, with pulse differentials between extremities (30% of patients), blood pressure differentials, or new aortic regurgitation murmur 1, 2
• Pulmonary Embolism: Acute dyspnea with pleuritic chest pain, tachycardia present in >90% of patients, tachypnea, and associated risk factors 1
• Cardiac Tamponade: Hemodynamic instability, muffled heart sounds, elevated jugular venous pressure 1, 3

Non-Cardiovascular Emergencies

• Tension Pneumothorax: Severe dyspnea, unilateral absence of breath sounds, pain with inspiration, hemodynamic compromise 1, 3
• Esophageal Rupture (Boerhaave Syndrome): Severe pain with abrupt onset, history of emesis, subcutaneous emphysema, pneumothorax in 20% of patients 1, 3

Serious But Non-Immediately Fatal Causes

Cardiac

• Pericarditis: Sharp, pleuritic chest pain that worsens when supine and improves when leaning forward, friction rub on examination, fever 1, 2
• Myocarditis: Chest pain with fever, signs of heart failure, S3 gallop 1, 2
• Valvular Disease: Aortic stenosis (systolic murmur, tardus/parvus carotid pulse), aortic regurgitation (diastolic murmur), hypertrophic cardiomyopathy (systolic murmur, prominent left ventricular impulse) 1

Pulmonary

• Pneumonia: Fever, localized pleuritic chest pain, regional dullness to percussion, egophony 1, 4
• Spontaneous Pneumothorax: Acute sharp chest pain with dyspnea, unilateral decreased breath sounds (not tension physiology) 1, 4
• Pleuritis: Pain related to breathing movements, characteristic of pleuritic chest diseases 4

Common Benign Causes

Musculoskeletal

• Costochondritis/Tietze Syndrome: Tenderness of costochondral joints on palpation, pain reproducible with chest wall pressure 1, 5
• Chest Wall Pain: Pain localized to very limited area, affected by palpation, breathing, turning, twisting, or bending 1

Gastrointestinal

• Gastroesophageal Reflux Disease/Esophagitis: Burning retrosternal pain related to meals, relieved by antacids 1, 5
• Peptic Ulcer Disease: Epigastric tenderness 1
• Biliary Disease: Right upper quadrant tenderness, Murphy sign 1

Other

• Herpes Zoster: Pain in dermatomal distribution triggered by touch, characteristic unilateral dermatomal rash 1
• Anxiety/Panic Disorder: Fleeting chest pain of seconds' duration, multiple site pain, psychogenic features 1, 5

Critical Historical Features to Distinguish Causes

Characteristics Suggesting ACS

• Gradual onset over minutes (not seconds or hours) 1
• Retrosternal pressure/heaviness/squeezing quality 1
• Radiation to left arm, neck, jaw 1
• Precipitated by exertion or emotional stress, or occurring at rest 1
• Associated with dyspnea, diaphoresis, nausea, lightheadedness 1

Characteristics Suggesting Non-Ischemic Etiology

• Sharp pain increasing with inspiration and lying supine (pericarditis) 1
• Fleeting pain lasting only seconds (unlikely ischemic) 1
• Pain localized to very small area or radiating below umbilicus (unlikely ischemic) 1
• Positional chest pain (musculoskeletal) 1
• Pain reproduced by palpation (musculoskeletal) 1

High-Risk Features Requiring Immediate Action

• Age >75 years with accompanying dyspnea, syncope, acute delirium, or unexplained fall 1
• Women presenting with atypical symptoms (more common than in men) 1
• Patients with diabetes, renal insufficiency, or dementia (higher rates of atypical presentations) 1

Common Pitfalls

• Do not use nitroglycerin response as a diagnostic criterion—esophageal spasm and other conditions also respond to nitroglycerin 1
• Do not dismiss chest pain in women or elderly patients—they frequently present with atypical symptoms including isolated dyspnea, nausea, or fatigue without classic chest pain 1
• Do not rely solely on pain severity—there is poor correlation between symptom intensity and disease seriousness 1