Differential Diagnosis of Chest Pain

I. Coronary Artery Disease (Cardiac Causes)

Angina Pectoris

• Character: Substernal, constricting, pressure-like, or squeezing
• Precipitants: Physical exertion, emotional stress, cold exposure
• Duration: 2–15 minutes; relieved by rest or nitroglycerin (NTG)
• Radiation: Left arm, neck, jaw, shoulder
• ECG: ST depression or T-wave changes during episodes; may be normal at rest
• Key feature: Prompt relief with NTG is characteristic

Acute Myocardial Infarction (AMI)

• Character: Substernal, crushing, severe; described as "heaviness" or "elephant on chest"
• Duration: Persistent (>20–30 min), not relieved by NTG
• Associated features: Diaphoresis, nausea, dyspnea, hemodynamic instability
• ECG: ST elevation (STEMI) or depression/T-wave inversion (NSTEMI); elevated troponin
• CXR: May show pulmonary vascular congestion or cardiomegaly

Variant (Prinzmetal) Angina

• Coronary vasospasm; may occur at rest or be elicited by exertion/emotional stress
• ST elevation during episodes; typically resolves with vasodilators

Other Cardiac Causes

ECG and troponin are the critical initial investigations to differentiate ischemic from non-ischemic cardiac chest pain. — Rosen's Emergency Medicine, p. 58

II. Gastrointestinal Causes

Gastroesophageal Reflux Disease (GERD)

• Most common GI cause of noncardiac chest pain (40–60% of cases)
• Character: Burning, retrosternal; may radiate to jaw/arms
• Triggers: Large meals, lying flat, acidic foods, alcohol
• Key feature: May respond to nitroglycerin (like cardiac pain), creating diagnostic confusion; responds better to antacids/PPIs
• Diagnosis: Ambulatory 24-hr pH monitoring; empiric PPI trial

Esophageal Spasm / Motility Disorders

• Diffuse esophageal spasm, jackhammer esophagus: Substernal chest pain, often severe; may occur spontaneously or with swallowing
• Associated with dysphagia; can mimic AMI
• Note: Contrary to popular belief, GERD is a far more common cause of noncardiac chest pain than spastic motility disorders — Yamada's Textbook of Gastroenterology

Peptic Ulcer Disease

• Epigastric/lower chest burning; related to meals; nocturnal pain; relieved by food/antacids
• May radiate to the chest; perforated ulcer presents acutely

Biliary Colic / Cholecystitis

• Right upper quadrant and lower chest/epigastric pain; may radiate to right shoulder/scapula
• Postprandial (especially fatty meals); nausea, vomiting
• Gallstones visible on abdominal ultrasound

Pancreatitis

• Severe epigastric pain radiating to the back and chest; associated nausea/vomiting
• Elevated amylase/lipase

Esophageal Perforation (Boerhaave Syndrome)

• Life-threatening: Sudden severe chest pain after vomiting/instrumentation
• Subcutaneous emphysema, mediastinitis, Hamman's crunch on auscultation
• Requires urgent imaging (CT/contrast esophagram)

Substernal chest pain is the main symptom in 80–90% of patients with esophageal motility disorders. The presence of dysphagia alongside chest pain strongly points to an esophageal origin. — Rosen's Emergency Medicine

III. Musculoskeletal Causes

Costochondritis (Tietze Syndrome)

• Most common musculoskeletal cause
• Inflammation of costochondral junctions (most commonly 2nd–4th ribs)
• Character: Dull, gnawing, aching; little relationship to breathing or movement
• Key diagnostic feature: Reproducible tenderness on palpation of the affected cartilage
• Tietze syndrome = redness, swelling, and enlargement of costal cartilages

Chest Wall Muscle Strain / Rib Fracture

• History of trauma, vigorous exercise, or repeated coughing
• Localized tenderness; pain worsened by palpation, movement, deep breathing
• Rib fracture confirmed by X-ray or CT

Intercostal Neuritis / Radiculitis

• Superficial, lancinating, "electric shock-like" pain
• Follows dermatomal distribution; may be worsened by deep breathing, coughing, sneezing
• Hyperalgesia or anesthesia of overlying skin
• Herpes Zoster (shingles): Unilateral dermatomal pain preceding the vesicular rash by 2–3 days — a notorious diagnostic trap

Cervical/Thoracic Spine Disorders (Cervical Radiculopathy)

• Nerve root compression at C4–T1 levels refers pain to the chest/arm
• Provoked by neck movement; associated neurological deficits

Other Musculoskeletal Causes

Musculoskeletal chest pain is identified by physical examination — reproducible tenderness on palpation is the diagnostic hallmark. — Yamada's Textbook of Gastroenterology; Murray & Nadel's Respiratory Medicine, p. 1026

IV. Psychogenic / Psychiatric Causes

Panic Disorder / Panic Attack

• Most common psychiatric cause of chest pain
• Sudden-onset chest tightness, palpitations, shortness of breath, dizziness, paresthesias, fear of dying
• Symptoms typically peak within 10 minutes and resolve within 30–60 minutes
• Strong association with mitral valve prolapse
• Patients may present repeatedly to emergency departments; diagnosis of exclusion
• Key feature: Anxiety precedes or accompanies somatic symptoms

Generalized Anxiety Disorder

• Chronic, low-level chest tightness; associated hyperventilation
• Hyperventilation → hypocapnia → coronary vasospasm → chest pain

Depression / Somatization

• Atypical chest pain with multiple somatic complaints
• Chronic, not related to exertion; accompanied by depressed mood, sleep disturbance, fatigue

Functional Chest Pain of Esophageal Origin (Functional Heartburn)

• No organic cause identified after thorough workup
• Central sensitization and visceral hypersensitivity are implicated mechanisms
• Classified under Rome IV criteria for functional GI disorders

In most patients with noncardiac chest pain, no clear cause will be identified and symptoms will be deemed functional. Panic attacks may be accompanied by a variety of somatic symptoms, chest pain being one of the most frequently encountered. — Yamada's Textbook of Gastroenterology

Summary Table: Key Differentiating Features

Clinical Approach

1. Rule out life threats first: ACS, aortic dissection, pulmonary embolism, tension pneumothorax, esophageal perforation
2. History: Onset, quality, radiation, severity, duration, triggers, relieving factors, associated symptoms
3. Physical exam: BP both arms (dissection), palpation for chest wall tenderness (musculoskeletal), cardiac auscultation
4. ECG: Mandatory in all chest pain presentations
5. Troponin: Serial measurements at 0 and 3 hours
6. CXR: Mediastinal widening, pneumothorax, consolidation
7. Targeted testing: Upper endoscopy/pH monitoring (GI), CT angiography (dissection/PE), psychiatric screening tools (psychogenic)