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Chest Pain: A Comprehensive Review

Overview

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PART 1: CORONARY ARTERY DISEASE (CAD) / ANGINA PECTORIS

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1.1 Definition

• Stable (typical) angina - the most common form; imbalance between chronic atherosclerotic coronary stenosis and increased myocardial demand. Does not occur at rest.
• Prinzmetal (variant) angina - episodic coronary artery spasm, unrelated to physical activity; can occur at rest; responds to vasodilators.
• Unstable angina - increasingly frequent, prolonged (>20 min), or severe angina at progressively lower activity levels or at rest; associated with plaque disruption, thrombosis, and distal embolization; a harbinger of MI.

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1.2 Epidemiology

• More than 17 million Americans have coronary heart disease; nearly 10 million have angina pectoris.
• Among adults aged 60-79 years: ~25% of men and ~16% of women have coronary heart disease; these percentages rise to 37% and 23%, respectively, in those >80 years.
• Males constitute ~70% of all patients with angina pectoris, with an even greater proportion in those <50 years.
• Globally, cardiovascular disease accounts for an estimated 18 million deaths per year (32% of all global deaths, 2019 Global Burden of Disease data).
• Coronary heart disease accounted for 365,000 of ~650,000 U.S. heart disease deaths in 2019.

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1.3 Etiology

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1.4 Pathogenesis

1. Demand angina - increased myocardial oxygen requirements (exertion, emotion, heavy meals, cold exposure) exceed what stenotic coronary arteries can deliver.
2. Supply angina - diminished oxygen delivery due to vasospasm, plaque disruption, or microvascular disease.

• An atheromatous plaque is eroded or suddenly disrupted by endothelial injury or mechanical forces, exposing subendothelial collagen.
• Platelets adhere, aggregate, and are activated, releasing thromboxane A2, ADP, and serotonin - causing further platelet aggregation and vasospasm.
• Activation of coagulation via tissue factor adds to the growing thrombus.
• Within minutes, the thrombus can completely occlude the coronary lumen.

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1.5 Histopathology

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1.6 Clinical Features

• Quality: Heaviness, pressure, squeezing, smothering, choking - rarely described as frank "pain"; patients may say "pressure, ache, discomfort, uneasy feelings."
• Location: Substernal; the classic Levine's sign - clenched fist placed over the sternum.
• Radiation: Left arm (especially ulnar aspect), left jaw, neck, back, interscapular region, epigastrium. Does NOT radiate to the trapezius (which suggests pericarditis instead).
• Duration: Stable angina: 2-5 minutes; relieved by rest or sublingual nitroglycerin. Unstable angina: >20 minutes; often occurs at rest.
• Precipitants: Exertion, emotion, cold temperature, heavy meals, sexual activity.
• Atypical presentations: Women, elderly, and diabetics may present with dyspnea, nausea, diaphoresis, fatigue, or jaw pain without classic chest discomfort.

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1.7 Diagnosis

• ECG: ST depression (stable angina, NSTEMI), ST elevation (STEMI), T-wave inversions; Prinzmetal: transient ST elevation during spasm.
• Cardiac biomarkers: Troponin I/T (preferred), CK-MB - elevated in MI (not in stable angina alone).
• Stress testing: Exercise ECG, nuclear perfusion imaging, or stress echocardiography to provoke reversible ischemia.
• Coronary angiography: Gold standard for defining coronary anatomy and stenosis severity.
• CT coronary angiography (CTCA): Non-invasive alternative; excellent for ruling out obstructive CAD.
• Diamond-Forrester Classification: Typical angina (all 3): (1) substernal pressure-like pain, (2) precipitated by exertion/emotion, (3) relieved by rest or nitroglycerin <30 min. Atypical: 2 of 3. Noncardiac: ≤1 of 3.

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1.8 Management

• Sublingual nitroglycerin - immediate relief of acute angina episodes
• Beta-blockers - reduce heart rate and contractility (decrease demand); first-line
• Calcium channel blockers - vasodilation and rate control; especially useful in Prinzmetal (vasospasm)
• Long-acting nitrates - adjunctive; tolerance may develop
• Ranolazine - late Na+ channel blocker; useful add-on

• Antiplatelet therapy (aspirin ± clopidogrel)
• Statins (LDL-lowering + plaque stabilization)
• ACE inhibitors/ARBs
• Control of hypertension, diabetes, smoking cessation

• PCI (percutaneous coronary intervention) - for significant single-vessel or multi-vessel CAD
• CABG (coronary artery bypass grafting) - for left main disease, 3-vessel disease, or diabetics with multi-vessel disease

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1.9 Prognosis

• Stable angina: generally benign with good medical management; annual mortality ~1-2% with modern therapy.
• Unstable angina/NSTEMI: significant risk of progression to STEMI or sudden cardiac death without intervention.
• STEMI: in-hospital mortality ~5-10% with modern reperfusion; higher without.

1.10 Complications

• Myocardial infarction
• Heart failure (systolic or diastolic)
• Cardiogenic shock
• Arrhythmias (ventricular fibrillation, complete heart block)
• Papillary muscle rupture / mitral regurgitation
• Ventricular septal defect (in MI)
• Sudden cardiac death
• Left ventricular aneurysm
• Dressler's syndrome (post-MI pericarditis)

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PART 2: GASTROINTESTINAL CHEST PAIN

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2.1 Definition

• Gastroesophageal reflux disease (GERD) - the most common GI cause of chest pain
• Esophageal spasm (diffuse esophageal spasm, nutcracker esophagus)
• Peptic ulcer disease
• Biliary colic
• Esophageal rupture (Boerhaave syndrome)

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2.2 Epidemiology

• GERD affects ~20% of the Western population; it is one of the most common causes of noncardiac chest pain.
• Up to 30-50% of patients presenting to the ER with chest pain eventually have a non-cardiac (often GI) etiology identified.
• Esophageal causes account for up to 30-60% of noncardiac chest pain cases.
• GERD prevalence in asthmatics is estimated at 34-89%.

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2.3 Etiology

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2.4 Pathogenesis

• H+ concentration, volume, and duration of acid exposure on esophageal mucosa
• Secondary esophageal spasm triggered by acid reflux
• Prolonged contractions of longitudinal esophageal muscles
• Activation of pain-sensitive chemoreceptors and mechanoreceptors in the esophageal wall
• Referred pain through shared sensory afferents with the heart (explaining the angina-like quality)

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2.5 Histopathology

• GERD: Esophageal mucosa shows basal zone hyperplasia, elongated papillae, intraepithelial eosinophils, and dilated intercellular spaces. Chronic exposure leads to Barrett's esophagus (intestinal metaplasia with goblet cells).
• Peptic ulcer: Mucosal defect extending through the muscularis mucosae; active ulcers show neutrophilic infiltrate; chronic ulcers show fibrous base with granulation tissue.
• Esophageal spasm: No specific histologic changes; diagnosis is manometric.

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2.6 Clinical Features

• GERD chest pain: Substernal burning or squeezing, often after meals, lying down, or bending over; may radiate to the back, neck, jaw, or arm - closely mimicking angina. Worsened by emotional stress. Lasts minutes to hours; often resolves spontaneously; may be eased by antacids.
• Associated features: Heartburn, regurgitation, sour taste, waterbrash, hoarseness, chronic cough, globus sensation.
• Esophageal spasm: Severe, intermittent substernal pain; may be associated with dysphagia; responds to nitroglycerin (mimicking angina even in its response to treatment).
• Biliary colic: Severe right upper quadrant or epigastric/chest pain, typically post-prandial (especially fatty meals); radiates to the right shoulder or scapula; nausea and vomiting.

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2.7 Diagnosis

• Upper endoscopy (EGD): Identifies esophagitis, Barrett's mucosa, peptic ulcer, malignancy.
• 24-hour esophageal pH monitoring / pH-impedance testing: Gold standard for diagnosing GERD; correlates symptoms with acid reflux events.
• Esophageal manometry: Diagnoses esophageal motility disorders (spasm, achalasia, nutcracker esophagus).
• PPI (proton pump inhibitor) trial: A clinical diagnostic test - chest pain episodes associated with documented reflux typically respond to acid antisecretory therapy.
• Ultrasound abdomen: For gallstones and biliary pathology.
• Esophagram (barium swallow): Useful for structural abnormalities.
• Cardiac workup first: Cardiac origin must be excluded before attributing chest pain to GI cause.

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2.8 Management

• GERD: Lifestyle modification (weight loss, head-of-bed elevation, avoiding precipitants); PPI therapy (first-line); H2 blockers; antacids for breakthrough. Fundoplication (Nissen) for refractory GERD.
• Esophageal spasm: Calcium channel blockers, nitrates, PPIs (if co-existing GERD), low-dose tricyclic antidepressants; botulinum toxin injection for severe cases.
• Peptic ulcer: H. pylori eradication (triple therapy); PPI therapy; stop NSAIDs.
• Biliary colic: Laparoscopic cholecystectomy (definitive); analgesics for acute episodes.
• Functional chest pain: CBT; low-dose antidepressants (TCAs, SSRIs); visceral analgesics.

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2.9 Prognosis

• GERD: excellent with PPI therapy; risk of Barrett's esophagus (~10-15% of chronic GERD) and esophageal adenocarcinoma with untreated long-standing disease.
• Esophageal spasm: benign but recurrent; rarely progressive.
• Esophageal rupture: life-threatening; requires urgent surgical intervention.

2.10 Complications

• Barrett's esophagus → esophageal adenocarcinoma
• Esophageal stricture (peptic)
• Aspiration pneumonia, pulmonary fibrosis (from GERD)
• Obstructive sleep apnea worsening
• Boerhaave syndrome (esophageal rupture) - fatal if untreated

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PART 3: MUSCULOSKELETAL CHEST PAIN

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3.1 Definition

• Costochondritis - inflammation of costal cartilages (Tietze syndrome if visible swelling is present)
• Chest wall trauma / rib fracture
• Cervical angina (radiculopathy) - chest pain from cervical nerve root compression (C4-C8)
• Chest wall tumors (rare)
• Precordial catch syndrome (Texidor's twinge) - benign, especially in young people

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3.2 Epidemiology

• Musculoskeletal disorders account for 20-40% of chest pain presentations in primary care and emergency settings.
• Costochondritis is particularly common in young adults and adolescents.
• In pediatric chest pain, musculoskeletal causes (including costochondritis and precordial catch syndrome) are the leading identifiable cause.
• Rib fractures are more common in the elderly (osteoporosis) and in those with trauma or malignancy.

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3.3 Etiology

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3.4 Pathogenesis

• Costochondritis: Inflammation (likely mechanical or post-infectious) of the costal cartilages at the costochondral or sternocostal junctions. Typically affects the 2nd-5th costal cartilages.
• Cervical angina: Compression of cervical nerve roots (C4-C8) - by herniated disc, osteophytes, or foraminal stenosis - produces referred pain to the chest, mimicking angina. The dermatomal distribution of these roots overlaps with the precordial region.
• Rib fractures: Periosteal pain receptors are activated; breathing and movement aggravate pain due to chest wall motion.

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3.5 Histopathology

• Costochondritis: Non-specific perichondral and cartilaginous inflammation with edema and neutrophilic or lymphocytic infiltrate in acute stages. No specific histologic criteria required (clinical diagnosis).
• Tietze syndrome: Swelling due to hypertrophy of costal cartilage ± inflammatory changes.
• Chest wall tumors: Vary by type - chondrosarcoma shows chondroid matrix; soft tissue sarcoma shows pleomorphic spindle cells.

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3.6 Clinical Features

• Location: Usually well-localized, anterior chest wall; often unilateral.
• Quality: Sharp, aching, or pleuritic.
• Key diagnostic feature: Pain reproducible on direct palpation of the chest wall - this is the hallmark that distinguishes musculoskeletal pain from angina.
• Costochondritis: Tenderness at costochondral or sternocostal junctions (2nd-5th ribs most commonly). No visible swelling (distinguishes from Tietze syndrome).
• Precordial catch syndrome: Sudden, sharp, focal pain - usually left peri-apical area; worsened by inspiration; resolves within minutes; not associated with dyspnea or dysrhythmias. Patients may say pain "took my breath away."
• Cervical angina: Chest pain associated with neck pain; often associated with arm/shoulder symptoms; may worsen with neck movement.
• Rib fracture: Localized tenderness over a rib; worsened by deep inspiration, coughing, or direct pressure.

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3.7 Diagnosis

• Clinical examination: Reproduced by chest wall palpation - the most important test.
• Chest X-ray: To exclude rib fractures, pneumothorax, pleural disease; may miss non-displaced fractures.
• CT thorax: More sensitive for rib fractures and chest wall masses.
• MRI/cervical spine: For suspected cervical radiculopathy.
• Bone scan: For occult fractures or metastatic disease.
• ECG and cardiac workup: Should be performed first to rule out cardiac cause, especially in those with risk factors.

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3.8 Management

• Costochondritis and rib fracture: NSAIDs (first-line), acetaminophen, local ice/heat; rest; intercostal nerve block for severe rib fracture pain; adequate analgesia to allow deep breathing.
• Cervical angina: Physical therapy, cervical traction, NSAIDs; surgical decompression for refractory cases.
• Precordial catch syndrome: Reassurance; self-limited; NSAIDs rarely needed.
• Tietze syndrome: NSAIDs; local corticosteroid injection for refractory cases.
• Chest wall tumors: Surgical resection is the primary treatment; adjuvant therapy depends on histology.

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3.9 Prognosis

• Costochondritis and precordial catch syndrome: benign, self-limiting; excellent prognosis.
• Rib fractures: good with conservative management; complications more common in elderly or with multiple fractures (flail chest).
• Cervical angina: good with appropriate treatment; may recur if underlying disc disease progresses.

3.10 Complications

• Multiple rib fractures: flail chest, pneumothorax, hemothorax
• Untreated chest wall malignancy: local extension, metastasis
• Chronic pain syndromes (costochondritis can rarely become chronic)

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PART 4: PSYCHOGENIC CHEST PAIN

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4.1 Definition

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4.2 Epidemiology

• Psychogenic causes account for approximately 10-30% of all noncardiac chest pain presentations.
• Panic disorder is the most frequently identified psychiatric condition associated with unexplained chest pain; up to 30-60% of patients with recurrent noncardiac chest pain meet criteria for panic disorder.
• Psychogenic chest pain is more common in young women and in patients with a history of anxiety, depression, or prior physical abuse.
• Patients with panic disorder also have higher rates of agoraphobia, major depression, and substance abuse.

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4.3 Etiology

• Panic disorder / panic attacks - the most common cause
• Generalized anxiety disorder (GAD)
• Major depressive disorder
• Somatization disorder / somatic symptom disorder
• Hyperventilation syndrome - lowered PCO2 causes cerebral vasoconstriction, alkalosis, and peripheral paresthesias
• Functional/visceral hypersensitivity - lowered pain thresholds in the esophagus or chest wall
• da Costa's syndrome (soldier's heart) - historically described in wartime; functional cardiac disorder

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4.4 Pathogenesis

• Autonomic dysregulation: Anxiety and panic trigger sympathetic hyperactivation, causing tachycardia, palpitations, and chest tightness - symptoms that are interpreted catastrophically by the patient.
• Hyperventilation: Leads to hypocapnia and respiratory alkalosis, causing coronary artery spasm, chest tightness, paresthesias, dizziness, and dyspnea.
• Central sensitization: Altered pain perception in the central nervous system lowers visceral pain thresholds.
• Cognitive amplification: Catastrophic misinterpretation of benign bodily sensations (e.g., palpitations from anxiety misread as heart attack) triggers a feedback cycle.
• The chest pain of panic disorder can be explained by increased wall tension of the esophagus, intercostal muscle spasm, and autonomic activation.

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4.5 Histopathology

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4.6 Clinical Features

• Quality: Typically sharp, stabbing, or vague; sometimes pressure-like (can mimic angina)
• Location: Variable; often left precordial or diffuse
• Duration: Can last seconds to hours; often prolonged compared with angina
• Associated features: Palpitations, dyspnea, diaphoresis, trembling, nausea, dizziness, depersonalization, fear of dying - classic panic attack features (4+ symptoms, peaking within 10 minutes)
• Triggers: Stress, anxiety-provoking situations; may occur without obvious trigger
• Response to treatment: Responds poorly to nitroglycerin and antacids; responds well to anxiolytics, breathing techniques, and CBT
• No reproducibility on palpation (unlike musculoskeletal pain)
• Normal cardiac workup despite often recurrent presentations

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4.7 Diagnosis

• Diagnosis of exclusion - cardiac, pulmonary, GI, and musculoskeletal causes must be ruled out first.
• DSM-5 criteria for panic disorder: recurrent unexpected panic attacks + persistent concern about future attacks or maladaptive behavior changes.
• Psychiatric evaluation: PHQ-9 (depression screening), GAD-7 (anxiety screening).
• Hyperventilation provocation test: Voluntary hyperventilation for 2-3 minutes reproducing symptoms.
• Cardiac workup: ECG, troponin, exercise stress test - all normal.
• Normal endoscopy and pH studies (distinguishes from GERD).

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4.8 Management

• The majority of patients with panic disorder can be effectively treated with either nonpharmacologic or pharmacologic modalities:
• Cognitive Behavioral Therapy (CBT) - first-line, most effective long-term treatment; addresses catastrophic thinking and avoidance
• SSRIs (e.g., paroxetine, sertraline, escitalopram) - first-line pharmacotherapy; takes 4-6 weeks for full effect
• SNRIs (venlafaxine) - alternative first-line pharmacotherapy
• Benzodiazepines - short-term relief; risk of dependence; not for long-term use
• Tricyclic antidepressants (TCAs) - imipramine; effective but side-effect profile limits use
• Breathing retraining: Diaphragmatic breathing to prevent hyperventilation
• Patient education and reassurance: Critical to break the fear-symptom-fear cycle

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4.9 Prognosis

• With appropriate treatment, the majority of patients with panic disorder have good outcomes.
• Untreated panic disorder tends to be chronic and disabling.
• Risk of developing agoraphobia and major depression if untreated.
• Recurrent ER visits for chest pain are common, with high healthcare utilization.

4.10 Complications

• Agoraphobia
• Major depressive disorder
• Substance abuse
• Social and occupational disability
• Increased cardiovascular risk (chronic anxiety is an independent cardiovascular risk factor)
• Iatrogenic harm from repeated unnecessary cardiac investigations

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DIFFERENTIAL DIAGNOSIS TABLE

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Key Clinical Pearls

1. Always exclude cardiac causes first - especially in those with risk factors (hypertension, diabetes, smoking, family history, hyperlipidemia, age >45 men / >55 women).
2. The Levine sign (clenched fist over sternum) is classic for angina. A finger pointing to a small, focal spot is less likely to be ischemic.
3. Reproducible chest wall tenderness on palpation strongly favors a musculoskeletal cause - but does NOT fully exclude cardiac pathology.
4. Nitroglycerin responsiveness is not specific for CAD - esophageal spasm also responds to nitroglycerin.
5. Women, elderly, and diabetics often present atypically with CAD - dyspnea, jaw pain, nausea, or fatigue may be the dominant symptom.
6. Panic disorder is extremely common in the emergency department chest pain population; a good psychiatric history after cardiac workup is essential.
7. GI chest pain is the most common noncardiac mimic of angina; a therapeutic PPI trial is both diagnostic and therapeutic.

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• Robbins & Cotran Pathologic Basis of Disease (9780443264528)
• Goldman-Cecil Medicine International Edition (9780323930345)
• Harrison's Principles of Internal Medicine, 22nd Ed. (9781265977061)
• Sleisenger & Fordtran's Gastrointestinal and Liver Disease (9780323609623)
• Yamada's Textbook of Gastroenterology, 7th Ed. (9781119600169)
• Fuster & Hurst's The Heart, 15th Ed. (9781264257560)
• Frameworks for Internal Medicine (9781496359308)