Chest pain differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2] Amresh Kumar MD [3]

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Overview

There are several life-threatening causes of chest pain which need to be evaluated for first, which include; myocardial infarction, aortic dissection, esophageal rupture, pulmonary embolism, and tension pneumothorax. The other possible causes of chest pain can be evaluated for by carefully assessing the nature of the pain, and obtaining a thorough patient history.

Differential Diagnosis

5 Life Threatening Diseases to Exclude Immediately

The frequency of conditions exclusive of acute myocardial infarction in a decreasing order is:[9]

Differentiating the Life Threatening and Ischemic Causes of Chest Pain from other Disorders

Thorough history including: onset, duration, type of pain, location, exacerbating factors, alleviating factors, and radiation. Risk factors for coronary artery disease: family history, smoking, hyperlipidemia, and diabetes.

Differential Diagnosis of Chest Pain:

When a patient presents with chest pain, the following differentials mentioned in the table below need to be ruled out to reach the appropriate diagnosis.[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45]

Abbreviations: ABG (arterial blood gas); ACE (angiotensin converting enzyme); BMI (body mass index); CBC (complete blood count); CSF (cerebrospinal fluid); CXR (chest X-ray); ECG (electrocardiogram); FEF (forced expiratory flow rate); FEV1 (forced expiratory volume); FVC (forced vital capacity); JVD (jugular vein distention); MCV (mean corpuscular volume); Plt (platelet); RV (residual volume); SIADH (syndrome of inappropriate antidiuretic hormone); TSH (thyroid stimulating hormone); Vt (tidal volume); WBC (white blood cell);

Differentials on the basis of Etiology Disease Clinical manifestations Diagnosis
Symptoms Physical exam Lab workup EKG Imaging Gold standard
Onset Duration Type of Pain Cough Fever Dyspnea Weight loss Associated Features
Cardiac Stable Angina Sudden (acute) 2-10 minutes
  • Heaviness/pressure/ tightness/squeezing/ burning (Levine's sign)
  • Retrosternal or left sided chest pain
- - +/- -
  • Cardiac enzymes normal
  • Exercise EKG test shows  ST-segment depression
  • Exercise Stress Testing
  • Stress Echocardiography
  • Coronary angiography
Unstable Angina Acute 10-20 minutes
  • Same as stable angina but often more severe
- - + -
  • ST-depression
  • T wave inversions
  • Transient ST-elevation
  • Echocardiography
  • SPECT and MRI
  • Myocardial Perfusion Imaging
  • Exercise Testing
  • Invasive coronary angiography
Myocardial Infarction[10][11][12][13] Acute Commonly > 20 minutes
  • Same as stable angina but often more severe
- - + -
  • ST elevation MI (STEMI)
  • Non-ST elevation MI (NSTEMI) or Non Q wave
  • Echocardiography
  • Coronary angiography
  • Multidetector computed tomography (MDCT) coronary angiography
  • Myocardial perfusion imaging (MPI) with single-photon emission CT (SPECT) or positron emission tomography (PET) scanning
  • Elevated cardiac biomarkers [Cardiac troponin I, cardiac troponin T)
Aortic Stenosis Acute, recurrent episodes of angina 2-10 minutes
  • Heaviness/pressure/ tightness/squeezing/ burning (Levine's sign)
  • Retrosternal
- - + -
  • Peripheral blood smear may show schistiocytes
  • Non specific (the voltage of the QRS complex is increased showing the presence of left ventricular hypertrophy)
  • CXR
  • Echocardiography
  • Cardiac Catheterization and Coronary Arteriography
  • Radionuclide Ventriculography
    • Transthoracic Echo
Aortic Dissection Sudden severe progressive pain (common) or chronic (rare) Variable
  • Tearing, ripping sensation, knife like
- - + -
  • Nonspecific ST and T wave changes
  • CXR: Mediastinal and/or aortic widening
  • CTA
  • MRA
  • TEE
  • MRI
Pericarditis Acute or subacute May last for hours to days
  • Sharp & localized retrosternal pain
+ + + -
  • EKG changes (typically widespread ST segment elevation or PR depressions)
  • Chest x-ray typically normal
  • Echocardiogram: normal or pericardial effusion
  • CT scan: Noncalcified pericardial thickening with pericardial effusion
  • CMR: inflamed pericardium and myocarditis
  • Pericardiocentesis
  • Pericardial biopsy
Pericardial Tamponade Acute or subacute May last for hours to days
  • Sharp and stabbing retrosternal pain
+/- + + - EKG findings:
  • Sinus tachycardia
  • Low QRS voltage
  • Electrical alternans
  • CXR: enlarged cardiac silhouette with clear lung fields
  • Echocardiography: Chamber collapse, Respiratory variation in volumes and flows, IVC plethora
  • Swan-Ganz Catheterization: Equilibration of average intracardiac diastolic pressures (usually between 10 and 30 mmHg) 
  • Echocardiography
Heart Failure Subacute or chronic Variable
  • Dull
  • Left sided chest pain
+ - + -
  • EKG findings are specific according to each cause of heart failure
  • CXR: Cardiomegaly
  • Radionuclide multiple-gated acquisition scanning
  • Electrocardiogram-gated myocardial perfusion imaging
  • Equilibrium radionuclide angiocardiography
  • Catheterization and Angiography
  • Echocardiography
Stress (takotsubo)

Cardiomyopathy

Acute Commonly > 20 minutes
  • Substernal heaviness or tightness
- - + -
  • Setting of physical or emotional stress or critical illness
  • ST segment elevation
  • ST depression
  • QT interval prolongation, T wave inversion, abnormal Q waves
  • Radionuclide myocardial perfusion imaging 
  • Ventriculography and invasive coronary angiography
Differentials on the basis of Etiology Disease Clinical manifestations Diagnosis
Symptoms Physical exam Lab workup EKG Imaging Gold standard
Onset Duration Type of Pain Cough Fever Dyspnea Weight loss Associated Features
Pulmonary Pulmonary Embolism Acute May last minutes to hours
  • Sharp or knifelike or pleuritic pain
  • Localized to side of lesion
+ +/- + -
  • Tachycardia and nonspecific ST-segment and T-wave changes (70 percent)
  • S1Q3T3 pattern
  • New right bundle branch block
  • Inferior Q-waves (leads II, III, and aVF)
  • Duplex Ultrasonography
  • Echocardiography
  • Venography
  • Ventilation-Perfusion Scanning
  • CT pulmonary angiography
Spontaneous Pneumothorax Acute May last minutes to hours
  • Sharp
  • Localized pleuritic
- - + -
  • Respiratory alkalosis on ABGs
  • Rightward shift in the mean electrical axis
  • Loss of precordial R waves
  • Diminution of the QRS voltage
  • Precordial T wave inversions
  • CXR: White visceral pleural line on the chest radiograph
  • Contrast-Enhanced Esophagography
  • Computed Tomography of Chest
  • CT scan
Tension Pneumothorax Acute May last minutes to hours
  • Sharp
  • Pleuritic
- - + -
  • Significant elevation of the ST-T segment from leads V1 to V4
  • CXR: White visceral pleural line on the chest radiograph
  • Ultrasonography
  • Computed Tomography of Chest
  • CT scan
Pneumonia Acute or chronic Variable
  • Dull
  • Localized to side of lesion
+ + + +/-
  • Sinus tachycardia
  • Nonspecific ST-segment or T-wave changes
  • CXR: lung infiltrates
  • Chest CT Scanning
  • Bronchoscopy with or without BAL
  • Presence of lung infiltrates on CXR
  • Blood cultures
Tracheitis/ Bronchitis Acute Variable
  • Dull
  • Substernal
+ + + -
  • Peaked P-wave
  • Radiography of the neck
  • Laryngotracheobronchoscopy
  • Bronchoscopy
Pleuritis Acute or subacute or chronic May last minutes to hours
  • Sharp
  • Localized pleuritic
+ + + -
  • EKG done to rule out other causes in differential diagnoses
  • Chest X Ray
  • Computerized tomography (CT) scan
  • Ultrasound
  • Video assisted thoracoscopic surgery
Pulmonary Hypertension Acute or subacute or chronic Variable
  • Substernal pressure like
+ - + -
  • Right axis deviation
  • An R wave/S wave ratio greater than one in lead V1
  • Incomplete or complete right bundle branch block
  • Increased P wave amplitude in lead II (P pulmonale) due to right atrial enlargement 
  • Chest Radiography
  • Echocardiography
  • Ventilation-Perfusion Lung Scanning
  • Right-sided cardiac catheterization
  • Cardiac catheterization
Pleural Effusion Acute or subacute or chronic Variable
  • Dull
  • Pleuritic pain
+ +/- + +/-
  • Typically not indicated
  • CT Scanning
  • Ultrasonography
  • Chest Radiography
  • Diagnostic Thoracentesis
  • Pleural biopsy
  • Computed tomography
Asthma & COPD Acute or subacute or chronic Variable
  • Tightness
+ +/- + +/-
  • Peaked P-wave
  • Reduced amplitude of the QRS complexes
  • Multifocal atrial tachycardia (MAT)
  • Chest Radiography
  • Chest CT Scanning
  • Electrocardiography
  • MRI
  • Nuclear Imaging
  • Spirometry
Pulmonary Malignancy Chronic Week to months
  • Dull aching
+ +/- + +
  • EKG may be performed before cancer treatment to identify any pre-existing conditions, or during treatment to check for possible heart damage
  • Chest radiography
  • CT scanning of the chest and abdomen
  • Endobronchial ultrasound (EBUS)
  • Endoscopic ultrasound
  • CT scanning/magnetic resonance imaging (MRI) of the brain with IV contrast
  • Bone scanning
  • CT Scan
Sarcoidosis Chronic Days to week
  • Chest fullness
+ - + -
  • Not any significant auscultatory finding
  • AV block
  • Prolongation of the PR interval (first-degree AV block)
  • Ventricular arrhythmias (sustained or nonsustained ventricular tachycardia and ventricular premature beats [VPBs]) 
  • Supraventricular arrhythmias
  • Chest radiograph
  • Pulmonary function tests
  • High-resolution CT (HRCT) scanning of the chest
  • Lung Biopsy
Acute chest syndrome (Sickle cell anemia) Acute May last minutes to hours
  • Chest tightness
+ +/- + -
  • EKG typically not indicated
  • Chest radiography
  • Plain radiography of the extremities
  • Magnetic Resonance Imaging
  • Computed Tomography
  • Nuclear Medicine Scans
  • Transcranial Doppler Ultrasonography
  • Abdominal Ultrasonography
  • Echocardiography
  • No any gold standard test for acute chest syndrome
Differentials on the basis of Etiology Disease Clinical manifestations Diagnosis
Symptoms Physical exam Lab workup EKG Imaging Gold standard
Onset Duration Type of Pain Cough Fever Dyspnea Weight loss Associated Features
Gastrointestinal GERD, Peptic Ulcer Acute +/- - - +/-
  • Not any auscultatory findings associated with this disease
  • Serum Gastrin Level
  • Secretin Stimulation Test
  • Ambulatory 24-Hour pH Monitoring
  • An electrocardiogram (ECG) can show T wave inversions in leads V2 through V4 consistent with myocardial ischemia in patients with peptic ulcer perforation
  • Upper Gastrointestinal Endoscopy
  • Esophageal Manometry
  • Barium esophagogram 
  • Ambulatory reflux monitoring
  • Nuclear Medicine Gastric Emptying Study
  • Intraluminal Esophageal Electrical Impedance
  • Ambulatory pH monitoring
Diffuse Esophageal Spasm Acute
  • Minutes to hours
  • Burning
  • Pressure
  • Retrosternal
+ - +/-
  • Not specific
  • No ECG findings associated with DES, but ECG is done to exclude variant angina due to higher concurrent association of variant angina with DES 
  • Barium swallow
  • Esophageal manometry is more than 20% premature contractions
  • CT scanning
  • Ultrasonography
  • Esophageal manometry
---
Esophagitis Acute Variable + + - +/-
  • No auscultatory finding in the this disease
  • ECG is done to rule out acute coronary syndrome for the cause of chest pain
  • Double-contrast esophageal barium study (esophagography)
  • Endoscopy
  • Biopsy
Eosinophilic Esophagitis Chronic Variable
  • Burning
  • Retrosternal
  • Abdominal
+ - - -
  • No auscultatory finding in the this disease
  • Elevated IgE
  • Elevated peripheral eosinophils
  • Skin prick testing
  • Blood allergy testing
  • Atopy patch testing
  • Typically no finding on EKG
  • Barium studies
  • Endoscopy
  • CT scan
  • MRI
Esophageal Perforation[15] Acute Minutes to hours
  • Burning
  • Upper abdominal
- +/- + -
  • CBC
  • Serum albumin levels
  • Thoracentesis with examination of the pleural fluid
  • Water-soluble contrast esophagram
  • Iodine, water-soluble contrast medium esophagography
Mediastinitis Acute, Chronic Variable
  • Retrosternal irritation
+/- + + -
  • Nonspecific
  • Crunching sound heard with a stethoscope over the precordium during systole called as Hamman sign
  • Positive organisms in sternal culture
  • Complete blood count (CBC)
  • Blood cultures
  • Diffuse ST elevation
  • CT
  • Chest X-Ray
  • Magnetic resonance imaging
  • Nuclear medicine
  • No any gold standard test for this disease yet
 Cholelithiasis Acute, subacute Minutes to hours - +/- -
  • No auscultatory finding associated with this disease
  • LFT's
  • Amylase levels
  • Llipase levels
  • CBC
  • Typically not indicated
  • Transabdominal ultrasound (TAUS)
  • Abdominal Radiography
  • CT Scan
  • Magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP)
  • Scintigraphy
  • Endoscopic Retrograde Cholangiopancreatography (ERCP)
  • Percutaneous Transhepatic Cholangiography (PTC)
  • Ultrasound
Pancreatitis Acute, Chronic Variable - + + +/-
  • No auscultatory finding associated with this disease
  • Amylase levels
  • Lipase levels 
  • Fecal tests
  • LFT's
  • Serum electrolytes
  • BUN and creatinine
  • Blood glucose, cholesterol, and triglycerides levels
  • CBC
  • C-reactive protein
  • T-wave inversion
  • ST-segment depression
  •  ST-segment elevation rarely
  • Q-waves
  • CT
  • MRI
  • Transabdominal ultrasound ((TAUS)
  • Abdominal radiography
  • Endoscopic Retrograde Cholangiopancreatography
  • Magnetic Resonance Cholangiopancreatography
  • Image-Guided Aspiration and Drainage
  • CT Scan
Sliding Hiatal Hernia Acute Variable + - + -
  • No auscultatory finding associated with this disease
  • No any specific laboratory test is done
  • T wave inversion in anterior lead.
  • Endoscopy
Musculoskeletal Costosternal syndromes (costochondritis) Acute, subacute Days to weeks
  • Pressure like on anterior part of chest wall
- + -
  • Chest wall pain occurs with a history of repeated minor trauma or unaccustomed activity (eg, painting, moving furniture) 
  • No specific diagnostic test for this disease
  • The workup is done for excluding cardiac disorders and other causes of chest pain
  • EKG is done to rule out other cardiovascular causes
  • CXR
  • MRI
  • No any gold standard test for this disease
Lower rib pain syndromes Chronic Variable
  • Aching
  • Lower chest
  • Upper abdomen
- - + -
  • Common in women with a mean age in the mid-40s
  • Hooking maneuver
  • No specific diagnostic test for this disease
  • The workup is done for excluding cardiac disorders and other causes of chest pain
  • EKG is done to rule out other cardiovascular causes
  • CXR
  • No any gold standard test for this disease
Sternalis syndrome Chronic Variable Pressure like pain
  • Over the body of sternum
  • Sternalis muscle
  • Left or middle side of the chest wall
- - - -
  • No specific diagnostic test for this disease
  • The workup is done for excluding cardiac disorders and other causes of chest pain
  • EKG is done to rule out other cardiovascular causes
  • No any gold standard test for this disease
Tietze's syndrome Acute Weeks Pressure like pain over - - - -
  • Most often involve the areas of 2nd and 3rd ribs
  • More common in young adults
  • No specific diagnostic test for this disease
  • The workup is done for excluding cardiac disorders and other causes of chest pain
  • EKG is done to rule out other cardiovascular causes
  • Tests are done to rule out other diseases
Xiphoidalgia Acute Variable Pressure like pain over
  • Over the xiphoid process
  • Sternum
  • Xiphisternal joint
- - - -
  • Symptoms are aggravated by twisting and bending movements
  • Provocative test
  • No specific diagnostic test for this disease
  • The workup is done for excluding cardiac disorders and other causes of chest pain
  • EKG is done to rule out other cardiovascular causes
  • X-ray
  • Tests are done to rule out other diseases
Spontaneous sternoclavicular subluxation Acute, Chronic Variable Aching pain over Sternoclavicular joint - - - -
  • More common in middle age women
  • Occurs in dominant hands with repetitive tasks of heavy or moderate quality
  • No specific diagnostic test for this disease
  • The workup is done for excluding cardiac disorders and other causes of chest pain
  • EKG is done to rule out other cardiovascular causes
Differentials on the basis of Etiology Disease Clinical manifestations Diagnosis
Symptoms Physical exam Lab workup EKG Imaging Gold standard
Onset Duration Type of Pain Cough Fever Dyspnea Weight loss Associated Features
Rheumatic Fibromyalgia Chronic Variable - - + -
  • Presence of tenderness in soft-tissue anatomic locations
  • P-wave dispersions (Pd)
  • MRI
  • No any gold standard test is availble
Rheumatoid arthritis Chronic Years Symmetrical joint pain in
  • Wrist
  • Fingers
  • Knees
  • Feet
  • Ankles
- + - +
  • Positive Rheumatic Factor
  • Anti-CCP body 
  • ECG is done rule out the heart failure as RA is one of the causes of heart failure
  • Plain film radiography of the affected joints
  • MRI
  • Ultrasonography
  • No any gold standard test for diagnosis of Rheumatoid Arthritis
Ankylosing spondylitis Chronic Years Intermittent pain in - - - -
  • ECG is done to rule out conductions defects and aortic insufficiency
  • Computed tomography (CT)
  • Magnetic resonance imaging (MRI)
  • Power Doppler ultrasonography
  • Plain films of the sacroiliac joints
Psoriatic arthritis Chronic Years Asymmetrical intermittent pain in - - - -
  • Serum complement
  • Levels of Long Prentaxin 3 protein (PTX3)
  • Increased levels of CRP
  • Erythrocyte sedimentation rate
  • Rheumatoid factor
  • Immunoglobulin
  • Longer PR interval 
  • X-ray of the involved joints
  • CT scanning
  • MRI
  • Ultrasonography
  • No any gold standard test is available for this test
Sternocostoclavicular hyperostosis (SAPHO syndrome) Chronic Years Recurrent and multifocal pain in

Sternoclavicular joint

- + - -
  • Depending on the type of joint affected
  • ECG is done to rule out conductions defects and aortic insufficiency
  • Plain radiography
  • Computed tomography
  • Bone scan
  • Magnetic resonance imaging
  • Positron emission tomography
  • No any gold standard test is available for this disease
Systemic lupus erythematosus  Chronic Years
  • Skin
  • Joints (fingers, wrist, knees)
  • Kidneys
  • SLE can affect any organ of the body
- + + +
  • HLA-genetic mutations
  • Female gender
  • Being younger than 50 
  • Joint radiography
  • Chest X-ray
  • CT Scan
  • MRI
  • Echocardiography
  • Arthrocentesis
  • Lumbar puncture
  • Anti-dsDNA antibody test
Relapsing polychondritis Chronic Years Intermittent pain in + + + +
  • Negative rheumatoid factor
  • Biopsy
  • Complete blood cell count (CBC) with differential
  • Metabolic panel
  • Serum creatinine
  • Liver transaminase and serum alkaline phosphatase studies
  • Urinalysis dipstick and microscopic evaluation of sediment
  • Cryoglobulins
  • Viral hepatitis panel
  • Antinuclear antibody (ANA)
  • Antineutrophil cytoplasmic antibody (ANCA)
  • ECG is done to rule out the cardiovascular complications of this disease
  • Chest radiography
  • Spiral CT scanning
  • FDG-PET/CT
  • MRI
  • Posteroanterior and lateral dye contrast pharyngotracheogram
  • Scintigraphy
  • No gold standard test for this disease
Psychiatric Panic attack/ Disorder Acute or subacute or chronic Variable Variable + - + -
  • Thyroid function tests
  • Complete blood count
  • Chemistry panel
  • Sinus Tachycardia
  • No any specific radiographic test is done
  • No gold standard test for panic attack
Others Substance abuse

(Cocaine)

Acute (hours) Minutes to hours Pressure like pain in the center of chest + + + +
    • QT prolongation
    • Sinus Tachycardia
    • Arrhythmias
    • Cardiac conduction abnormalities
  • Brain CT scan
  • Gold standard test depends on the type of substance is abuse
Herpes Zoster Acute or Chronic Variable Burning pain on
  • Chest
  • Upper back
  • Lower back
- + - -
  • ECG is done to rule out other cardiovascular causes of chest pain
  • Magnetic resonance imaging (MRI)
  • Viral tissue culture

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