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]

An expert algorithm to assist in the diagnosis of Chest pain can be found here.

To go back to the main page on Unstable angina, click here.


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 determined by carefully assessing the nature of the pain, and obtaining a thorough patient history.

2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines[1]

Recommendation for Evaluation of Acute Chest Pain With Suspected Noncardiac Causes

Class I
"1. Patients with acute chest pain should be evaluated for noncardiac causes if they have persistent or recurring symptoms despite a negative stress

test or anatomic cardiac evaluation, or a low-risk designation by a CDP. (Level of Evidence: C-EO)"

Differential Diagnosis of Chest Pain

5 Life Threatening Diseases to Exclude Immediately

The frequency of conditions exclusive of acute myocardial infarction in a decreasing order is:[10]

Differential Diagnosis of Non-Cardiac Chest pain
Chest wall
The above table adopted from 2021 AHA/ACC/ASE Guideline[11]

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

To review the differential diagnosis of chest pain, click here.

To review the differential diagnosis of chest pain and cough, click here.

To review the differential diagnosis of chest pain and fever, click here.

To review the differential diagnosis of chest pain and dyspnea, click here.

To review the differential diagnosis of chest pain and weight loss, click here.

To review the differential diagnosis of chest pain, cough, and fever, click here.

To review the differential diagnosis of chest pain, cough, and dyspnea, click here.

To review the differential diagnosis of chest pain, cough, and weight loss, click here.

To review the differential diagnosis of chest pain, fever, and dyspnea, click here.

To review the differential diagnosis of chest pain, fever, and weight loss, click here.

To review the differential diagnosis of chest pain, dyspnea, and weight loss, click here.

The following table outlines the major differential diagnoses of chest pain:[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][46][47]

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); Coronary CT angiography (CCTA); multidetector row scanners (MDCT); Cardiovascular magnetic resonance — CMRI; Myocardial perfusion imaging (MPI); single-photon emission CT (SPECT); Positron emission tomography (PET) scanning; Magnetic resonance (MR) angiography, Computed tomographic (CT) angiography, and Transesophageal echocardiography (TEE), late gadolinium enhancement (LGE); right ventricular hypertrophy (RVH), right atrial enlargement (RAE), functional tricuspid regurgitation (TR), Pulmonary artery systolic pressure (PASP; adenosine deaminase (ADA); Serum amyloid A (SAA), soluble interleukin-2 receptor (sIL2R); High-resolution CT (HRCT) scanning

Differentials on the Basis of Etiology Disease Clinical Manifestations Diagnosis
Symptoms Risk Factors Physical Exam Lab Findings EKG Imaging Gold Standard
Onset Duration Quality of Pain Cough Fever Dyspnea Weight Loss Associated Features
Stable Angina[48] Sudden (acute) 2-10 minutes - - +/- -
  • Exercise EKG: ST-segment depression
COVID-19-associated myocardial infarction[49] Sudden (acute) Commonly > 20 minutes
  • Retrosternal or left sided chest pain
  • Same as stable angina but often more severe
+/- +/- +/- -
  • ST elevation MI (STEMI)
  • Non-ST elevation MI (NSTEMI) or Non Q wave
  • Exercise Stress Testing: Decreased myocardial perfusion
  • Transthoracic echocardiography:
    • Localized wall motion abnormalities
    • Diffuse hypokinesia
    • Left ventricular ejection fraction was lower than 50% in about 61% of the individuals
Unstable Angina[50][51][52] Acute 10-20 minutes
  • Same as stable angina but often more severe
- - + -
Myocardial Infarction[12][13][14][15] Acute Commonly > 20 minutes - - + -
  • ST elevation MI (STEMI)
  • Non-ST elevation MI (NSTEMI) or Non Q wave
  • CCTA combined with MPI
Cardiac Vasospastic/ Prinzmetal/ Variant Angina[53][54] Gradual in onset and offset Episodic, gradual in onset and offset
  • Chest discomfort described as squeezing, tightness, pressure, constriction, strangling, burning, heart burn, fullness in the chest, a band-like sensation, knot in the center of the chest, lump in the throat, ache, and heavy weight on chest
- - + -
  • Multiple drugs (ephedrine-based products, cocaine, marijuana, alcohol, butane, sumatriptan, and amphetamines)
  • Food-born botulism
  • Guide wire or balloon dilatation while doing PCI
  • Magnesium deficiency
  • Urine drug screen may be positive for cocaine or other drugs
  • Transient (less than 15 minutes) ischemic ST changes in multiple leads
  • A tall and broad R wave,
  • Disappearance of the S wave
  • A taller T wave
  • Negative U waves
Aortic Dissection[55][56] Sudden severe progressive pain (common) or chronic (rare) Variable
  • Tearing, ripping sensation, knife like
- - + -
  • Nonspecific ST and T wave changes
Pericarditis[57][58][59] Acute or subacute May last for hours to days + + + -
Pericardial Tamponade[60][61] Acute or subacute May last for hours to days +/- + + - EKG findings:
Myocarditis[62][63][64] Acute or subacute Variable +/- + + -
Hypertrophic cardiomyopathy[65][66][67] Acute or subacute Variable Typical or atypical chest pain - - + - Non-specific


Genetic testing for HCM
Stress (takotsubo)


Acute Commonly > 20 minutes - - + -
  • Setting of physical or emotional stress or critical illness
Aortic Stenosis[72][73][74] Acute, recurrent episodes of angina 2-10 minutes - - + -
Heart Failure[75][76][77] Subacute or chronic Variable
  • Dull
  • Left sided chest pain
+ +/- + + Dyslipidemia, hypertension, smoking, family history of premature disease, and diabetes
Differentials on the Basis of Etiology Disease Clinical Manifestations Diagnosis
Symptoms Risk Factors Physical Exam Lab Findings EKG Imaging Gold Standard
Onset Duration Quality of Pain Cough Fever Dyspnea Weight Loss Associated Features
Pulmonary Pulmonary Embolism[78][79] Acute May last minutes to hours + +/- + -  Hormone replacement therapy

Cancer Oral contraceptive pills Stroke  Pregnancy Postpartum  Prior history of VTE Thrombophilia 

Spontaneous Pneumothorax[80][81] Acute May last minutes to hours - - + -
  • 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
  • CT: small amounts of intrapleural gas, atypical collections of pleural gas, and loculated pneumothoraces
  • CT scan
Tension Pneumothorax[82][83] Acute May last minutes to hours - - + -
  • Trauma
  • Significant elevation of the ST-T segment from leads V1 to V4
Pneumonia[84][85][86] Acute or chronic Variable
  • Dull
  • Localized to side of lesion
+ + + +/-
  • Long hospital stay
  • Ill contact exposure
  • Aspiration
Tracheitis/ Bronchitis[87][88][89][90] Acute Variable + + + -
  • Peaked P-wave
Pleuritis Acute or subacute or chronic May last minutes to hours + + + -
  • EKG done to rule out other causes in differential diagnoses
Pulmonary Hypertension[91][92][93] Acute or subacute or chronic Variable + - + -
Pleural Effusion[94][95][96] Acute or subacute or chronic Variable + +/- + +/-
  • Typically not indicated
Asthma & COPD[97][98][99][100] Acute or subacute or chronic Variable
  • Tightness
+ +/- + +/-
Pulmonary Malignancy[101][102][103][104] Chronic Variable
  • Dull aching
+ +/- + +
  • EKG may be performed before cancer treatment to identify any pre-existing conditions, or during treatment to check for possible heart damage
Sarcoidosis[105][106][107][108] Chronic Days to week
  • Chest fullness
+ - + +
  • Diminished respiratory sounds
Acute chest syndrome (Sickle cell anemia)[109][110][111] Acute May last minutes to hours
  • Chest tightness
+ +/- + -
  • EKG typically not indicated
Differentials on the Basis of Etiology Disease Clinical Manifestations Diagnosis
Symptoms Risk Factors Physical Exam Lab Findings EKG Imaging Gold Standard
Onset Duration Quality of Pain Cough Fever Dyspnea Weight Loss Associated Features
Gastrointestinal GERD, Peptic Ulcer[112][113][114] Acute +/- - - +/-
  • Not any auscultatory findings associated with this disease
  • Enamel erosion or other dental manifestations
Diffuse Esophageal Spasm[115][116][117][118] Acute
  • Minutes to hours
  • 5 to 60 minutes
+ - +/- +/- --- ---
  • Barium swallow: Multiple areas of spasm throughout the length of the esophagus
  • Impedance testing: Higher amplitudes and better transit of swallowed boluses
  • No ECG findings associated with DES, but ECG is done to exclude variant angina due to higher concurrent association of variant angina with DES 
  • Esophageal manometry : ≥20 percent premature contractions (distal latency <4.5 seconds)
Esophagitis[119][120][121] Acute Variable + + - +/-
  • No auscultatory finding
Eosinophilic Esophagitis[122][123][124][125][126][127] Chronic Variable + - - -
  • No auscultatory finding in the this disease
  • Typically no finding on EKG
Esophageal Perforation[17] Acute Minutes to hours
  • Burning
  • Upper abdominal
- +/- + -
    • Confirmed by water-soluble contrast esophagram
Mediastinitis[128][129][130][131] Acute, Chronic Variable
  • Retrosternal irritation
+/- + + -
  • Nonspecific
  • Infection
  • Esophageal perforation
  • Post operative complication
  • Positive organisms in sternal culture
  • Leukocytosis
  • Positive blood cultures
  • Diffuse ST elevation
  • CT: Localize the infection and extent of spread
  • MRI: Assesses vascular involvement and complications
CT scan
 Cholelithiasis[132][133][134][135] Acute, subacute Minutes to hours - +/- - -
  • The presence of a common bile duct stone on transabdominal ultrasound

•Clinical acute cholangitis •A serum bilirubin greater than 4 mg/dL (68 micromol/L)

  • Murphy sign negative
  • Jaundice
  • ↑ALT
  • ↑AST
  • Amylase levels
  • ↑ALP
  • Typically not indicated
  • Transabdominal ultrasound (TAUS): shows gallstones
  • EUS: Detects biliary sludge
  • MRCP: Detects stones >6mm
  • Endoscopic Retrograde Cholangiopancreatography (ERCP): Diagnostic and therapeutic removal of stones
  • Endoscopic ultrasound and MECP
Pancreatitis[136][137][138][139][140] Acute, Chronic Variable - + + +/-
  • Alcohol abuse
  • Smoking
  • Genetic predisposition
  •  Tachypnea
  • Hypoxemia
  • Hypotension
  • Cullen's sign
  • Grey Turner sign 
  • T-wave inversion
  • ST-segment depression
  •  ST-segment elevation rarely
  • Q-waves
  • CT: focal or diffuse enlargement of the pancreas
  • MRI: Pancreatic enlargement
  • CT Scan
Sliding Hiatal Hernia[141][142][143] Acute Variable + - + -
  • Trauma
  • Iatrogenic
  • Congenital malformation
  • Bowel sounds may be heard in the chest
  • Non specific
  • T wave inversion in anterior lead.
  • Barium swallow: At least three rugal folds traversing the diaphragm 
  • Upper endoscopy: A greater than 2-cm separation between the squamocolumnar junction and the diaphragmatic impression
  • High resolution manometry: The separation of the crural diaphragm from the lower esophageal sphincter (LES) by a pressure trough
  • Upper endoscopy
  • High resolution manometry (for smaller hernias)
Musculoskeletal Costosternal syndromes (costochondritis)[144][145][146][147] Acute, subacute Days to weeks
  • Pressure like on anterior part of chest wall
- + - -
  • History of repeated minor trauma or unaccustomed activity (eg, painting, moving furniture) 
  • Trauma
  • Pain by palpation of tender areas
  • Maneuvers, such as the "crowing rooster" and horizontal arm flexion maneuver
  • Non specific
  • EKG is done to rule out other cardiovascular causes
  • CXR: To rule out fracture
  • Pain by palpation of tender areas
Lower rib pain syndromes[148] Chronic Variable
  • Aching
  • Lower chest
  • Upper abdomen
- - + -
  • Common in women with a mean age in the mid-40s
  • Hooking maneuver
  • Reproduces pain by pressing a tender spot on the costal margin
  • Non specific
  • The workup is done for excluding cardiac disorders and other causes of chest pain
  • EKG is done to rule out other cardiovascular causes
  • CXR: To rule out fracture
Sternalis syndrome Chronic Variable Pressure like pain
  • Over the body of sternum
  • Sternalis muscle
  • Left or middle side of the chest wall
- - - -
  • Localized tenderness is found directly over the body of the sternum or overlying sternalis muscle
  • 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 : To rule out fracture
  • Physical exam
Tietze's syndrome[149] Acute Weeks Pressure like pain over - - - -
  • Most often involve the areas of 2nd and 3rd ribs
  • More common in young adults
  • Sternocostoclavicular hyperostosis
  • Ankylosing spondylitis
  • Upper respiratory infections
  • Excessive coughing
  • 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: To rule out fracture
  • Tests are done to rule out other diseases
Xiphoidalgia[150] Acute Variable Pressure like pain over
  • Over the xiphoid process
  • Sternum
  • Xiphisternal joint
- - - -
  • Symptoms are aggravated by twisting and bending movements
  • Cough
  • Heavy work
  • 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: To rule out fracture
  • Tests are done to rule out other diseases
Spontaneous sternoclavicular subluxation[151] 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
  • Trauma
  • 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: Sclerosis of the medial clavicle 
  • X-ray
Differentials on the Basis of Etiology Disease Clinical Manifestations Diagnosis
Symptoms Risk Factors Physical Exam Lab Findings EKG Imaging Gold Standard
Onset Duration Quality of Pain Cough Fever Dyspnea Weight loss Associated Features
Rheumatic Fibromyalgia[152][153][154] Chronic Variable - - + - ---
  • Presence of tenderness in soft-tissue anatomic locations
  • Non specific
  • Normal Blood and urine test (mandatory to rule out other diseases)
  • P-wave dispersions (Pd)
--- ---
Rheumatoid arthritis[155] Chronic Years Symmetrical joint pain in
  • Wrist
  • Fingers
  • Knees
  • Feet
  • Ankles
- + - +
  • Old age
  • Smoking
  • Autoimmune conditions
  • Positive Rheumatic Factor
  • Anti-CCP body 
  • Synovial fluid analysis: WBC between 1500 and 25,000/cubicmm, low glucose, low C3 and C4 complement level.
  • Thrombocytosis
  • Anemia
  • Mild leukocytosis
  • ECG is done rule out the heart failure as RA is one of the causes of heart failure
  • Plain film radiography: periarticular osteopenia, joint space narrowing, and bone erosions
  • MRI: Bone erosions
  • Ultrasonography: Degree of inflammation and the volume of inflamed tissue
Ankylosing spondylitis[156][157][158][159] Chronic Years Intermittent pain in - - - -
  • Patients with HLA-27 variant
  • Extra-articular joint involvements
  • Restrictive pulmonary disease
  • Acute coronary syndromes (ACS), strokes, venous thromboembolism, conduction abnormalities
  • Genetics (Monozygotic twins)
  • ↑ESR
  • ↑CRP
  • ↑ALP
  • ↑IgA
  • Antigen HLA-27 positive
  • Negative Rheumatic Factor
  • ECG is done to rule out conductions defects and aortic insufficiency
  • Plain radiography: Erosions, ankylosis, changes in joint width, or sclerosis.
  • Magnetic resonance imaging (MRI): Osteitis" or "bone marrow edema" (BME)
  • Plain films of the sacroiliac joints
Psoriatic arthritis[158] Chronic Years Asymmetrical intermittent pain in - - - -
  • Psoriasis
  • HLA-B*27 positive
Non specific
  • Longer PR interval 
  • X-ray: "pencil-in-cup" deformity, erosive changes and new bone formation, lysis of the terminal phalanges; fluffy periostitis
  • MRI: Detects articular, periarticular, and soft-tissue inflammation, enthesitis
  • X-ray
Sternocostoclavicular hyperostosis (SAPHO syndrome)[158][160][161][162][163] Chronic Years Recurrent and multifocal pain in

Sternoclavicular joint

- + - -

Positive family history of:

  • Spondyloarthritis
  • IBD
  • Psoriasis
  • Rheumatoid arthritis
  • Other autoimmune/autoinflammatory disease
  • Hyperostosis
  • Osteitis
  • Synovitis
  • Pustular eruptions
  • Inflammatory nodules or plaques
  • Serologic testing to exclude other diseases
  • Non specific
  • ECG is done to rule out conductions defects and aortic insufficiency
  • Plain radiography: Hyperostotic changes (thickening of periosteum, cortex, and endosteum), sclerotic lesions, osteolysis, periosteal reaction, and osteoproliferation
  • Bone scan: "bull's head" change
  • Magnetic resonance imaging: Osteitis and soft tissue involvement
  • Fluorodeoxyglucose positron emission tomography (FDG-PET)/CT: Differentiates active versus inactive lesions 
  • Bone scan
Systemic lupus erythematosus[164] [165][166] 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 
  • Autoimmune conditions
  • Genetic predisposition
  • Positive family history
  • Related to specific organ involvent
  • Anti-dsDNA antibody test
Relapsing polychondritis[167] Chronic Years Intermittent pain in: + + + +
  • Autoimmune diseases
  • Negative rheumatoid factor
  • Anti-type II collagen antibodies
  • Antineutrophil cytoplasmic antibodies
  • ECG is done to rule out the cardiovascular complications of this disease
  • Non specific
  • Related to specific organ involvent
  • No gold standard test for this disease
Psychiatric Panic attack/ Disorder[168][18][169] Acute or subacute or chronic Variable Variable + - + -
  • Psychiatric disorders
  • Anxious
  • Tachypneic
  • Thyroid function tests
  • Complete blood count
  • Chemistry panel
  • Sinus Tachycardia
  • No any specific radiographic test is done


Substance abuse


Acute (hours) Minutes to hours Pressure like pain in the center of chest + + + +
  • Psychiatric disorders
    • QT prolongation
    • Sinus Tachycardia
    • Arrhythmias
    • Cardiac conduction abnormalities
  • Gold standard test depends on the type of substance is abuse
Herpes Zoster[173][174][175] Acute or Chronic Variable Burning pain on
  • Chest
  • Upper back
  • Lower back
- + - -
  • Immunosuppression
  • Viral culture
  • Direct immunofluorescence testing,
  • Polymerase chain reaction assay (PCR)
  • ECG is done to rule out other cardiovascular causes of chest pain
  • Magnetic resonance imaging (MRI): To rule out encephalitis
  • Viral tissue culture


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