Chest pain differential diagnosis

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

• Aortic dissection
• Esophageal rupture
• Myocardial infarction
• Pulmonary embolism
• Tension pneumothorax

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

• Gastroesophageal disease
• Ischemic heart disease (angina, not myocardial infarction)
• Chest wall syndromes

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

Differentials on the basis of Etiology	Disease	Clinical manifestations									Diagnosis
		Symptoms								Physical exam	Lab Findings	EKG	Imaging	Gold standard
		Onset	Duration	Type of Pain	Cough	Fever	Dyspnea	Weight loss	Associated Features	Auscultation Findings
Cardiac	Stable Angina	Sudden (acute)	2-10 minutes	Heaviness/pressure/ tightness/squeezing/ burning (Levine's sign) Retrosternal or left sided chest pain	-	-	+/-	-	Nausea and vomiting Diaphoresis		Cardiac biomarkers [Cardiac troponin I, cardiac troponin T and MB isoenzyme of creatine kinase (CK-MB)] CBC	Normal EKG at rest Exercise EKG test shows  ST-segment depression	Chest radiograph findings are usually normal Exercise Stress Testing Stress Echocardiography	Coronary angiography
	Unstable Angina	Acute	10-20 minutes	Same as stable angina but often more severe	-	-	+	-	Nausea and vomiting Diaphoresis Presyncope Palpitations		Cardiac biomarkers [Cardiac troponin I, cardiac troponin T and MB isoenzyme of creatine kinase (CK-MB)] CBC	ST-depression T wave inversions Transient ST-elevation	Echocardiography SPECT and MRI Myocardial Perfusion Imaging Exercise Testing	Invasive coronary angiography
	Myocardial Infarction	Acute	Commonly > 20 minutes	Same as stable angina but often more severe	-	-	+	-	Nausea and vomiting Diaphoresis Presyncope Palpitations		Elevated cardiac enzymes B-Type Natriuretic Peptide CBC Serum chemistry panel	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	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	-	-	+	-		S2 is soft, single and paradoxically split A2 delayed and tends to occur simultaneously with P2 Aortic ejection click  Fourth heart sound (S4) can also be heard Crescendo–decrescendo murmur	Serum electrolyte levels, Cardiac biomarkers Complete blood count (CBC)	The voltage of the QRS complex is increased showing the presence of left ventricular hypertrophy and are therefore not specific.	Chest Radiography Echocardiography Cardiac Catheterization and Coronary Arteriography Radionuclide Ventriculography Exercise Stress Testing	Transthoracic Echo
	Aortic Dissection	Sudden severe progressive pain (common) or chronic (rare)	Variable	Tearing, ripping sensation, knife like	-	-	+	-		Pulse deficit New diastolic murmur Hypotension Diastolic decrescendo murmur	D-dimer Measurements of soluble elastin fragments, smooth muscle myosin heavy chain, high-sensitivity C-reactive protein, fibrinogen, and fibrillin fragments	Tot indicated for diagnosis of AR	CXR: Mediastinal and/or aortic widening CTA MRA TEE	MRI
	Pericarditis	Acute or subacute	May last for hours to days	Sharp & localized retrosternal pain	+/-	+	+	-	Pericardial friction rub	Pericardial friction rub heard with the diaphragm of stethoscope	Complete blood count, Troponin level Erythrocyte sedimentation rate Serum C-reactive protein level Blood cultures	EKG changes (typically widespread ST segment elevation or PR depressions)	Chest x-ray Echocardiogram CMR and/or CT	Pericardiocentesis, guided by fluoroscopy or echocardiography and pericardial biopsy
	Pericardial Tamponade	Acute or subacute	May last for hours to days	Sharp and stabbing retrosternal pain	+/-	+	+	-	Pulsus paradoxus Pericardial rub	Kussmaul sign Beck triad Pulsus paradoxus	Creatine kinase and isoenzymes Renal profile and complete blood count (CBC) Coagulation panel Antinuclear antibody assay, erythrocyte sedimentation rate, and rheumatoid factor HIV testing Purified protein derivative testing Pulse Oximetry	EKG findings: Sinus tachycardia, low QRS voltage, and electrical alternans(Alternation of QRS complexes, usually in a 2:1 ratio, on electrocardiographic findings is called electrical alternans)	Chest radiography Electrocardiography CT scanning Swan-Ganz Catheterization	Echocardiography
	Heart Failure	Subacute or chronic	Variable	Dull Left sided chest pain	+	-	+	-	Orthopnea Peripheral edema Hemoptysis	S3 Elevated JVP Peripheral edema	Serum electrolytes (particularly serum sodium) Complete blood count (CBC) Renal function (eg, blood urea nitrogen and serum creatinine) Thyroid function tests Serum albumin, liver function tests (serum bilirubin and serum aminotransferase levels) Serum brain natriuretic peptide (BNP) or NT-proBNP level Genetic Testing	EKG findings are specific according to each cause of heart failure	Chest radiograph Echocardiogram Exercise testing Computed tomography (CT) scanning  Magnetic resonance imaging (MRI) 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	Murmurs and rales may be present on auscultation in the setting of acute pulmonary edema	Catecholamines transiently elevated TnT level BNP level	ST segment elevation ST depression QT interval prolongation, T wave inversion, abnormal Q waves	Chest radiographs Echocardiography Cardiac Angiography Cardiac MRI	Ventriculography and invasive coronary angiography
Pulmonary	Pulmonary Embolism	Acute	May last minutes to hours	Sharp or knifelike or pleuritic pain Localized to side of lesion	+	+/-	+	-	Hemoptysis History of venous thromboembolism or coagulation abnormalities.	S 3 or S 4 gallop	D-Dimer Ischemia-Modified Albumin levels White Blood Cell Count Arterial Blood Gases Troponin levels	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)	Chest Radiography Duplex Ultrasonography Echocardiography Magnetic Resonance Imaging Venography Ventilation-Perfusion Scanning	CT pulmonary angiography
	Spontaneous Pneumothorax	Acute	May last minutes to hours	Sharp Localized pleuritic	-	-	+	-	Respiratory distress Tachypnea  Asymmetric lung expansion Hyperresonance on percussion Decreased tactile fremitus Tachycardia Cardiac apical displacement	Decreased breath sounds on involved side Lung sounds transmitted from the unaffected hemithorax are minimal with auscultation at the midaxillary line Adventitious lung sounds (crackles, wheeze; an ipsilateral finding) Pulsus paradoxus	Arterial Blood Gas Analysis	Rightward shift in the mean electrical axis  Loss of precordial R waves Diminution of the QRS voltage Precordial T wave inversions	Chest Radiography Contrast-Enhanced Esophagography Computed Tomography of Chest Ultrasonography	CT scan
	Tension Pneumothorax	Acute	May last minutes to hours	Sharp Pleuritic	-	-	+	-	Hypotension Jugular venous distention Respiratory distress	Decreased breath sounds on involved side Lung sounds transmitted from the unaffected hemithorax are minimal with auscultation at the midaxillary line Adventitious lung sounds (crackles, wheeze; an ipsilateral finding) Pulsus paradoxus	Arterial Blood Gas Analysis	Significant elevation of the ST-T segment from leads V1 to V4	Chest Radiography Contrast-Enhanced Esophagography Computed Tomography of Chest Ultrasonography	CT scan
	Pneumonia	Acute or chronic	Variable	Dull Localized to side of lesion	+	+	+	+/-	Altered mental status Tachycardia Rust-colored sputum Green sputum Red currant-jelly sputum Central cyanosis	Wheezing Rhonchi Rales Decreased breath sounds Pleural friction rub	Viral cultures Viral nucleic material amplification, such as hybridizations, various polymerase chain reactions (PCRs) and serologic tests Lung Biopsy Serum chemistry panel Arterial blood gas (ABG)  Venous blood gas determination Complete blood cell (CBC) count with differential Sputum Evaluation	Sinus tachycardia Nonspecific ST-segment or T-wave changes	Chest Radiology Chest CT Scanning Chest Ultrasonography Thoracentesis Bronchoscopy With or Without BAL	Presence of lung infiltrates indicated by chest radiography Blood culture
	Tracheitis/ Bronchitis	Acute	Variable	Dull Substernal	+	+	+	-	Tachypnea Respiratory distress Hoarseness Dyspnea Nasal flaring Cyanosis Sore throat Odynophagia Dysphonia	Inspiratory stridor (with or without expiratory stridor)	Obtain bacterial culture and Gram stain of tracheal secretions and blood cultures	Peaked P-wave	Radiography of the neck Laryngotracheobronchoscopy	Bronchoscopy
	Pleuritis	Acute or subacute or chronic	May last minutes to hours	Sharp Localized pleuritic	+	+	+	-	Sharp chest pain with breathing Itching in sites on the back Dizziness	Pleural Rubs	CBC Blood cultures Arterial blood gas (ABG)  Thoracentesis	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	+	-	+	-	Dyspnea Symptoms of right heart failure (edema) Past history of heart murmur Deep venous thrombosis (DVT) Arthritis or arthralgias Rash Family history of pulmonary hypertension Heavy snoring Heavy alcohol consumption Drug use, in particularly diet drugs Morbid obesity Heavy alcohol consumption	The intensity of the pulmonic component of the second heart sound (P 2) may be increased and the P 2 may demonstrate fixed or paradoxical splitting.  Systolic ejection murmur A right-sided fourth heart sound (S 4) with a left parasternal heave	Complete blood count (CBC) Biochemistry panel Prothrombin time (PT) Activated partial thromboplastin time (aPTT) Arterial blood gas Erythrocyte sedimentation rate (ESR) Rheumatoid factor (RF) levels Antinuclear antibody (ANA) levels Antineutrophil cytoplasmic antibody (ANCA) SCL70 Liver function test results Brain natriuretic peptide (BNP of NT-proBNP) HIV testing Iron deficiency Pulmonary Function Testing Polysomnography	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	+	+/-	+	+/-	Increasing lower extremity edema Orthopnea Paroxysmal nocturnal dyspnea Night sweats Hemoptysis	Diminished or inaudible breath sounds Pleural friction rub Egophony (known as "E-to-A" changes)	Pleural Fluid LDH, Glucose, and pH CBC Pleural Fluid Cell Count Differential Pleural Fluid Culture and Cytology Pleural fluid amylase levels Pleural fluid triglyceride and cholesterol levels Pleural fluid antinuclear antibody and rheumatoid factor	Typically not indicated	CT Scanning Ultrasonography Chest Radiography Diagnostic Thoracentesis Pleural biopsy	Computed tomography
	Asthma & COPD	Acute or subacute or chronic	Variable	Tightness	+	+/-	+	+/-	Cyanosis Elevated jugular venous pulse (JVP) Peripheral edema Hyperinflation (barrel chest) Rapidity of onset Signs of atopy or allergic rhinitis Nail Clubbing	Wheezing Diffusely decreased breath sounds Coarse crackles beginning with inspiration	Pulmonary function tests Arterial Blood Gas Analysis Serum Chemistries Alpha1-Antitrypsin Sputum Evaluation B-Type Natriuretic Peptide Blood and Sputum Eosinophils Serum Immunoglobulin E Pulse Oximetry Assessment Allergy Skin Testing Bronchoprovocation Alpha1-Antitrypsin	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	+	+/-	+	+	Bone pain Fatigue Neurologic dysfunction Superior vena cava (SVC) obstruction Hoarseness Hemidiaphragm paralysis Dysphagia Paraneoplastic syndromes Hypercalcemia	Depending upon complications caused by the spread of cancer	Complete blood cell count Serum chemistries Transthoracic needle aspiration Thoracoscopy Serum electrolytes levels Liver function tests (LFTs) Renal function tests (RFTs) Serum lactate dehydrogenase (LDH) level Serum alkaline phosphatase (ALP) level	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	+	-	+	-	Löfgren syndrome (fever, bilateral hilar lymphadenopathy (BHL), and polyarthralgias) Uveitis Heart block Lymphocytic meningitis Diabetes insipidus Fatigue Hypercalciuria	Not any significant auscultatory finding	Serum amyloid A (SAA), soluble interleukin-2 receptor (sIL-2R), lysozyme, angiotensin-converting enzyme (ACE) and the glycoprotein KL-6 Elevated 1, 25-dihydroxyvitamin D levels CBC LFTS Kidney function test Urine DR Carbon monoxide diffusion capacity test	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	Acute	May last minutes to hours	Chest tightness	+/-	+/-	+	-	Sickle cell anemia			EKG typically not indicated
Gastrointestinal	GERD, Peptic Ulcer	Acute	Minutes to hours (gastroesophageal reflux) Prolonged (peptic ulcer)	Burning Substernal Epigastric	+/-	-	-	+/-	Not specific			An electrocardiogram (ECG) can show T wave inversions in leads V2 through V4 consistent with myocardial ischemia in patients with peptic ulcer perforation	Ambulatory reflux monitoring
	Diffuse Esophageal Spasm	Acute	Minutes to hours	Burning Pressure Retrosternal	+	-	-	+/-	Not specific		Blood glucose levels Hemoglobin A1C levels Esophagogastroduodenoscopy (EGD), or upper endoscopy	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	Burning Epigastric	+	+	-	+/-	Heartburn (dyspepsia) Abdominal pain	No auscultatory finding in the this disease	Troponin or other cardiac markers Complete blood (CBC) cell count CD4 count Human immunodeficiency virus (HIV) test Collagen disorder workup Blind Brush Cytology	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	+	-	-	-	Alergic diseases Asthma Rinithis Eczema	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	More than 15 eosinophils per high-power field
	Esophageal Perforation	Acute	Minutes to hours	Burning Upper abdominal	-	+/-	+	-	Eating disorders such as bulimia			EKG may be indicated to assess for myocardial ischemia due to acute gastrointestinal bleeding, especially if there is coexisting:Cardiovascular disease, significant anemia and advanced age	Water-soluble contrast esophagram
	Mediastinitis	Acute, Chronic	Variable	Retrosternal irritation	+/-	+	+	-			Postive organisms in sternal culture	Diffuse ST elevation	CT X-Ray
	Cholelithiasis	Acute, subacute	Minutes to hours	Burning Colicky Right upper abdomen Substernal epigastric	-	+/-	-	-	Obesity Fertile females		LFT's Amylase levels Llipase levels	Typically not indicated	Transabdominal ultrasound (TAUS) X-ray
	Pancreatitis	Acute, Chronic	Variable	Epigastric Upper left side of the abdomen Pressure like	-	+	+	+/-	Primary cirrhosis Primary sclerosing cholangitis		Amylase levels Lipase levels	T-wave inversion ST-segment depression  ST-segment elevation rarely Q-waves	CT MRI Transabdominal ultrasound ((TAUS)
	Sliding Hiatal Hernia	Acute	Variable	Epigastric Burning	+	-	+	-	Obstruction Cameron ulcers			T wave inversion in anterior lead.	Endoscopy Manometry
Musculoskeletal	Costosternal syndromes (costochondritis)	Acute, subacute	Days to weeks	Pressure like on anterior part of chest wall	-	+/-	+	-		Palpation of tender areas		EKG is done to rule out other cardiovascular causes	CXR MRI
	Lower rib pain syndromes	Chronic	Variable	Aching Lower chest Upper abdomen	-	-	+	-		Hooking maneuver		EKG is done to rule out other cardiovascular causes
	Sternalis syndrome	Chronic	Variable	Pressure like pain Over the body of sternum Sternalis muscle Left or middle side of the chest wall	-	-	-	-	Cardiac diseases			EKG is done to rule out other cardiovascular causes	X-ray
	Tietze's syndrome	Acute	Weeks	Pressure like pain over Costosternal joint Sternoclavicular joint Costochondral joint Second and thrid ribs								EKG is done to rule out other cardiovascular causes	X-ray MRI	Tests are done to rule out other diseases
	Xiphoidalgia	Acute	Variable	Pressure like pain over Over the xiphoid process Sternum Xiphosternal joint						Provocative test		EKG is done to rule out other cardiovascular causes
	Spontaneous sternoclavicular subluxation	Acute, Chronic	Variable	Aching pain over Sternoclavicular joint								EKG is done to rule out other cardiovascular causes	CT Esclerosis in X-ray	Esclerosis in X-ray
Rheumatic	Fibromyalgia	Chronic	Variable	Deep ache and burning pain on Shoulders Back of the Neck Chest Lower Back Elbows Hips Shin Knees					Somatization Depression		Normal Blood and urine test (mandatory to rule out other diseases)	P-wave dispersions (Pd)
	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
	Ankylosing spondylitis	Chronic	Years	Intermittent pain in Spine joint Sacroiliac joint					Patients with HLA-27 variant		Complete blood count (CBC) Erythrocyte sedimetation rate (ESR) Antigen HLA-27 Negative Rheumatic Factor	ECG is done to rule out conductions defects and aortic insufficiency
	Psoriatic arthritis	Chronic	Years	Asymmetrical intermittent pain in Interphalangeal joints Nails Wrist Knees Ankles Lower Back					Psoriasis		Serum complement Levels of Long Prentaxin 3 protein (PTX3) Increased levels of CRP	Longer PR interval
	Sternocostoclavicular hyperostosis (SAPHO syndrome)	Chronic	Years	Recurrent and multifocal pain in Sternoclavicular joint					Palmoplantar pustulosis (PPP)		Serologic testing to exclude other diseases High levels of alkaline phosphatase	ECG is done to rule out conductions defects and aortic insufficiency
	Systemic lupus erythematosus	Chronic	Years	Skin Joints (fingers, wrist, knees) Kidneys					HLA-genetic mutations Female gender Being younger than 50		Elevation of autoantibodies (ANA, anti-dsDNA, anti-SM, antiphospholipid) Complement levels decreased	Sinus tachycardia, ST segment changes, and ventricular conduction disturbances
	Relapsing polychondritis	Chronic	Years	Intermittent pain in Tissues that cover the end of the joints Cartilage of costal rib					Hodkin's lymphoma Myelodysplastic syndromes Gastrointestinal disorders Type 1 Diabetes mellitus		Negative rheumatoid factor Biopsy	ECG is done to rule out the cardiovascular complications of this disease
Psychiatric	Panic attack/ Disorder	Acute or subacute or chronic	Variable	Variable					History of Depression Panic attacks Agoraphobia			Sinus Tachycardia
Others	Substance abuse (Cocaine)	Acute (hours)	Pressure like pain in the center of chest						Anxiety Dyspnea Nausea Palpitations		Serum biomarkers (Troponin I, Troponin T)	QT prolongation Sinus Tachycardia Arrhythmias Cardiac conduction abnormalities
	Herpes Zoster	Acute or Chronic	Variable	Burning pain on Chest Upper back Lower back					People who had chickenpox		Nerve test Blood test	ECG is done to rule out other cardiovascular causes of chest pain
	Sickle cell disease	Chronic	Since birth	Aching pain on Lower back Legs Chest Abdomen Arms					Anxiety Depression		Blood test: High performance liquid chromatography Prenatal test: DNA samples from chorionic villus from 8-10 weeks of gestation	QT prolongation First-degree AV block Nonspecific ST-T wave changes Ventricular arrhythmias