Difference between revisions of "Prinzmetal's angina"

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==Natural History, Complications and Prognosis==
==Natural History, Complications and Prognosis==
* There are no findings characteristic for vasospastic angina. However, during an episode, tachycardia, hypertension, diaphoresis, and a gallop rhythm may be present.
*Bradycardia and hypotension can be observed if the sinus nodal, atrioventricular nodal, and right ventricular arteries are involved during proximal right coronary artery vasospasm.
* If left untreated, 25% of patients with prinzmetal angina may progress to develop myocardial infarction and life threatening arrhythmias.<ref name="pmid18355592">{{cite journal| author=Kishida H, Tada Y, Tetsuoh Y, Yamazaki Y, Saito T, Fukuma N et al.| title=A new strategy for the reduction of acute myocardial infarction in variant angina. | journal=Am Heart J | year= 1991 | volume= 122 | issue= 6 | pages= 1554-61 | pmid=1835559 | doi=10.1016/0002-8703(91)90271-i | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1835559  }}</ref><ref name="pmid1574091">{{cite journal| author=Myerburg RJ, Kessler KM, Mallon SM, Cox MM, deMarchena E, Interian A et al.| title=Life-threatening ventricular arrhythmias in patients with silent myocardial ischemia due to coronary-artery spasm. | journal=N Engl J Med | year= 1992 | volume= 326 | issue= 22 | pages= 1451-5 | pmid=1574091 | doi=10.1056/NEJM199205283262202 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1574091  }}</ref>
* If left untreated, 25% of patients with prinzmetal angina may progress to develop myocardial infarction and life threatening arrhythmias.<ref name="pmid18355592">{{cite journal| author=Kishida H, Tada Y, Tetsuoh Y, Yamazaki Y, Saito T, Fukuma N et al.| title=A new strategy for the reduction of acute myocardial infarction in variant angina. | journal=Am Heart J | year= 1991 | volume= 122 | issue= 6 | pages= 1554-61 | pmid=1835559 | doi=10.1016/0002-8703(91)90271-i | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1835559  }}</ref><ref name="pmid1574091">{{cite journal| author=Myerburg RJ, Kessler KM, Mallon SM, Cox MM, deMarchena E, Interian A et al.| title=Life-threatening ventricular arrhythmias in patients with silent myocardial ischemia due to coronary-artery spasm. | journal=N Engl J Med | year= 1992 | volume= 326 | issue= 22 | pages= 1451-5 | pmid=1574091 | doi=10.1056/NEJM199205283262202 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1574091  }}</ref>
* Two-thirds of patients have concurrent [[atherosclerosis]] of a major coronary artery. This is often mild or not in proportion to the degree of symptoms.
* Two-thirds of patients have concurrent [[atherosclerosis]] of a major coronary artery. This is often mild or not in proportion to the degree of symptoms.

Revision as of 15:22, 9 March 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2], Roukoz A. Karam, M.D.[3] Synonyms and Keywords: Variant angina; angina inversa; vasospastic angina


Vasospastic angina was previously referred to as Prinzmetal or variant angina. Vasospastic angina is a syndrome typically consisting of angina (cardiac chest pain) at rest that occurs in periodic cycles. Vasospastic angina is caused by vasospasm, a narrowing of the coronary arteries caused by contraction of the smooth muscle tissue in the vessel walls rather than fixed narrowings of the coronary arteries due to atherosclerosis (buildup of fatty plaque and hardening of the arteries).

Historical Perspective

Printzmetal's angina was first described as a variant form in 1959 by the American cardiologist Dr. Myron Prinzmetal.[1]

It was first documented by coronary arteriography in 1973.[2]


Classification by Location

Coronary artery spasm can be classified according to the location of vasoconstriction:

Focal coronary spasm

Focal coronary spasm is limited to a localized segment of the coronary artery.

Multifocal coronary spasm

Multifocal coronary spasm involves several localized segments of the same coronary artery.

Multivessel coronary spasm

Multivessel coronary spasm involves several coronary arteries.[3][4]

Classification by Clinical Syndrome

Coronary artery vasospasm can be classified into either spontaneous or iatrogenic.




  • The exact pathogenesis of coronary vasospasm is not well understood, but some causes and contributing factors are known.
  • A significant group of patients with variant angina have underlying obstructive coronary artery disease.[7]

Epidemiology and Demographics

  • Incidence or prevalence of Prinzmetal angina is still unknown.
  • Young patients with fewer cardiovascular risk factors (with the exception of smoking) are at a higher risk for coronary vasospasm, as are noncalcified lesions and eccentric plaques.
  • Some studies show that the Japanese population has an increased risk of developing vasospastic angina when compared with Caucasian populations.
  • The average age of presentation of vasospastic angina is around the fifth decade of life.[8]

Risk Factors

  • Smoking[9]
  • Genetic factors and insulin resistance
    • There is some evidence that genetic factors and insulin resistance are associated with vasospastic angina
  • Patients with vasospastic angina are often younger and exhibit fewer classic cardiovascular risk factors (except smoking).
  • Vasospastic angina may be associated with other vasospastic disorders, such as Raynaud's phenomenon and migraine headache or its treatment [54-56].
  • A history of drug abuse such as cocaine may be present.
  • Hyperventilation can precipitate attacks of vasospastic angina [57].

Differential diagnosis

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

The following table outlines the major differential diagnoses of chest pain:[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); 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[46] Sudden (acute) 2-10 minutes - - +/- -
  • Exercise EKG: ST-segment depression
Unstable Angina[47][48][49] Acute 10-20 minutes
  • Same as stable angina but often more severe
- - + -
Myocardial Infarction[10][11][12][13] 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[50][51] 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[52][53] Sudden severe progressive pain (common) or chronic (rare) Variable
  • Tearing, ripping sensation, knife like
- - + -
  • Nonspecific ST and T wave changes
Pericarditis[54][55][56] Acute or subacute May last for hours to days + + + -
Pericardial Tamponade[57][58] Acute or subacute May last for hours to days +/- + + - EKG findings:
Myocarditis[59][60][61] Acute or subacute Variable +/- + + -
Hypertrophic cardiomyopathy[62][63][64] 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[69][70][71] Acute, recurrent episodes of angina 2-10 minutes - - + -
Heart Failure[72][73][74] 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[75][76] Acute May last minutes to hours + +/- + -  Hormone replacement therapy

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

Spontaneous Pneumothorax[77][78] 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[79][80] Acute May last minutes to hours - - + -
  • Trauma
  • Significant elevation of the ST-T segment from leads V1 to V4
Pneumonia[81][82][83] Acute or chronic Variable
  • Dull
  • Localized to side of lesion
+ + + +/-
  • Long hospital stay
  • Ill contact exposure
  • Aspiration
Tracheitis/ Bronchitis[84][85][86][87] 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[88][89][90] Acute or subacute or chronic Variable + - + -
Pleural Effusion[91][92][93] Acute or subacute or chronic Variable + +/- + +/-
  • Typically not indicated
Asthma & COPD[94][95][96][97] Acute or subacute or chronic Variable
  • Tightness
+ +/- + +/-
Pulmonary Malignancy[98][99][100][101] 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[102][103][104][105] Chronic Days to week
  • Chest fullness
+ - + +
  • Diminished respiratory sounds
Acute chest syndrome (Sickle cell anemia)[106][107][108] 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[109][110][111] Acute +/- - - +/-
  • Not any auscultatory findings associated with this disease
  • Enamel erosion or other dental manifestations
Diffuse Esophageal Spasm[112][113][114][115] 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[116][117][118] Acute Variable + + - +/-
  • No auscultatory finding
Eosinophilic Esophagitis[119][120][121][122][123][124] Chronic Variable + - - -
  • No auscultatory finding in the this disease
  • Typically no finding on EKG
Esophageal Perforation[15] Acute Minutes to hours
  • Burning
  • Upper abdominal
- +/- + -
    • Confirmed by water-soluble contrast esophagram
Mediastinitis[125][126][127][128] 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[129][130][131][132] 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[133][134][135][136][137] 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[138][139][140] 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)[141][142][143][144] 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[145] 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[146] 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[147] 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[148] 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[149][150][151] 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[152] 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[153][154][155][156] 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[155] 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)[155][157][158][159][160] 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[161] [162][163] 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[164] 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[165][16][166] 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[170][171][172] 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

Natural History, Complications and Prognosis

  • There are no findings characteristic for vasospastic angina. However, during an episode, tachycardia, hypertension, diaphoresis, and a gallop rhythm may be present.
  • Bradycardia and hypotension can be observed if the sinus nodal, atrioventricular nodal, and right ventricular arteries are involved during proximal right coronary artery vasospasm.
  • If left untreated, 25% of patients with prinzmetal angina may progress to develop myocardial infarction and life threatening arrhythmias.[173][174]
  • Two-thirds of patients have concurrent atherosclerosis of a major coronary artery. This is often mild or not in proportion to the degree of symptoms.
  • Coronary vasospasm can lead to life-threatening arrhythmias, depending on the vessel that is involved.
  • Once detected, aggressive management of coronary vasospasm is necessary, as vasospasm can provoke fatal arrhythmias or myocardial infarction.[175]
  • Patients who have coronary artery disease in addition to coronary vasospasm have an overall worse prognosis.[176]
  • The prognosis of vasospastic angina depends on the extent of underlying coronary artery disease (CAD).

History and Symptoms

While the symptoms of chronic stable angina occur with exertion, the symptoms of Prinzmetal's angina typically occur at rest. The symptoms may occur reproducibly at certain times of the day or night. In the classic description, the symptoms often come on at night.

Characteristic pain features for vasospastic angina include:

  • Discomfort better describes the spasms than pain. Other common ways to describe the episodes: 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.
  • Each episode is typically gradual in onset and offset.
  • There is no change in the quality of pain with respiration or position.
  • The patient may have some difficulty in describing the location of the pain, although the substernal location is common. Radiation to the neck, throat, lower jaw, teeth, upper extremity, or shoulder is common.
  • During each episode, symptoms of nausea, sweating, dizziness, dyspnea, and palpitations may be present.


  • Physicians should suspect vasospasm if ST segment elevation is detected in patients experiencing angina, and if the ECG completely returns to baseline upon resolution of symptoms.
    • These changes are usually transient (less than 15 minutes) and may occur in multiple leads of a 12-lead ECG.
  • Patients who develop cardiac chest pain are generally treated empirically as an "acute coronary syndrome" patient, and are generally evaluated with serial testing of cardiac enzymes such as creatine kinase isoenzymes or troponin I or T. These may in some cases be abnormal or positive, as coronary spasm can lead to myocardial necrosis in severe cases.
  • The gold standard test is coronary angiography including the administration of provocative agents, such as acetylcholine or ergonovine, via the intracoronary route. The definitive diagnosis of coronary vasospasm is made angiographically by demonstration of reduction of luminal diameter in a discrete segment of the vessel, which is proven to be reversible. Reversibility may be demonstrated by previous or subsequent enlargement of luminal diameter, often after the administration of intracoronary vasodilators.
  • It should be noted that two-thirds of patients with Prinzmetal's angina have concurrent atherosclerosis of a major coronary artery, but the extent of the atherosclerosis is generally mild, and the symptoms are out of proportion to the extent of disease. Depending on the local protocol, provocative testing may utilize either ergonovine, methylergonovine or acetylcholine. Exaggerated spasm is diagnostic of Prinzmetal's angina. Care should be taken to have nitrates and calcium channel agents readily available to reverse the spasm.


Prinzmetal's angina is associated with transmural injury and ST segment elevation rather than ST segment depression.

The most important ECG change during a focal proximal coronary spasm is in around 50% of cases the appearance of peaked and symmetrical T wave that is followed, if the spasm persist, by progressive ST-segment elevation that last for a few minutes, and later progressively resolve.[177]

The most frequent ECG changes associated with ST-segment elevation are:

  • Increased height of the R wave
  • Coincident S-wave diminution
  • Upsloping TQ in many cases
  • Alternans of the elevated ST-segment
  • Negative T wave deepness
    • In 20% of cases.


Prinzmetal angina typically responds to nitrates and calcium channel blockers. Patients with multivessel spasm, refractory spasm, spasm that results in sudden death may benefit from dual calcium channel blocker therapy.

  • Calcium channel blockers:
    • Generally, well tolerated and can aid with hypertension control.[178]
    • A combination of dihyropyridine and non-dihydropyridine calcium channel blockers should be used in patients with refractory coronary vasospasm, particularly if it has resulted in ventricular arrhythmia.
    • Multiple calcium channel blockers may be required in patients with refractory or multi-vessel spasm.
    • A patient who has suffered ventricular tachycardia or ventricular fibrillation due to spontaneous vasospasm (not due to acute infarction) should also likely undergo ICD placement.
      • Diltiazem 240-360 mg PO qd
      • Verapamil 240-480 mg PO qd
      • Nifedipine XL 60-120 mg PO qd
      • Nicardipine 40-160 mg PO qd
  • Long-acting nitrates:
    • Generally, well tolerated and can aid with hypertension control.[179]
      • Isosorbide mononitrate (Imdur) 60-240 mg PO qd
      • Isosorbide dinitrate (Isordil) 20-40 mg PO tid
  • Statins:
    • May improve endothelial dysfunction and lower inflammation. A small, randomized control trial showed that fluvastatin 30 mg daily reduced rates of vasospasm. Statins also provide benefits of LDL lowering and plaque stabilization.[180]
      • Fluvastatin 30 mg PO qd
  • Hormone replacement therapy:
    • This remains controversial, particularly due to the risk of concern of increased cardiac events.
  • Smoking cessation:
  • Percutaneous coronary intervention:
    • While resolution occurs following PTCA/stenting in some cases, spasm can propagate to a new location, proximal or distal to the stented site.[182]
    • PCI is not commonly indicated for patients with focal spasm and minimal obstructive disease. However, it may be helpful if significant obstructive coronary disease is present and thought to be a potential trigger for focal spasm.
  • ICD placement:
  • Surgical autonomic denervation/plexectomy:
    • Can be useful in cases that are refractory to medical therapy or percutaneous intervention. It's reserved only for the most refractory cases.

Making a Selection

  • Treatment of chronic vasospasm should be performed in this order (step-wise fashion): medical therapy, percutaneous intervention, and then, surgery.

Medical Therapy

  • Risk factor modification (smoking cessation, lipid control) is recommended for all patients.
  • Begin pharmacologic therapy with oral calcium channel blockers (diltiazem, verapamil, nifedipine) and/or nitrates. If monotherapy is ineffective, begin combination therapy which is generally well tolerated (10% of patients may require 2 calcium channel blockers). If refractory or multi-vessel spasm is present, multiple CCBs are likely necessary, as these patients are at high risk for ventricular arrhythmias. Alpha blockers may also be useful if there is incomplete response to CCB and nitrates.
  • Due to their ability to improve endothelial function, statins should be considered for vasospasm.
  • Certain medications should be avoided: nonselective beta blockers, aspirin, and sumatriptan can exacerbate vasospasm. Hormone replacement therapy (estrogen-progestin) have been associated with an increase in cardiac events (HERS-II and WHI trials) and should also be avoided.

Percutaneous Intervention (PCI)

  • If vasospasm has a clearly definable area that is associated with coronary artery disease and refractory to medical therapy, stenting may be an effective strategy. However, stenting may simply propagate the spasm to a proximal or distal location in the vessel.
  • Following any PCI, adjunctive medical therapy must be continued.
  • Resolution of symptoms, ECG changes, and angiographic vasospasm is usually apparent within one minute post-procedure.
  • Refractory spasm occurring during PCI is likely secondary to dissection, which requires stenting unless the artery is small and the patient is clinically stable.
  • The role of revascularization in the setting of multivessel vasospasm is uncertain.


  • In the rare circumstance that a patient is refractory to pharmacologic and percutaneous therapy, surgical denervation and plexectomy have been effective.

2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes (DO NOT EDIT) [183]

Recommendations for Prizmental's angina

Class I
"1.CCBs alone or in combination with long-acting nitrates are useful to treat and reduce the frequency of vasospastic angina.(Level of Evidence: B)"
"2.Treatment with HMG-CoA reductase inhibitor, cessation of tobacco use, and additional atherosclerosis risk factor modification and are useful in patients with vasospastic angina. (Level of Evidence: B)"
"3.Coronary angiography (invasive or noninvasive) is recommended in patients with episodic chest pain accompanied by transient ST-elevation to rule out severe obstructive CAD. (Level of Evidence: C)"
Class IIb
"1. Provocative testing during invasive coronary angiography†† may be considered in patients with suspected vasospastic angina when clinical criteria and noninvasive testing fail to establish the diagnosis (Level of Evidence: B)"

ESC Guidelines for Diagnostic Tests in Suspected Vasospastic Angina (DO NOT EDIT)[184]

Class I
"1. ECG during angina if possible. (Level of Evidence: B)"
"2. Coronary arteriography in patients with characteristic episodic chest pain and ST-segment changes that resolve with nitrates and/or calcium channel blockers to determine the extent of underlying coronary disease. (Level of Evidence: B)"
Class IIa
"1. Intracoronary provocative testing to identify coronary spasm in patients with normal findings or nonobstructive lesions on coronary arteriography and the clinical picture of coronary spasm. (Level of Evidence: B)"
"2. Ambulatory ST Segment Monitoring to identify ST-deviation. (Level of Evidence: C)"

ESC Guidelines for Pharmacological Therapy of Vasospastic Angina (DO NOT EDIT)[184]

Class I
"1. Treatment with calcium channel blocker and if necessary nitrates in patients whose coronary arteriogram is normal or shows only non-obstructive lesions. (Level of Evidence: B)"


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