Basics
Description
- Variant angina is characterized by a transient, abrupt, marked reduction in the luminal diameter of an epicardial coronary artery which leads to symptomatic myocardial ischemia.
- ST-segment elevation rapidly returns to baseline with relief of symptoms.
- Exercise tolerance commonly preserved.
- Symptoms often occur in early morning hours.
- Most commonly occurs in right coronary artery, but can occur in left, and, less commonly, in coronary artery bypass grafts.
- Synonym(s): Prinzmetal angina, cardiac syndrome X (angina pectoris with normal coronary arteries)
- System(s) affected: Cardiovascular
Epidemiology
- Patients younger than those with exertional angina
- Other than tobacco use, classic cardiovascular risk factors uncommon
- Associated with other vasospastic disorders
- Substance abuse an important risk factor
- Female predominance
Incidence
- Exact incidence unknown
- Less common than exertional angina
Prevalence
Exact prevalence unknown �
Risk Factors
- Smoking (#1 risk factor)
- cocaine may precipitate vasospasm
- Patients with pure vasospasm younger than patients with exertional angina (average age 48)
- Female gender
- Traditional coronary disease risk factors may be lacking.
Genetics
- Increased prevalence in certain geographic locations, including Canada, Italy, and Japan
- Specific mutations in eNOS gene have significantly greater incidence in patients with variant angina compared with controls.
- Defects in genes encoding for Kir6.1 or SUR2 greater in patients with variant angina than controls.
General Prevention
- Avoidance of tobacco
- Avoid cocaine use
Pathophysiology
- Abnormalities of cardiac autonomic tone (particularly α-adrenergic receptors)
- Abnormal heart rate variability
- Endothelial dysfunction
- Adhesion molecules [leukocyte function-associated molecule-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1)]
Etiology
- Transient coronary artery spasm, usually focal, with normal coronary anatomy or at site of atherosclerotic plaque. Coronary spasm may be contributing factor in development, progression of atherosclerosis.
- Vasospasm superimposed on a fixed obstructive coronary heart disease (CHD) lesion has worse prognosis.
- IVUS often demonstrates atherosclerotic plaque and intimal thickening in coronary arteries at site of spasm even in angiographically normal coronary arteries.
- Thrombus may form at site of vasospasm.
Associated Conditions
- Migraine headaches
- Raynaud phenomenon
- Ocular spasm
- Aspirin-induced asthma
- Churg-Strauss syndrome
- Hyperthyroidism
- Hypomagnesemia
- Hyperinsulinemia
Diagnosis
History
Commonly associated with provocative factor(s): �
- Tobacco use
- Cocaine use
- Relationship to exercise
- Hyperventilation
Physical Exam
- Often unremarkable
- A 4th heart sound can be present indicating ischemia.
- CHF can occur in cases of significant ischemia with resultant LV dysfunction or ischemic mitral regurgitation.
Tests
Lab
Lab
- ECG during pain and after relief of pain
- Ambulatory ECG monitoring helpful in establishing diagnosis
Lab
- Patient is at highest risk for sudden death or MI during acute, active phase of disease.
- Treatment goal is prevention of coronary spasm.
- Smoking cessation of paramount importance.
- Control risk factors for atherosclerosis.
- Avoid Cocaine use.
- Medication compliance
Imaging
- Coronary angiography recommended
- Consider provocative testing with ergonovine, which produces focal spasm in ~90% of patients (high sensitivity and specificity) with variant angina.
- Provocative testing with intracoronary acetylcholine; low frequency of complications (0.6% incidence)
Surgery
- Exercise testing may provoke angina, ST elevation.
- Dobutamine stress echo may provoke vasospasm in some patients with variant angina
- Patients with positive hyperventilation test are more likely to have increased frequency of anginal attacks, multivessel spasm, AV block, ventricular tachycardia (sensitivity and specificity of 62% and 100%, respectively).
Pathological Findings
Histologic exam of coronary artery plaques reveals neointimal hyperplasia significantly more often in variant angina than in chronic stable exertional angina (68% vs. 8%). �
Differential Diagnosis
- Angina pectoris
- Pericarditis
- Aortic dissection
- Pulmonary processes, pulmonary embolism
- GI disorders (particularly GERD)
- Neurologic disorders
- Musculoskeletal disorders
- Psychiatric disorders
Treatment
Medication
First Line
- Calcium channel blockers:
- >50% of patients become asymptomatic with calcium channel blocker therapy.
- Dihydropyridine and nondihydropyridine agents effective.
- High doses may be required.
- If symptoms not completely relieved with one drug, may be beneficial to add 2nd calcium channel blocker.
- Calcium channel blocker may decrease risk of MI.
- Long-acting nitrates effective, but patients may develop tolerance.
- Statins (fluvastatin 30 mg/d, most studied)
- Sublingual nitrates indicated for acute episodes
- Low-dose aspirin
Second Line
- Imipramine
- Aminophylline
- Contraindications:
- β-Blockers, nonselective agents in particular, may exacerbate vasospasm.
- Attacks may be provoked by 5-fluorouracil, cyclophosphamide.
- High-dose aspirin may exacerbate attacks by inhibiting coronary vasodilator prostacyclin.
- Precautions:
- Calcium channel blocker withdrawal may cause rebound.
- AHA recommends against menopausal hormone therapy, based on the Women's Health Initiative (WHI) and the Heart and Estrogen/Progestin Replacement Study-II (HERS-II)
Additional Treatment
- May be effective in refractory cases, but not approved for this use in the U.S.:
- Amiodarone
- Guanethidine
- Prazosin
- Clonidine
- Corticosteroids
Issues for Referral
- Close follow-up with cardiologist
- Aggressive coronary risk factor modification
- Smoking cessation program for tobacco users
- Drug rehabilitation for illegal drug abusers
Surgery
- Consider percutaneous transluminal coronary angioplasty (PTCA)/stenting for patients with significant fixed coronary lesions.
- PTCA with stenting also used successfully in patients refractory to medical treatment without a fixed stenosis.
- Recurrence rate of symptoms and angiographic disease after PTCA/stenting higher in patients with variant angina than stable angina
- Reports of spasm recurring proximal to the stent
- Reports of continued symptoms in occasional patients without objective evidence of spasm.
- Other surgical options:
- Consider coronary artery bypass graft surgery in patients with significant multivessel disease.
- Surgical denervation and plexectomy have been used in refractory cases.
In-Patient Considerations
Admission Criteria
- Unstable symptoms
- Syncope
- Malignant or symptomatic arrhythmias
- MI
IV Fluids
Volume resuscitation with saline if evidence of volume depletion �
Nursing
Routine cardiac nursing care �
Discharge Criteria
- Resolution of chest pain and associated electrocardiographic changes
- Referral for smoking cessation of paramount importance in outpatient setting.
- Control risk factors for atherosclerosis.
- Cessation of cocaine and other illegal drug use.
Ongoing Care
Follow-Up Recommendations
Patient Monitoring
- Monitor for relief of symptoms.
- Telemetry
- Ambulatory ECG monitoring helpful as some patients have silent attacks
Diet
Low-fat, low-cholesterol diet, low-salt because 2/3 of coronary spasm occurs at site of angiographic atherosclerotic coronary lesion. �
Patient Education
- Smoking cessation of utmost importance
- Coronary risk factor control
- Avoidance of cocaine
- Compliance with medications
Prognosis
- Arrhythmias or syncope during episodes increase risk of sudden death.
- ST elevation in both inferior and anterior leads on ECG marker of increased risk of sudden death.
- Predictors of poor outcome include extensive and severe coronary artery disease, abnormal LV function, absence of treatment with calcium channel blockers, continued tobacco abuse, and ventricular arrhythmias during episodes.
- Acute active phase usually lasts 3-6 mo; then symptoms often remit.
- In absence of underlying coronary atherosclerosis, once patient past acute active phase, chance of long-term survival is excellent (89-97%).
Complications
- Sudden death, MI, ventricular arrhythmias, AV block, syncope
- Greatest risk of adverse outcomes during acute, active phase of disease
- Sudden death and MI occur most often during acute active phase.
Additional Reading
1
Beller �GA.
Calcium antagonists in the treatment of Prinzmetal's angina and unstable angina pectoris. Circulation. 1989;80(Suppl IV):IV-78-IV-87. 2
Braunwald �E
Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine: Coronary Blood Flow and Myocardial Ischemia
8th edition.
Philadelphia: WB Saunders, 2008:1167-1177. 3
Delehanty �JM.
Variant angina. In: Rose �BDWaltham MA: UpToDate, 2005. 4
Hong �MK. Intravascular ultrasound findings of negative arterial remodeling at sites of focal coronary spasm in patients with vasospastic angina. Am Heart J. 2000;140:395-401. �[View Abstract] 5
Nakayama �M, Yasue �H, Yoshimura �M. T-786 to C mutation in the 5"�-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm. Circulation. 1999;99:2864. �[View Abstract] 6
Suzuki �H, Kawai �S, Aizawa �T. Histologic evaluation of coronary plaque in patients with variant angina: Relationship between vasospasm and neointimal hyperplasia in primary coronary lesions. J Am Coll Cardiol. 1999;33:198. �[View Abstract]
Codes
ICD9
413.1 Prinzmetal angina �
SNOMED
87343002 prinzmetal angina (disorder) �
Clinical Pearls
- Female predominance
- Substance abuse an important risk factor
- In absence of underlying coronary atherosclerosis, overall long-term survival is excellent (89-97%).