Treatment tips for Prinzmetal's variant angina

PVA attacks can precipitate cardiac rhythm disturbances such as AV blocks, asystole, or ventricular tachyarrhythmias

Mrs Smith's family called for an ambulance after she developed severe chest pain. She is 34 years old and has not been seen by a physician for more than 10 years. Today she has been drinking whiskey for the past several hours. When EMS arrives they find her alert and verbally abusive. She is still complaining of substernal pain without radiation. A 12 lead ECG shows ST wave elevation in the lateral leads. After refusing treatment for 20 minutes the paramedics and family finally convince her to allow transport to the local hospital.

During the transport she is given 4 baby aspirin, nitroglycerin 0.4 mg sublingual two times, oxygen via nasal cannula and an intravenous line is started. Once in the emergency department another 12 lead ECG is completed, now 50 minutes after the initial 12 lead. The patient presently denies pain and the 12 lead shows normal sinus rhythm without ST wave abnormalities.

Was there an error on the initial 12 lead? Does this patient still need to go directly to a cardiovascular lab? What specific risk factors should you be aware of?

Prinzmetal and colleagues1 described a syndrome of ischemic pain accompanied by ST elevation that occurs at rest that is now referred to as Prinzmetal's or "variant" angina (PVA). This population typically can tolerate exertion well without inducing chest pain.

The syndrome is generally a result of focal vasospasm in the Caucasian population and more of generalized coronary artery hyperactivity in the Japanese or Korean population2. The site of the spasm can fluctuate from one coronary artery to another3, or several at the same time. The right coronary artery is the most frequently affected vessel, followed by the left coronary artery4. Coronary spasm occurs most often between midnight to around 8 AM. The incidence of PVA is greater in the Japanese5.

PVA patients can be much younger than those with stable or unstable angina secondary to coronary artery disease (CAD). Many patients share the risk factor of heavy cigarette smoking.

PVA attacks can precipitate cardiac rhythm disturbances such as AV blocks, asystole, or ventricular tachyarrhythmias. These are more frequent in populations with underlying CAD. Angina associated with CAD or ischemia frequently causes ST depression instead of elevation.

Clinical findings
The key to diagnosing PVA is detection of ST segment elevation during episodes of chest pain. The ST segment elevation disappears promptly as chest pain resolves especially if administration of nitroglycerin is responsible for pain resolution. Patients with PVA may have CAD and luminal narrowing or they can have angiographically normal coronary arteries. All patients with variant angina should be examined in a cardiovascular lab (CVL) unless a contraindication is present6.

Patients should be encouraged to stop smoking. The mainstay of therapy consists of calcium channel blockers (CCB) and some patients also benefit from the addition of long acting nitrates. Acute Myocardial Infarction (AMI) is a frequent consequence for patients that have underlying multivessel disease and evidence suggests CCB therapy may reduce the risk of AMI7.

Nitroglycerin relieves symptoms rapidly and should be used as a first line therapy. Long-acting nitrates are effective at preventing attacks, but development of tolerance may limit their long-term utility.

Calcium channel blockers
CCBs are effective at preventing attacks6. More than 50 percent of patients treated become completely asymptomatic, but higher than normal doses are frequently required. Diltiazem, verapamil, amlodipine, and nifedipine are equally effective at preventing PVA attacks.

Beta blockers
Beta blockers should not be used. They have a tendency of increasing the frequency and duration of attacks 8,9.

Aspirin is not indicated for the diagnosis of PVA. Doses of 81 mg to 325 mg have been tolerated without complications, however higher doses have been shown to exacerbate coronary spasm10 (325 mg 4 times daily or greater).

Coronary artery bypass graft and CVL
In patients with significant organic stenoses present where bypass surgery is indicated elimination of PVA can be very successful, but only when the anastomosis can be placed distal to the focal spasm site. Patients requiring CVL intervention or CABG may have recurring vasospasm symptoms if calcium channel blockers are not continued as new spasm sites may develop at a different location10

Take home points

  • Nitroglycerin sublingual or intravenous is a first line medication
  • ST elevation rapidly resolves as chest pain subsides
  • Exercise is usually well tolerated without symptoms
  • Patients with underlying CAD are at high risk for life threatening dysrhythmias



1) Prinzmetal M, Kennemer R, Merliss R, et al. Angina pectoris: I. A variant form of angina pectoris. Am J Med 1959;27:375-388.

2) Yamagishi M, Miyatake K, Tamai J, et al. Intravascular ultrasound detection of atherosclerosis at the site of focal vasospasm in angiographically normal or minimally narrowed coronary segments. J Am Coll Cardiol 1994;23:352-357.

3) Ozaki et al. Fluctuation of spastic location in patients with vasospastic angina: a quantitative angiographic study. J Am Coll Cardiol (1995) vol. 26 (7) pp. 1606-14

4) Chevalier et al. Arrhythmic cardiac arrest due to isolated coronary artery spasm: long-term outcome of seven resuscitated patients. J Am Coll Cardiol (1998) vol. 31 (1) pp. 57-61.

5) Lilly, L. S. (2008). Braunwald's heart disease review and assessment. (Vol. 2, pp. 1337-1340). eighth edition, Philadelphia, W B Saunders Co.

6) Fuster, V., Alexander, R. W., Hurst, J. W., & O, R. A. (2004). Hurst's the heart. (pp. 1269-1271). eleventh edition, New York, McGraw-Hill.

7) Waters et al. Spontaneous remission is a frequent outcome of variant angina. J Am Coll Cardiol (1983) vol. 2 (2) pp. 195-9.

8) Walling et al. Long-term prognosis of patients with variant angina. Circulation (1987) vol. 76 (5) pp. 990-7

9) Tilmant et al. Detrimental effect of propranolol in patients with coronary arterial spasm countered by combination with diltiazem. Am J Cardiol (1983) vol. 52 (3) pp. 230-3

10) Shubrooks et al. Variant angina pectoris: Clinical and anatomic spectrum and results of coronary bypass surgery. Am J Cardiol (1975) vol. 36 (2) pp. 142-7

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