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Coronary Artery Vasospasm

  • Author: Stanley S Wang, MD, JD, MPH; Chief Editor: Eric H Yang, MD  more...
 
Updated: Nov 21, 2015
 

Background

Coronary artery vasospasm, or smooth muscle constriction of the coronary artery, is an important cause of chest pain syndromes that can lead to myocardial infarction (MI), ventricular arrhythmias, and sudden death. It also plays a key role in the development of atherosclerotic lesions.

In 1959, Prinzmetal et al described a syndrome of nonexertional chest pain with ST-segment elevation on electrocardiography (ECG).[1] Unlike patients with typical angina, these patients characteristically had normal exercise tolerance, and their pain patterns tended to be cyclical, with most episodes occurring in the early morning hours without regard to cardiac workload. This syndrome became known as Prinzmetal or variant angina, and was believed to be due to vasospasm in coronary arteries without obstructive lesions.

Subsequently, Maseri et al described the clinical, ECG, and angiographic features of 138 patients with variant angina and concluded that the syndrome was considerably more polymorphic than was initially inferred by Prinzmetal.[2]

For patient education resources, see the Heart Center and Chest Pain.

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Etiopathophysiology

The pathophysiologic mechanisms leading to coronary artery vasospasm are not yet completely understood. Coronary arterial tone varies normally via physiologic mechanisms, but the degree of vasoconstriction can range along a spectrum extending from undetectable constriction to complete arterial occlusion.

In some patients with partial vasoconstriction, symptoms can arise with activities that exceed a threshold of myocardial demand.[3] In other patients, constriction may be so severe that myocardial ischemia develops at rest. Many observers use the presence of constriction-induced ischemia as the threshold for defining clinical coronary artery vasospasm,[4] which has also been called vasospastic angina or variant angina.

In many cases, coronary artery vasospasm can occur spontaneously without an identifiable cause. Known triggers of spasm in susceptible patients include hyperventilation, cocaine or tobacco use, and administration of provocative agents such as acetylcholine, ergonovine, histamine, or serotonin.[5]

That coronary artery vasospasm can be induced through stimulation of alpha receptors[6] or intracoronary injection of the parasympathetic neurotransmitter acetylcholine[7] indicates that there are different mechanisms of action.

Acetylcholine causes coronary vasodilation in healthy coronary arteries through the release of endothelial nitric oxide (NO); however, in atherosclerotic arteries, vasoconstriction ensues instead. Patients with coronary artery vasospasm appear to have a heightened vasoconstrictor response to acetylcholine as well as an enhanced response to the vasodilator effects of nitrates, an observation that is consistent with a deficiency of endogenous NO activity.[4]

Thus, NO deficiency is believed to play an important role in the development of coronary artery vasospasm. This may also explain the correlation between coronary artery vasospasm and increased intimal thickening: NO deficiency results in enhanced activity of potent vasoconstrictors and stimulators of vascular smooth muscle proliferation, such as angiotensin II and endothelin 1.[4]

Several genetic polymorphisms that compromise endothelial NO production have been found to be significantly associated with coronary artery vasospasm.[8] Some have even been found to have prognostic value, including the -786T/C polymorphism.[9] However, additional studies showing that NO levels are not decreased at the sites of coronary artery vasospasm dispute the primacy of the role of NO.[10]

Alternative (or coexisting) mechanisms of coronary artery vasospasm include enhanced phospholipase C activity.[11] In addition, coronary artery vasospasm is associated with increased markers of oxidative stress and inflammation, including thioredoxin, C-reactive protein (CRP), and monocyte levels.[4] Certain behavioral traits (eg, type A personality, panic disorder, and severe anxiety) are also described as being associated with coronary artery vasospasm.[12]

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Epidemiology

United States statistics

The reported prevalence of vasospastic angina varies considerably between clinical studies, depending in large part on the geographic location of the population studied, as well as on the criteria used to test and define the condition.[13] In the United States, the frequency is among the lowest in the world, with about 4% of patients who undergo coronary angiography showing evidence of focal spasm (defined as a 75% reduction in artery diameter on the administration of ergonovine).[14]

International statistics

In France, about 12% of patients had positive ergonovine-based studies,[15] whereas in Japan, where the greatest number of publications on coronary artery vasospasm originate, positive study rates are in the range of 30%.[16] The incidence of coronary artery vasospasm may be increasing in Japan, at least on the basis of provocation of spasm by the administration of acetylcholine.[17]

[#IntroductionRace]

Age-, sex-, and race-related demographics

The age at which symptoms first appear is highly variable, but on average, patients are in their 50s at symptom onset.[18]

Variant angina is believed to be more common in female patients,[19, 20] although some prognostic studies of patients with variant angina suggest a male preponderance. A 2012 study of Korean patients showed that men were more likely to develop coronary artery vasospasm in response to an intracoronary acetylcholine challenge.[21] Among women, variant angina may be relatively more common in white patients (22%) than in Japanese patients (11%).

[#Clinical]

Overall, Japanese patients are much more likely to develop coronary artery vasospasm than Caucasian patients. When evaluated by the same team, Japanese patients had a 3-fold higher incidence of spasm than their Caucasian counterparts even though the 2 groups of patients had similar average basal coronary tone.[22]

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Prognosis

The natural history of patients undergoing medical therapy for coronary vasospasm may involve significant morbidity, but mortality is low in most cases, even on long-term follow-up.[18] Patients often have 3- to 6-month clusters of recurrent attacks, separated by relatively asymptomatic periods, with a gradual reduction of symptoms in the long term.[4] In a study of 59 patients followed for an average of 5.9 years, 93% experienced rest angina and 19% sustained frank MIs.[23] However, there were no cardiac deaths.

Long-term survival is believed to be good, especially in patients who tolerate calcium antagonists and avoid smoking.[18] Predictors of poorer prognosis include the presence of concurrent coronary atherosclerosis,[24] ongoing smoking, intolerance of calcium antagonists, and spasm of multiple coronary arteries.[25]

In patients with no or even single-vessel atherosclerosis, the prognosis is benign, with survival rates as high as 99% at 1 year and 94% at 5 years. On the other hand, survival in patients with multivessel atherosclerotic disease fell to 87% at 1 year and 77% at 5 years. Survival rates were also lower in patients with multivessel spasm.[26]

A 3-year follow-up to the Coronary Artery Spasm as a Frequent Cause for Acute Coronary Syndrome (CASPAR) study concluded that patients with acute coronary syndrome (ACS) who do not have a culprit lesion have a better prognosis than patients with obstructive ACS.[27] Persistent angina is challenging, and repeated coronary angioplasty may be required.

The Japanese Coronary Spasm Association (JCSA) derived the "JCSA risk score" to guide prognostication for patients with coronary vasospasm. Elements of the score include the following:

  • History of out-of-hospital cardiac arrest (4 points)
  • Smoking, angina at rest alone, organic coronary stenosis, multivessel spasm (2 points each)
  • Beta blocker use, ST elevation during angina (1 point each)

Stratification of patients by score led to differentiation in their risk of major adverse cardiac events (MACE). Patients with a low score of 0-2 had a MACE of 2.5%. Those with an intermediate score of 3-5 had a MACE of 7%, and those whose scores were 6 or higher had a MACE of 13%.[28]

Complications

Myocardial infarction (MI) is a potential complication of variant angina, especially in the myocardial territory corresponding to the location of the electrocardiographic (ECG) changes during previous anginal attacks. The incidence of MI depends on diagnostic criteria, but has been reported to be as high as 30% in some series.

The incidence and prognosis of MI in patients with variant angina appear to be associated with the extent and severity of any underlying atherosclerotic coronary stenoses. Adverse outcomes are more likely and survival poorer in patients with multivessel atherosclerotic CAD.[24]

Arrhythmias may occur with severe vasospastic angina. Both atrioventricular conduction abnormalities and ventricular arrhythmias can cause life-threatening hemodynamic deterioration and syncope. Coronary vasospasm has been identified as an important cause of out-of-hospital cardiac arrest.[29]  The risk of sudden death is approximately 2% and is most common in patients with multivessel spasm[26]  and prior serious arrhythmia during anginal attacks. In extreme cases, defibrillator implantation may be considered.[30]

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Contributor Information and Disclosures
Author

Stanley S Wang, MD, JD, MPH Clinical Cardiologist, Austin Heart South; Director of Legislative Affairs, Austin Heart; Director, Sleep Disorders Center at Heart Hospital of Austin; Assistant Professor of Medicine (Adjunct), University of North Carolina School of Medicine

Stanley S Wang, MD, JD, MPH is a member of the following medical societies: Alpha Omega Alpha, American College of Cardiology, American Heart Association, American Society of Echocardiography, Texas Medical Association, American Academy of Sleep Medicine, American Stroke Association, American Society of Nuclear Cardiology

Disclosure: Nothing to disclose.

Chief Editor

Eric H Yang, MD Associate Professor of Medicine, Director of Cardiac Catherization Laboratory and Interventional Cardiology, Mayo Clinic Arizona

Eric H Yang, MD is a member of the following medical societies: Alpha Omega Alpha

Disclosure: Nothing to disclose.

Acknowledgements

Steven J Compton, MD, FACC, FACP Director of Cardiac Electrophysiology, Alaska Heart Institute, Providence and Alaska Regional Hospitals

Steven J Compton, MD, FACC, FACP is a member of the following medical societies: Alaska State Medical Association, American College of Cardiology, American College of Physicians, American Heart Association, American Medical Association, and Heart Rhythm Society

Disclosure: Nothing to disclose.

Gregory J Dehmer, MD Director, Division of Cardiology, Scott & White Healthcare; Professor of Medicine, Texas A&M Health Science Center College of Medicine

Gregory J Dehmer, MD is a member of the following medical societies: American College of Cardiology, American Heart Association, Society for Cardiac Angiography and Interventions, and Society of Cardiac Angiography and Interventions

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

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This electrocardiogram (ECG) is from a patient who underwent urgent cardiac catheterization, which revealed diffuse severe coronary spasm (most marked in the left circumflex system) without any fixed obstructive lesions. Severe left ventricular wall motion abnormalities were present, involving the anterior and inferior segments. A question of so-called takotsubo cardiomyopathy (left ventricular apical ballooning syndrome) is also raised (see Bybee et al. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction. Ann Int Med 2004:141:858-65). The latter is most often reported in postmenopausal, middle-aged to elderly women in the context of acute emotional stress and may cause ST elevations acutely with subsequent T wave inversions. A cocaine-induced cardiomyopathy (possibly related to coronary vasospasm) is a consideration but was excluded here. Myocarditis may also be associated with this type of ECG and the cardiomyopathic findings shown here. No fixed obstructive epicardial coronary lesions were detected by coronary arteriography. The findings in this ECG include low-amplitude QRS complexes in the limb leads (with an indeterminate QRS axis), loss of normal precordial R wave progression (leads V1-V3), and prominent anterior/lateral T wave inversions. Image courtesy of http://ecg.bidmc.harvard.edu .
 
 
 
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