Typical anginal symptoms are characterized by recurrent attacks of retrosternal chest pain brought on by effort and emotion, and relieved by rest or by the administration of nitroglycerine. In 1960, Dr. Prinzmetal and his colleagues described symptoms different from typical anginal symptoms as “variant angina.”1 Variant or Prinzmetal’s angina occurs at rest and is not provoked by exercise or emotion. It usually accompanied by ST-segment changes in the distribution of one large coronary artery. A temporary increase in vascular tone in a vessel with atherosclerotic changes may transiently lead to critically diminished blood supply to an area of myocardium, resulting in symptoms of variant angina and EKG abnormalities.1 In this report, we describe a case of recurrent angina in two coronary arteries.
A 53-year-old male with a history of smoking initially came to our hospital with chest pain. He had ST-segment elevation in the inferior leads and was emergently taken to the cardiac cath lab, where angiography showed moderate disease in the left circumflex artery and mild disease in the first diagonal branch. Coronary intervention of left circumflex artery was performed. A 3.5x15 mm bare metal stent was deployed in the proximal left circumflex artery. Cardiac enzymes were minimally elevated after coronary intervention. The patient was discharged home in stable condition.
He returned to the emergency department within two weeks, complaining of similar chest pain. The patient stated he had been experiencing this pain for the past year, but the previous two episodes had been more severe. There was 1 mm ST-segment elevation in leads I and AVL. He was started on intravenous nitroglycerine and bivalirudin, and taken emergently to the cardiac cath lab. In the cath lab, prior to the coronary angiogram, resolution of ST-segment elevation was noted. Fluoroscopy showed minimal atherosclerotic disease at the ostium of first diagonal branch, with no evidence of unstable plaque morphology. TIMI-3 flow was noted in all major vessels of the heart and branches. The patient was diagnosed with variant angina. He was instructed to refrain from smoking, and treated with isosorbide nitrate and amlodipine. The patient was discharged in stable condition with a Holter monitor on follow-up.
Variant or Prinzmetal’s angina is not uncommon. It is currently recognized with increasing frequency and is a significant determinant of cardiac morbidity and mortality. Prinzmetal’s angina is associated with significant arrhythmia, such as second or third degree arterio-venous (A-V) block, ventricular tachycardia, ventricular fibrillation, and asystole.2,3,4 A 24-48 hour Holter monitor study can be very definitive in the diagnosis of Prinzmetal’s angina and also rule out significant arrhythmia. Transient coronary artery spasm during an attack of variant angina has also been demonstrated by coronary angiography.5,6 The likely origins of coronary artery spasm include activation of the autonomic nervous system and endothelial dysfunction. Some studies suggest sympathetic denervation of autonomic system improves symptoms of angina,7,8 while another study revealed endothelial dysfunction, as seen by intravascular ultrasound, in patients with variant angina.9 Lower levels of estradiols (a sex hormone present in males and females) worsen endothelial dysfunction and are associated with an increased frequency of angina attacks.10 In healthy coronary arteries, acetylcholine causes coronary vasodilatation through the release of endothelial nitric oxide, but, in atherosclerotic arteries, vasoconstriction ensues instead. Patients with coronary artery vasospasm appear to have a heightened vasoconstrictor response to acetylcholine.11 As a result, acetylcholine and ergonovine have been used in the cardiac cath lab to diagnose coronary artery spasm.12 Use of non-selective beta-blockers should be avoided, as they result in a blockade of vasodilatory effects of β-adrenergic receptors, coverting the effects of sympathetic stimulation into a pure α-adrenergic vasoconstrictor response.13 Likewise, avoid high doses of aspirin, which can decrease prostaglandin production, such as prostacycline (a vasodilator) and aggravate coronary artery spasm.14 Nitrates and calcium channel blockers (nifedipine, amlodipine, verapamil, and diltiazem) are the mainstay of treatment, although amlodipine may be preferable due to its long half-life.15 Other agents have been tried with variable success, including endothelin antagonists such as bosentan.16
Dr. Ahmed can be contacted at email@example.com.
- Prinzmetal M, Ekmekci A, Kennamer R, Kwocznski JK, Shubin H, Toyoshima H. Variant form of angina pectoris, previously undelineated syndrome. JAMA 1960 Dec 3; 174: 1794-800.
- Unverdorben M, Haag M, Fuerste T, Weber H, Vallbracht C. Vasospasm in smooth coronary arteries as a cause of asystole and syncope. Cathet Cardiovasc Diagn 1997; 41(4): 430-434.
- Chin A, Casey M. Variant angina complicated by polymorphic ventricular tachycardia. Int J Cardiol 2010; 145(2): e47-e49.
- Krzciuk M, Wozakowska-Kapłon B. Syncope as a first manifestation of Prinzmetal’s angina in a 49-year-old woman. Kardiol Pol 2006; 64(7): 728-731.
- Olivia PB, Potts DE, Plus RG. Coronary arterial spasm in Prinzmetal angina. Documentation by coronary arterigraphy. N Engl J Med 1973; 283: 745.
- Dhurandhar RW, Watt DL, Silver MD, et al. Prinzmetal’s variant form of angina with arteriographic evidence of coronary arterial spasm. Am J Cardiol 1972; 30: 902.
- Betrand, ME, Leblanche, JM, Tilmant, PY, et al. Complete denervation of the heart (autotransplant) for treatment of severe, refractory coronary spasm. Am J Cardiol 1981; 47: 1375.
- Betrand, ME, Leblanche, JM, Tilmant, PY, et al. Treatment of Prinzmetal’s variant angina. Role of medical therapy with nifedipine and surgical coronary revascularization combined with plexectomy. Am J Cardiol 1981; 47: 174.
- Hamabe A, Takase B, Uehata A, Kurita A, Ohsuzu F, Tamai S. Impaired endothelium-dependent vasodilation in the brachial artery in variant angina pectoris and the effect of intravenous administration of vitamin C. Am J Cardiol 2001; 87(10): 1154-1159.
- Kawano H, Motoyama T, Ohgushi M, Kugiyama K, Ogawa H, Yasue H. Menstrual cyclic variation of myocardial ischemia in premenopausal women with variant angina. Ann Intern Med 2001; 135(11): 977-981.
- Yasue H, Nakagawa H, Itoh T, Harada E, Mizuno Y. Coronary artery spasm--clinical features, diagnosis, pathogenesis, and treatment. J Cardiol 2008; 51(1): 2-17.
- Horimoto M, Igarashi K, Takenaka T, Inoue H, Yamazaki K, Sakuragi H. Acetylcholine- and ergonovine-induced coronary microvascular spasm reflected by increased coronary vascular resistance and myocardial lactate production. Clin Cardiol 2000; 23(3): 221-225.
- Robertson RM, Wood AJJ, Vaughn WK, et al. Exacerbation of vasotonic angina pectoris by propranolol. Circulation 1982; 65: 281-285.
- Miwa K, Kambara H, Kawai C. Effect of aspirin in large doses on attacks of variant angina. Am Heart J 1983; 105: 351-355.
- Taylor SH. Usefulness of amlodipine for angina pectoris. Am J Cardiol 1994; 73(3): 28A-33A.
- Krishnan U, Win W, Fisher M. First report of the successful use of bosentan in refractory vasospastic angina. Cardiology 2010; 116(1): 26-28.