a b s t r a c t

Chest pain is one of the most common symptoms of patients presenting to the emergency department (ED) in the United States, accounting for up to eight million cases annually. We present a 55-year-old male who was brought in to the ED with sudden onset chest pain and was found to have ST-segment elevations in the infero-lateral leads on electrocardiogram (ECG). These changes resolved with nitroglycerin. Coronary artery vasospasm was diag- nosed as coronary angiogram was normal. Calcium channel blocker was prescribed with good symptom relief. The most important teaching point is, coronary vasospasm as a cause of ST-segment elevation is missed fre- quently and should be considered among the differentials in patients presenting with chest pain. Nitrates and/ or calcium channel blockers along with avoidance of triggers can help in symptom management.

(C) 2020

Introduction

In everyday practice, ED physicians experience a high burden of pa- tients with chest pain [1]. Acute coronary syndrome is suspected based on history, ECG changes, and cardiac markers. Biomarkers may be nor- mal in the early phase. There may be transient St-segment elevations in up to 25% of the patients presenting with chest pain [2,3]. Coronary vasospasm is one of the major causes of transient ST-segment elevations and its prevalence is not well studied. A prompt and accurate diagnosis may allow proper management of the symptoms.

Case

A 55-year-old male smoker with no medical history presented to the ED with sudden onset severe substernal chest pain radiating to his right arm, which began earlier that morning while he was sitting in his chair. He had associated sweating and lightheadedness but denied nausea or

Abbreviations: ECG, electrocardiogram; MI, myocardial infarction; STEMI- ST, segment elevation myocardial infarction.

* Corresponding author at: Department of Internal Medicine, Rochester General Hospital, 1425 Portland Ave, Rochester, NY 14621, United States of America.

E-mail address: [email protected] (V.S. Pendela).

vomiting. He tried high-dose aspirin with no relief. On examination, heart rate was 74 bpm, blood pressure 156/72 mmHg and oxygen satu- ration was 100% on room air. Examination of the cardiac and respiratory systems was normal.

His chest pain resolved at the time of admission to the ED but had a recurrence an hour later. The ECG (Fig. 1A) done at the time of the chest pain showed significant tombstone ST-segment elevations in leads V4 – V6, II, III, and aVF with reciprocal ST depression in leads V1-V3, I, aVL, and aVR, suggestive of acute inferolateral myocardial-infarction (MI). Tro- ponin I was elevated to 0.37 ng/ml. Chest pain subsided with sublingual nitroglycerin (0.4 mg). Subsequent ECG was normal (Fig. 1B). Coronary angiogram showed normal coronaries (Videos 1, 2). Transthoracic echo- cardiography revealed normal cardiac contractility (Videos 3, 4). Diagno- sis of coronary vasospasm was made. He was started on verapamil (180 mg extended-release once daily) with relief of symptoms.

Discussion

Coronary vasospasm was initially described by Prinzmetal et al. as “Variant angina”, as it differed from classic angina seen with exertion. Most patients are between 40 and 70 years of age. A higher preva- lence is seen in the Asian population compared to the western

https://doi.org/10.1016/j.ajem.2020.04.066

0735-6757/(C) 2020

1699.e2 V.S. Pendela et al. / American Journal of Emergency Medicine 38 (2020) 1699.e1–1699.e3

Fig. 1. (A) EKG of the patient at presentation showing significant tombstone ST-segment elevations in leads V4 – V6, II, III, and aVF. (B) EKG changes resolved after sublingual Nitroglycerin.

world. These patients typically present with chest pain at rest and significant ST-T changes on ECG, which can mimic acute myocardial infarction. The degree of ST-segment elevation can indicate the se- verity of spasm and reciprocal changes are often noted [4]. These ST abnormalities normalize instantly with sublingual nitroglycerin [5]. The ST-segment changes usually occur in the same leads during each episode, which indicates that spasm is in the same coronary ar- tery. Vasospasm may be triggered by cocaine, amphetamines, che- motherapy medications (Capecitabine, 5-fluorouracil, etc.), or alcohol binge. However, it can also occur without any triggers and sometimes follows a circadian rhythm. It is commonly observed be- tween midnight to early morning and is secondary to sympathetic surge during the rapid eye movement sleep. The chest pain quality is similar to typical anginal pain but can last for longer periods. A

coronary angiogram is usually needed to exclude severe obstructive lesions. provocative testing with intracoronary acetylcholine or er- gonovine (unavailable in the United States) is indicated if there is a Diagnostic dilemma [6]. An echocardiogram done at the time of chest pain can reveal elevated ventricular filling pressures due to de- creased contractility and impaired ventricular relaxation.

The most common mechanism in coronary vasospasm is vagal with- drawal. Another hypothesis is endothelial dysfunction secondary to re- duced bioavailability of nitric oxide synthetase causing hypercontractility of the vascular smooth muscle. One study suggests increased phospholipase C enzyme activity as a culprit for hypersensi- tivity of vascular smooth muscle in these patients [7].

Coronary angiogram during an episode will demonstrate vasospasm of a localized segment of one or multiple epicardial coronaries [8,9].

V.S. Pendela et al. / American Journal of Emergency Medicine 38 (2020) 1699.e1–1699.e3 1699.e3

Silent episodes of coronary vasospasm can be detected by Holter moni- toring. Behavioral patterns causing sympathetic surges like severe anx- iety and panic disorders were described as associations. Coronary arteries are prone to spasm during coronary angiography in up to 0.3-3% cases [10]. It is important to differentiate between catheter tip induced spasm which occurs at the site of impact and spontaneous spasm which can occur at any other site. These patients have a good prognosis unless multiple vessels are involved at the same time which can lead to ventricular arrhythmias [11]. Chest pain secondary to coro- nary stent induced vasospasm responds well to intravenous nitroglyc- erin. This should be differentiated from in-Stent thrombosis, which needs an invasive procedure.

Complications include myocardial infarction, arrhythmias/heart blocks, and rarely sudden cardiac death. Beta-blockers are contraindi- cated in these patients as they convert the effects of sympathetic stimu- lation into a pure alpha-adrenergic vasoconstrictor response causing an exacerbation of chest pain. The most important therapeutic strategy in- cludes dihydropyridine calcium channel blockers and nitrates. In pa- tients with normal coronary angiogram and coronary vasospasm, routine prescription of aspirin or statins is not recommended. Circadian rhythm of coronary vasospasm should be observed and medication should be administered early based on the timing of the episode. If chest pain is intractable to a single agent, the combined use of two dif- ferent calcium channel blockers can be effective [12]. Patients requiring more than one medication will likely have vasospasm of multiple coro- naries [4]. There are reports of medically intractable coronary vaso- spasm treated with internal mammary artery grafting, despite normal coronaries on angiography [13]. Implantable cardioverter-defibrillator can be considered for life-threatening ventricular arrhythmias.

In conclusion, coronary vasospasm as a cause of ST-segment eleva- tion is missed frequently and should be considered among the differen- tials in patients presenting with chest pain. Several potential triggers have been identified in the literature. Nitrates and/or calcium channel blockers along with avoidance of these triggers can help in symptom management.

Supplementary data to this article can be found online at https://doi. org/10.1016/j.ajem.2020.04.066.

Author roles

Venkata Satish Pendela – Conception, drafting the manuscript, final review.

Pujitha Kudaravalli – Drafting the discussion, editing the article and

final review.

Mamta Chhabria – Editing the article and final review.

Mallory Balmer-Swain – Conception, editing the article and mentoring.

Article guarantor

Venkata Satish Pendela, the corresponding author accepts full re- sponsibility for the conduct of the study.

Financial support or competing interests

Authors declare no actual or potential conflict.

Notice of prior presentation of the case report

None.

Patient consent

Informed patient consent was obtained.

Acknowledgements

None.

Funding

This research did not receive any specific grant from funding agen- cies in the public, commercial, or not-for-profit sectors.

References

1. https://www.cdc.gov/nchs/data/nhamcs/web_tables/2016_ed_web_tables.pdf.
2. Meisel SR, Dagan Y, Blondheim DS, Dacca S, Shochat M, Kazatsker M, et al. Transient ST-elevation myocardial infarction: clinical course with intense medical therapy and early invasive approach, and comparison with persistent ST-elevation myocardial infarction. Am Heart J 2008;155(5):848-54. https://doi.org/10.1016/j.ahj.2007.12. 010.
3. Stern S, Bayes de Luna A. coronary artery spasm: a 2009 update. Circulation 2009; 119:2531-4. https://doi.org/10.4244/eijv9i1a9.
4. 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. https://doi.org/10.1016/j.jjcc.2008.01.001.
5. Stern S, Bayes de Luna A. Coronary artery spasm: a 2009 update. Circulation 2009; 119:2531-4. https://doi.org/10.1161/CIRCULATIONAHA.108.843474.
6. Sueda S, Saeki H, Otani T, et al. major complications during spasm provocation tests with an intracoronary injection of acetylcholine. Am J Cardiol 2000;85:391-4. https://doi.org/10.1016/S0002-9149(99)00754-7.
7. Nakano T, Osanai T, Yomita H, Sekimata M, Homma Y, Okumura K. Enhanced activity of variant phospholipase C-?1 protein (R257H) detected in patients with coronary artery spasm. Circulation 2002;105(17):2024-9. https://doi.org/10.1161/01.CIR. 0000014613.36469.3F.
8. Lanza GA, Careri G, Crea F. Mechanisms of coronary artery spasm. Circulation 2011; 124(16):1774-82. https://doi.org/10.1161/circulationaha.111.037283 Oct 18.
9. Lanza GA, Sestito A, Sgueglia GA, Infusino F, Manolfi M, Crea F, et al. Current clinical features, diagnostic assessment and prognostic determinants of patients with vari- ant angina. Int J Cardiol 2007;118:41-7. https://doi.org/10.1016/j.ijcard.2006.06. 016.
10. Hung MJ, Hu P, Hung MY. Coronary artery spasm: review and update. Int J Med Sci 2014;11(11):1161-71. https://doi.org/10.7150/ijms.9623.
11. Onaka H, Hirota Y, Shimada S, Suzuki S, Kono T, Suzuki J, et al. Prognostic significance of the pattern of multivessel spasm in patients with variant angina. Jpn Circ J 1999; 63(7):509-13. https://doi.org/10.1253/jcj.63.509.
12. Song JK. Coronary artery vasospasm. Korean Circ J 2018;48(9):767-77. https://doi. org/10.4070/kcj.2018.0251.
13. Ono T, Ohashi T, Asakura T, Shin T. Internal mammary revascularization in patients with variant angina and Normal coronary arteries. Interact Cardiovasc Thorac Surg 2005;4(5):426-8. https://doi.org/10.1510/icvts.2005.107128.