Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Cardiology in Review •  Volume 23, Number 6, November/December 2015 www.cardiologyinreview.com  |  303 REVIEW ARTICLE Abstract: With each successive year, the number of Emergency Department (ED) visits related to illicit drug abuse has progressively increased. Cocaine is the most common illegal drug to cause a visit to the ED. Cocaine use results in a variety of pathophysiological changes with regards to the cardiovascu- lar system, such as constriction of coronary vessels, dysfunction of vascular endothelium, decreased aortic elasticity, hemodynamic disruptions, a hyper- coagulable state, and direct toxicity to myocardial and vascular tissue. The clinical course of patients with cocaine-induced chest pain (CCP) is often challenging, and electrocardiographic findings can be potentially misleading in terms of diagnosing a myocardial infarction. In addition, there is no current satisfactory study regarding outcomes of use of various pharmacological drug therapies to manage CCP. At present, calcium-channel blockers and nitroglyc- erin are two pharmacological agents that are advocated as first-line drugs for CCP management, although the role of labetalol has been controversial and warrants further investigation. We performed an extensive search of available literature through a large number of scholarly articles previously published and listed on Index Medicus. In this review, we put forward a concise sum- mary of the current approach to a patient presenting to the ED with CCP and management of the clinical scenario. The purpose of this review is to sum- marize the understanding of cocaine’s cardiovascular pathophysiology and to examine the current approach for proper evaluation and management of CCP. Key Words: cocaine, myocardial ischemia, chest pain, β-blockers, illicit drug use, observation unit (Cardiology in Review 2015;23: 303–311) A ccording to the 2011 Drug Abuse Warning Network report, illicit drug use caused 402 Emergency Department (ED) visits per 100,000 of the population, and the most commonly involved drug was cocaine, which caused 162 ED visits per 100,000 population. 1 North America and Western and Central Europe remain the domi- nant markets for cocaine use, although a rising trend is evident in South America, Africa, and Asia. 2 A large number of patients pres- ent to the ED each year with a history of recent cocaine-abuse and cocaine-associated chest pain complaints. There is also a tendency to deny any illicit drug abuse, and thus many cases go unreported. Cardiovascular complaints arising from cocaine abuse are common, and the most frequent presenting symptom is chest pain (39.5% of patients). 3 Cocaine also increases the risk of a variety of cardiovascu- lar conditions other than acute coronary syndrome [ACS, myocardial ischemia and myocardial infarction (MI)], such as acute aortic syn- drome (aortic dissection and rupture), myocarditis, coronary artery aneurysm, cardiomyopathy and arrhythmias 4,5 (Fig. 1). CARDIOVASCULAR PATHOPHYSIOLOGY Cocaine exerts its major pathophysiological effects on the car- diovascular system by inhibiting the reuptake of the neurotransmit- ter norepinephrine by sympathetic neurons from the synaptic cleft, 4 thereby causing an increased response to sympathetic stimuli and to catecholamines. Catecholamine release from central and peripheral stores may also be increased due to the contributory role of cocaine. 5 Increased sympathetic activity resulting from such effects causes an increase in heart rate, systemic blood pressure, myocardial con- tractility, and coronary vasoconstriction—all of which concurrently increase myocardial oxygen demand 6 (Fig. 2). Likewise, catechol- amine excess has been implicated in the pathogenesis of Takotsubo cardiomyopathy (TCM), also known as “stress cardiomyopathy,” because it occurs almost exclusively in women after severe stress. 7 TCM presents with chest pain, ST-segment elevation, a release of cardiac enzymes, and transient left ventricular apical ballooning; it mimics ACS and has been recognized to be important in the differen- tial diagnosis of ACS. 7,8 Cocaine abuse is deemed to be uncommon, although a possible trigger for TCM. 9 As demonstrated in previous studies, a decrease in the diameter of coronary arteries by 11–45% occurs after cocaine administration. 10–12 The epicardial coronary arteries develop vasoconstriction mainly due to cocaine-mediated stimulation of the α-adrenergic receptor. 6 The coronary arteries that have preexisting atherosclerotic changes show greater constriction. 10 Also, a greater constriction occurs when cocaine administration is combined with cigarette smoking. 11 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 1061-5377/15/2306-0303 DOI: 10.1097/CRD.0000000000000050 From the *Department of Medicine, Surat Municipal Institute of Medical Educa- tion and Research, Surat, Gujarat, India; †Zena and Michael A. Wiener Cardio- vascular Institute, Mount Sinai Medical Center, New York, NY; ‡Department of Internal Medicine, St John Hospital and Medical Center, Wayne State Uni- versity School of Medicine, Detroit, MI;§Department of Internal Medicine, Presence Saint Joseph Hospital, Chicago, IL; and ¶VA Ann Arbor Health Care System, University of Michigan, Ann Arbor, MI. Disclosure: The authors have no conflicts of interest to report. Correspondence: Pratik R. Agrawal, MD, Zena and Michael A. Wiener Cardio- vascular Institute, Mount Sinai Medical Center, One Gustave L. Levy Place, Box 1030, New York, NY 10029-6574. E-mail: dr.pratik.agrawal@gmail.com Current Strategies in the Evaluation and Management of  Cocaine-Induced Chest Pain Pratik R. Agrawal, MD,*† Tiziano M. Scarabelli, MD, PhD,†‡ Louis Saravolatz, MD,‡ Annapoorna Kini, MD,† Abhijay Jalota, MD,§ Carol Chen-Scarabelli, PhD,¶ Valentin Fuster, MD, PhD,† and Jonathan L. Halperin, MD† FIGURE 1. Number of ED visits related to illicit drug abuse  per 100,000 population, according to 2011 Drug Abuse  Warning Network Report. 1 ED indicates Emergency Depart- ment; PCP, phencyclidine.