Management of Cocaine-Associated Chest Pain and Myocardial Infarction
2008; Lippincott Williams & Wilkins; Volume: 117; Issue: 14 Linguagem: Inglês
10.1161/circulationaha.107.188950
ISSN1524-4539
AutoresJames McCord, Hani Jneid, Judd E. Hollander, James A. de Lemos, Bojan Cercek, Priscilla Y. Hsue, W. Brian Gibler, E. Magnus Ohman, Barbara J. Drew, George J. Philippides, L. Kristin Newby,
Tópico(s)Cardiac electrophysiology and arrhythmias
ResumoHomeCirculationVol. 117, No. 14Management of Cocaine-Associated Chest Pain and Myocardial Infarction Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBManagement of Cocaine-Associated Chest Pain and Myocardial InfarctionA Scientific Statement From the American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology James McCord, MD, Hani Jneid, MD, Judd E. Hollander, MD, James A. de Lemos, MD, Bojan Cercek, MD, FAHA, Priscilla Hsue, MD, W. Brian Gibler, MD, E. Magnus Ohman, MD, Barbara Drew, RN, PhD, FAHA, George Philippides, MD and L. Kristin Newby, MD, MHS James McCordJames McCord , Hani JneidHani Jneid , Judd E. HollanderJudd E. Hollander , James A. de LemosJames A. de Lemos , Bojan CercekBojan Cercek , Priscilla HsuePriscilla Hsue , W. Brian GiblerW. Brian Gibler , E. Magnus OhmanE. Magnus Ohman , Barbara DrewBarbara Drew , George PhilippidesGeorge Philippides and L. Kristin NewbyL. Kristin Newby Originally published17 Mar 2008https://doi.org/10.1161/CIRCULATIONAHA.107.188950Circulation. 2008;117:1897–1907Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: March 17, 2008: Previous Version 1 The goals of the present article are to provide a critical review of the literature on cocaine-associated chest pain and myocardial infarction (MI) and to give guidance for diagnostic and therapeutic interventions. Classification of recommendations and levels of evidence are expressed in the American College of Cardiology/American Heart Association (ACC/AHA) format as follows: Class I: Conditions for which there is evidence for and/or general agreement that the procedure or treatment is beneficial, useful, and effective.Class II: Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment. Class IIa: Weight of evidence/opinion is in favor of usefulness/efficacy. Class IIb: Usefulness/efficacy is less well established by evidence/opinion.Class III: Conditions for which there is evidence and/or general agreement that the procedure/treatment is not useful/effective and in some cases may be harmful.Level of Evidence A: Data derived from multiple randomized clinical trials.Level of Evidence B: Data derived from a single randomized trial or nonrandomized studies.Level of Evidence C: Only consensus opinion of experts, case studies, or standard of care.MethodsThe Writing Committee conducted a comprehensive search of the medical literature concerning cocaine-associated chest pain and MI. The literature search included English-language publications on humans and animals from 1960 to 2007. In addition to broad-based searching concerning cocaine, specific targeted searches were performed on cocaine and the following topics: MI, chest pain, emergency department (ED), aspirin, nitroglycerin, calcium channel blocker, benzodiazepine, thrombolytics, phentolamine, heparin, primary angioplasty, ECG, and stress testing. Literature citations were generally limited to published articles listed in Index Medicus. The article was reviewed by 4 outside reviewers nominated by the AHA.EpidemiologyCocaine is the second most commonly used illicit drug in the United States, with only marijuana being abused more frequently.1 Cocaine is also the illicit drug that leads to the most ED visits.2 The 2004 National Survey on Drug Use and Health estimated that 14% of people 12 years of age or older (34 million individuals) in the United States have tried cocaine at least once,3 and over 2000 individuals per day use cocaine for the first time.4 In the 2002 to 2003 calendar year, more than 1.5 million (0.6%) Americans ≥12 years of age had abused cocaine in the past year. Cocaine use is concentrated among select demographics: individuals 18 to 25 years of age (1.2%) have the highest rate of cocaine use; males (0.9%) had more than twice the use rate of females (0.4%); and rates according to race are 1.1% for blacks, 0.9% for Hispanics, 0.5% for whites, and 0.1% for Asians.6In 2005, there were 448 481 cocaine-related visits to EDs in the United States.7 Chest discomfort has been reported in 40% of patients who present to the ED after cocaine use.8 The Drug Abuse Warning Network (DAWN) reported that in the last 6 months of 2004, there were ≈126 000 cocaine-related ED visits in the United States, or ≈40% of all ED visits related to substance abuse (illicit or otherwise).9 The most frequent age group for these visits was 35 to 44 years of age; this group accounted for 37% of all cocaine-related ED encounters. Cocaine-related ED visits increased by 47% from 1999 to 2002.2 Thus, the number of ED encounters with patients with cocaine-associated chest pain will likely be increasing.PathophysiologyCocaine has multiple cardiovascular and hematologic effects that likely contribute to the development of myocardial ischemia and/or MI. Cocaine blocks the reuptake of norepinephrine and dopamine at the presynaptic adrenergic terminals, causing an accumulation of catecholamines at the postsynaptic receptor and thus acting as a powerful sympathomimetic agent.10,11 Cocaine causes increased heart rate and blood pressure in a dose-dependent fashion.12 In humans, intranasal cocaine use resulted in an increase in heart rate (17±16% beats/min), mean systemic arterial pressure (8±7% mm Hg), cardiac index (18±18% liters/min per m2), and dP/dt (18±20% mm Hg/s).13 The chronotropic effects of cocaine use are intensified in the setting of alcohol use.14 In addition, cocaine administration can reduce left ventricular function and increase end-systolic wall stress.15 By increasing heart rate, blood pressure, and contractility, cocaine leads to increased myocardial demand.Even small doses of cocaine taken intranasally have been associated with vasoconstriction of coronary arteries.16 Coronary vasoconstriction may be more accentuated in patients with preexisting coronary artery disease.17 Many cocaine users tend to be young men who also smoke cigarettes.18,19 The combination of cocaine and cigarette use results in greater increases in heart rate and vasoconstriction than either cocaine use or cigarette smoking alone.20 Vasoconstriction in the setting of cocaine use is most likely secondary to stimulation of the α-adrenergic receptors in smooth muscle cells in the coronary arteries, as pure α-adrenergic antagonists reduce coronary vasoconstriction in cocaine users.20 In addition to α-adrenergic stimulation, cocaine has been shown to increase levels of endothelin-1, which is a powerful vasoconstrictor,21 and to decrease production of nitric oxide, which is a vasodilator.22 Thus, cocaine decreases oxygen supply and induces myocardial ischemia through a variety of mechanisms.Acute thrombosis of coronary arteries shortly after cocaine use has been described.23 The propensity for thrombus formation in the setting of cocaine intake may be mediated by an increase in plasminogen-activator inhibitor.24 Cocaine use has also been associated with an increase in platelet count,25 increased platelet activation,26 and platelet hyper-aggregability.27 Autopsy studies demonstrated the presence of coronary atherosclerosis in young cocaine users along with associated thrombus formation; thus, cocaine use is associated with premature coronary atherosclerosis and thrombosis.28 Cocaine users have elevated levels of C-reactive protein, von Willebrand factor, and fibrinogen that may also contribute to thrombosis.29 Cocaine, therefore, causes myocardial ischemia or MI in a multifactorial fashion that includes: (1) increasing myocardial oxygen demand by increasing heart rate, blood pressure, and contractility; (2) decreasing oxygen supply via vasoconstriction; (3) inducing a prothrombotic state by stimulating platelet activation and altering the balance between procoagulant and anticoagulant factors; and (4) accelerating atherosclerosis.Incidence of Myocardial InfarctionSince an early description by Coleman and colleagues,30 many reports have emerged that link cocaine use to myocardial ischemia and MI. Many of the initial studies reported a temporal association between cocaine use and MI,19,31,32 whereas multiple experimental and observational studies subsequently elucidated the mechanisms for cocaine-associated MI.13,16,23,25–27,33–35In the COCaine Associated CHest PAin (COCHPA) study, cocaine-associated MI occurred in 6% of patients who presented to the ED with chest pain after cocaine use.19 In that prospective multicenter study, the diagnosis of MI was made by creatine kinase-MB isoenzyme measurements among 246 patients presenting to the ED with chest pain after cocaine ingestion.19 Weber and colleagues36 found a similar 6% rate of MI in patients with cocaine-associated chest pain in a retrospective analysis in an urban university–affiliated hospital.Other studies of cocaine-associated chest pain have reported lower incidences of MI. The prospective Acute Cardiac Ischemia-Time Insensitive Predictive Instrument (ACI-TIPI) study reported a 0.7% rate of MI among 293 patients with preceding cocaine ingestion who presented to the ED with chest pain or other ischemic symptoms37; another study documented a 2.8% rate of MI in a series of 218 patients with similar presentation.38 The ACI-TIPI study involved urban, suburban, and semirural hospitals and enrolled patients with chest pain, left arm pain, jaw pain, epigastric pain, dyspnea, dizziness, and palpitations. In contrast, the COCHPA trial involved a solely urban population that presented only with chest pain. These differences may explain the different rates of MI. Although the overall incidence of cocaine-associated MI varies between studies from 0.7% to 6% of those presenting with chest pain after cocaine ingestion (some of the variance may relate to differences in MI diagnostic criteria), cocaine appears to be an important contributor to MI among the young. In a study of 130 patients with cocaine-associated MI, the average age was only 38 years.39Clinical PresentationCardiopulmonary complaints are the most frequently reported symptoms among cocaine users (occurring in up to 56%), with chest pain being the single most frequent symptom.8 Cocaine-associated chest pain is usually perceived as pressure-like in quality.19 Other frequent symptoms include dyspnea, anxiety, palpitations, dizziness, and nausea.8 Dyspnea and diaphoresis are particularly common, occurring in 60% and 40% of patients, respectively.19 In one study, only 44% of 91 patients with cocaine-associated MI reported antecedent chest pain.32 Thus, the presence of chest pain appears to have little value for discriminating an ischemic from nonischemic cause in these patients. In another study of 130 patients with cocaine-associated MI, there was equal distribution between anterior (45%) and inferior (44%) MI, and most were non-Q wave (61%).40Cocaine-associated chest pain may be caused by not only MI but also by aortic dissection, and this must be considered in the differential diagnosis. Information concerning cocaine-induced aortic dissection is limited, but one study of 38 consecutive patients with aortic dissection in a US urban center demonstrated a surprisingly high number (14, 37%) that were associated with cocaine use.41 Among 921 cases in the International Registry of Aortic Dissection (IRAD) in which a history of cocaine use was known, however, only 0.5% of aortic dissection cases were associated with cocaine use.42 In addition to MI and aortic dissection, cocaine use may lead to pulmonary hypertension and associated chest pain and dyspnea.43 Finally, an acute pulmonary syndrome called "crack lung," which involves hypoxemia, hemoptysis, respiratory failure, and diffuse pulmonary infiltrates and occurs after inhalation of freebase cocaine, has been described.44Timing Between Cocaine Use and Myocardial InfarctionCocaine-associated MI appears to occur most often soon after cocaine ingestion. In one study, two thirds of MI events occurred within 3 hours of cocaine ingestion.32 In a survey of 3946 patients with recent MI, 38 patients admitted to cocaine use in the preceding year, and 9 patients reported ingestion in the 60 minutes preceding the onset of MI symptoms.18 This survey reported a striking 24-fold higher risk of MI in the first hour after cocaine use, with a rapid decrease in risk after this time.18Investigators have noted, however, that the onset of ischemic symptoms could still occur several hours after cocaine ingestion, at a time when the blood concentration is low or undetectable. Amin et al45 reported an 18-hour median length of time between cocaine use and MI onset among 22 patients presenting with chest pain after cocaine ingestion. This accounted for an unusually high rate of MI of 31% in this retrospective analysis, whereas other studies reported a range extending from 1 minute to up to 4 days.32 These findings are attributed to cocaine metabolites, which rise in concentrations several hours after cocaine ingestion, persist in the circulation for up to 24 hours, and may cause delayed or recurrent coronary vasoconstriction.46Patient CharacteristicsThe Cocaine-Associated Myocardial Infarction study retrospectively identified 130 patients who sustained a total of 136 cocaine-associated MI events. In this cohort, the majority of patients were young (mean age 38 years), nonwhite (72%), and smokers (91%) and had a history of cocaine use in the preceding 24 hours (88%).47 Mittleman et al18 also demonstrated that cocaine users with recent MI were more likely to be male (87%), current cigarette smokers (84%), young (44 years of age), and nonwhite (63%) than a comparable group with MI and no recent cocaine use. These characteristics appear to be similar in most patients presenting with cocaine-associated chest pain,19 making it exceedingly difficult to predict those at risk for MI, given the low incidence of cocaine-associated MI.19,36–38Complications and PrognosisIn the 130 patients in the Cocaine-Associated Myocardial Infarction study, 38% had cardiac complications.47 Heart failure occurred in 7% and arrhythmias in up to 43%, which accounted for the majority of these complications. The arrhythmias included ventricular tachycardia (18%), supraventricular tachycardia (5%), and bradyarrhythmia (20%). Notably, 90% of these complications occurred within the first 12 hours after presentation to the hospital and did not lead to significant adverse events, with an in-hospital mortality rate of 0%. In addition, in a study of 22 patients who suffered cardiac arrest in the setting of cocaine use, only 10 (46%) died compared with 32 of 41 (78%) aged-matched controls (P 1.2 cm in 44% of users compared with 11% in nonusers).56 As the cavity size was normal in all patients, it was postulated that long-term cocaine use appears to be associated with concentric left ventricular hypertrophy.56 These findings potentially explain the baseline ECG changes associated with cocaine use. This may also decrease the utility of echocardiography to look for ischemia in the evaluation of chest pain, as left ventricular hypertrophy often masks regional wall motion abnormalities.57 Echocardiography also yields information concerning systolic and diastolic function and valvular structure that may affect treatment strategies.Dobutamine stress echocardiography has been safely performed in subjects admitted with chest pain after cocaine use, provided they exhibited no signs of ongoing cocaine toxicity.58 Among 24 patients with chest pain but no specific ECG changes or positive cardiac markers, dobutamine stress echocardiography was successfully completed in 19 patients who achieved their target heart rates. Two patients did not have adequate resting images, 1 test was terminated because of atrial conduction abnormalities, 1 test was cancelled because of baseline wall motion abnormalities, and 1 patient failed to achieve the target heart rate. None of the patients had an exaggerated adrenergic response (defined as development of systolic blood pressure >200 mm Hg or a tachyarrhythmia), and only 1 patient had new wall motion abnormalities with dobutamine infusion.The appropriate diagnostic evaluation for these patients remains unclear. Practitioners should follow general principles for risk stratification of patients with possible ACS. In light of the underlying electrocardiographic abnormalities, if a stress test is ordered, most patients would benefit from stress testing with imaging, either echocardiography or nuclear.38,58Coronary AngiographyIn a study of 734 patients (mean age 43±7 years) evaluated for symptoms compatible with ischemia after cocaine use, 90 underwent coronary angiography.59 In this selected, higher-risk group, 50% had no significant stenosis, 32% had single-vessel disease, 10% had 2-vessel disease, and 5.6% had 3-vessel disease. Of patients with proven MI, 77% had significant coronary artery disease. Of patients without MI, only 35% had significant coronary artery disease.59 In a smaller report of 91 cases of cocaine-associated MI, 54 patients underwent coronary angiography,32 and 34 (55%) of those patients were found to have significant coronary artery disease or thrombotic occlusion. In another study of patients with proven MI after cocaine use, 80% of patients had significant coronary artery disease.13Evaluation in a Chest Pain UnitAs only 0.7% to 6% of patients with cocaine-associated chest pain have an MI,36,37 risk stratification of these patients in an observation unit may significantly reduce unnecessary admissions and improve resource utilization. In a prospective randomized study,49 344 patients were evaluated for cocaine-associated chest pain. Forty-two (12%) high-risk patients with ST-segment elevation or depression >1 mm, elevated serum cardiac markers, recurrent chest pain, or hemodynamic instability were directly admitted. Of the 42 patients admitted, 10 (24%) had an MI and another 10 (24%) were diagnosed with unstable angina. The other 302 intermediate- to low-risk patients were successfully evaluated in an observation unit for 6 to 12 hours with clinical and ECG monitoring and repeat cardiac troponin I determination. The observation period was followed by nonmandatory stress testing before discharge. Patients were treated with aspirin and nitrates, and 30% received benzodiazepines as well.Among the patients evaluated in the observation unit, there were no cardiovascular deaths; however, 4 of 256 (2%) patients sustained a nonfatal MI. Before discharge, 158 (52%) patients underwent a stress test. Only 4 (3%) had positive results and underwent angiography. Two patients had multivessel disease, 1 had nonocclusive disease, and 1 had no evidence of coronary artery disease. In a retrospective review of 197 patients with cocaine-associated chest pain evaluated in a chest pain unit, 171 (87%) were discharged and 12% required hospital admission. Only 1 patient (4.5%) developed an MI. Of the patients sent home, only 1 (1%) had a cardiac complication.60These studies suggest that risk stratification on the basis of well-established criteria, including ECG changes and positive cardiac troponin,61 is feasible and safe in patients with chest pain associated with cocaine use. Patients at high risk should be admitted to monitored beds. High-risk patients have a 23% incidence of MI, and another 23% will ultimately be diagnosed with unstable angina.49 Among patients in whom coronary angiography was performed, over 75% had significant coronary artery stenoses. The in-hospital course will likely be uneventful with over 90% of patients categorized as uncomplicated, Killip class I.49 In the absence of ischemic electrocardiographic changes or positive cardiac markers, intermediate- and low-risk patients can be safely managed in a chest pain observation unit for 9 to 12 hours, which can obviate the need for hospital admission in the majority of these patients. The likelihood of underlying coronary artery disease or adverse cardiac events in patients in which MI is ruled out is low. In the study by Weber et al,49 no differences in 30-day outcomes among patients managed with or without stress testing before discharge were seen. We recommend that stress testing be optional for patients with cocaine-associated chest pain who have had an uneventful 9 to 12 hours of observation. Stress testing can be performed at the time of observation or on an outpatient basis and should be considered depending on cardiac risk factors and ongoing symptoms.Therapeutic StrategiesGeneral ConsiderationsPatients with cocaine-associated chest pain, unstable angina, or MI should be treated similarly to those with traditional ACS or possible ACS,62,63 with some notable exceptions (Figure). No randomized, placebo-controlled trials regarding therapies to improve outcomes of patients sustaining a cocaine-associated MI have been reported. Therapeutic recommendations are based on animal studies, cardiac catheterization studies, observational studies, case series, and case reports (Table). Unlike patients with ACS unrelated to cocaine use, cocaine users should be provided with intravenous benzodiazepines as early management.32,64–66 In the setting of cocaine use, benzodiazepines relieve chest pain and have beneficial cardiac hemodynamic effects.67,68 The neuropsychiatric symptoms and cardiovascular complications of cocaine use are interrelated; therefore, management of neuropsychiatric manifestations favorably impacts the systemic manifestations of cocaine toxicity. In animal models, benzodiazepines decrease the central stimulatory effects of cocaine, thereby indirectly reducing cardiovascular toxicity. Download figureDownload PowerPointFigure. Therapeutic and diagnostic recommendations in cocaine-associated chest pain. ASA indicates aspirin; NTG, nitroglycerin; STEMI, ST-segment–elevation MI; NSTE ACS, non–ST-segment–elevation ACS; CPU, chest pain unit; PCI, percutaneous coronary intervention; B-blockers, β-blockers; and ACE, angiotensin-converting enzyme inhibitor.Table. Scientific Strength for Treatment Recommendations for Initial Management of Cocaine-Associated Myocardial Ischemia or InfarctionTherapyClassification of Recommendation/Level of EvidenceControlled Clinical TrialsCardiac Catheterization Laboratory StudiesCase Series or Observational StudiesCase ReportsControlled In Vivo Animal ExperimentsNo. of patients in studies/reports: benzodiazepines, 67; nitroglycerin, 67; phentolamine, 45; calcium channel blocker, 15; β-blockers without α-blocking properties, 30; labetalol, 15; and fibrinolytics, 66.BenzodiazepinesI/BXXXAspirinI/CXNitroglycerinI/BXXXCalcium channel blockerIIb/CXXPhentolamineIIb/CXXXβ-BlockersIII/CXXXLabetalolIII/CXXXHypertension and tachycardia may not require direct treatment. In a patient with definite ACS, these signs need to be addressed. In a patient with chest pain of unclear origin, hypertension and tachycardia should be treated conservatively. Resolution of anxiety with a benzodiazepine will often lead to resolution of the hypertension and tachycardia. When sedation is not successful, hypertension can be managed with sodium nitroprusside, nitroglycerin, or intravenous phentolamine.16,46ST-Segment–Elevation Myocardial InfarctionTimely percutaneous coronary intervention by experienced operators in high-volume centers is preferred over fibrinolytics in ST-segment–elevation MI and is even more desirable in the setting of cocaine use.64–66,68–70 Many young patients have benign early repolarization, and only a small percentage of patients with cocaine-associated chest pain
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