Frequency of acute coronary syndrome in patients presenting to the Emergency Department with chest pain after methamphetamine use

The Journal of Emergency Medicine, Vol. 24, No. 4, pp. 369 –373, 2003 Copyright © 2003 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/03 $–see front matter

doi:10.1016/S0736-4679(03)00031-3

Original Contributions

FREQUENCY OF ACUTE CORONARY SYNDROME IN PATIENTS PRESENTING TO THE EMERGENCY DEPARTMENT WITH CHEST PAIN AFTER METHAMPHETAMINE USE Samuel D. Turnipseed,

MD,*

John R. Richards, MD,* J. Douglas Kirk, and Ezra A. Amsterdam, MD†

MD,*

Deborah B. Diercks,

MD,*

Department of Internal Medicine and *Divisions of Emergency Medicine and †Cardiovascular Medicine, University of California, Davis School of Medicine, Sacramento, California Reprint Address: Samuel D. Turnipseed, MD, Division of Emergency Medicine, University of California, Davis Medical Center, 4150 V Street, Suite 2100, Sacramento, CA 95817

e Abstract—We reviewed the frequency of acute coronary syndrome (ACS) in patients presenting to our Emergency Department (ED) with chest pain after methamphetamine (MAP) use during a 2-year interval. Thirty-three patients (25 males, 8 females; average age 40.4 ⴞ 8.0 years) with a total of 36 visits met study inclusion criteria: 1) non-traumatic chest pain, 2) positive MAP urine toxicology screen, 3) admission to “rule-out” myocardial infarction, 4) chest radiograph demonstrating no infiltrates. An ACS was diagnosed in 9 patients (25%). Three patients (8%) (2 ACS and 1 non-ACS) suffered cardiac complications (ventricular fibrillation, ventricular tachycardia, supraventricular tachycardia, respectively). Age, gender, cardiac risk factors, prior coronary artery disease, initial systolic blood pressure and heart rate did not differ significantly in the ACS and non-ACS groups. The initial and subsequent electrocardiograms (EKG) were normal in 1/9 (11%) patients with ACS and 16/27 (59%) without ACS (p < 0.05). Our findings suggest that: 1) ACS is common in patients hospitalized for chest pain after MAP use, and 2) the frequency of other potentially life-threatening cardiac complications is not negligible. A normal EKG lowers the likelihood of ACS, but an abnormal EKG is not helpful in distinguishing patients with or without ACS. © 2003 Elsevier Inc.

INTRODUCTION Methamphetamine (MAP) is a synthetic central nervous system stimulant with a history of abuse dating to its development approximately 80 years ago (1). Illicit MAP use has been rapidly increasing worldwide and MAP is now a major drug of abuse in patients presenting to Emergency Departments (ED) in the western United States (2). Several properties distinguish MAP from cocaine, a stimulant that has been more extensively studied. Unlike cocaine, MAP is readily synthesized in home laboratories and has a low street price (3). MAP produces a rapid “high” similar to cocaine but its effects are more prolonged. Further, smoking MAP induces effects as rapidly as intravenous use, thus increasing its ease of administration for illicit purposes (4). Among the most important potential adverse effects of both cocaine and MAP are acute coronary syndromes (ACS) in which chest pain is the major symptom. Multiple studies have evaluated patients who present to the ED with chest pain after cocaine use (5– 8). However, there are limited data on patients presenting to the ED with chest pain after MAP use. Richards and colleagues report that chest pain was the chief complaint in 8% of 461 MAP users presenting to an urban ED, but the

e Keywords—acute coronary syndrome; chest pain; emergency department; methamphetamine

RECEIVED: 15 September 2002; FINAL ACCEPTED: 9 August 2002

SUBMISSION RECEIVED:

22 July 2002;

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frequency of ACS or cardiac complications was not noted in this study (9). Medline search reveals only six brief reports of isolated acute myocardial infarction (MI) after amphetamine use (10 –15). Routes of drug administration in these cases were oral, intranasal, and intravenous. However, three of the six reports did not verify use of stimulants by confirmatory toxicology screen. Therefore, we reviewed the frequency of ACS and its complications in hospitalized patients who presented to our ED with chest pain after documented MAP use.

MATERIALS AND METHODS We reviewed the medical records of patients admitted to the University of California, Davis Medical Center for chest pain associated with MAP use between January 1994 and January 1996. Our Institutional Review Board approved the study as “exempt.” All patients were initially evaluated in the ED, which has an annual census of 60,000 visits. Cases were identified from two sources. The first was a computer-generated list using International Classification of Disease (ICD) billing codes matching discharge diagnoses of “methamphetamine use” and “chest pain” or “heart diagnosis.” Twenty-four categories (with multiple subgroups) were used to determine “heart diagnosis.” Examples included myocardial infarction, angina, unstable angina, ischemic heart disease, acute pericarditis, endocarditis, myocarditis, cardiomyopathy, cardiac dysrhythmia, abnormal electrocardiogram (EKG), tachycardia, and heart failure (16). The second source was our Chest Pain Evaluation Unit (CPEU) data base that records MAP use in all patients evaluated for chest pain. Inclusion criteria for the study group were: 1) chief complaint of non-traumatic chest pain, 2) urine toxicology screen positive for MAP and negative for cocaine, 3) admission for “rule out MI” (three serial measurements of the MB fraction of creatine phosphokinase [CPK-MB] over 12 h), 4) chest radiograph demonstrating no infiltrates. A homogeneous enzyme immunoassay using a Beckman Synchron CX7 (Beckman Industries, Fullerton, CA) was used as a screening test for amphetamines and cocaine; confirmation testing was performed by gas chromatography-mass spectrometry. The following clinical characteristics were obtained: age, sex, history of coronary artery disease (CAD), cardiac risk factors (diabetes, hypercholesterolemia, cigarette smoking, hypertension, family history of early MI [⬍ 55 years old in male first-degree relative, ⬍ 65 years old in female first-degree relative]). Data recorded were ED triage heart rate and blood pressure, EKG findings, cardiac serum enzymes, non-invasive cardiac stress testing results (exercise electrocardiography, myocardial scintig-

raphy, or echocardiography), coronary angiography, and discharge diagnosis. The EKGs were categorized as: 1) normal, 2) acute injury or ischemia, 3) abnormal but not diagnostic of ischemia, 4) dysrhythmias. An acute injury pattern was defined as ST segment elevation ⱖ 1.0 mm in two contiguous leads. Ischemia was defined as ⱖ 1.0 mm horizontal or downsloping regional ST segment depression or regional symmetric T-wave inversions (ⱖ 3 mm). Dysrhythmias were defined as supraventricular or ventricular tachycardias. The EKGs were read by two boardcertified Emergency Physicians, and any differences in interpretation were resolved by a third reader, a cardiologist. An acute coronary syndrome was defined as Q wave MI, non-Q wave MI (non-Q MI), or unstable angina (UA). In patients with chest pain suggestive of myocardial ischemia, Q wave MI was defined by evolution of EKG Q-waves ⱖ 0.04 s and elevation of CPK-MB greater than twice normal with a relative index (CPKMB ⫻ 100/Total CPK) ⱖ 3.0 and characteristic evolution on serial testing. Non-Q MI was diagnosed by positive serum CPK-MB in the absence of pathologic Q waves. Unstable angina was diagnosed by normal serum CPK-MB relative index and evidence of myocardial ischemia on non-invasive cardiac stress testing or significant CAD by coronary angiography (ⱖ 70% stenosis in a major coronary artery). Cardiac complications were defined as death, cardiogenic shock, pulmonary edema, and dysrhythmias requiring emergent treatment. Group data are presented as mean ⫾ SD. Results were compared using Student’s t-test and Mann-Whitney U test for continuous data and Chi square analysis for categorical variables. A p value ⬍ 0.05 was considered significant.

RESULTS The charts of 171 patients with “chest pain” or “heart diagnosis” associated with MAP use were identified from our two sources (ICD billing codes and CPEU data base). Inclusion criteria were met by 33 patients, 3 of whom had repeat visits (36 total patient visits). Of the 138 patients who were excluded, 127 either had no chief complaint of chest pain or had a negative toxicology screen for MAP or had both. In the remaining 11 patients, clinical data were incomplete. Acute coronary syndrome was diagnosed in 9 patients (25%) during the 36 admissions. Three patients were admitted twice during the study period; ACS was diagnosed only once in one patient (during these 6 admissions). The clinical characteristics of the patients in whom ACS was diagnosed and those in the non-ACS

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Table 1. Comparison of Patients With and Without Acute Coronary Syndrome (ACS)

Male Female Age (years) Mean no. CRF Prior CAD SBP (mm Hg) HR (bpm)

ACS (n ⫽ 9)

Non-ACS (n ⫽ 27)

p

8 (89%) 1 41.3 ⫾ 6.0 1.6 ⫾ 0.5 2 142 ⫾ 19 114 ⫾ 47

20 (74%) 7 40.1 ⫾ 8.7 1.5 ⫾ 0.9 1 140 ⫾ 25 98 ⫾ 24

ns ns ns ns ns ns

CRF ⫽ cardiac risk factors; CAD ⫽ coronary artery disease; SBP ⫽ systolic blood pressure; HR ⫽ heart rate.

group are presented in Table 1. Age, gender, cardiac risk factors, prior CAD, initial systolic blood pressure and heart rate did not differ significantly between the two groups. As shown in Table 2, the initial EKG was normal in 1/9 (11%) patients with ACS and 16/27 (59%) without ACS (p ⬍ 0.05). The EKG abnormalities in the ACS group included ST segment elevation [1], right bundle branch block [3], non-specific ST-T wave changes [4], and ventricular tachycardia [1]. Abnormalities in the non-ACS group included ST segment elevation [2], right bundle branch block [1], non-specific ST-T wave changes [5], and supraventricular tachycardia [1]. Clinical data and outcomes in the 9 patients with ACS are shown in Table 3. One patient (with no history of CAD) had acute anterior Q wave MI with cardiac arrest and successful resuscitation. Seven patients (2 with previously known CAD) suffered non-Q MI and unstable angina was diagnosed in one patient. One patient in the non-Q MI group presented with ventricular tachycardia that responded to lidocaine in the ED. Further evaluation included coronary angiography in 3 patients (positive for CAD in all) and exercise treadmill testing in 2 patients (1 normal and 1 non-diagnostic for ischemia). The remaining 4 (including the 2 patients with previously diagnosed CAD and 1 with normal coronary angiography 3 months earlier) had no further cardiac evaluation during hospitalization. Twenty-seven patients (75%) did not have ACS. Further inpatient evaluation included: exercise treadmill testing in 12 (5 negative, 7 non-diagnostic), myocardial

scintigraphy in 2 (both normal), exercise echocardiography in 1 (normal), and coronary angiography in 2 (both normal). Further testing was not performed in 10 patients by the decision of the patients [3] or attending physicians [7]. The only complication in this group was supraventricular tachycardia in one patient who responded to adenosine in the ED. Two patients (males aged 41 and 46 years) in the non-ACS group presented with ST-segment elevation on EKG and received intravenous thrombolytic therapy in the ED. However, subsequent evaluation in both patients was negative for acute MI, including EKGs that remained unchanged throughout the hospital course and normal serial cardiac serum enzymes. Cardiac catheterization performed in one patient revealed normal coronary arteries and left ventricular function. Exercise echocardiography in the second patient revealed normal cardiac structure and function with no stress-induced wall motion abnormalities. DISCUSSION This is a series of patients evaluated for chest pain and ACS after MAP use. Previous publications comprise single case reports of myocardial infarction after amphetamine use, but positive toxicology screens for stimulants are documented in only half (10 –15). Our data suggest that hospitalized patients presenting with chest pain after MAP use have a high rate of ACS, as indicated by the 25% frequency in our patients. Furthermore, other potentially life-threatening cardiac complications occurred in 8% (3/36) of this group. These adverse events are especially noteworthy in our study group that was characterized by a relatively young age (average 41 years) and a low rate of prior cardiac disease. The use of MAP has dramatically increased during the past decade. A pure form of MAP-hydrochloride, also known as “ice” or “crystal,” is readily synthesized in home laboratories and can be smoked. The less pure powder is known as “speed” or “crank,” deriving its name from outlaw motorcycle groups that transported MAP throughout the United States in the crank cases of their vehicles during the 1960s. MAP stimulates the release and blocks the reuptake of

Table 2. Electrocardiogram (EKG) Results in Patients With and Without Acute Coronary Syndrome (ACS) EKG

Total (n ⫽ 36)

ACS (n ⫽ 9)

Non-ACS (n ⫽ 27)

Odds Ratio (95% CI)

p

Normal Acute injury/ischemia Abnormal/non-diagnostic Dysrhythmia

17 3 14 2

1 1 6 1

16 2 8 1

0.09 (0.01–0.8) 1.6 (0.1–19.6) 4.75 (0.9–23.9) 3.25 (0.2–58.1)

⬍0.01 ns ns ns

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Table 3. Patients With Acute Coronary Syndrome Associated With Methamphetamine Use Patient 1 2 3 4 5 6 7 8 9

Sex

Age (years)

CAD

Diagnosis

m m m m m m m m f

47 40 48 32 33 48 43 42 40

no no no no no yes yes no no

Q-wave MI Non Q-wave MI Non Q-wave MI Non Q-wave MI Non Q-wave MI Non Q-wave MI Non Q-Wave MI Unstable angina Non Q-wave MI

Management PTCA Medical Medical PTCA Medical Medical Medical CABG Medical

CAD ⫽ coronary artery disease; MI ⫽ myocardial infarction; PTCA ⫽ percutaneous transluminal coronary angioplasty; CABG ⫽ coronary artery bypass graft surgery.

catecholamines such as dopamine and norepinephrine, resulting in a hyperadrenergic state or catecholamine hyperstimulaton (17,18). N-Methyl substitution of amphetamine forms MAP, which has approximately twice the potency of amphetamine. Usual adult daily doses (for treatment of obesity, narcolepsy) are 5– 60 mg for amphetamine with therapeutic levels of 30 – 40 mg/ml and 2.5–5.0 mg for MAP with therapeutic levels of 20 –30 mg/ml. Canine studies demonstrate the LD50 for amphetamine is 20 –27 mg/kg and 11 mg/kg for MAP. The majority of our patients most likely used MAP rather than other forms of amphetamines, consistent with the finding that all toxicology screens (22 of 36) that were confirmed by gas chromatography revealed MAP (9). The half-life of MAP is 6 –15 h depending on urine pH. Adverse clinical cardiovascular manifestations of MAP include chest pain, palpitations, shortness of breath, hypertension or hypotension, myocardial ischemia, atrial and ventricular dysrhythmias, and circulatory collapse (4,18,19). Animal studies have shown that MAP has both positive and negative cardiac inotropic effects and is directly toxic to the myocardium (20,21). In addition to acute MI in humans, MAP has been reported to cause cardiomyopathy, acute pulmonary edema, and pulmonary hypertension (22–25). Although not confirmed, it is likely that MAP produces myocardial ischemia by mechanisms similar to those of cocaine, which include one or more of the following: 1) coronary artery vasospasm, 2) thrombus formation, 3) increased myocardial oxygen demand, 4) direct myocardial toxicity (26 –31). It is of interest that skeletal muscle necrosis (rhabdomyolysis) has been proposed as a mechanism of non-cardiac chest pain after cocaine use and this complication may be a factor in chest pain associated with MAP use (8). Previous reports describe amphetamine-induced myocardial infarction in association with both normal coronary arteries and coronary artery stenosis (11–15). In our study, all three patients who underwent coronary angiog-

raphy had significant CAD treated by myocardial revascularization. A fourth patient, who had a non-Q MI, had angiographically normal coronary arteries 1 month before his admission. These findings suggest that the interplay of several of the aforementioned mechanisms (vasospasm, thrombosis, increased myocardial oxygen demand) may have accounted for MAP-induced myocardial ischemia or infarction in our heterogeneous patient population. It is unclear whether prolonged exposure to MAP is atherogenic. It has been speculated that the hemodynamic effects of MAP, mediated by catecholamine release, can contribute to atherosclerosis by increasing blood pressure, platelet aggregability, and shear forces (32–34). In this regard, a pathologic study demonstrated that coronary artery disease was significantly more common in MAP users than controls, but the latter were younger than the former, diminishing the significance of this finding (35). Patients who present with chest pain after MAP use pose a challenge to the Emergency Physician. Although clinical parameters (age, gender, cardiac risk factors, prior CAD, initial systolic blood pressure and heart rate) were not helpful in distinguishing patents with and without ACS, patients with normal initial EKGs were unlikely to have ACS. However, the frequency of abnormal EKGs did not differ significantly in patients with and without ACS, a factor that may confound clinical assessment. This problem is reflected by the two patients in our series with abnormal EKGs who received intravenous thrombolytic therapy but in whom subsequent evaluation revealed no evidence of MI or CAD. The retrospective methodology of this study precludes detailed characterization of our patients’ chest pain but prior studies in patients using cocaine have shown that descriptors of this symptom do not reliably identify those with ACS (6). Our study has several limitations. First, because it is retrospective, all pertinent data may not be available. However, ours is a series of patients with chest pain after

Chest Pain and Methamphetamine

MAP use reported from a single institution, and inclusion required positive toxicologic evidence of MAP, documentation of essential clinical data, and assessment of outcomes in all patients. Second, our study population is relatively small and includes only hospitalized patients. In this regard, our objective was to evaluate patients who, in the judgement of experienced Emergency Physicians, required hospitalization for evaluation of chest pain after MAP use. Finally, all patients did not undergo non-invasive cardiac stress testing or coronary angiography, because management was at the discretion of the individual attending physician. Our findings suggest that ACS is common in patients hospitalized for chest pain after MAP use and the frequency of other potentially life-threatening cardiac complications is not negligible. These events occur in patients with and without underlying coronary disease and may involve multiple pathophysiologic mechanisms. Although a normal initial EKG lowers the likelihood of ACS, an abnormal EKG is not helpful in distinguishing patients with and without ACS after MAP use. REFERENCES 1. Yoshida T. Use and misuse of amphetamines: an international overview. In: Klee H, ed. Amphetamine misuse: international perspectives on current trends. Amsterdam: Harwood Publishers; 1997:1–18. 2. Centers for Disease Control. Increasing morbidity and mortality associated with abuse of amphetamine—United States, 1991–1994. Morb Mortal Wkly Rep 1995;44:881– 6. 3. Morgan P, Beck JE. The legacy and the paradox: hidden contexts of methamphetamine use in the United States. In: Klee H, ed. Amphetamine misuse: international perspectives on current trends. Amsterdam: Harwood Publishers; 1997:135– 62. 4. Derlet RW, Heischober B. Methamphetamine. Stimulant of the 1990s? West J Med 1990;153:625– 8. 5. Minor RL, Scott BD, Brown DD, Winniford MD. Cocaine-induced myocardial infarction in patients with normal coronary arteries. Ann Intern Med 1991;115:797– 806. 6. Hollander JE, Hoffman RS, Gennis P, et al. Prospective multicenter evaluation of cocaine-associated chest pain. Acad Emerg Med 1994;1:330 –9. 7. Hollander JE, Brooks DE, Valentine SM. Assessment of cocaine use in patients with chest pain syndromes. Arch Intern Med 1998; 158:62– 6. 8. Kontos MC, Schmidt KL, Nicholson CS, Ornato JP, Jesse RL, Tatum JL. Myocardial perfusion imaging with technetium-99 sestamibi in patients with cocaine-associated chest pain. Ann Emerg Med 1999;33:639 – 45. 9. Richards JR, Bretz SW, Johnson EB, Turnipseed SD, Brofeldt BT, Derlet RW. Methamphetamine abuse and emergency department utilization. West J Med 1999;170:198 –202. 10. Carson P, Oldroyd K, Phadke K. Myocardial infarction due to amphetamine. BMJ 1987;294:1525– 6. 11. Packe GE, Garton MJ, Jennings K. Acute myocardial infarction caused by intravenous amphetamine abuse. Br Heart J 1990;64: 23– 4. 12. Furst SR, Fallon SP, Reznik GN, Shah PK. Myocardial infarction after inhalation of methamphetamine. N Engl J Med 1990;323: 1147– 8.

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