Cocaine and the Heart

E-chocardiography Journal: Alphabetical List / Chronological List / Images / Home Page

Mittleman MA. Mintzer D. Maclure M. Tofler GH. Sherwood JB. Muller JE.
Institute for Prevention of Cardiovascular Disease, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Triggering of myocardial infarction by cocaine.
Circulation. 99(21):2737-41, 1999 Jun 1.

BACKGROUND: Cocaine has been implicated as a trigger of acute myocardial infarction in patients with and those without underlying coronary atherosclerosis. However, the magnitude of the increase in risk of acute myocardial infarction immediately after cocaine use remains unknown. METHODS AND RESULTS: In the Determinants of Myocardial Infarction Onset Study, we interviewed 3946 patients (1282 women) with acute myocardial infarction an average of 4 days after infarction onset. Data were collected on the use of cocaine and other potential triggers of myocardial infarction. We compared the reported use of cocaine in the hour preceding the onset of myocardial infarction symptoms with its expected frequency by using self-matched control data based on the case-crossover study design. Of the 3946 patients interviewed, 38 (1%) reported cocaine use in the prior year and 9 reported use within the 60 minutes preceding the onset of infarction symptoms. Compared with nonusers, cocaine users were more likely to be male (87% vs 67%, P=0.01), current cigarette smokers (84% vs 32%, P<0.001), younger (44+/-8 vs 61+/-13 years, P<0.001), and minority group members (63% vs 11%, P<0.001). The risk of myocardial infarction onset was elevated 23.7 times over baseline (95% CI 8.5 to 66.3) in the 60 minutes after cocaine use. The elevated risk rapidly decreased thereafter. CONCLUSIONS: Cocaine use is associated with a large abrupt and transient increase in the risk of acute myocardial infarction in patients who are otherwise at relatively low risk. This finding suggests that studying the pathophysiological changes produced by cocaine may provide insights into the mechanisms by which myocardial infarction is triggered by other stressors.

Hollander JE. Levitt MA. Young GP. Briglia E. Wetli CV. Gawad Y.
Department of Emergency Medicine, Hospital of the University of Pennsylvania, Philadelphia 19104-4283, USA.
Effect of recent cocaine use on the specificity of cardiac markers for diagnosis of acute myocardial infarction.
American Heart Journal. 135(2 Pt 1):245-52, 1998 Feb.

We evaluated whether recent cocaine use alters the specificity of CK-MB, myoglobin, and cardiac troponin I for acute myocardial infarction (AMI) in patients who are seen in the emergency department for chest pain. Patients <60 years old with potential myocardial ischemia underwent a standardized history and physical examination and routine CK-MB assays every 8 to 12 hours and had study serum obtained at presentation for CK-MB, myoglobin, and cardiac troponin I immunoassays, as well as benzoylecgonine, cocaine's main metabolite. We enrolled 97 patients, 19 (20%) of whom had recent used cocaine. Patients with and without cocaine use were similar with regards to sex, race, renal and muscular disease, diabetes, family history, and hypertension and rate of AMI (12% vs 11%, p = 1.0). In patients without MI, the mean myoglobin level was higher in cocaine users than noncocaine users (179 vs 74 ng/ml; Mann-Whitney p = 0.003), but the mean values were similar for CK-MB (2.2 vs 2.1 ng/ml; Mann-Whitney p = 0.58) and for cardiac troponin-I (0.02 vs 0.02 ng/ml; Mann-Whitney p = 0.87). The specificities of the markers in patients with and without cocaine use were as follows: cardiac troponin I, 94% vs 94%, (p = 1.0); CK-MB, 75% vs 88% (p = 0.24); and myoglobin, 50% vs 82%, (p = 0.02), respectively. Our data demonstrate that the specificity of myoglobin was altered by recent cocaine use. The specificity of CK-MB was affected less and the specificity of cardiac troponin I was not affected by recent cocaine use.

Hollander JE. Shih RD. Hoffman RS. Harchelroad FP. Phillips S. Brent J. Kulig K. Thode HC Jr.
Department of Emergency Medicine, University Medical Center, Stony Brook, New York 11794-8350, USA.
Predictors of coronary artery disease in patients with cocaine-associated myocardial infarction. Cocaine-Associated Myocardial Infarction (CAMI) Study Group. American Journal of Medicine. 102(2):158-63, 1997 Feb.

PURPOSE: To identify clinical criteria predictive of underlying coronary artery disease in patients with cocaine-associated myocardial infarction. PATIENTS AND METHODS: Using a retrospective cross-sectional study design at 29 acute care hospitals, we identified 70 patients with cocaine-associated myocardial infarction who had a determination of the presence or absence of coronary artery disease. Clinical characteristics of patients with coronary artery disease (> 50% stenosis on cardiac catheterization or reversible ischemia on stress test) were compared with patients without coronary artery disease (< 50% stenosis on cardiac catheterization). RESULTS: Compared with patients without coronary artery disease (n = 21), patients with coronary artery disease (n = 49) were older (42 versus 31 years; P < 0.001), had more traditional cardiac risk factors (2.3 versus 1.5; P < 0.001), more frequent history of hypertension (odds ratio [OR], 5.3; 95% confidence interval [CI], 1.4 to 20.4); more frequent family history of myocardial infarction (OR, 4.4; 95% CI, 1.3 to 15.1), more bradydysrhythmias (OR, 8.0; 95% CI, 1.0 to 65.5), and more likely to have an inferior infarct location (P = 0.04). CONCLUSION: Age, number of cardiac risk factors, location of myocardial infarction, and bradydysrhythmias predict underlying coronary artery disease in patients with cocaine-associated myocardial infarction. If validated, this knowledge may be used to develop a medically appropriate, cost-effective evaluation strategy for patients following cocaine-associated myocardial infarction.

Hollander JE.
Department of Emergency Medicine, University Medical Center, Stony Brook, New York 11794-8350, USA.
Cocaine-associated myocardial infarction.
Journal of the Royal Society of Medicine. 89(8):443-7, 1996 Aug.

Myocardial ischaemia and infarction has become a well-recognized sequelae of cocaine use. The possibility of recent cocaine use should be assessed in patients with potential myocardial ischaemia because the treatment of patients with myocardial ischaemia related to cocaine differs from that of patients with myocardial ischaemia unrelated to cocaine. Patients with cocaine-associated myocardial ischaemia should receive initial treatment with benzodiazepines to decrease central adrenergic stimulation. Aspirin should be used to reduce thrombus formation, and nitroglycerin to reverse coronary vasoconstriction. Patients with continued ischaemia can be treated with either low doses of phentolamine, or verapamil. If ischaemia continues after treatment with these agents mechanical reperfusion or thrombolytic therapy should be considered depending upon the clinical circumstances. Patients with myocardial ischaemia secondary to cocaine should not receive treatment with beta adrenergic antagonists as these agents enhance coronary vasoconstriction thereby worsening ischaemia. [References: 69]

Hollander JE. Hoffman RS. Burstein JL. Shih RD. Thode HC Jr.
Department of Emergency Medicine, University Medical Center, Stony Brook, NY, USA.
Cocaine-associated myocardial infarction. Mortality and complications. Cocaine-Associated Myocardial Infarction Study Group.
Archives of Internal Medicine. 155(10):1081-6, 1995 May 22.

BACKGROUND: The frequency of complications in patients with cocaine-associated myocardial infarction is unknown. This study was performed to determine the short-term morbidity and mortality secondary to cocaine-associated myocardial infarction. METHODS: We performed a retrospective cohort study at 29 hospital centers throughout the United States. Patients with cocaine-associated myocardial infarction that occurred between 1987 and 1993 were identified through record review. The primary outcome measures were in-hospital mortality and the incidence and timing of major cardiovascular complications. RESULTS: Cocaine-associated myocardial infarction was identified 136 times in 130 patients. Patients were generally young (mean age, 38 years), nonwhite (72%), tobacco smokers (91%) with a history of cocaine use in the past 24 hours (88%). The initial electrocardiogram disclosed infarction in 44% and ischemia in an additional 18% of patients. Myocardial infarctions were evenly distributed between anterior (45%) and inferior (44%) and were most often non-Q-wave (61%). Complications occurred 64 times in 49 patients (36%; 95% confidence interval, 28% to 44%), including congestive heart failure in nine patients, ventricular tachycardia in 23 patients, supraventricular tachycardia in six patients, and brady-dysrhythmias in 26 patients. Most patients who had complications (90%) had them within 12 hours of presentation. Acute in-hospital mortality was 0% (95% confidence interval, 0% to 2%). CONCLUSIONS: The mortality of patients hospitalized with cocaine-associated myocardial infarction was low. The majority of complications occurred within 12 hours of presentation.

Hollander JE. Hoffman RS.
Emergency Department, Bronx Municipal Hospital Center, Albert Einstein College of Medicine, NY 10461.
Cocaine-induced myocardial infarction: an analysis and review of the literature.
Journal of Emergency Medicine. 10(2):169-77, 1992 Mar-Apr.

The objectives of this paper are to analyze the case reports of cocaine-induced myocardial infarction and to better define the clinical characteristics of this syndrome. An English language literature search was carried out using MEDLINE, and a bibliographic review of all identified articles and book chapters was conducted. Ninety-one cases of cocaine-induced myocardial infarction were identified. Intranasal, intravenous, and inhalational routes of abuse all resulted in myocardial infarction. Fourty-four percent of patients had previously noted chest pain. Eighty-seven percent of patients were cigarette smokers. Two-thirds of patients had their myocardial infarction within 3 hours of the use of cocaine (with a range of 1 minute to 4 days). Cardiac catheterizations were abnormal in 30 of 54 patients (55%). Of the 24 patients with reported follow-up, 14 (58%) had further ischemic events after discharge. In conclusion, cocaine-induced myocardial infarction identifies a group of young individuals who may be prone to recurrent complications after initial presentation. [References: 59]

Clin Cardiol. 1995 Feb;18(2):67-72.
Cardiac complications of cocaine abuse.
Chakko S, Myerburg RJ.
University of Miami School of Medicine, Florida, USA.

Cardiac complications of cocaine abuse and a rational approach to evaluating and managing them are described. Cardiac abnormalities reported among asymptomatic cocaine abusers include echocardiographic left ventricular hypertrophy and segmental wall motion abnormalities. Electrocardiogram may reveal increased QRS voltage, ST-T changes, and pathologic Q waves. Episodes of ST elevation may be seen during Holter monitoring. The management of cocaine-abusing patients who present to an emergency room with acute chest pain is controversial because the two reported studies yielded conflicting results regarding the incidence of myocardial infarction (MI). Even in the absence of infarction, electrocardiographic abnormalities are common among these patients, which complicates the decision-making regarding hospitalization. Pathophysiology of cocaine-related MI is discussed. Distinct clinical features of cocaine-related MI make it clear that the association between the two is not just temporal. However, considering the number of persons abusing cocaine, it is a rarity. Beta-adrenergic blockers should be avoided in the treatment of cocaine-induced myocardial ischemia which is best treated with nitrates and calcium-channel blockers. Reports of cocaine-induced myocarditis and cardiomyopathy are reviewed. Experimental studies and clinical case reports suggest that cocaine may cause lethal arrhythmias. Cocaine prolongs repolarization by a depressant effect on potassium current and may generate early afterdepolarizations. It is possible that cocaine-associated arrhythmias are secondary to vasospasm-related ischemia and reperfusion as well.

Pharmacol Biochem Behav. 1996 Jun;54(2):343-54.
Possible novel pharmacodynamic action of cocaine: cardiovascular and behavioral evidence.
Tella SR.
Department of Pharmacology, Georgetown University School of Medicine, NW, Washington, DC 20007.

Intravenous cocaine (0.03-3 mg/kg) produced two distinct and temporally separable effects in rats. One is an initial, large, and brief increase in blood pressure (BP) and heart rate (HR) of a rapid onset (abrupt hemodynamic stimulation). A rapid, brief, and intense behavioral arousal accompanied this abrupt hemodynamic stimulation. The other effect of cocaine is a prolonged locomotor activation of a relatively slower onset. Prolonged increases in BP and HR accompanied this locomotor effect. The threshold doses of cocaine to produce abrupt hemodynamic stimulation and locomotion are 0.03 and 0.3 mg/kg, respectively. Dopamine receptor antagonists, SCH 23390 or eticlopride, at a 0.03 mg/kg dose antagonized the locomotion and the parallel prolonged increases in BP and HR, but not the initial brief behavioral arousal and abrupt hemodynamic stimulation responses to cocaine. Peripheral dopamine receptor antagonist, domperidone, altered neither behavioral nor cardiovascular effects of cocaine. Chlorisondamine (1 mg/kg), an autonomic ganglionic blocker, did not alter either the initial brief behavioral arousal or the locomotor responses to cocaine, but it prevented the cardiovascular changes that accompanied both these behavioral responses. Norepinephrine, a direct adrenergic vasoconstrictor, although produced rapid and large increase in BP, did not cause abrupt behavioral arousal or locomotor activation. Unlike cocaine, monoamine reuptake inhibitors that are selective for norepinephrine (nisoxetine, 0.1-1 mg/kg) or serotonin (fluoxetine, 0.3-3 mg/kg) produced neither brief behavioral arousal and abrupt hemodynamic stimulation nor locomotor activation. Dopamine-selective reuptake inhibitor, GBR 12,909, also did not elicit the initial brief behavioral arousal and abrupt hemodynamic stimulation. But, GBR 12,909, like cocaine, produced a prolonged locomotor effect and parallel increases in BP and HR. These effects of GBR 12,909 were prevented by SCH 23,390 and eticlopride, but not by domperidone. Similar to cocaine, cardiovascular, but not the locomotor effects of GBR 12,909 were prevented by chlorisondamine. Lidocaine (0.3-3 mg/kg), a sodium channel blocker and local anesthetic, produced neither behavioral nor physiological changes. Both cocaine (3 mg/kg) and GBR 12,909 (1 mg/kg) increased plasma norepinephrine and epinephrine concentrations. These increases were antagonized by both eticlopride and SCH 23,390. These results indicate that behavioral and cardiovascular effects of cocaine are intricately related with respect to the molecular mechanisms involved. Two pharmacodynamic actions of cocaine appear to mediate these effects. One is a dopamine-dependent while the other is a monoamine- and sodium channel-independent novel action. The former mediates cocaine's locomotor effect and the accompanying prolonged increases in BP and HR, while the latter mediates the initial brief behavioral arousal and the accompanying abrupt hemodynamic stimulation.

J Pharmacol Exp Ther. 1995 Feb;272(2):791-8.
Calcium channel blockers antagonize some of cocaine's cardiovascular effects, but fail to alter cocaine's behavioral effects.
Schindler CW, Tella SR, Prada J, Goldberg SR.
Preclinical Pharmacology Laboratory, Addiction Research Center, Baltimore, Maryland.

The effects of cocaine alone and in combination with the calcium channel blockers nimodipine, verapamil and diltiazem were determined for different groups of squirrel monkeys on cardiovascular function, schedule-controlled behavior and drug self-administration. Cocaine alone (0.3 mg/kg) produced increases in both blood pressure and heart rate. All three calcium channel blockers antagonized the pressor effect, but were ineffective against the tachycardiac effect of cocaine. Nimodipine was the most potent agent in antagonizing the pressor effect of cocaine. Response rates for monkeys responding on a second-order schedule of food presentation were increased by intermediate doses of cocaine (0.1-1.0 mg/kg) and were primarily decreased at a higher dose (3.0 mg/kg). Quarter-life values, an index of response patterning, were only decreased by cocaine. None of the calcium channel blockers altered cocaine's effects on either response rate or response patterning. In the self-administration experiments, the training dose of 56 micrograms/kg cocaine maintained high rates of responding on a simple fixed-ratio schedule. As with schedule-controlled behavior, none of the calcium channel blockers altered cocaine self-administration even when administered before self-administration sessions during 5 consecutive days. These results suggest that the calcium channel blockers may be useful in treating cardiovascular-related complications after cocaine use, but they would not be effective as long-term treatment agents for cocaine abuse.

J Vasc Surg. 2004 Aug;40(2):291-5.
Acute arterial thrombosis associated with cocaine abuse.
Zhou W, Lin PH, Bush RL, Nguyen L, Lumsden AB.
Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine & Methodist Hospital, Houston, TX 77030, USA.

PURPOSE: Cocaine-induced arterial thrombosis is uncommon, and most reported cases involved small-diameter vessels such as the cerebral and coronary arteries. This study was undertaken to review our experience with peripheral arterial thrombosis presumed caused by cocaine abuse. METHODS: Hospital records were reviewed for all patients admitted over 10 years with acute arterial occlusion involving the peripheral arterial system. Patients with confirmation of cocaine use or of its derivative, crack cocaine, within 24 hours of hospital admission formed the basis of this study. Symptoms at presentation, management, and outcome in these patients were reviewed. RESULTS: Three hundred eighty-two patients with acute peripheral arterial occlusion were identified during the study period. The presumptive diagnosis of cocaine-induced arterial occlusion was made in 5 patients (4 men, mean age 38 years). Cocaine use was achieved via intranasal inhalation in 2 patients (40%), whereas the 3 remaining patients smoked crack cocaine (60%). The mean time between cocaine use and onset of arterial thrombosis was 9.2 hours (range, 2-20 hours). Symptoms at presentation included acute limb ischemia without pedal Doppler signals (3 patients, 60%) and abdominal pain without femoral pulses (2 patients, 40%). Arterial occlusion was confirmed on angiograms in all patients, which revealed aortic thrombosis in 1 patient (20%), iliac thrombosis in 2 patients (40%), superficial femoral artery thrombosis in 1 patient (20%), and popliteal artery occlusion in 1 patient (20%). Surgical thrombectomy was successfully performed in 4 patients (80%), and 1 patient (20%) underwent successful thrombolytic therapy for femoropopliteal artery occlusion. There was no perioperative mortality. All 5 patients who were discharged were available for follow-up (mean, 36 months; range, 6-75 months). There was 1 late death from myocardial infarction. In 1 patient recurrent lower extremity arterial thrombosis developed after 28 months, which was successfully treated with thrombolytic therapy. CONCLUSIONS: Our study underscores cocaine abuse as a potential cause of acute arterial thrombosis. Cocaine-induced arterial thrombosis should be suspected in patients with recent history of cocaine abuse with acute limb ischemia without an identifiable source or overt cardiovascular risk factors. Prompt angiography with operative or endovascular intervention should be performed to avert arterial ischemic sequelae.

Forensic Sci Int. 2004 May 10;141(2-3):137-42.
Thoracic aortic dissection associated with cocaine abuse.
Palmiere C, Burkhardt S, Staub C, Hallenbarter M, Paolo Pizzolato G, Dettmeyer R, La Harpe R.
Institut de Medecine Legale, Centre Medical Universitaire, Universite de Geneve, 9 Avenue de Champel, 1211 Geneve 4, Switzerland.

Cardiovascular complications of cocaine abuse include myocardial ischemia and infarction, dysrhythmias, cardiomyopathies and aortic dissection. The case in point pertains to a 26-year-old, Caucasian male, substance abuser who suffered a thoracic aortic dissection following the use of crack cocaine. The autopsy and histological findings showed a connective tissue abnormality including a focal microcystic medial necrosis and a fragmentation of the elastic fibers in the arterial walls. Blood concentrations of cocaine and benzoylecgonine, taken individually, were considered to be within a potentially toxic range. Blood concentrations of methadone also indicated use of this drug at the same time. The small amounts of morphine found in the blood and urine were compatible with heroine or morphine use more than 24 h before death.

Back to E-chocardiography Home Page.

The contents and links on this page were last verified on June 11, 2005.