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Cocaine-Related Cardiomyopathy

  • Author: Michal Kazimir, MD; Chief Editor: Henry H Ooi, MD, MRCPI  more...
 
Updated: Dec 18, 2014
 

Overview

The fact that subacute, or even chronic, cardiomyopathy may result from the use of cocaine is being increasingly recognized. While most cases of cocaine-related cardiomyopathy have proved to be reversible, others have resulted in permanent cardiac dysfunction or death. However, because morbidity and mortality information associated with cocaine-related cardiomyopathy is based on case reports, it may be underreported. Many deaths in the drug abuse population are ascribed to drug toxicity without further attempts at defining the exact etiology.

Complications of cocaine use also include embolic disease (cerebral and in other organs). Ischemic stroke is seen in the highest frequency in the first few hours after cocaine use, likely due to a thrombogenic effect associated with platelet activation. However, stroke onset may be delayed as long as 1 week, possibly due to the formation of longer-acting secondary metabolites. Cerebral atrophy is also a known feature of chronic cocaine use.

Patient Education

The patient should be educated regarding the absolute necessity of abstinence from cocaine. For patient education information, see Cocaine Abuse, Drug Dependence and Abuse, and Substance Abuse.

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Cardiac Effects of Cocaine

The effect of cocaine on cardiac muscle and coronary vessels remains poorly understood. In acute cocaine exposure, the vasoconstrictive action of the drug seems to have the predominant effect. Coronary vasoconstriction resulting in myocardial ischemia or infarction and systemic vasoconstriction resulting in hypertension or organ ischemia (particularly cerebral) are observed.[1]

Cocaine is known to block the reuptake of norepinephrine and dopamine at preganglionic sympathetic nerve endings, and this action by the drug is presumed to cause the increase in heart rate and blood pressure and the acute vasospastic syndromes observed in individuals who use cocaine.

Moreover, pathologic similarities between cocaine-related cardiomyopathy and cardiomyopathy associated with pheochromocytomas suggest that chronic adrenergic stimulation may play a role in the development of cocaine-related cardiomyopathy.

Cocaine inhibits the transient inward flux of sodium across the cell membrane during depolarization and causes local anesthesia. Neurotransmitters released from cardiac sympathetic nerves bind to alpha- and beta-adrenergic receptors, eliciting a cascade of intracellular responses. Beta-adrenergic stimulation activates adenylate cyclase, which increases cyclic adenosine monophosphate (AMP) levels and causes increased calcium influx into myocardial cells. The resultant increased intracellular levels of free calcium, including calcium released from cytosolic stores, results in increased force of contraction of the myocyte.

Alpha-adrenergic receptor stimulation produces a cascade of second messenger systems that subsequently regulate calcium channels and in turn elicit increases in cytosolic calcium. Elevated cytosolic calcium can provoke oscillatory depolarizations of the cardiac membrane and trigger sustained action potential generation and extra systoles.

Cellular effects that have been suggested include changes in calcium flux that are similar to those of other cardiac toxins, including digoxin. Increased intracellular concentrations of calcium have been suggested as a cause of depolarization of the cardiac membrane and, therefore, a trigger of sustained action potentials, extra systoles, and tachycardia (sinus, supraventricular, or ventricular). This effect may be present with acute cocaine use. Also, a high concentration of calcium may decrease myofilament responsiveness.

Oxidative stress and mitochondrial dysfunction have been implicated in cocaine-related cardiomyopathy.[2, 3] In male Wistar rats injected with cocaine to produce left ventricular dysfunction, Isabelle et al prevented cocaine-related cardiomyopathy with administration of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and xanthine oxidoreductase inhibitors, thereby preventing excess production of reactive oxygen species.[2]

Decreased calcium concentrations may occur later in the course of cocaine use and result in depressed myocardial function. A local anesthetic action is also observed, similar to lidocaine, which can acutely depress myocardial contractility.

Several studies demonstrate that chronic cocaine use has a direct depressive effect on left ventricular function. This effect seems to be independent of myocardial blood flow and coronary artery diameter. Long-term cocaine use has been associated with regional left ventricular diastolic dysfunction when analyzed by magnetic resonance imaging (MRI).

Regarding the subacute and chronic cardiomyopathies, a clear association has been made between ischemic cardiomyopathy and cocaine use. Regional wall motion abnormalities can be observed, even in patients with no history of myocardial infarction. This syndrome is characterized by evidence of multiple infarcts with normal coronary arteries upon catheterization. This is presumed to be present because of vasospasm or thrombosis. Cocaine use has been shown to increase platelet aggregation and lead to thrombus formation.

Chronic cocaine use has been estimated to increase left ventricular muscle mass by up to approximately 70% without associated increases in arterial blood pressure, heart rate, renin, aldosterone, or cortisol. This has been related to an increase in cardiomyocyte protein content by protein kinase C alpha ̶ dependent mechanisms, leading to cardiomyopathy and cardiac hypertrophy.

Cardiac failure due to multiple infarcts is distinct from true cocaine-related cardiomyopathy. Cocaine-related cardiomyopathy shows global myocardial dysfunction. Both entities may be associated with normal coronary arteries or minimal atherosclerotic disease. The situation is further complicated by reports of left ventricular aneurysm formation with embolization in patients with cocaine-related cardiomyopathy. Whether these cases represent cocaine-related cardiomyopathy or ischemic cardiomyopathy due to cocaine is unclear. The presence of both entities in the same patient also is theoretically possible.

Contributing factors

Other agents, particularly adulterants in street cocaine, such as arsenic and magnesium, have been suggested as contributing to cocaine-related cardiomyopathy. Vitamin deficiencies associated with the use of street drugs have also been suggested as contributing factors.

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Epidemiology

The 2005 National Survey on Drug Use and Health[4] reported that approximately 33.7 million Americans aged 12 years and older (13.8% of Americans in that age group) had tried cocaine at least once. In 2005, 2.4 million persons were actively using cocaine.

The reports of cardiomyopathy are case reports, which would seem to imply that it is an infrequent result of cocaine use and may represent an idiosyncratic reaction. However, the true incidence of cardiomyopathy may be substantially underreported. Felker et al reported 1278 cases of dilated cardiomyopathy treated at Johns Hopkins; only 10 cases were ascribed to cocaine use.[5] Bertolet et al reported that in a group of chronic cocaine users studied who did not have cardiac symptoms, 7% had left ventricular systolic dysfunction shown by radionuclide angiography.[6] No cases of cardiomyopathy have been reported following therapeutic use of cocaine.

The age distribution of cocaine-related cardiomyopathy generally follows the age distribution of cocaine use. Most cases are reported in the 30- to 40-year-old age group, with additional patients being somewhat older and somewhat younger.

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Patient History

A cocaine-related etiology for cardiomyopathy should be suspected in any patient with a history of cocaine use, particularly binge use, and heart failure, without another established etiology for the heart failure, such as coronary artery disease. While direct questioning of the patient may yield the necessary drug-use information, if the clinical suspicion is high, the diagnosis of cocaine use should be investigated further, perhaps with a urine screen for cocaine and its metabolites.

Patients who use cocaine may have various symptoms referable to the cardiac system. Symptoms can include chest pain with or without myocardial ischemia or aortic dissection, hypertension with or without hypertensive crisis, cerebral ischemia, and hemorrhage. Symptoms of headache and stroke may occur. Patients also may present with acute myocardial decompensation with or without pulmonary edema and shock. In this case, shortness of breath and hypoperfusion dominate the clinical picture.

A study by Chang et al determined that cocaine users who have low to intermediate probability of developing an acute coronary syndrome do not have any increased risk for developing coronary artery disease.[7] As a result, other factors and past medical history are necessary for determining the probability of coronary disease development.

Myocardial ischemia or infarct

Symptoms of chest pain may be of muscular origin but may represent ischemia or infarct. Associated symptoms of myocardial ischemia/infarct usually are present, including diaphoresis, nausea/vomiting, dyspnea, and a sense of impending catastrophe. In patients presenting with chest pain, aortic dissection also should be considered.

Congestive heart failure

The symptoms of cocaine-related cardiomyopathy are the same as symptoms for other forms of congestive heart failure. The onset may be very sudden and of short duration.

A history of myocardial infarction (due to cocaine-induced vasospastic ischemia) may be present but often is absent. Symptoms of chronic congestive heart failure usually are absent, but a history of prior congestive heart failure related to cocaine use may be present.

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Physical Examination

Although older and younger patients are common, patients in case reports of cocaine-related cardiomyopathy usually are aged 30-40 years. This is younger than would be expected for a diagnosis of ischemic cardiomyopathy, but viral, toxic, or idiopathic etiologies (including postpartum) are well within this age range. Older patients should be considered if other etiologies are not apparent.

Acute adrenergic findings

Cocaine intoxication usually presents with symptoms of adrenergic excess. Hypertension, occasionally in the range of hypertensive crisis, may be present. Cerebral vascular accidents of either thrombotic or hemorrhagic origin are not uncommon. Acute delirium and mania may be present, particularly if other drugs were used concurrently.

Tachycardia and arrhythmias also occur, particularly atrial fibrillation and premature ventricular contractions. Ventricular tachycardia and fibrillation are observed as well. Acute chest pain syndromes are common and may be due to chest wall pain syndromes or acute myocardial ischemia or infarct.

Finally, an increased incidence of aortic dissection and rupture occurs and must be included in the differential diagnosis. The clinician should search for the appropriate physical findings in these cases.

Findings of acute congestive heart failure

With acute binge use of cocaine, the patient may present with acute congestive heart failure and pulmonary edema. Hypotension, rather than hypertension, may predominate, making the diagnosis and treatment more difficult.

Cocaine-related cardiomyopathy presents more acutely than other types of congestive heart failure, and fewer findings of chronic congestive heart failure are present. Otherwise, the physical findings are similar. Diaphoresis, pallor, and acute dyspnea are present. Cardiogenic shock or evidence of cardiac ischemia also may be present.

Endocarditis

Bacterial endocarditis may accompany cocaine use if the drug was used intravenously. For unknown reasons, cocaine use has been observed as a greater independent risk factor for the development of endocarditis when compared with the use of other drugs. Endocarditis associated with cocaine abuse has been observed to involve left-side cardiac valves more often, which is contrary to endocarditis associated with other drugs. The clinician should search for evidence of valvular dysfunction, possibly acute, and embolic disease.

Findings related to drug abuse

If cocaine has been used intranasally, septal perforation and other signs of cocaine abuse may be present. Needle tracks and other skin changes may be seen, consistent with intravenous (IV) drug use. Psychologic changes, with paranoid ideation, may be present and may make management more difficult.

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Laboratory Studies

The laboratory investigation of cardiomyopathy of any etiology generally shows abnormalities of electrolytes and compromised renal function, with elevation of blood urea nitrogen (BUN) and creatinine.

Cocaine usually is evident on a urine toxicology screen, because these cases almost always present immediately after use of the drug. Because individuals who use cocaine are predisposed to the development of endocarditis, consider blood cultures if the setting is at all appropriate.

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Imaging Studies

In cases of cardiomyopathy, the chest radiograph usually shows evidence of cardiomegaly and congestive heart failure. Evidence of septic emboli may be present if endocarditis is present. The radiograph may be normal in many cases.

Echocardiographic evaluation shows chamber dilation and global dysfunction or regional wall motion abnormalities if myocardial infarction is present. Echocardiographic studies have shown that individuals who abuse cocaine have an increased left ventricular mass index with a higher tendency toward increased posterior wall thickness.

Cardiac catheterization usually shows normal coronary arteries or only minimal disease, even in the presence of myocardial infarction.

In acute chest pain syndromes, the electrocardiogram (ECG) may show evidence of acute ischemia or infarction. In cases of cardiomyopathy, the ECG is not specific but may show evidence of left ventricular hypertrophy and nonspecific ST-T wave changes. Arrhythmias also may be detected, and continuous monitoring may be advisable.

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Histologic Findings

Chokshi et al were among the first authors to describe a reversible cocaine-related cardiomyopathy. The patient in their report, a 35-year-old woman, underwent endomyocardial biopsy that failed to reveal any necrosis, fibrosis, or inflammatory infiltrate.[8]

In autopsies of 40 patients, 31 of whom died cocaine-related deaths and 9 of whom were homicide victims with detectable blood cocaine levels, Virmani et al found that 20% of the patients showed evidence of myocarditis on toxic screening tests.[9] Tazelaar, in an autopsy study, reported contraction-based myocardial necrosis similar to that observed in pheochromocytoma.[10]

In a case report by Robledo-Carmona, histologic findings of the left ventricular myocardium included sparse mononuclear infiltrates associated with degenerative changes, myocyte necrosis, and severe interstitial fibrosis.[11]

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Treatment for Hypertension

Patients who present with hypertension may require no treatment except monitoring and the occasional use of benzodiazepines for sedation. In some cases, however, hypertension may be more severe, and patients may require treatment for hypertensive crisis. This should include IV vasodilators and, occasionally, diuretics.

Nitroglycerin is particularly useful if evidence of myocardial ischemia is present. If sympathetic blockers are needed (arrhythmia or ischemia), beta blockers should not be used as the sole agents, because this may lead to unopposed alpha activity and may worsen hypertension. An alpha blocker or ganglionic blocker may be used in conjunction with beta blockers.

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Treatment for Myocardial Ischemia

Chest pain is a common presentation in patients who use cocaine; this may be secondary to either myocardial ischemia or chest wall pain syndromes of other etiologies. An electrocardiographic evaluation is required in all such cases to aid in differentiating these possibilities.

If myocardial ischemia without ST segment elevation is present, the patient should receive nitroglycerin, preferably intravenously. Narcotics also may be helpful if relief cannot be obtained with nitroglycerin.

If an ST elevation is present, prompt cardiac catheterization should be performed. If that is not available, thrombolytic therapy should be considered. However, special care must be taken to exclude aortic dissection and intracranial bleeding, both of which are associated with cocaine use.

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Treatment for Congestive Heart Failure

Treatment consists of the standard therapy for congestive heart failure, ie, diuretics and vasodilators as tolerated. If shock is present, inotropic agents and vasopressors are indicated.

If evidence of ongoing ischemia is present, aggressive use of agents directed at relieving vasospasm (nitrates and calcium channel ̶ blocking drugs) are indicated. Endotracheal intubation may be necessary. If arrhythmias are present and are felt to be compromising the clinical situation, they should be treated aggressively. The use of beta-blocking drugs as single agents is contraindicated.

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Additional Treatment Considerations

Because many patients with cocaine-related cardiomyopathy must be treated for shock and because appropriate fluid management is difficult in this setting, a pulmonary artery line frequently is placed. An arterial line may be placed in order to adequately manage blood pressure. The use of an intra-aortic balloon has been described, in order to bridge the gap until cardiac function can improve.

Endocarditis may be present if the patient was using cocaine intravenously, and this should be considered if the patient’s condition does not improve as anticipated. Other complications of drug use also should be considered (eg, hepatitis, human immunodeficiency virus [HIV] infection).

As improvement occurs, treatment should be tapered. Withdraw pressor and inotropic agents, and transfer the patient from IV to oral diuretics and vasodilators. At the time of hospital discharge, some patients may require no therapy at all.

Cocaine cessation

In most of reported cases of cocaine-related cardiomyopathy, patients have shown significant improvement following the cessation of cocaine use. In some cases, patients have returned to normal cardiac function, but recurrence is reported if the patient relapses into cocaine use.

Efforts to assist the patient with their drug addiction should be a part of every treatment plan. Hospitalization for detoxification may be necessary, particularly if other drugs also are being abused. Outpatient treatment of drug dependence is strongly advised. Abstinence from cocaine use is mandatory.

Consultations

Consultation with a cardiologist is advisable. Consultation with a psychiatrist is advisable as well, for assistance with drug abuse treatment issues.

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Outpatient Care

Diuretics or vasodilators (angiotensin-converting enzyme [ACE] inhibitors) may be helpful in some cases but are not always needed. Therapy is highly individualized, because the severity of the residual cardiac dysfunction is quite variable. Consider issues of compliance. The use of beta blockers, which would ordinarily be considered in the treatment of congestive heart failure, probably should be avoided.

Outpatient treatment of drug abuse issues is of extreme importance, and every effort should be made to assist the patient in this regard. Recurrent congestive heart failure has been reported in patients who return to cocaine use.

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Contributor Information and Disclosures
Author

Michal Kazimir, MD Staff Physician, Department of Internal Medicine, Lutheran Medical Center

Michal Kazimir, MD is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Heart Association

Disclosure: Received ownership interest from Drogue Medical, LLC for management position.

Coauthor(s)

James V Talano, MD, MBA MM, FACC, FAHA, Director of Cardiovascular Medicine, SWICFT Institute

James V Talano, MD, MBA is a member of the following medical societies: American College of Cardiology, Heart Failure Society of America, Society of Geriatric Cardiology, American Society of Nuclear Cardiology, American College of Chest Physicians, American Association for Physician Leadership, American College of Physicians, American Heart Association, American Society of Echocardiography

Disclosure: Nothing to disclose.

Shelah Hayes, EMT University of Colorado Denver

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Henry H Ooi, MD, MRCPI Director, Advanced Heart Failure and Cardiac Transplant Program, Nashville Veterans Affairs Medical Center; Assistant Professor of Medicine, Vanderbilt University School of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Gary Edward Sander, MD, PhD, FACC, FAHA, FACP, FASH Professor of Medicine, Director of CME Programs, Team Leader, Root Cause Analysis, Tulane University Heart and Vascular Institute; Director of In-Patient Cardiology, Tulane Service, University Hospital; Visiting Physician, Medical Center of Louisiana at New Orleans; Faculty, Pennington Biomedical Research Institute, Louisiana State University; Professor, Tulane University School of Medicine

Gary Edward Sander, MD, PhD, FACC, FAHA, FACP, FASH is a member of the following medical societies: Alpha Omega Alpha, American Chemical Society, American College of Cardiology, American College of Chest Physicians, American College of Physicians, American Federation for Clinical Research, American Federation for Medical Research, American Heart Association, American Society for Pharmacology and Experimental Therapeutics, American Society of Hypertension, American Thoracic Society, Heart Failure Society of America, National Lipid Association, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Camille Michals, LSW,to the development and writing of the source article.

References
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  2. Isabelle M, Vergeade A, Moritz F, Dautreaux B, Henry JP, Lallemand F, et al. NADPH Oxidase Inhibition Prevents Cocaine-Induced Up-Regulation of Xanthine Oxidoreductase and Cardiac Dysfunction. J Mol Cell Cardiol. 2007. 42:326-332. [Medline].

  3. Liaudet L, Calderari B, Pacher P. Pathophysiological mechanisms of catecholamine and cocaine-mediated cardiotoxicity. Heart Fail Rev. 2014 Nov. 19(6):815-24. [Medline].

  4. US Department of Health and Human Services. Substance Abuse and Mental Health Services Administration, Results from the 2005 National Survey on Drug Use and Health: National Findings. September 2006. [Full Text].

  5. Felker GM, Hu W, Hare JM. The spectrum of dilated cardiomyopathy. The Johns Hopkins experience with 1,278 patients. Medicine (Baltimore). 1999 Jul. 78(4):270-83. [Medline].

  6. Bertolet BD, Freund G, Martin CA. Unrecognized left ventricular dysfunction in an apparently healthy cocaine abuse population. Clin Cardiol. 1990. May;13(5):323-8.

  7. Chang AM, Walsh KM, Shofer FS, McCusker CM, Litt HI, Hollander JE. Relationship between cocaine use and coronary artery disease in patients with symptoms consistent with an acute coronary syndrome. Acad Emerg Med. January 2011. 18:1-9. [Medline]. [Full Text].

  8. Chokshi SK, Moore R, Pandian NG. Reversible cardiomyopathy associated with cocaine intoxication. Ann Intern Med. 1989 Dec 15. 111(12):1039-40. [Medline].

  9. Virmani R, Robinowitz M, Smialek JE, Smyth DF. Cardiovascular effects of cocaine: an autopsy study of 40 patients. Am Heart J. Jun 1989. 117(6):1298-9. [Medline].

  10. Tazelaar HD, Karch SB, Stephens BG. Cocaine and the heart. Hum Pathol. 1987 Feb. 18(2):195-9. [Medline].

  11. Robledo-Carmona J, Ortega-Jimenez M, Garcia-Pinilla J, Cabra B, de Teresa E. Severe Cardiomyopathy Associated to Cocaine Abuse. Int J Cardiol. 2006. 112:130-131. [Medline].

 
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