eMedicine Specialties > Cardiology > Myocardial Disease and Cardiomyopathies

Cardiomyopathy, Cocaine

Author: Michal Kazimir, MD, Staff Physician, Department of Internal Medicine, Lehigh Valley Hospital
Coauthor(s): Paul A Janson, MD, Instructor, Tufts University School of Medicine; Director, EMT/RN Consultants; Consulting Staff, Department of Emergency Medicine, Lawrence General Hospital; James V Talano, MD, MM, FACC, Director of Cardiovascular Medicine, SWICFT Institute; Carla Vaccaro, MD, Consulting Staff, Department of Family Practice, Merrimack Family Medicine
Contributor Information and Disclosures

Updated: Mar 24, 2008

Introduction

Background

Cocaine abuse is a significant problem in the United States and worldwide. The effects of this epidemic are numerous, including medical, psychosocial, and economic. Among the medical consequences, the cardiac effects of cocaine use are well described. Most of the information deals with acute toxicity. However, the fact that subacute or even chronic cardiomyopathy may result from the use of cocaine is being increasingly recognized. While most cases have proved to be reversible, others have gone on to result in death or permanent cardiac dysfunction.

Pathophysiology

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 be the predominant effect. Both coronary vasoconstriction resulting in myocardial ischemia or infarction and systemic vasoconstriction resulting in hypertension or organ ischemia (particularly cerebral) are observed. Cocaine is known to block the reuptake of norepinephrine and dopamine at preganglionic sympathetic nerve endings, and this action of cocaine is presumed responsible for the increase in heart rate and blood pressure and the acute vasospastic syndromes observed in individuals who use cocaine. Pathologic similarities between cocaine cardiomyopathy and those seen in pheochromocytomas suggest that chronic adrenergic stimulation may play a role in the development of cocaine 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 both alpha and beta adrenergic receptors, eliciting a cascade of intracellular responses. Beta-adrenergic stimulation activates adenylate cyclase, which increases cyclic AMP levels and causes increased calcium influx into myocardial cells. The resultant increased intracellular free calcium levels, including increased release from cytosolic stores, results in increased force of contraction of the myocyte. Alpha-adrenergic receptor stimulation produced 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 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 has been implicated as an early triggering event of cocaine-induced cardiomyopathy. Experiments by Isabelle et al used male Wistar rats injected with cocaine to produce left ventricular dysfunction.¹  This cocaine-induced cardiomyopathy was prevented by administration of NADPH oxidase and xanthine oxidoreductase inhibitors, thus preventing excess production of these reactive oxygen species.

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 MRI.

Regarding the subacute and chronic cardiomyopathies, a clear association has been made with 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 increasing cardiomyocyte protein content by protein kinase C alpha-dependent mechanisms, which leads to cardiomyopathy and cardiac hypertrophy.

Cardiac failure due to multiple infarcts is distinct from true cocaine cardiomyopathy. Cocaine 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 cardiomyopathy. Whether these cases represent cocaine cardiomyopathy or ischemic cardiomyopathy due to cocaine is unclear. The presence of both entities in the same patient also is theoretically possible.

Frequency

United States

Cocaine use in the United States has been reported to be as high as 5 million regular users, with as many as 30 million with a history of past use.

The 2005 National Survey on Drug Use and Health² reported approximately 33.7 million Americans aged 12 and older (13.8% of Americans in that age group) tried cocaine at least once. In 2005, 2.4 million persons currently used 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.

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.³ Bertolet et al reported that 7% of chronic cocaine users without cardiac symptoms have left ventricular systolic dysfunction shown by radionuclide angiography.⁴

Mortality/Morbidity

The morbidity and mortality associated with cocaine-induced cardiomyopathy is based on case reports and therefore may be underreported. Many deaths in the drug abuse population are ascribed to drug toxicity without further attempts at defining the exact etiology.

Race

At present, no increased susceptibility has been reported in any racial group.

Sex

No sexual predilection has been reported.

Age

The distribution of cocaine cardiomyopathy generally follows the 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.

Clinical

History

Patients who use cocaine may have a variety of symptoms referable to the cardiac system. Symptoms may include chest pain with or without myocardial ischemia or aortic dissection, hypertension with or without hypertensive crisis, cerebral ischemia, and hemorrhage. This may result in symptoms of headache and stroke. 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.

• 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.
• Symptoms of congestive heart failure
  • The symptoms of cocaine cardiomyopathy are the same as symptoms for other forms of congestive heart failure. The onset may be very sudden and of short duration.
  • Many patients present in shock and require intubation and vasopressors at the time of presentation.
  • 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.
• History of cocaine use
  • A history of cocaine use is a requirement for establishing the diagnosis. This etiology of cardiomyopathy should be suspected in any patient with a history of cocaine use, particularly binge use, and heart failure without another established etiology such as coronary artery disease.
  • The clinician should suspect this in any patient with appropriate presentation, particularly in a patient who is younger than would be expected to have atherosclerotic cardiovascular disease.
  • Evidence of drug use (needle tracks, perforated nasal septum) should raise clinical suspicion.
  • While direct questioning of the patient may yield the necessary 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.
• Appropriate age
  • Patients in the case reports usually are aged 30-40 years, although both older and younger patients are common. 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.

Physical

• 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 also are observed. 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 also 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, the patient may present with acute congestive heart failure and pulmonary edema. Hypotension, rather than hypertension, may predominate and makes the diagnosis and treatment more difficult.
  • Cocaine 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.
• 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 drug use.
  • Psychologic changes of paranoid ideation may be present and may make management more difficult.
• 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.

Causes

• Cocaine use is the principal cause, and the diagnosis cannot be made in its absence. Other contributing etiologies have been suggested, including contaminants and vitamin deficiencies associated with use of "street" drugs.
• Adulterants
  • No cases have been reported following therapeutic use of cocaine.
  • Other agents, particularly adulterants in the street drug, have been suggested as contributing to this syndrome, including arsenic, magnesium, and others.

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