Cardiovascular Complications of Cocaine Abuse Payal Nanda Scotty Gadlin Ken Arney (aka Night Floaticians)

Introduction Cocaine is the 2nd most commonly used illicit drug in the U.S. In 2005, there were ~450,000 cocaine-related ED visits with 40% due to chest pain. Even casual use of cocaine is associated with cardiovascular toxicity. Cocaine use is associated with acute more often than chronic cardiovascular illness. Cocaine users can present with ACS, arrhythmias, myocarditis, aortic dissection and rupture, and hypertensive emergency. Therefore, identifying cocaine exposure is an important part of cardiovascular history-taking.

Cardiovascular Effects of Cocaine The major cardiovascular effects of cocaine are caused by inhibition of norepinephrine/dopamine reuptake into the synaptic cleft by sympathetic neurons. This inhibition results in potentiation of the response to sympathetic stimulation of innervated organs, causing a powerful sympathomimetic response. Also enhances the release of catecholamines from central and peripheral stores. Cocaine also promotes thrombus formation via activation of platelets and stimulation of platelet aggregability.

Cardiovascular Conditions Associated with Cocaine Use Myocardial ischemia/infarction Cardiomyopathy Myocarditis Arrhythmias Stroke Aortic dissection Coronary artery aneurysms

Myocardial Ischemia Most common complication; associated with all routes of cocaine intake Three proposed mechanisms: Increased myocardial oxygen demand Resulting from sympathomimetic actions of cocaine that increase myocardial inotropy, heart rate, and BP in dose-dependent manner Exacerbated by underlying CAD (e.g. fixed stenoses) Coronary vasoconstriction and spasm  decreased oxygen Cocaine constricts coronary vessels via stimulation of alpha-adrenergic receptors, increased endothelin-1, and decreased NO Coronary thrombosis Platelet activation/aggregation and premature atherosclerosis Most patients have no other cardiac risk factors

Myocardial Infarction Incidence of MI in cocaine-related chest pain is 0.5-5.7% Increased incidence in younger patients NHANES III study: 25% of nonfatal MIs were between ages of 18-45 MI is temporally related to cocaine use; two thirds of cases occur within 3 hours. Most MIs occur in absence of high-grade atherosclerotic coronary stenoses. Complications post-MI include heart failure and ventricular/supraventricular arrhythmias, typically occurring within first 12 hours (same as in non-cocaine induced infarctions).

Relative Risk of MI Onset After Cocaine Use

Cardiomyopathy Dilated CM is well-documented among cocaine users. Pathogenesis: Direct toxic effects on the heart, which lead to the destruction of myofibrils, interstitial fibrosis, myocardial dilation, and heart failure Hyperadrenergic state may produce contraction band necrosis in the heart Myocarditis and CM may be caused by infectious agents in patients who abuse cocaine parenterally via direct invasion of myocardium or stimulation of an autoimmune reaction Abstinence usually leads to complete reversal of myocardial dysfunction.

Arrhythmias Hyperadrenergic state can produce or exacerbate arrhythmias. Cocaine acts like a class I anti-arrhythmic agent, producing local anesthetic effects via sodium channel blockade in the heart. Sinus tachycardia/bradycardia Bundle branch block Vfib/Vtach/asystole Accelerated idioventricular rhythms SVTs Torsades de pointe Brugada pattern on EKG Rhythm disturbances are transient and disappear when the drug is metabolized.

Stroke Cocaine use significantly increases the risk of ischemic stroke via vasospasm from dopamine release, thrombus formation, and changes in cerebral vasculature (vasculitis). Subtle and severe neurologic deficits can occur Repetitive ischemic insults can lead to intracerebral and subarachnoid hemorrhage

Diagnosis Hx and physical exam: Young patient with hx of cocaine or polysubstance abuse who presents with chest pain, dyspnea, palpitations, agitation, or nausea Usually no other cardiac risk factors Toxicology screen EKG: STEMI, T-wave changes, arrhythmias, LVH, LAD Difficult to interpret in young patients who have a relatively high incidence of early repolarization changes and left ventricular hypertrophy. Up to 43% of cocaine abusers without an MI may have ST segment elevation ≥0.1 mV in two or more contiguous ECG leads. Because of the difficulty in identifying cocaine users with chest pain who are at low risk of infarction, most are admitted to the hospital. Serum markers: Troponins and CK-MB most sensitive and specific in cocaine-related MI

Management There are no well-designed, randomized, prospective clinical trials to compare treatment strategies for cocaine-associated myocardial ischemia

The Beta-Blocker Controversy Beta Blockers for Chest Pain Associated With Recent Cocaine Use Rangel, et.al. Archives of Internal Medicine 2010. Retrospective study of consecutive patients admitted to San Francisco General Hospital between 2001-2006. Chest pain and urine toxicology positive for cocaine The primary predictor was receipt of a B-blocker in the ED, and the primary outcome was death. Treatment of chest pain in the setting of recent cocaine use was not dictated by any established protocol, and B-blocker use was determined by the discretion of the treating physicians. 151 patients received B-blockers; IV metoprolol in 113 (74%), oral metoprolol in 17 (11%); the rest received labetalol, atenolol, or propranolol. There were no meaningful differences in EKG changes, troponin levels, length of stay, use of vasopressor agents, intubation, ventricular tachycardia/ventricular fibrillation, or death between those who did and did not receive a B-blocker. B-Blockers did not appear to be associated with adverse events in patients with chest pain with recent cocaine use. Over a median follow-up of 972 days, patients discharged on a beta-blocker regimen exhibited a significant reduction in cardiovascular death.

Outcomes with Beta-Blockers in Cocaine-Associated Chest Pain

Where the Crack At?

References McCord, et.al. Management of Cocaine-Associated Chest Pain and Myocardial Infarction: A Scientific Statement From the American Heart Association Acute Cardiac Care Committee of the Council Clinical Cardiology. Circulation 2008. Rangel, et.al. Beta-blockers for Chest Pain Associated with Recent Cocaine Use. Arch Intern Med. 2010. 170(10):874-879 UpToDate