Cardiology Conference

Rodney Samaan, MD, MPH 11/18/09

History
1884 Sigmund Freud publishes On Coca ; he recommends the use of cocaine in the treatment of various conditions 1886 Introduction of Coca-Cola: contains cocaine syrup

1895 First cases of associated deaths reported in the Lancet 1912 5000 cocaine related fatalities per year 1914 Harrison¶s Narcotics Act:"An Act To provide for the registration of, with

collectors of internal revenue, and to impose a special tax on all persons who produce, import, manufacture, compound, deal in, dispense, sell, distribute, or give away opium or coca leaves, their salts, derivatives, or preparations, and for other purposes."

1970¶s -80¶s Days of Glory Mid-80¶s Freebase cocaine

Onset and duration of action
ROUTE ONSET Seconds Inhalation or Iv 1-3 min Insufflation 20-30 60-90 DURATION PEAK (min) (min) 3-5 15-30

Pathophysiology
Cocaine users have elevated levels of C-reactive protein, von Willebrand factor, and fibrinogen that may also contribute to thrombosis Cocaine, therefore, causes myocardial ischemia or MI in a multifactorial fashion that includes: (1) increasing myocardial oxygen demand by increasing heart rate, blood pressure, and contractility; (2) decreasing oxygen supply via vasoconstriction; (3) inducing a prothrombotic state by stimulating platelet activation and altering the balance between procoagulant and anticoagulant factors; and (4) accelerating atherosclerosis.

Increased Prevalence of Coronary Artery Aneurysms Among Cocaine Users
Coronary artery aneurysms (CAAs), defined as aneurysmal dilatations >1.5 times the normal coronary segment, can be divided into discrete aneurysms (localized dilatation, either saccular or fusiform) or ectasia (diffuse dilatation involving 50% of the artery).

The incidence of CAA ranges from 0.2% to 5.3% with the largest antemortem series found in the Coronary Artery Surgery Study (CASS) registry (4.9% of 20 087 patients referred for coronary angiography). CAAs are most commonly associated with atherosclerosis but also are reported with Kawasaki¶s disease, arteritis (polyarteritis nodosa, syphilis, systemic lupus erythematosis, Takayasu¶s arteritis), mycoses, trauma, connective tissue disorders (Marfan¶s and Ehlers-Danlos syndromes), metastatic tumors, polycystic kidney disease After observing the presence of severe coronary ectasia in several young cocaine users, the authors hypothesized that cocaine use increases the prevalence of CAA The study population included 112 consecutive patients over a 10-year period with a history of cocaine use and coronary angiography. Of the patients with reliable documentation regarding frequency and method of cocaine abuse, 66% reported at least weekly use.

Cont
Sixty-nine percent reported smoking or intranasal use; 7%, intravenous use; and 24%, multiple routes of administration. To provide a control group, a cohort of 79 patients of similar age and risk factors was selected from a preexisting angiographic database of 300 consecutive patients within the time period of the study group.

To provide a similar age distribution, all patients <52 years of age were included, with cocaine use the only exclusionary criterion. Although the control group was similar in nearly all clinical characteristics, there was a higher rate of diabetes (33% vs 16%, p=0.01) in controls and a higher rate of cigarette smoking (95% vs 71%, p<0.001) in cocaine users. Indications for angiography among the cocaine users were as follows: 34% acute coronary syndromes, 20% stable angina/positive stress test, 27% congestive heart failure/cardiomyopathy, 16% atypical chest pain, and 4% arrhythmias/valvular disease. Indications for angiography among the control group included 47% acute coronary syndromes, 34% stable angina/positive stress test, 5% congestive heart failure/cardiomyopathy, 9% atypical chest pain, and 5% arrhythmias/valvular disease.

Hollander and al. Annals of emergency medicine 1994
Prevalence of cocaine use in patients older then 18 y presenting with CP 359 patients Anonymous urine collection on everybody Found 20 % prevalence in urban area Prevalence of 7% at the rural sites 28% of positives denied use

In the COCaine Associated CHest PAin (COCHPA) study, cocaine-associated MI occurred in 6% of patients who presented to the ED with chest pain after cocaine use Overall incidence of cocaine-associated MI varies between studies from 0.7% to 6% of those presenting with chest pain after cocaine ingestion (some of the variance may relate to differences in MI diagnostic criteria), cocaine appears to be an important contributor to MI among the young

Hollander JE, Hoffman RS, Gennis P, Fairweather P, DiSano MJ, Schumb DA, Feldman JA, Fish SS, Dyer S, Wax P, Whelan C, Schwartzwald E. Prospective multicenter evaluation of cocaine-associated chest pain. Cocaine Associated Chest Pain (COCHPA) Study Group. Acad Emerg Med. 1994; 1: 330±339.

Rich, Annals of EM, June 1991
Cocaine related Symptoms in patients presenting to the ED

146 patients Retrospective chart review Overall prevalence 16% for CP (23 patients) Total of 3 patients admitted Stronger association with nasal route (11/23)

Brody, Am. Journal of medicine, 1990
Cocaine-related medical problems

233 patients Retrospective chart review 40% prevalence of CP Most had acute complaints (3 h<) Overall mortality 1%

Prevalence studies-Cocaine MI

Timing Between Cocaine Use and Myocardial Infarction
Hollander JE, Hoffman RS. Cocaine-induced myocardial infarction: an analysis and review of the literature. J Emerg Med. 1992; 10: 169±177

Cocaine-associated MI appears to occur most often soon after cocaine ingestion. In one study, two thirds of MI events occurred within 3 hours of cocaine ingestion Survey of 3946 patients with recent MI, 38 patients admitted to cocaine use in the preceding year, and 9 patients reported ingestion in the 60 minutes preceding the onset of MI symptoms This survey reported a striking 24-fold higher risk of MI in the first hour after cocaine use, with a rapid decrease in risk after this time

Frequent vs non-frequent users
Third National Health and Nutrition survey 10 085 patients aged 1845 yo 731 infrequent users 532 frequent users ( about 5% of population) 46 non fatal MI¶s

Results: 1) OR 6.9 for *frequent users. CI95% 1.3 to 58 2) OR 0.1 infrequent users. CI95% 0.002 to 0.8 *More smokers, HTN

NHANES III ¶88-¶94

EKG
An abnormal ECG has been reported in 56% to 84% of patients with cocaine-associated chest pain; however, many of these patients are young and commonly have the normal variant of early repolarization, which may be interpreted by physicians as an abnormal ECG finding Gitter and colleagues reported an early repolarization pattern in 32% of patients with cocaine-associated chest pain, a left ventricular hypertrophy pattern in 16%, and a normal ECG in only 32% of patients.

Overall, 42% of patients in their cohort of 101 patients manifested electrocardiographic ST-segment elevation, although all of them eventually had MI excluded by cardiac marker testing

In the COCHPA (Cocaine Associated Chest Pain) study, the sensitivity of an ECG revealing ischemia or MI to predict a true MI was only 36%

Gitter MJ, Goldsmith SR, Dunbar DN, Sharkey SW. Cocaine and chest pain: clinical features and outcome of patients hospitalized to rule out myocardial infarction. Ann Intern Med. 1991;115:277±282.

Cardiac Biomarkers
Hollander, Am. J. of Cardiology, 1998

All studies reviewed using CK-MB Is the specificity of cardiac markers changed in cocaine users ? Answer: 1) Mildly for CK-MB ( 75% users vs 88% in non-users) 2) Troponin I : not affected (94% in both group)
Cocaine ingestion may cause rhabdomyolysis with consequent elevation in myoglobin and total creatine kinase levels, which may confound the diagnosis of cocaine-associated MI

Treatment
ASA Benzodiazepines Nitrates
- blockers

- blockers Calcium channel blockers Anticoagulants Reperfusion strategies

Benzodiazepines
Works by stimulation of GABA receptors Agent of choice to control agitation and other sympatomimetic symptoms Protects against seizures Anxiolytic effect Mechanism of action in cocaine-induced CP; more related to its neuro effects that subsequently affect the CVS (decrease adrenegic response) Decreases O2 requirements and workload No demonstrated effect on coronaries

Are benzos better then nitro in cocaine-induced chest pain?

Baumann, Acad. Emerg Med, 2000
Randomised double-blind placebo controlled study 40 patients, Diazepam, Nitro, or both Outcomes: chest pain score, vital signs and hemodynamic monitoring Results: - No difference between the 2 drugs - No beneficial effect of combination of both

Nitroglycerin
Standard of care in ACS Coronary vasodilator in ACS Experimental evidence of reversal of coronary vasospam caused by cocaine Good to lower BP No advantage over benzos ( Baumann 2000)

Calcium Channel blockers
This observation raises a question as to the role, if any, of calcium antagonists in cocaine toxicity Studies supporting the use of calcium channel blockers have been performed only in animal models Consistent with a local anesthetic mechanism of its toxic effects, calcium channel blockers have not been shown to reduce cocaine toxicity in humans Furthermore, they increase the lethality of cocaine. This additive lethality may result from the negative inotropic effects

Calcium channel blockers
Coronary artery vasodilator Decreases afterload One human study (10 patients) Conclusion: Cannot recommend routinely

Negus BH, Willard JE, Hillis LD, et al. Alleviation of cocaine-induced coronary vasoconstriction with intravenous verapamil. Am J Cardiol 1994;73:510-513

Beta Blockers
Controversy in the literature 2000 AHA TOX-ACLS recommendations: Good quality evidence to exclude non-selective -blockers Selective -blockers and mixed contraindicated / (labetalol) are not recommended but not

Propranolol exacerbates the depression of coronary blood flow induced by cocaine because of unopposed alpha stimulation after beta-blockade Esmolol is a selective beta1-adrenergic blocker with rapid onset and short duration of action (elimination half-life, 9 min) Coadministration of esmolol and sodium nitroprusside should be reserved for severe hypertension that is unresponsive to other treatment and/or complicated by aortic dissection

Beta Blockers
Third-line agent for drug-induced hypertensive emergencies However, labetalol, a combined alpha- and beta-blocking agent, has an alpha-to-beta blockade ratio of 1:7 Therefore, it may not provide enough protection for cocaine-toxic patients from (relatively) unopposed alpha stimulation Its risk of exacerbating myocardial ischemia parallels the risk of other beta-blockers

-Blockers
phentolamine
AHA 2000 : Class IIb Reverses vasoconstriction Based on animal and human studies No randomized clinical trials or safety studies

Hollander JE, Carter WA, Hoffman RS. Use of phentolamine for cocaineinduced myocardial ischemia. N Engl J Med 1992;327:361-361

Cocaine-associated VF
Cocaine activation of myocardial alpha-adrenergic receptors, specifically alpha1A-adrenergic receptors, may substantially contribute to VF during myocardial ischemia Activation of these receptors elevates cytosolic calcium levels and provokes delayed after-depolarizations Therefore, calcium overload may be the final common pathway linking enhanced adrenergic activity to cocaineinduced VF

Thrombolysis
Pros: - Improved mortality/morbidity in traditionnal AMI - Available in most centers

Thrombolysis
Cons - No proven benefit in cocaine-AMI - Risk of hemorrhage - Difficult EKG interpretation in this population

Thrombolysis- complications
Traditionnal AMI risk of intracranial bleed is 0.95% in a series of 71 000 AMI patients Reported thrombolysis complication rate for cocaine-related AMI is 0 to 12% (95%CI)

ACLS in cocaine users
Because of the similarity in the cardiovascular effects caused by cocaine and epinephrine, the administration of epinephrine to a patient who arrests in a hyperadrenergic state has been likened to pouring gasoline on a fire. In theory, vasopressin may offer considerable advantages over epinephrine in cardiac arrest secondary to cocaine toxicity 
The hyperadrenergic state caused by cocaine increases myocardial oxygen demand. Epinephrine has the same effect. Vasopressin, on the other hand, increases coronary blood flow, and thereby myocardial oxygen availablility

AHA Statement on Cocaine-Associated Chest Pain: Avoid Beta Blockers, DES
Cocaine increases the risk of myocardial ischemia by raising oxygen demand (via elevated heart rate, blood pressure, and cardiac contractility) and lowering supply (via vasoconstriction) as well as by promoting thrombosis. In general, the evaluation of patients with chest pain suspected of cocaine use is the same as for anyone with possible acute coronary syndrome (ACS). Patients should be stratified according to risk factors, such as positive ECG changes and cardiac troponin. Those at high risk should be assigned to monitored beds. Individuals in whom myocardial infarction (MI) has been ruled out need only be observed for 9 to 12 hours; their risk of underlying coronary artery disease or adverse cardiac events is low. Beta-Blockers Bad, Bare-Metal Good Use of beta blockers is contraindicated. Experimental models have shown that when cocaine is present, beta-adrenergic antagonists can lead to reduced coronary blood flow, increased risk of seizure, and increased mortality. Because only a small proportion of patients with cocaine-associated chest pain are actually having an MI, the established preference for PCI over fibrinolytics is even stronger. Case reports suggest cocaine may increase fibrinolytics¶ risk of intracranial hemorrhage. If PCI is performed, the authors suggest that ³very careful consideration´ be given to the likelihood that chronic cocaine users will not comply with long-term antiplatelet therapy.

Therefore, they recommend using a bare-metal stent over a drug-eluting one to reduce the

Conclusion
Chest pain is the most common chief complaint of cocaine users High prevalence of CAD and CAA in this population Up to 10% will have an acute coronary syndrome History and EKG may be misleading

Conclusion
Observe and obtain serial enzymes Treat keeping in mind the pathophysiology of cocaine related AMI, avoid BB, use BDZ Disposition: 12h observation period Close follow-up for stress-testing Treat the addiction Avoid DES and Thrombolysis

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