Acute myocardial infarction is the commonest cardiac consequence of cocaine use, followed by arrhythmia. There have been over 100 case reports of cocaine-induced acute myocardial infarction since the early 1980s. Preexisting coronary artery disease is not required: 33% of those with apparent cocaine-induced myocardial infarction had no coronary lesions at angiography. Those affected are relatively young (mean 34 years), male (90%), and have no history of note. The risk of cocaine-related infarction is maximal (between 24 and 31 times baseline) in the first hour after ingestion. However, recent prospective studies show the increase in lifetime risk vs nonusers to be much lower, approximately 6%.
The acute effects of cocaine are depressed myocardial contractility, decreased coronary diameter and flow, increased heart rate and blood pressure, electrical abnormalities (tachyarrhythmia, bradyarrhythmia, sudden death), ischemia, and myocardial infarction. Chronic use is associated with accelerated atherosclerosis (myocardial infarction in young patients) and severe cardiomyopathy.
Cardiotoxicity is due to the pharmacologic action of cocaine on excitable tissue, including reversible Na+ channel inhibition and diminished Na+ conductance (local anesthetic effect, cell membrane stabilization). Cocaine depresses myocyte depolarization velocity and action potential amplitude, reduces conduction velocity, and increases the effective refractory period. It also inhibits norepinephrine and dopamine reuptake by presynaptic neurons in the central and peripheral nervous systems, thus increasing sympathetic output and catecholamine activity (sympathomimetic effect). Stimulation of sympathetic central outflow leads to vasoconstriction and tachycardia. Cocaine stimulates a- and P-adrenoceptors, thus increasing the levels of the second messenger, cyclic adenosine monophosphate (cAMP), and hence those of cytosolic calcium. This induces a sustained action potential and hyperstimulation. Conduction is impaired, and reentry increases.
Cocaine increases the heart’s oxygen requirement while decreasing its supply (coronary vasoconstriction), thus promoting myocardial ischemia and/or infarction. It also increases platelet aggregation, which compounds the ischemic risk, not only in users with preexisting coronary disease, but in young people with normal coronary arteries. Myocarditis, endocarditis, and aortic rupture may also be present, together with hypothyroidism. Cardiac overload indices include elevated atrial natriuretic peptide levels, ventricular hypertrophy, and fibrosis (accumulation of type I and II collagen).
Marked myofibril loss and sarcoplasmic vacuolization suggest direct cardiomyotoxicity. These changes are not the result of ischemia, since the necrosis is usually limited and focal (even absent), involving single cells surrounded by an inflammatory infiltrate (as after doxorubicin). Coagulation myocytolysis is also present. Mitochondrial cardiotoxicity, due partly to acidosis, results from direct inhibition of the respiratory chain targeting the NADH dehydrogenase complex. Loss of Ca2+ homeostasis is due in part to the catecholamines, but also to a direct effect on sarcolemmal integrity, with the induction of myocyte necrosis, myocyte contraction bands, and catecholamine hypersensitivity. Certain genetic differences identified in rat a-adrenoceptors could account for differing susceptibilities to cocaine cardiotoxicity.