Epidemiologic studies have consistently shown that light to moderate alcohol consumption is associated with reduced morbidity and mortality from coronary heart disease (CHD) (1). However, higher levels of alcohol use can be cardiotoxic and contribute to hypertension, arrhythmias, and cardiomyopathy and ultimately lead to increased cardiovascular disease (CVD). In addition, other disease endpoints, including cancer, cirrhosis, and accidental and violent death, are increased at higher levels of alcohol consumption. This J-shaped relationship between alcohol intake and survival has been extensively described (2).

Approximately 63% of the U.S. population consumes alcohol, and approximately one tenth of these are considered heavy drinkers. The prevalence of alcohol consumption differs by gender and by age, and is higher in men and in younger individuals (3). Among the identifiable etiologies of nonischemic dilated cardiomyopathy (DCM) in the United States, alcohol is the most common in both sexes and all races, accounting for almost half of all cases (4). Furthermore, excessive alcohol intake is reported in 3% to 40% of patients with otherwise unexplained idiopathic DCM (5). With early detection and abstinence from further alcohol, cardiac function can recover in some cases (6,7).

Specimens from autopsies and biopsies of alcoholic hearts have shown varying degrees of morphologic abnormalities, depending on the stage and progression of the disease. During the preclinical phase, left ventricular (LV) dilation and a normal or moderately increased LV mass may be seen. Some patients may also have wall thickening, which may offset the LV dilation and lead to a compensated, asymptomatic state. With progression of the disease, varying degrees of cardiomegaly reflecting chamber dilation are seen, particularly when there is concomitant mitral insufficiency. On gross observation, the heart appears flabby, large, and pale (4).

The exact pathogenesis of alcoholic cardiomyopathy is incompletely understood. At a microscopic level, alcohol affects mitochondrial structure and function, which can be observed on biopsy (8). Changes in the sarcoplasmic reticulum, contractile proteins, and calcium homeostasis also contribute to myocardial cell dysfunction (4).

Acutely, ethanol ingestion exerts a transient direct toxic effect on cardiac performance, acting as a negative inotrope (9,10,11). Increased autonomic activity may lead to a modest increase in heart rate (10). Because these actions of alcohol tend to have opposing effects, overt evidence of hemodynamic derangements from alcohol can be minimal in healthy individuals. Still, asymptomatic cardiac dysfunction may be present even in healthy “social drinkers” who consume smaller quantities of alcohol (12).

The transient negative inotropic effect on myocardial function can become permanent with chronic consumption. In addition, chronic users often exhibit greater hemodynamic derangements from alcohol, especially in the setting of underlying cardiac disease. Increased diastolic stiffness, possibly due to accumulation of myocardial collagen in the extracellular matrix, may contribute to clinical presentations of the alcoholic heart. The role of ethanol in the accumulation of collagen can be enhanced by the use of tobacco (13), which is a common coaddiction. With both acute and chronic ingestion, abnormalities in myofibrillar protein turnover can contribute to myocardial damage, perhaps with involvement of oxidative stress (14). Reactive oxygen species may impair myocyte function by interfering with calcium handling (4). Toxic effects of acetaldehyde and fatty acid ethyl esters, metabolites and byproducts of alcohol, may also potentiate myocardial damage via impairment of mitochondrial oxidative phosphorylation (9).

Alcohol-induced hypertension also contributes to chronic myocardial dysfunction in chronic drinkers, in a dose-related fashion (15,16,17,18). Individuals who drink more than two
alcoholic beverages per day have twice the incidence of hypertension compared with nondrinkers (19).

Thiamine deficiency is another factor contributing to alcoholic cardiomyopathy in many instances. Approximately 15% of asymptomatic alcoholics are moderately deficient in thiamine (20). The physiologic derangements seen in beriberi heart disease, however, are different from those seen in alcoholic cardiomyopathy, and include a hyperdynamic state with decreased peripheral vascular resistance, increased cardiac output, tachycardia, and biventricular failure (21).

Finally, some alcoholic beverages contain additives such as cobalt that may be directly cardiotoxic (22).