Varied Cardiac Abnormalities in Alcoholics Timothy J. Regan, M.D. and Philip 0. Ettinger, M.D. The toxic effects of acute or chronic use of alcohol on cerebral and hepatic function have long been recog nized, but it has been thought that the heart was not similarly affected. This study reexamines this tradk tional thought and Indicates that ethyl aicohol may have chronic toxic effects on the cardiovascular system.

HE toxic effects of acute or chronic ethyl T alcohol use on cerebral and hepatic function have long been recognized. It has been traditionally thought that the heart was not similarly affected. In fact, alcohol, at least in modest amounts, was commonly viewed as a medicinal agent. Appearance of heart disease in an alcoholic individual usually was attributed to underlying heart disease of rheumatic, hypertensive, or coronary etiology, often without good supporting evidence. When the specific entity of beriberi heart disease was associated with alcoholism, the patient was treated for thiamine deficiency, frequently with success. Consequently, correction of malnutrition was considered the major therapeutic modality in alcoholic patients with heart disease. CARDIAC EPIDEMIOLOGY

A number of recent observations have indicated, however, that ethyl alcohol may have chronic toxic effects on the cardiovascular system. An epidemiologic survey of industrial workers in Chicago revealed that problem drinkers had a significantly higher 15-yr mortality rate from cardiovascular diseases and sudden death than nonaddicted individuals. This difference was not attributable to the traditional cardiac risk factors.' Although there was no significant difference in the alcoholic and nonalFrom the Department of Medicine, College of Medicine and Dentistry of New Jersey-New Jersey Medico1 School, Newark, N. J. Supported in part by Reseorch Grani AA00242 from the National Institute on Alcohol Abuse ond Alcoholism and Postgraduate Training Grant H L 05510 from the National Heart, Lung and Blood Institute. Reprint requests should be addressed to Timothy J . Regan. M.D., CMDNJ-New Jersey Medical School, I 0 0 Bergen Street, Newark. N. J. 07103. 1979 by Grune dr Straiion. Inc. 0145-6OO8/79/0301-OOO8$01 .00/0 Q


coholic groups in terms of serum cholesterol, recent evidence has indicated that chronic ethanol use may be associated with enhanced levels of high density lipoproteins, which are thought to facilitate the removal of cholesterol from lipidladen arteries. However, this property is not characteristic of all species of high density lipoprotein; the influence of ethanol on the individual species is not yet known, and this should not be the basis for encouraging the use of alcohol. EXPERIMENTAL EVIDENCE FOR CHRONIC MYOCARDIAL TOXICITY

The major clinical evidence for the view that the chronic ingestion of large quantities of ethanol could adversely affect heart muscle and produce heart failure has been obtained from a number of urban centers over the past 15 yr. Uncertainty as to the quantity of ethanol intake, the nutritional status of the patient, including electrolyte deficits, and the possibility of heart disease from other causes have obscured the relationship of excessive ethanol use and cardiomyopathy. Previous chronic experiments with ethanol to examine this point have yielded conflicting data in terms of the production of a functional deficit, but the negative studies used smaller quantities and were relatively shortterm. To eliminate some of the variables that exist in a clinical setting, a group of young adult male dogs was maintained in a relatively normal nutritional state while receiving up to 36% of calories as ethanol, approximating the quantity reported in many human alcoholics.* After an average of 18 mo, they were found to have maintained weight, hematocrit, serum proteins, vitamins, and electrolytes to an extent similar to normal controls. When these two groups were compared, the heart of the alcoholic animal exhibited a distinctly abnormal pumping ability as well as abnormalities of cell structure on microscopic examination. Although, with time, most species appear to develop myocardial abnormalities, the duration and quantity of alcohol ingestion required to develop functional or morphological alterations appear to vary. Thus, the rhesus monkey surpris-

Alcoholism: Clinical and Experimental Research, Vol. 3, No. 1 (January), 1979


ingly has shown early fibrosis after 3 mo of ethanol as 40% of calories. It is possible that the feeding modality, relatively rapid by stomach tube, or the synthetic liquid diet contributed to this response. In the rat, ethanol as 10% of total calories apparently has produced ultrastructural abnormalities as early as 7 wk. Prior experience with rodents and their proclivity for viral infection raises the question of possible conditioning of the myocardium, with sensitization to the early development of lesions at relatively low doses. PRECLINICAL MALFUNCTION IN MAN

To determine if there was an equivalent functional abnormality in man, studies were performed in alcoholic subjects with no symptoms or clinical evidence of heart disease or maln~trition.~ Documentation of 10-1 5 yr of alcoholism and the type of ethanol used was obtained from the patients’ histories or from close relatives. Whiskey was the predominant alcoholic beverage, consumed several times a week, in amounts ranging from 0.5 to 2 pints/day. Liver biopsy revealed fatty liver without fibrosis. Left ventricular performance was studied by increasing blood pressure. The noncardiac alcoholic exhibited a significant depression of ventricular function as well as an abnormal index of contractility. Diminished ventricular performance has also been observed in male cirrhotic patients without clinical evidence of cardiac disease,’ a phenomenon to which female alcoholics seem less susceptible. Some degree of cardiac interstitial fibrosis may be present at this stage, as suggested by postmortem studies of accident victims who were alcoholic. Evidence of preclinical cardiomyopathy has been found in five separate laboratories so that it is presumably relatively common in the long-term male alcoholic. It is important as an aid in the diagnosis of chronic alcoholism and as an indicator of those individuals at risk for developing arrhythmiasS or heart failure. In circumstances marked by progression of cardiac dysfunction in alcoholic individuals, pulmonary congestion may lead to exertional or nocturnal dyspnea. If long sustained, or after repeated episodes, pulmonary hypertension and right ventricular heart failure may become evident. Unless there is complicating papillary


muscle insufficiency, giving rise to mitral regurgitation, cardiomegaly may be moderate in extent and heart size may revert to near normal after central congestion is corrected. In some patients, systemic or pulmonary emboli from mural thrombi may adversely affect the patient’s course. These clinical episodes frequently seem to be precipitated by intensified drinking episodes. ARRHYTHMIAS AND THE ECG

An association between alcohor use and cardiac arrhythmias, particularly atrial fibrillation, has long been suspected. However, the specific etiologic role of alcohol is difficult to establish and doubt has existed as to the presence of any heart disease when overt cardiomyopathy is not present. Over a 4-yr period, we have observed or reviewed 32 separate dysrhythmic episodes occurring in 24 patients who drank heavily and habitually (Table 1). In each instance, hospitalization was deemed necessary for treatment. All patients have histories of prolonged ethanol use, with superimposition of especially heavy ingestion prior to the arrhythmia. Overt alcoholic cardiomyopathy was not present, as the only patients included were those with normal or borderline heart size (by x-ray) and normal (or minimally abnormal) ECGs after return to sinus rhythm.s Cardiac arrhythmias developing in these circumstances are probably often misdiagnosed as “idiopathic,” as little or no clinical evidence of heart disease remains after resolution of the rhythm problem and the extent of alcohol use may be unrecognized. Because of a rather typical weekend or holiday presentation, we have called this the “holiday heart syndrome,” which we define as “an acute cardiac rhythm and/or conduction disturbance Table 1. 36 Alcohol-Associated Arrhythmias in 24 Patients Rhythm Abnormality


Isolated APCs Atrial fibrillation Atrial flutter Paroxysmal atrial tachycardia Junctional tachycardia Isolated Pvcs Ventricular tachycardia

4 12 6 3 4 (3 in 1 patient) 6

1 (after treadmill exercise)



Fig. 1. Electrocardiograms of Ulustratlve caws. (A) Atrial tibrillation la reen In top strlp with one aberrated (Ashman) beat (tho 6th). Wlthin 10 min (next 2 strips), the rate accelerated with rungs of wide corn plexer (?aberration or vontrlcw lor tachycardia) at rate of 240/min. (B) Atrial flutter wlth 1:l conduction (verM.d later by carotid marsage) at rate of 250/mln wlth right bundla branch block (RBBB) aberration. A ringle normally conducted beat I8 wen. (C) Runs of ventrle ular tachycardla 1 min following the end of a treadmill stress test (both rtrlpr). (Reproduced by permi8rion from the Ame&an h a r t Joufna/.)

with heavy ethanol consumption in a person without other clinical evidence of heart disease and disappearing, without evident residual, with abstinence.” Our report details numerous atrial and ventricular arrhythmias and one instance of transitory atrioventricular block (Fig. 1). The unusual seasonal peak at year-end and early in the “New Year” corresponds to the known peak of liquor sales a t that time.

The mechanism by which these arrhythmias occur is not yet clear. In recent investigations from our laboratory, mild chronic conduction abnormalities, including H-V and QRS prolongation, were induced in otherwise healthy and well nourished dogs that drank ethyl alcohol in significant quantity for longer than 1 yr.6 In these animals, infiltration of the myocardial interstitium with Alcian blue-positive material



and electron microscopic evidence of intercalated disc disruption were observed, either of which alteration could have been responsible for prolonged conduction. These animals also exhibit a reduced ventricular fibrillation threshold during ethanol intoxication.’ Cardiac conduction delays are believed to play an important role in arrhythmia production by facilitating reentry. Although the PR, QRS and QT prolongations observed in the above series of patients were of minor degree, it is possible that more severe localized areas of delay are present. Indeed, histologic evaluation of the heart in human cardiomyopathy and after alcoholic ingestion by animals emphasizes a variable, patchy distribution of lesions. Because of the evident ventricular dysfunction in most (Fig. 2), we believe this to be an indication of preclinical cardiomyopathy in the majority of these patients. A few had systolic time intervals that were normal. Although we have not yet observed the transition to overt cardiomyopathy in any patient, perhaps because of the limited period of follow-up, our patient group includes at least three patients in whom a diagnosis of a possible cardiomyopathy might be entertained because of borderline cardiomegaly. P-=O.OOI

0.560 0













0.240 0.200 0.160


It is important to be aware that a relatively high incidence of sudden unexpected death has been observed in a group of young adult alcoholics.* These patients had fatty liver as the principal pathologic finding. In this respect, they were similar to alcoholics previously found to have physiologic evidence of cardiac malfunction. Ventricular fibrillation may have occurred in these patients. ATYPICAL MYOCARDIAL INFARCTION

The occurrence of myocardial infarction traditionally has been attributed to occlusive disease of the coronary arteries and, in patients who succumb, the arterial pathology usually is represented as diffuse atherosclerosis of extramural vessels. However, variations from this general observation have recently been reported during coronary angiography after infarction. Individual cases or reports of small groups have been presented showing little evidence of luminal narrowing of the coronary arteries, usually in subjects without known risk factors. Precordial pain is observed not infrequently in myopathies of varied etiology; however, the association of alcoholism with the clinical syndrome of acute myocardial infarction has not been observed previously. Transmural myocardial scar has been found at postmortem examination in subjects with alcoholism and without significant coronary atherosclerosis. To elucidate this relationship, alcoholic subjects admitted to a coronary care unit (CCU) with unequivocal evidence of acute transmural myocardial infarction were in~estigated.~ Ten of 12 were without traditional coronary risk factors. Those with prior ECGs frequently exhibited absent Q waves in leads I, V, and V,, which became manifest as the infarction evolved. Examination of the coronary arteries at postmortem or by angiography revealed no significant occlusive lesions. Morphological examination of the myocardium revealed concentric periarterial fibrosis, which was postulated to restrict coronary flow increments during periods of high blood flow requirements. This phenomenon is considered analogous to cardiac muscle necrosis associated with the periarterial lesions of constrictive pericarditis, perhaps conditioned by the abnormal


0.400 0.44C




Fig. 2. Systolic time Interval ratios (PEPILVET) In alcoholic patients who had presented with arrhythmlas (left) and normals (right). Filled clrcles are individual data pointo; means aro open circles and standard errors are shown. (Roproducod by permission from the Amerlcan Heart Joufn8/.)



metabolism of cardiac cells in chronic alcoholism. A thromboembolic process was deemed unlikely in this study on the basis of several observations. The patients without previous infarction did not have prior heart failure, cardiomegaly, evidence of arrhythmias or valvular disease, which appear to be prerequisites for embolization from the left heart chambers. Thrombocytosis and drugs affecting platelets were also absent. These patients were considered to have a preclinical form of toxic heart muscle disease prior to infarction, and mural thrombi have not been described at this stage. Crucial to the thromboembolic postulate is the demonstration in such patients that emboli emanating from the left heart are distributed to the systemic circulation in an incidence approximating that of proved mural thrombi. As a clinical model for the distribution of emboli in the arterial circulation, patients with prosthetic valves and a relatively high incidence of embolization show a striking noncoronary preponderance.I0 None of the total of 12 patients in this series, representing 20% of CCU admissions for the given period, had evidence of embolization to any organ. Since angiography was not feasible during acute infarction, the presence of thromboembolism was assessed indirectly by serial determinations of circulating platelet levels, which are known to be altered during systemic thomboembolic phenomena." The absence of a change in platelet count during the first day suggested that accelerated platelet turnover as a reflection of arterial thromboembolism was unlikely in these patients. HYPERTENSION

Although problem drinkers as a group may have higher pressures than a control group on random measurement,' these are usually within the range of normal. Intoxication may contribute to blood pressure rise, and the withdrawal state is not infrequently associated with transient elevation of arterial pressure. Ethanol administration produces vasoconstriction of skeletal muscle vessels associated with dilatation of vessels to the skin. Predominance of the former may account for transient hypertension, but there is no evidence that chronic hypertension is produced. After a short period of abstinence in

noncardiacs, arterial pressure does not appear to differ from a control group.c6 It should be noted that during periods of severe congestive heart failure, diastolic-arterial pressure may initially be substantially elevated which may lead to the false diagnosis of hypertensive heart disease. The blood pressure usually returns to normal following the response to therapy for cardiac decompensation. ETHANOL QUANTITATION

Several reports of cardiomyopathy have emphasized the difficulty in obtaining a history of alcoholism. There is a male predominance, and suggestive diagnostic aspects include social disruption, accident proneness, and a familial history. Hepatic cirrhosis and clear evidence of peripheral neuropathy are present infrequently in patients with alcoholic cardiomyopathy. Maintained function at an occupation, even an executive position, does not exclude the diagnosis. The major positive diagnostic feature is the history of ingesting ethanol in intoxicating amounts for many years, frequently with spree episodes. This information often may be obtained only through careful, persistent questioning of the patient or from relatives and should be related to blood assays for ethanol, when possible. Negative aspects include exclusion of other causes of heart disease, namely, hypertension, coronary artery disease, cor pulmonale, and congenital or valvular disease. Other forms of cardiomyopathy (viral, infiltrative, metabolic, etc.) must also be considered. Not only are the quantity, frequency, and duration of ethanol intake difficult to assess, but their relationship to organ pathology is not straightforward. It is probable that these factors have a similar importance for the varied chronic diseases secondary to alcohol abuse, so that information in relation to liver disease, for which there are more complete data, may, in a general way, be applicable to the heart.I2 Alcoholic hepatitis usually develops after years of excessive drinking, although in a few patients it appears within a few years, but may not develop in many even after several decades of drinking. More than 80%of patients were drinking 5 yr or longer before developing symptoms. The probability of developing alcoholic hepatitis is small in those who drink less than 80 g/day of ethanol (approx-



imately 8 oz of 86-proof whiskey or 1 liter of wine) or if ethanol provides less than 20% of calories. As the daily ethanol consumption increases to 90-160 g/day and the duration of drinking becomes longer, the risk of developing alcoholic liver disease increases. The probability of alcoholic hepatitis or cirrhosis is great if the daily ethanol consumption exceeds 160 g (for example, 1 pint of whiskey, the approximate daily metabolic capacity for an average nondrinking person) and if the drinking (either steady or in sprees) persists for 10-15 yr or longer. TREATMENT AND REVERSlBlLlTY

Management of alcoholic cardiomyopathy depends on the state of the disease when the addicted individual is first seen. Even in the absence of cardiac failure or enlargement, patients presenting with unexplained arrhythmias or absent septa1 Q waves should raise a high index of suspicion requiring verification of a negative history of alcoholism. The key to treatment at all stages involves complete abstinence. The alcoholic with cardiac abnormality may be approached effectively on an individual physi-

cian-patient relationship as well as in group therapy. In the only available study of its kind, almost one-third of patients followed on an outpatient basis were found to have apparently maintained abstinence over a 3-yr period.’) The majority of these had an improved or unchanged cardiac status. Deaths occurred preponderantly in those who did not abstain. Some uncertainties exist, since the relative cardiac status on admission to the study was not described. It is noteworthy that more than 20% of those who allegedly were abstinent deteriorated in cardiac status. Presumably, at certain stages of the disease, the pathogenetic mechanisms may continue unabated. After the onset of clinical manifestations, traditional antiarrhythmic agents, DC countershock, digitalis, and diuretics may be used as needed. Electrolyte abnormalities may exist either during the acute stage or can develop readily in patients with low salt intake or during diuresis. Since thromboembolism from endocardial thrombi is a prominent feature, occurring in as many as 80% of individuals in one series, anticoagulants are important when clinical evidence of heart disease is present.

REFERENCES 1. Dyer AR, Stamler J. Paul 0, et al: Alcohol consump

tion, cardiovascular risk factors, and mortality in two Chicago epidemiologic studies. Circulation 56:1067-1074. 1977 2. Regan TJ, Khan MI, Ettinger PO, et al: Myocardial

function and lipid metabolism in the chronic alcoholic animal. J Clin Invest 54:74&752, 1974 3. Regan TJ, Levinson GE, Oldewurtel HA, et al: Ventricular function in noncardiacs with alcoholic fatty liver: Role of ethanol in the production of cardiomyopathy. J Clin Invest 4k397-407, 1969 4. Wu CF, Sudhakar M, Jaferi G , et al: Preclinical cardiomyopathy in chronic alcoholics: A sex difference. Am Heart J 91:281-286, 1976 5. Ettinger PO, Wu CF, DeLa Cruz CL Jr. et al: Arrhythmias and the “holiday heart.” Alcohol-associated cardiac rhythm disorders. Am Heart J (in press) 6. Ettinger PO, Lyons M, Oldewurtel HA, et al: Cardiac conduction abnormalities produced by chronic alcoholism. Am Heart J 91:66-78, 1976

7. DeLa Cruz CL Jr, Haider B, Ettinger PO, et al: Effects of ethanol on ventricular electrical stability in the chronic alcoholic animals. Clin Res 24:419A, 1976 (abstr) 8. Kramer K, Kuller L, Fisher R: The increasing mortality attributed to cirrhosis and fatty liver in Baltimore (1957-1966). Ann Intern Med 69:273-282, 1968 9. Regan TJ, Wu CF, Weisse AB, et al: Acute myocardial infarction in toxic cardiomyopathy without coronary obstruction. Circulation 51 : 4 5 3 4 6 I. 1975 10. Cleland J. Molloy PJ: Thromboembolic complications of the cloth-covered Starr-Edwards prosthesis No. 2300 aortic and No. 6300 mitral. Thorax 28:41, 1973 11. Harker LA, Slichter SJ: Platelet and fibrinogen consumption in man. N Engl J Med 287:999, 1972 12. Galambos JT: Alcoholic hepatitis, in Schaffner F, et al (eds): The Liver and Its Diseases. New York, Intercontinental Medical, 1974, pp 265-267 13. Demakis JG. Proskey A, Rahimtoola SH, et al: The natural course of alcoholic cardiomyopathy. Ann Intern Med 80:293-297. 1974

Varied cardiac abnormalities in alcoholics.

Varied Cardiac Abnormalities in Alcoholics Timothy J. Regan, M.D. and Philip 0. Ettinger, M.D. The toxic effects of acute or chronic use of alcohol on...
548KB Sizes 0 Downloads 0 Views