alcohol and new onset atrial fibrillation: case-control study of ...alcohol andatrialfibrillation...

Br Heart J 1987;57:468-73

Alcohol and new onset atrial fibrillation: a case-controlstudy of a current seriesPEKKA KOSKINEN, MARKKU KUPARI, HANNU LEINONEN,KIMMO LUOMANMAKI

From the First Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland

SUMMARY The aetiological role of alcohol in new onset atrial fibrillation was evaluated in acase-control study of 100 consecutive patients aged 21-64 years. Clinical examination, routinediagnostic tests, and echocardiography revealed an underlying disease or other identifiable factorfor atrial fibrillation in 65 patients (group 1); 35 patients had idiopathic atrial fibrillation (group2). The most common diseases associated with atrial fibrillation were ischaemic heart disease(21%), hypertension (13%), and cardiomyopathy (8%). Data on alcohol consumption wereobtained by interviewing the patients and their age and sex matched controls on admission. Themean daily alcohol intake of group 2 patients during the week preceding atrial fibrillation wassignificantly larger than that of either their controls or group 1 patients. Compared with controlssignificantly more patients in both groups with atrial fibrillation had consumed alcohol within twodays of the onset of the arrhythmia. Significantly more patients had onset of arrhythmia onWednesday, Thursday, or Friday than on any other weekday, including patients with high alcoholintake.This study establishes alcohol as an important precipitating factor for new onset atrial

fibrillation.

Alcohol has recently been incriminated as a commonprecipitating factor for atrial fibrillation,I-3 andelectrophysiological studies have verified its ar-rhythmogenicity in long term alcoholics.45 Not onlyhabitual heavy drinkers seem to be liable to arrhyth-mias; even apparently healthy moderate or infre-quent drinkers may suffer an episode of atrialfibrillation after an alcohol binge.6-8The incidence of alcohol related arrhythmias is

uncertain and may vary between populations withdifferent alcohol cultures. All previous studies on thesubject have been either retrospective surveys or iso-lated case reports. In one study, up to 47% of all newcases of atrial fibrillation in middle aged patientswere thought to be caused by alcohol,' whereas otherreports have given rates from less than 300 o8 to63/o2 of otherwise unexplainable atrial fibrillation.We have recently began a series of studies to eval-

Requests for reprints to Dr Markku Kupari, Cardiovascular Labo-ratory, Helsinki University Central Hospital, SF-00290 Helsinki,Finland.

Accepted for publication 2 December 1986

uate the frequency and clinical importance of alcoholrelated arrhythmias in the emergency ward of ourhospital. In the present report we describe the ae-tiological factors in 100 consecutive young and mid-dle aged patients with new onset atrial fibrillationand compare their drinking habits with those of amatched control patient population.

Patients and methods

The study was carried out between 1 January and 20September 1985 in the emergency ward of HelsinkiUniversity Central Hospital. The hospital serves apopulation of approximately 900 000 and there are1600-1900 patient visits every month to theemergency ward. During the study period 101 pa-tients aged < 65 years were admitted for their firstdocumented episode of atrial fibrillation. These werethe patients that we studied.

AETIOLOGICAL EVALUATIONThe patients were examined by a cardiologist on theday of admission or the next morning, when sinusrhythm had been restored in almost all of them. The

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Alcohol and atrial fibrillation

identification of cardiac or non-cardiac diseases wasbased on history and clinical examination com-plemented by chest x rays, cross sectional and Mmode echocardiographic examination (Irex SystemIII echocardiograph), blood tests (Coulter auto-analyser), serum sodium and potassium (ion selec-tive electrode), calcium (enzymatic or atomicabsorption spectrophotometry), magnesium (atomicabsorption spectrophotometry), aspartate and ala-nine aminotransferases (enzymatic), y glutamyltranspeptidase (enzymatic), creatine kinase iso-enzymes (enzymatic and electrophoretic), thyroxine(radioimmunoassay), triiodothyronine uptake (ra-dioimmunoassay and Sephadex uptake), and bloodethanol (enzymatic). Lung function was studied ifthis was needed to confirm or exclude the presenceof pulmonary disease.

ASSESSMENT OF DRINKING HABITSAt admission every patient was questioned by one ofus about the types and amounts of alcoholic bever-ages they had consumed each day during the weekpreceding the arrhythmia. The total amount of alco-hol was recorded as grams of ethanol. The patientswere also asked to estimate if this was more or less,or approximately the same they were accustomed to.If the patient was not aware of the time of onset ofatrial fibrillation information about alcohol intakeduring the week before admission was collected. Thepatients were also asked the number of weeks theyhad been totally abstinent during the past year.Blood ethanol concentration on admission was notmeasured in all patients because the first laboratorytests were ordered by the attending physician andnot one of the investigators. The smoking and coffeedrinking habits of the patients and controls were alsorecorded.

CONTROL PATIENTSAfter the case had been identified the diagnoses onemergency ward records were checked to find a suit-able control patient. The control patient had to be ofthe same age (± 10 years) and sex as the case and thediagnosis or symptom for hospital admission had tobe one of an acute illness. The majority of the con-trols were found and interviewed on the same day asthe cases, and the rest were found within two or threedays. They too were questioned about their alcoholand coffee consumption and smoking habits in theweek before admission. We did not select the con-trols totally randomly because hospital patients arenot a representative sample of the population. Byexcluding patients admitted with conditions knownto be alcohol related, such as acute pancreatitis ordrug intoxications, and with severe chronic diseases,such as cancer, we tried to avoid overrepresentation

469Table 1 The referral diagnoses or symptoms of the controlpatientsDiagnosis or symptom No

Acute asthma or bronchitis 11Suspicion of deep venous thrombosis 11*Ureteral colic 10Pneumothorax (2 traumatic, 7 spontaneous) 9Miscellaneous acute infectious disease 8Acute appendicitis 7Pleuropneumonia 7Erysipelas 3Minor traumas 3Headache 3Hernias 3Miscellaneous (wound infection, haematuria,abdominal pain, vertigo) 23

*Deep venous thrombosis was confirmed by venography in eightpatients.

ofheavy drinkers and abstainers, respectively, in ourcontrol population. We also excluded patients ad-mitted for acute cardiac diseases because the presentstudy is part of a large project designed to evaluatethe role of alcohol in various cardiac emergencies.Table 1 lists the diagnoses and symptoms of thecontrol patients.

STATISTICAL ANALYSISThe statistical comparisons between cases and con-trols were performed by McNemar's test when therewere only two outcomes and Stuart-Maxwellstatistics9 when there were more. We also tested fora linear trend in the (log) risk of atrial fibrillationwith increasing alcohol consumption.10 The atrialfibrillation groups were compared by the X2 test andStudent's t test for independent data. The distribu-tion of the onset of the arrhythmia between differentweekdays was analysed by a X2 test for goodness offit.

Results

There were 19 women and 82 men (mean age 48years (range 21-64)). The mean age of the controlswas also 48 years. One patient, a male alcoholic,could not be examined and he was excluded from theanalysis. Data on alcohol and coffee drinking andsmoking were obtained in 98 patients; one patientdied of diabetic coma and pneumonia before hecould be interviewed and one patient admitted afteran electrical shock did not answer the questions.Cross sectional echocardiograms were obtained in 95patients; two patients refused echocardiography (anotherwise healthy 21 year old man and a male alco-holic with previous myocardial infarction) and onepatient died of acute myocardial infarction before the



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Table 2 Diseases associated with new onset atrialfibrillation

Coronary heart disease:Acute myocardial infarction 7Old myocardial infarction 7Angina pectoris 7*Total 21**

Hypertension 13Cardiomyopathy:

Dilated 4Hypertrophic 4Total 8

Chronic obstructive pulmonary disease 5Previous myopericarditis 4Mitral valve disease:Rheumatic 2Prolapse 1Total 3

Ischaemic heart disease with normal coronary arteries 2Athletic heart syndrome 2Electrical shock 2Aortic valve disease 1Pre-excitation syndrome 1Toxic shock with myopericarditis 1Thyrotoxicosis 1Diabetic ketoacidosis with pneumonia 1Idiopathic 35

*1 patient also had pulmonary embolism; **5 patients also hadhypertension

examination. Good quality echocardiographicrecordings were obtained in 85 patients.

DISEASES AETIOLOGICALLY ASSOCIATED WITHATRIAL FIBRILLATIONSixty five patients (group 1) had a disease or otheridentifiable factor that could be aetiologically associ-ated with atrial fibrillation (table 2). Twenty one ofthem had coronary heart disease; seven gave a his-tory of typical effort related angina pectoris and 14had acute or old myocardial infarction indicated bya history of prolonged chest pain and changes in theelectrocardiogram or in serum enzymes or in leftventricular echocardiography. Hypertension was di-agnosed in 18 patients; 16 were on antihypertensivetreatment and two patients with previously un-diagnosed hypertension had supine diastolic bloodpressure > 110 mm Hg in repeated measurementsafter admission. Five of the hypertensive patientsalso had coronary heart disease. Only four patientshad hypertensive left ventricular disease (wall thick-ness > 14 mm on echocardiography). Dilated cardio-myopathy was diagnosed in four patients who hadheart failure without other explanation and diffuselypoor contraction of the left ventricle with an in-creased diastolic dimension (>60 mm) on echo-cardiography. Another four patients had thehypertrophic form of cardiomyopathy; the electro-cardiogram showed increased left ventricular volt-ages in all, and the septal or free wall thicknessexceeded 14 mm on echocardiography. Five patients

Koskinen, Kupari, Leinonen, Luomanmaki

had chronic obstructive pulmonary disease; theygave a long history of productive cough and dys-pnoea without heart disease and clinical exam-ination, chest x rays, or lung function tests supportedthis diagnosis. Old myopericarditis was diagnosed infour patients and acute myopericarditis in one; allgave a history of a febrile illness (diphtheria in one,rheumatic fever in one, acute toxic shock in one,unspecified in two) and had localised or diffuse ab-normalities of myocardial contractions and peri-cardial thickening or effusion on echocardiography.Significant valvar disease was found in four patients(one rheumatic mitral stenosis, one rheumatic mitralregurgitation, one aortic regurgitation, and one mi-tral valve prolapse). One of the patients had under-gone cardiac catheterisation; in others the diagnosiswas based on clinical and echocardiographic exam-inations. Athletic heart syndrome" was diagnosedin two patients; both had a long history of endurancetraining and an increased left ventricular end di-astolic diameter (>56 mm) on echocardiographywithout impairment of left ventricular systolic func-tion. Two patients had syndromeX (ischaemic heartdisease despite patent coronary arteries); both hadpreviously undergone coronary angiographic andperfusion studies.'2 Other illnesses diagnosed ingroup 1 were thyrotoxicosis (one patient), pre-excitation syndrome (one patient), and diabetic comawith pneumonia (one patient). Two patients hadonset of arrhythmia after an electrical shock.

In 35 patients (six women and 29 men) we foundno evidence of concomitant cardiac or non-cardiacdisease (group 2).

DATA ON ALCOHOL CONSUMPTIONNine patients (three women, six men) in group 1 and10 (five women, five men) controls had not drunk anyalcohol during the past year. In group 2, five patients(three women, two men) and five controls (onewoman, four men) had been teetotallers for thewhole year. Table 3 shows the patients' and controls'estimates of their alcohol consumption for the week

Table 3 Estimation of alcohol consumption during theweek before atrial fibrillation compared with normal use incases and controls

Alcohol consumption

More Less The same p

All cases/controls 17/9 4/12 77/77

Alcohol and atrial fibrillation

Group 1 (p= NS) Group 2

0 1-30 >30 0Ethanol (g/day)

Fig 1 Average daily alcohol consumption of(black columns) and their controls (white colthe week preceding the atrial fibrillation. Groifibrillation with an associated disease. Group,'atrial fibrillation.

preceding atrial fibrillation compared wimal alcohol intake.To analyse the data on the average am

hol consumed daily during the week 'fibrillation we divided the patients and (three groups: (a) abstainers; (b) those vage daily consumption of 1-30 g of ethaiwith an average daily alcohol consumptiof ethanol. Figure 1 shows the distribpatients and controls in these groups. FIatrial fibrillation had drunk more than(X2 = 10A407; p < 0-01). This diffeimainly from group 2 patients whosesumption had been significantly largertheir controls (X2 = 8X658; p < 0-025)difference between patients in group 1 ar

Table 4 Frequency of abnormal laboratory Jpatients with new onset atrial fibrillation

Variable Group

MCV >96 fl 6 (57)Serum potassium < 3-7 mmol/l 12 (59)

< 3-0 mmol/l 1 (59)Serum calcium 50 IU/I 18 (53)Blood ethanol >1 mmol/l 5 (12)

The figures in parentheses are the number of padMCV, mean red cell corpuscular volume; S-Aaminotransferase (serum); S-ALAT, alanine a(serum); S-y-GT, y glutamyl transpeptidase (seruGroup 1, atrial fibrillation with an aetiologically asGroup 2, idiopathic atrial fibrillation.

(p 75 g of ethanol daily) duringthe week preceding the arrhythmia: five of 35 ingroup 2 (vs none of their controls) and two of 63 ingroup 1 (vs one of their controls).

Alcohol use immediately before the arrhythmiawas evaluated separately by our noting whether ornot the cases and controls had drunk any alcoholduring the two days preceding the arrhythmia or

1-30 >30 admission. There were 25 drinkers in group 1 (vs 13controls; x2 = 4-321, p < 0 05) and 19 of 35 in group

the patients 2 (vs 4 controls; x2 = 11-529; p < 0-001). Twelve ofumns) during the 29 patients whose blood ethanol concentration,up 1, atrial was measured on admission had been drinking re-2, idiopathic cently. Their blood ethanol concentration was over

1 mmol/l (table 4).

ith their nor- DATA ON COFFEE DRINKING AND SMOKINGCoffee drinking and smoking habits were not

ount of alco- significantly different in cases and controls. In groupbefore atrial 1, 78% of cases and 83% of controls drank coffeecontrols into daily and 35% of both cases and controls were cur-vith an aver- rent smokers. In group 2, 77% of cases were coffeenol; (c) those drinkers and 34% were smokers; the correspondingion of > 30 g figures for the controls were 89% and 29%.iution of the?atients with COMPARISONS BETWEEN THE TWO GROUPSthe controls WITH ATRIAL FIBRILLATIONrence came Group 1 patients were significantly (p < 0 001) olderalcohol con- than those of group 2 (mean age 52 and 43 years,than that of respectively), but there was no difference in the sexwhereas the distribution. Patients in group 2 had usedad their con- significantly larger amounts of alcohol daily during

the week preceding atrial fibrillation than those infindings in group 1 (X2 = 7.753; p < 0-025) (fig 1). In contrast

there was no statistical difference between the groupsfor alcohol use in the two days before atrial

I Group 2 fibrillation; 38% in group 1 and 54% in group 2 had1(29) used alcohol during that time.8 (35) Table 4 shows the frequencies ofabnormal labora-2 (35) tory findings. There were no statistically significant10 (30) differences between the groups for any of the labora-2 (30)3 (27) tory measurements. Fifty per cent of cases in group8(33) 1 and 54% in group 2 who had drunk > 30 g of10 (32)8 (31) ethanol daily had one or more of the liver enzyme7 (17) values above normal limits. Only one patient in the

ents tested. highest alcohol consumption category had increased,SAT, aspartate mean red cell corpuscular volume. The abnormallyuninotransferase low electrolyte values were evenly distributed be-smociated disease tween the groups and they were not related to the

amount of alcohol used.

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Fig 2 Distribution of the onset of atrial fibrillation in 84patients by days of the week. The hatched columns indicatepatients with atrial fibrillation and an associated diseaseand the stippled columns show patients with idiopathicatrial fibrillation.

VARIATION BY WEEKDAYS IN THE ONSET OFATRIAL FIBRILLATIONEighty four patients (50 in group 1 and 34 in group2) were certain of the day on which arrhythmia hadstarted. Figure 2 shows the day by day distributionof the onset of atrial fibrillation in both groups. Thedistribution differed significantly from a chance oc-currence (X2 = 15 332; p < 0-025) with the highestfrequencies occurring in the middle of the week. Inboth groups 1 and 2 there was a similar trend but thisdid not quite reach statistical significance. Patientswith high alcohol consumption showed a similarvariation by weekday as did other cases. Fourteen(70%) of those 20 patients who had consumed > 30g/day during the previous week had onset of arrhyth-mia on Wednesday, Thursday, or Friday.

Discussion

Taken together with earlier investigations, -3 ourstudy strongly supports the idea that alcohol plays asignificant role in the genesis of otherwise inexplic-able atrial fibrillation. The frequency of alcohol re-lated atrial fibrillation, however, was clearly lower inour study than in two recent retrospective studies.1 2Only one third of patients admitted for idiopathicatrial fibrillation had consumed more than 30 g ofethanol daily during the preceding week and notmore than five of 35 patients had had more than75 g a day. These data suggest that in about 15-30%of patients with idiopathic atrial fibrillation the ar-rhythmia may be alcohol related and that about5-10% of all new episodes of atrial fibrillation can beexplained by alcohol use. Among other identifiablediagnoses associated with new onset atrial fibrillation(table 2) alcohol abuse would thus rank above well-known factors such as valvar heart disease, chronic

Koskinen, Kupari, Leinonen, Luomanmakiobstructive pulmonary disease, and thyrotoxicosis.The true aetiological contribution of alcohol to atrialfibrillation may be somewhat larger because by caus-ing dilated cardiomyopathy'3 or myocardial in-farction despite patent coronary arteries" it can bethe primary, although not the immediate, cause ofthe arrhythmia. Two of our four patients with di-lated cardiomyopathy were alcoholics; they deniedrecent drinking. As well as being the main cause ofatrial fibrillation in some patients, alcohol may be atriggering factor in patients with other heart dis-eases. This is suggested by our finding that a largerproportion of patients with aetiologically identifiableatrial fibrillation than of controls had used alcoholwithin the two days preceding the onset of the ar-rhythmia.The selection of control patients in a hospital

based study is always difficult and open to criticism.In our study, however, the alcohol consumption ofthe controls resembled that of a representative sam-ple of 15-69 year old Finns whose alcohol use wasstudied in 1984.15 In that study 3870 people werequestioned in detail about their drinking habits dur-ing one week and their alcohol use in general duringthe past year was evaluated. Twenty seven per centof women and 12o% of men had abstained in theprevious year. The calculated mean yearly alcoholconsumption (alcohol used during the week in ques-tion times 52) of the male drinkers was 4-1 kg (me-dian 1 9 kg) of ethanol and for female drinkers it was1 1 kg (median 0 4 kg). In our control group thefrequencies of teetotallers (320% in women, 11% inmen) were very close to those found in the popu-lation study. Mean yearly ethanol consumption ofthose controls who had drunk alcohol during the pastyear was 3-8 kg (median 1 5 kg) in men and 0 2 kg(median 0) in women. The consumption of our malecontrols accords well with the population studywhereas that of our female patients seems too small.There were only 13 drinkers among our female con-trols, however, and this may partly explain the dis-crepancy, especially as we evaluated only one week'salcohol intake. An important finding was that thepatients with atrial fibrillation had drunk muchlarger quantities of ethanol: the mean values foryearly consumption were 9 1 kg (median 5-3 kg) inmale drinkers and 6 3 kg (median 0) in female drink-ers. In our view these data support our conclusionthat atrial fibrillation may be precipitated by a highintake of alcohol.

Probable mechanisms by which alcohol may in-duce atrial fibrillation have been discussed re-cently.15 Alcohol can increase the concentration ofcirculating catecholamines,'6 change conductiontimes and refractory periods in the myo-cardium,4 5 17 evoke sudden increases in vagal tone



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Alcohol and atrial fibrillation 473(vomiting), and produce subclinical myocardial in-jury when used heavily for many years.13 It may wellbe that in most cases a combination of two or moreof these influences triggers the arrhythmia afterbinge drinking. It is our impression that factors suchas physical or mental stress, lack of sleep, or febrilerespiratory infections may at times increase the ar-rhythmogenic capacity of alcohol, probably by aug-menting the basal sympathoadrenergic tone. In thepresent study electrolyte disturbances were not re-lated to alcohol use and most patients had serumelectrolytes within normal range on admission, al-though there were a surprising number with mar-ginally lowered concentrations of serum totalcalcium. Unfortunately, serum albumin and ionisedcalcium were not measured, so there is no proof ofreal hypocalcaemia in these patients.The term "holiday heart", introduced by Ettinger

et alO3 has been widely adopted to describe alcoholrelated arrhythmias clustering after the weekend andafter holidays such as Christmas and New Year. Inour study, however, the frequencies of the onset ofatrial fibrillation were lowest during the weekendand in the days afterwards and highest in the middleof the week, irrespective of the aetiology of the ar-rhythmia. Nor did we see any excess of cases afterfestivals such as the New Year, May Day, or Mid-summer Day which are all associated with alcoholsprees in Finland. In their retrospective study, Richet al did not find clusters of admissions for alcoholrelated atrial fibrillation after weekends or holidays.2It is possible that occupational mental or physicalstress, which increases during the working week, to-gether with other factors such as alcohol contributeto the onset of fibrillation.Our study shows that ischaemic heart disease, hy-

pertension, and cardiomyopathy are currently themost common diseases associated with new onsetatrial fibrillation in young and middle aged popu-lation. Mitral valve disease and thyrotoxicosis, bothstill cited in textbooks as important causes of atrialfibrillation, now seem to be rare in this age group.About one third of patients presenting with theirfirst episode of atrial fibrillation do not have anyrecognisable heart disease but many of them(15-30%) are frequent drinkers and some drinkquite heavily. There is no doubt that alcohol shouldbe included among the most common aetiologicalfactors causing atrial fibrillation in those of workingage.

References

1 Lowenstein AJ, Gabow PA, Cramer J, Oliva PB, Rat-ner K. The role of alcohol in new-onset atrialfibrillation. Arch Intern Med 1983;143:1882-5.

2 Rich EC, Siebold C, Campion B. Alcohol-related acuteatrial fibrillation. A case-control study and review of40 patients. Arch Intern Med 1985;145:830-3.

3 Ettinger PO, Wu CF, De La Cruz C, Weisse AB,Ahmed SS, Regan TJ. Arrhythmias and the "holidayheart": alcohol-associated cardiac rhythm disorders.Am Heart J 1978;95:555-62.

4 Greenspon AJ, Shchaal SF. The "holiday heart": elec-trophysiologic studies of alcohol effects in alcoholics.Ann Intern Med 1983;98:135-9.

5 Engel TR, Luck JC. Effect of whisky on atrial vulner-ability and "holiday heart". J Am Coll Cardiol1983;1:816-8.

6 Thornton JR. Atrial fibrillation in healthy non-alcoholic people after an alcoholic binge. Lancet1984;li:1013-4.

7 Lamb LE, Pollard LW. Atrial fibrillation in flying per-sonel. Report of 60 cases. Circulation1964;29:694-701.

8 Peter RH, Gracey JG, Beach TB. A clinical profile ofidiopathic atrial fibrillation. A functional disorder ofatrial rhythm. Ann Intern Med 1968;68:1288-95.

9 Fleiss JL, Everitt BS. Comparing the marginal totals ofsquare contingency tables. Br J Math Stat Psychol1971;24:117-23.

10 Breslow NE, Day NE. Statistical methods in cancer re-search. Lyon: International Agency for Research onCancer, 1980:182-8.

11 Huston TP, Puffer JC, Rodney WM. The athletic heartsyndrome. N Engl J Med 1985;313:24-32.

12 Virtanen KS. Evidence of myocardial ischaemia inpatients with chest pain syndromes and normal coro-nary angiograms. Acta Med Scand [Suppll1984;694:58-68.

13 Bridgen W, Robinson J. Alcoholic heart disease. BrMed J 1964;ii:1283-9.

14 Regan TJ, Wu CF, Weisse AB, Moschos CB, AhmedSS, Lyons MM. Acute myocardial infarction in toxiccardiomyopathy without coronary obstruction. Cir-culation 1975;51:453-61.

15 Simpura J, ed. Finnish drinking habits. Results from in-terview surveys in 1968, 1976 and 1984. Helsinki:Finnish Foundation for Alcohol Studies, 1987.

16 Anonymous. Alcohol and atrial fibrillation. Lancet1985;i:1374.

17 Perman ES. The effect of ethyl alcohol on the secretionfrom adrenal medulla in man. Acta Physiol Scand1958;44:241-7.

18 Gould L, Reddy CVR, Becker W, Oh K-C, Kim SG.Electrophysiologic properties of alcohol in man. JElectrocardiol 1978;11:219-26.



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