Echocardiography in chronic alcoholics

following prolonged periods of abstinence

William C. Reeves, M.D. Navin C. Nanda, M.D. Raymond Gramiak, M.D. Rochester, N. Y.

Left ventricular studies utilizing M-mode echo- cardiography have proved valuable in the nonin- vasive assessment of left ventricular function.‘+ Furthermore, recent investigation supports echo- cardiography as a sensitive technique for detect- ing small changes in left ventricular end-diastolic volumes.? Systolic time intervals derived conven- tjonally from simultaneous recordings of the carotid pulse and the ECG have also been useful in the evaluation of left ventricular function.8, 9 These intervals can also be conveniently and accurately derived from echocardiographic re- cordings of the aortic root.10-‘2 McDonald and Hobson13 have concluded that the combined information derived from the measurement of left ventricular dimensions and systolic time intervals was superior to either method used alone.

Alcohol has been incriminated as an etiologic factor in the development of left ventricular failure by a direct cardiotoxic effect.14-18 Abnor- malities of left ventricular function have been documented utilizing both invasive and noninva- sive methods in chronic alcoholics.lg-Z’ Transient depression. of left ventricular function has also been noted in normal volunteers immediately following alcohol consumption.“5-27

From the Cardiology Unit, Department of Medicine, and the Depart- ment of Radiology, University of Rochester School of Medicine and Dentistry, and Strong Memorial Hospital, Rochester, N. Y. This work was ?upported by contract HL 05500 from the National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Md.

Received for publication Mar. 15, 1977. Accepted for publication Apr. 11, 1977.

Reprint requests: Dr. Navin C. Nanda, Cardiology Unit, Box 679, Strong Memorial Hospital, 601 Elmwood Avenue, Rochester, N. Y. 14642.

578 May, 1978, Vol. 95, No. 5

Although alcohol is known to freely pass the placental barrier,28 no analysis of left ventricular function has been made in children born of alcoholic mothers.

We have elected to utilize echocardiographic techniques of left ventricular function in studying chronic asymptomatic alcoholics following a long period of abstinence and a small group of asymp- tomatic children born of chronic alcoholic mothers who were actively drinking during their pregnancy.

Materials and methods

Twenty-six adult volunteers (19 men and 7 women; mean age 45 years; range 25 to 62 years) form the basis of this study. The duration of active alcoholism in these individuals averaged 18.3 years (range 4 to 40 years). Their mean duration of abstinence from alcohol was 3.1 years (range 3 months to 17 years) (Table I). Addition- ally, seven asymptomatic children born of four alcoholic mothers belonging to the above group who were drinking throughout their pregnancy was also included in the study. Their average age was 14.1 years (range 4 to 19 years). A comparison group of age-matched normal individuals (13 adults and 8 children) was also studied.

A detailed medical history, physical examina- tion, 12-lead ECG, and an echocardiographic examination performed in the standard manner were obtained in all.

All echo examinations were performed with a commercially available Picker echograph and a 2.25 m. Hz transducer. Continuous records were obtained at 125 mm./sec. on 35 mm. film using a slave oscilloscope and a Fairchild record camera.

0002-8703/78/0595-0578$00.60/O 0 1978 The C. V. Mosby Co.

Echo in alcoholics

The following echo parameters were studied (Figs. 1 and 2):

1. Percentage of left ventricular dimension shortening (per cent AS):?

%AS =D,x 100 D,

The left ventricular diastolic dimension (D,) measured in mm. was the perpendicular distance between the left septal and left ventricular poste- rior wall endocardial surfaces measured at the R wave peak of a simultaneously recorded ECG. The left ventricular systolic dimension (D,) was measured in mm. as the shortest perpendicular distance between the endocardial surfaces of the left side of the ventricular septum and the ieft ventricular posterior wall during systole.

2. Left ventricular ejection fraction (EF):’ EF = b”-Ds’ x 1oo

DD” 3. Mean velocity of circumferential fiber short-

ening (mean V,,): y b-D, mean V,, =- D, x dt

This was expressed in circumferences/second. Left ventricular ejection time (dt) measured in msec. was the period from the onset of systolic anterior motion of the left ventricular posterior wall to its maximal anterior excursion.

4. Systolic velocities of the ventricular septum and left ventricular posterior wall? These were measured in mm./sec. as the maximal slope of the endocardial surfaces of the ventricular septum and left ventricular posterior wall, respectively, during systole.

5. Excursion of the ventricular septum and left ventricular posterior wall:?9 These were mea- sured in mm. as the maximum perpendicular distance from the diastolic endocardial surface of the ventricular septum and left ventrtcular poste- rior wall to the level of their maximal systolic excursions.

6. The systolic time interval ratio (PEP/ LVET):‘O-‘* Pre-ejection period (PEP) measured in msec. was the interval from the onset of the Q wave of the ECG to the point of opening of the aortic valve on the echogram. Left ventricular ejection time (LVET) measured in msec. was the interval from the opening to the closing of the aortic valve on the echogram.

7. Ventricular septal thickness:“” This was measured in mm. as the distance between the right and left endocardial surfaces of the ventric-

I second . I

- I second -C

Fig. 1. Diagram showing relationship between ECG tracing, excursion of ventricular septum and LV posterior wall, and other phenomena. VS = ventricular septum; KS Ex = max- imal excursion of ventricular septum; VS uel = maximal systolic velocity of the ventricular septum; PW = left ventric- ular posterior wall; PW En = maximal excursion of the left ventricular posterior wall; PW vel = maximal systolic velocity of the left ventricular posterior wall; PWT = poste- rior wall thickness; VWT = ventricular septal thickness; Dd = end-diastolic dimension; Ds = end-systolic dimension; dt = duration of left ventricular systole.

+&--+-I PEP LVET

Fig. 2. Diagram showing relationship between ECG tracing and pre-ejection period and left ventricular ejection time in the aortic valve. AV = aortic valve; PEP = pre-ejection period; LVET = left ventricular ejection time.

ular septum at the time of the R wave peak from a simultaneously recorded ECG.

8. Left ventricular posterior wall thickness:30 This was measured in mm. as the distance from left ventricular endocardial to epicardial surfaces at the time of the R wave peak from a simulta- neously recorded ECG.

9. Mitral valve EF slope? This was measured as the maximal slope of the tangent between the mitral valve E to F points in diastole and was expressed in mm. /sec.

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Reeves, Nanda, and Gramiak

Table I. Duration of abstinence Results

History, physical exam, and ECG. None of the 26 alcoholics had evidence on physical examina- tion of cardiac abnormality. Two had mild chronic obstructive pulmonary disease. One indi- vidual had a myocardial infarction approximately one year ago but no residual ECG abnormalities. None of the others had ECG abnormalities apart from one adult individual who had congenital complete heart block.

The seven children had no evidence of cardiac abnormality by history, physical examination, or ECG.

Echocardiography. These results are summa- rized in Tables II and III.

Adequate echograms of the left ventricular cavity (Fig. 3) were obtained in all adult alco- holics and children of alcoholic mothers. The parameters of left ventricular function were found to be normal in all except one adult alcoholic when compared to age-matched con- trols. This individual was a 41-year-old white male with a 19 year history of alcoholism and a one year period of abstinence. He had no history of cardiac disease, no cardiovascular symptoms, and his physical examination and ECG were normal. His per cent AS (21 per cent), EF (42 per cent), and mean Vv,, (0.40 circumferences/set.) were depressed. His PEP/LVET ratio could not be measured since adequate recordings of the aortic valve were not obtained. One additional adult alcoholic had a slightly thickened ventric- ular septum (14 mm.).

PEP/LVET ratios were obtained in 20 of 26 adult alcoholics and two of the seven children (Figs. 2 and 4). None had an abnormal value.

Discussion

Alcohol has a direct toxic effect on cardiac musculature.” Mitochondrial damage with de- creased mitochondrial oxidative enzymes results in diminished energy production and decreased contractility.lp. I5 Changes in sarcoplasmic retic- ulum appear responsible for impaired excita- tion-contraction coupling with decreased calcium delivery to the contractile apparatus.17‘ ** Addi- tionally, acetaldehyde, the principal metabolite of ethanol, causes myocardial release of norepi- nephrine, and this catecholamine depletion may contribute to decreased left ventricular contrac- tility.‘” Although the associated nutritional defi- ciencies of thiamine and nicotinic acid may occa- sionally play a role in the cardiovascuIar disease

Period I Number of patients

3 months to 1 year 9

2 to 5 years 7 6 to 10 years 4 Over 10 years 6

Table II. Echocardio&aphic values in adults

Normal (13 subjects)

Mean Range

Alcoholic (26 subjects)

Mean Range

PW Ex (mm.) 12.8 8-22 Vel (mm./sec.) 45.0 30-100 Thick (mm.) 7.2 6-10

VS Ex (mm.) 8.6 5-13 Vel (mm./sec.) 33.9 20-50 Thick (mm.) 9.1 7-11

AS 6) 39 30-59 EF (%) 78 66-97 V(., (circum- 1.18 0.80-1.58

ferences /sec.)

PEP/LVET 0.29 0.23-0.36 EF slope (mm./ 102.0 70-130

13.6 8-20 50.6 30-80

7.8 7-9 7.7 5-12

32.9 25-50 9.4 7-14

38 21-54 75 42-90 1.13 0.40-1.67

0.31 0.23-0.36* 106.0 75-140

sec.)

*Includes only 20 subjects. Abbreviations: PW = left ventricular posterior wall; Ex = maximal excursion; Vel = maximal systolic velocity; Thick = thickness; VS = ventricular septum; %A5 = % shortening of left ventricular dimension; EF = ejection fraction; V,., = mean velocity of circum- ferential fiber shortening; PEP/LVET = pre-ejection period/left ventricular ejection; EF slope = maximal mitral valve EF slope.

Table Ill. Echocardiographic values in children

.~

1 Mean 1 Range 1 Mean 1 Range

PW Ex (mm.) 12.6 Vel (mm./sec.) 50.0 Thick (mm.) 7.5

VS Ex (mm.) 6.7 Vel (mm./sex.) 33.6 Thick (mm.) 9.0

AS 6) 42 EF (8) 80 V,., (cir./sec.) 1.21 PEP/LyET 0.28 EF slope 108.0

(mm./sec.)

7-17 10.3 a13 35-75 41.4 35-50

6-8 7.6 7-8 59 6.9 5-10

20-50 35.0 25-50 7-11 9.2 7-11

30-48 37 30-45 68-86 74 66-83

0.82-1.65 1.14 0.86-1.5 0.25-0.33 0.29 0.27-0.32*

85-130 110.0 loo-125

*Includes only two subjects. For abbreviations please refer to Table II.

580 May, 1978, Vol. 95, No. 5

Echo in alcoholics

Fig. 3. Normal echocardiogram of a left ventricular dimension in a chronic alcoholic patient following a long period of abstinence. VS = ventricular septum; PW = left ventricular posterior wall; ECG = electrocardiogram.

of chronic alcoholism,32. 33 the hyperkinetic left ventricular abnormality produced by these states differs greatly from the hypokinetic low cardiac output syndrome associated with the cardiac failure of the chronic alcoholic.”

Clinical experiments using normal volunteers and animals have shown transient depression of left ventricular function following acute ingestion of alcohol. This has been demonstrated by cardiac catheterization, echocardiography, and systolic time intervals measured in the conventional manner.25~27 Cardiomyopathy with clinically ob- vious cardiac decompensation has been docu- mented in chronic alcoholics who had no known evidence for underlying heart disease.15. 17-lg

Depression of left ventricular function has also been noted in chronic alcoholics who have had no clinical evidence of cardiac dysfunction.‘“. *I. L’3. 24 Regan and colleagues1g studied a group of chronic alcoholic subjects with cardiac catheterization using angiotensin infusion to increase left ventric- ular afterload. Significant abnormal elevation of left ventricular diastolic pressure as well as decreased left ventricular contractility were noted.

In two separate investigations Spodick and co- workersZ1 and Wu and associatesz3 studied chronic alcoholics who had no cardiac symptoms and found abnormal systolic time intervals indicating left ventricular dysfunction in both groups. Matthews and colleaguesz4 utilized echocardiog- raphy to evaluate 26 asymptomatic alcoholics and found 81 per cent with thickened left ventric- ular posterior walls and 35 per cent with decreased mitral EF slopes.

All except one in our study had normal echo- cardiographic indices of left ventricular function while none had evidence by history, physical

Fig. 4. Normal echocardiogram of the aortic root in a chronic alcoholic patient following a long period of abstinence. AV = aortic valve; CW = chest wall; ECG = electrocardio- gram.

examination, or ECG of ventricular dysfunction. The longer period of abstinence of our alcoholic population may account for this difference. The studies of Regan and colleagues1g were performed after approximately 3 weeks’ hospitalization, and the investigation of Wu and associateP was conducted on alcoholics with mean periods of abstinence of only 12 days. The alcoholics in the study by Spodick and co-workerP were examined 2 to 3 days after their last alcohol ingestion while the alcoholic group of Matthews and colleagueP were studied after only a two week minimum interval of abstinence. On the other hand, all our alcoholics had not ingested alcohol for a signifi- cantly longer period (mean duration 3.1 years) (Table I).

The period of active alcoholism in our group ‘appears comparable in duration to that of Regan and associates!9 (at least 10 years), Matthews and co-workers*’ (at least 6 years), and Wu and colleaguesZ3 (average duration of 15 years), while no information regarding this factor is found in the study by Spodick and collaborators.21

In view of the left ventricular dysfunction documented by others in chronic asymptomatic alcoholics within a short period of abstinence, it is possible that our population had abnormal left ventricular function when they were actively drinking or earlier in their period of abstinence and later reverted to normal. However, none of our subjects were studied while actively drinking or earlier in their period of abstinence and no data are available regarding the functional status of their left ventricle during that time. No assumptions can thus be made regarding the presence of left ventricular dysfunction in our subjects in the early stages of rehabilitation

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Reeves, Nanda, and Gramiak

despite the accounts in the literature. Although no longitudinal objective studies have so far been performed in symptomatic alcoholics with car- diac dysfunction, clinically demonstrable im- provement of their left ventricular failure has been- r&ported in significant numbers following complete cetiation of alcohol consumption.‘“, Is. 3’ Additiontilly, reversal of alcoholic cardiomyop- athy following abstention from alcohol has been documented by cardiac catheterization and angiography in a single instance.“j

It has been suggested that alcohol might damage the developing fetus, although direct proof is lacking.“” Alcohol freely passes the placental barrier, and high blood levels have been found in newborn infants comparable to those of their mothers.28 Alcohol withdrawal syndrome as well as central nervous system depression have been reported in the newborn.“7-39

In the present investigation only a small number of children with prolonged exposure to alcohol in utero were studied. However, the finding of normal left ventricular parameters in all of them would suggest that alcohol does not affect left ventricular function when these chil- dren are assessed by echocardiography after a long interval following exposure to alcohol.

shortening of the left ventricle (per cent AS), ejection fraction, mean velocity of circumferen- tial fiber shortening (mean V,,), excursions and maximal systolic velocities of the ventricular septum and left ventricular posterior wall, pre- ejection period/left ventricular ejection time ratios, mitral valve EF slopes, and thicknesses df the left ventricular posterior wall and ventricular septum were obtained in all. Normal left ventric- ular function was found in all but one adult alcoholic. In this patient, the per cent AS, ejection fraction, and mean V,, were reduced. One addi- tional adult alcoholic had a minimally thickened ventricular septum. Our results differ from other studies which have shown significant left ventric- ular dysfunction in asymptomatic chronic alco- holics. A possible explanation is the much longer period of abstinence of our chronic alcoholics at the time of their examinations. It also appears that left ventricular function in children born of alcoholic mothers is not affected when assessed after the long interval following prolonged expo- sure to alcohol in utero.

We are indebted to Carl Hatch of the Rochester Mental Health Center and to J. Chandler Terhune for help with this study. We thank Mrs. Summer King for typing the manu- script.

In conclusidn, our study demonstrates no clin- ical or echocaidiographic evidence of left ventric- ular dysfunction in asymptomatic chronic alco- holic agults or in children born of alcoholic mothers when studied following a long period after alcohol exposure. Although it might prove difficult, there is a need for a prospective longitu- dinal study of chronic alcoholics while they are drinking and serially during the course of their rehabilitation to objectively determine the inci- dence of left ventricular dysfunction induced by alcohol and its potential reversibility following alcohol withdrawal.

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Summary

Left ventricular function was analyzed using standard echocardiographic techniques in 26 chronic asymptomatic alcoholics without clinical evidence of cardiovascular disease. All were studied following a long period of abstinence (mean 3.1 years; range 3 months to 17 years). Seven asymptomatic children (mean age 14.1 years; range 4 to 19 years) whose mothers had been actively drinking throughout their pregnan- cies were also studied. The calculated fractional

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