Coexistence Of Cardiomyopathy And Chronic Liver Disease Health And Social Care Essay

Introduction: The dose-response relationship suggests a toxic effect of alcohol on heart and liver and

the possibility of a correlation between alcohol-induced liver and heart disease. The present study

was aimed to look into the relationship between chronic liver and heart muscle disease among the

non-moderate drinkers in our context.

Methods: An observational study on non-moderate chronic drinkers was carried out. Clinical

evaluation along with detail sonographic study of heart and liver was conducted.

Results: Fifty-eight percent had echocardiographic features consistent with heart muscle disease,

either as a dilated cardiomyopathy, categorized by the presence of echo features of impaired LV

systolic function and dilated left ventricle or as a possible cardiomyopathy categorized by the

presence of any of these two echo features. Similarly, 56 of the total recruits showed ultrasonographic

evidence of chronic liver disease as cirrhosis or early cirrhosis. Approximately, 86% of these 56 nonmoderate

drinkers with chronic liver disease also had echocardiographic features of heart muscle

disease and 83% of the 58 non-moderate drinkers showing echo features of heart muscle disease had

ultrasonographic features of chronic liver disease.

Conclusions: Our study showed a strongly positive relationship on the coexistence of chronic liver

disease and cardiomyopathy among the non-moderate drinkers. Non-moderate drinkers with

chronic liver disease have a high likelihood of having a concurrent clinical or sub-clinical heart

muscle disease and vice versa.

________________________________________________________________________________________

Keywords: alcohol; chronic liver disease; heart muscle disease; non-moderate drinking.

________________________________________________________________________________________

______________________________________

Correspondence: Dr. Mani Prasad Gautam, College of Medical

Sciences, Bharatpur, Chitwan, Nepal. Email: manigautam@hotmail.com,

Phone: 9851076043.

INTRODUCTION

Alcoholic beverages have been used and abused since

the dawn of history. In western communities, 90%

people drink alcohol once in a life time, 40 to 50%

of men have temporary alcohol induced problems and

10 to 20% of men and 3 to 10% of women develop

pervasive and persistent alcohol related problems.1,2

The effect of alcohol consumption on human health is

complex. Although the moderate intake appears to exert

a protective effect against coronary heart disease,3-5 the

non-moderate drinking increases overall mortality6 and

morbidity due to cardiovascular diseases.3 Alcoholism

CC S

BY NC OPEN ACCESS

original article J Nepal Med Assoc 2013;52(189):217-23

218 JNMA I VOL 52 I NO. 5 I ISSUE 189 I JAN-MAR, 2013

is associated with various adverse consequences to

health, including hypertension, dilated cardiomyopathy

(DCM), arrhythmias and stroke. Long-term alcohol

consumption is often complicated by various forms of

chronic liver disease (CLD) and heart muscle disease

(HMD) including DCM.7,8 It also has other effects

including the increase in cancer risk, adverse interaction

with other medications and exacerbation of most

medical and psychiatric disorders.

The pathogenesis of these alcohol-induced disorders

remains speculative.9,10 Both CLD,11 and HMD,12 have

been related to the total lifetime dose of ethanol intake.

Alcohol-induced HMD is a group of life style-related

cardiovascular disorders caused by excessive alcohol

consumption for a long time, where a putative role of

alcohol is determinant and alcohol and its metabolites

have a direct role in pathogenesis. Alcohol-induced CLD

is a group of liver diseases caused by excessive and

prolonged intake of alcohol; it might comprise various

liver changes such as fatty liver, early cirrhosis and

cirrhosis. Because of its multi-factorial origin including

obesity, diabetes and other various medical conditions,

the fatty liver cannot be solely considered as a condition

due to alcohol intake. Nevertheless, these doseresponse

relationships suggest a toxic effect of ethanol

on these tissues and the possibility of a relationship

between alcohol-induced disorders of the liver and

the heart. Contrary to such expectation, there was an

anecdotal perception of an inverse relationship between

cirrhosis and cardiomyopathy in chronic alcoholics,13,14

and it was widely believed that alcoholics who develop

cirrhosis are somehow spared from heart disease,

and vice versa. However, a number of studies has

questioned the inverse relationship between these two

complications of alcoholism,15 and had shown that

patients with alcohol-induced cirrhosis do suffer from

subclinical or clinical impairment of cardiac function.16-18

To investigate this issue, we studied the liver and heart of

non-moderate drinkers who were admitted or consulted

to the hospital for various medical problems related or

unrelated to cardiovascular and gastrointestinal system.

METHODS

This study was conducted during 2010-2011 at a

1050-bedded multispecialty tertiary referral center

in central Nepal. Study was approved by the Ethical

Committee of the hospital.

Patient Selection: Over a period of one year, 228

non-moderate drinkers were recruited and evaluated

out of which only 100 subjects were included in final

analysis. Patients were selected from in-patient and

outpatient department independent of symptoms. All

subjects were Nepalese. No patient objected to being

in the study, and all gave informed consent for the noninvasive

procedures, data collection and sharing.

Any subjects with non-moderate drinking; i.e. at risk

drinking equivalent to a minimum of two standard drinks

or 25 gram of ethanol per day (more than two standard

drinks per day is equivalent to 250 ml of homemade

liquor or 230 ml of non- fortified wine, 86 ml of whisky

or vodka) for 10 or more years aged between 35–55

years were included in the study.19,20

Subjects with severe hypertension, known rheumatic

heart disease, known coronary heart disease, congenital

heart disease, advance neurological disorders, chronic

kidney disease stage III-V, cor pulmonale and heart

failure NYHA IV were excluded from the study. The

subjects with a chronic liver disease of known cause

except alcohol and subjects with positive serology to

HIV, HBsAg, and anti-HCV were excluded from the

study. Similarly the subjects with known hypertension,

females in peripartum period, seriously ill subjects and

subjects with unsatisfactory echo window or incomplete

data were also excluded.

Study Protocol: A detailed clinical and social history

was obtained and detail clinical examination was carried

out to establish a clinical diagnosis. The history of

alcohol drinking including types, frequency and average

amount were recorded. The current daily intake was

considered to be the average of alcohol consumed per

day during the last month. Life events such as marriage,

military service, festivals and work posts were used

as ‘anchor points’ to assist in recollection (time-line

follow-back method).21 Information regarding signs or

symptoms referable to heart or liver disease was also

obtained. These data were independently confirmed

with family members. The total lifetime dose of ethanol

was estimated by adding the total amounts ingested

during these anchor points as well. Each subject was

taken for detail echocardiographic examination. The

presence of chronic liver disease was ascertained

by the ultrasonographic examination of liver. For the

calculation of daily intake amount and lifetime intake

amount of ethanol, the strength of various alcoholic

beverages was taken as: beers - 3.4 - 9% v/v, white

wine - 8 - 13% v/v, vodka - 37.5 - 57.5% v/v, whisky

- 32 - 40% v/v, rum - 32 - 40% v/v.22

Heart Disease: Cardiovascular examination was

performed in the morning in empty stomach with

abstinence of alcohol at least for 12 hours but not

more than 24 hours to avoid the acute effects of

ethanol on the cardiovascular system and to avoid

Mani et al. Coexistence of Cardiomyopathy and Chronic Liver Disease in Non-Moderate Drinkers

JNMA I VOL 52 I NO. 5 I ISSUE 189 I JAN-MAR, 2013 219

the onset of withdrawal features. Apart from routine

cardiovascular evaluation with ECG and chest X-ray,

detail echocardiographic evaluation with M-mode,

2D and Doppler study including wall motion analysis

was carried out to establish structural and functional

abnormalities. The mass of the left ventricle was also

calculated and interpreted as described elsewhere.23 All

these measurements were performed according to the

recommended standards of the American Society of

Echocardiography.24 Diastolic dysfunction was defined

as E/A ratio equal or less than one, dilated left atrium

(LA) and LV were defined as index more than 2.2 cm/

m2 and 3.2 cm/m2 respectively.25 Alcohol-induced heart

muscle disease was defined as the conditions causes by

chronic consumption of alcohol with echocardiographic

features suggestive of DCM or possible DCM. Subjects

were labeled as having DCM,26 in the presence of LVEF

< 45% and dilated LV i.e. LVIDd/BSA >3.2 cm/m2.

If there was only one of them, possible DCM was

diagnosed.27 Subjects having other structural changes

such as LV hypertrophy, LV diastolic dysfunction and

valvular lesions were not included in the HMD as the

causative relationship of alcohol and these conditions is

not well established.28

Liver Disease: Detail clinical and laboratory evaluation

including liver function test and serological markers

was carried out to reach a clinical diagnosis for the liver

condition. Liver condition was assessed mainly based

on ultrasonographic (USG) features and classified as

normal, fatty liver, early cirrhosis and cirrhosis. Invasive

procedures were not used for the diagnosis. Increased

liver size more than 12 cm with fatty deposition of

various grades was classified as fatty liver and it was

not included in alcohol-induced CLD while analyzing

final results because of presumed multi-factorial origin

of this condition. Alcohol-induced CLD for the analysis

purpose was defined as a condition with USG features

suggestive of cirrhosis or early cirrhosis; hepatomegaly

with coarse echotexture without the features of

portal hypertension was labeled as early cirrhosis and

decreased liver size or normal liver size with coarse

echo texture and the presence of portal hypertension

was classified as cirrhosis.

Statistical Analysis: The data obtained were analyzed

using statistical software package SPSS 17.0. The mean

and standard deviation (SD) of various variables were

calculated and expressed as mean ± SD. Parametric

and nonparametric tests were used as appropriate.

The significance of any differences in means between

various groups was tested using F or student’s t test.

The confidence intervals were calculated at the 95%

level. P values <0.05 were considered statistically

significant at 5% level and <0.01 at 1% level.

RESULTS

Out of total 228 subjects evaluated only 100 nonmoderate

drinkers’ subjects were included in the data

analysis. Out of 128 subjects excluded, 84 subjects

had alternative diagnosis for their echocardiographic

and USG features other than alcohol. Twenty-four

subjects had inadequate USG parameters to comment

on liver changes and 20 subjects had poor quality of

echo window for satisfactory interpretation (Figure 1).

Mean age was 45.1±7.7 years. Two-thirds were male

(Table 1).

Figure 1. Distribution of study subjects.

subject evaluated

228

subject excluded

128

subject included

100

Alternative

diagnosis

84

Poor echo

window

20

Subjects

without HMS

42

Subjects

with CLD

48

Subjects

without CLD

10

Subjects

without CLD

34

Subjects

without CLD

44

Subjects

with CLD

8

Subjects

with CLD

56

Subjects

with HMS

58

Incomplete

USG report

24

___________________________________________________

Mani et al. Coexistence of Cardiomyopathy and Chronic Liver Disease in Non-Moderate Drinkers

220 JNMA I VOL 52 I NO. 5 I ISSUE 189 I JAN-MAR, 2013

Table 1. Characteristics of subjects.

Parameters Male (n = 68) Female (n = 32) Total (n = 100)

Mean age 44.9±8.1 45.6±6.9 45.1± 7.7

Male:Female 2.13:1

Age range (years) 30-55 32-55 30-55

BMI (kg/m2) 20.9±3.1 23.4±4.8 21.7±3.9

BSA (m2) 1.6±0.2 1.5±0.2 1.6±0.2

Smoking (%) 68 63 66

Daily alcohol intake (g) 68.7±32.9 56.25±26.43 64.7±22.1

Lifetime intake amount (kg) 575.4±336.7 414.6±234.2 523.9±314.6

Duration of alcohol intake (years) 22.6±7.9 21.1±8.2 22.1±7.9

Lifetime intake range (kg) 91.3-1277.5 175.2-1007.4 91.25-1277.5

_____________________________________________________________________________________

Their reported daily intake of ethanol ranged from

25 to 150 g (mean, 64.7±22.1 g)over a period of

22.1±7.9 years. Mean lifetime alcohol amount was

523.9±314.6 kg with a range of 91.2 to 1277.5 kg.

The lifetime intake of alcohol was less than 250 kg in

14%, 250-500 kg in 44% and more than 500 kg in 42%

alcohol users. Only 32% subjects were symptomatic

for cardiovascular symptoms; palpitation and dyspnea

in combination were the only specific symptoms

significantly associated with impaired LVEF (P <0.05).

Other symptoms were equally common in subjects

with or without HMD. Similarly only 40% subjects

were symptomatic for chronic liver disease. Abdominal

distension and gastrointestinal bleeding were the only

specific symptoms significantly associated with the

presence of CLD (P <0.01). Fifty-eight percent and

56% alcoholic subjects had HMD and CLD respectively

with almost similar rate among male and female, with a

trend to lower value of lifetime intake amount of alcohol

(575.4±336.9 vs 414.6±234.2 kg) in women.

In an analysis where a comparison was made between

the subjects with CLD (subjects with USG features

suggestive of cirrhosis and early cirrhosis) and the

subjects without CLD (subjects with USG features

suggestive of normal or fatty liver), significantly higher

amount of daily intake alcohol (79.5 vs 45.9 g/day,

P <0.001), duration (24.3 vs 19.5 years, P <0.05)

and total lifetime intake amount (694.3 vs 307.2 kg,

P <0.001) was observed in CLD and without CLD

subjects respectively. Similarly the CLD group had

low mean LVEF (40 vs 58%, P <0.001) and the high

incidence of HMD (86 vs 23%, P <0.001) (Table 2).

Table 2. Various drinking parameters in subjects with CLD and without CLD.

Parameters CLD (n = 56) No CLD (n = 44) P value

Age 45.9 ±6.2 44.2±9.4 NS

M:F 2.22:1 2:1 NS

Daily intake of alcohol (g/day) 79.5±30.3 45.9±21 <0.001

Duration of alcohol intake (years) 24.25±6.6 19.5±8.8 <0.05

Lifetime intake amount (kg) 694.3±299.3 307.2±166.6 <0.001

HMD (%) 86 23 <0.001

LVEF (%) 39.8±10.9 58.2±7.9 <0.001

Impaired LVEF (%) 64 9 <0.001

LVM Index (kg/m2) 121.0±27.8 95.4±26.4 <0.001

Increased in LVM (%) 57 32 NS

Diastolic dysfunction (%) 36 59 NS

Dilated LV (%) 82 14 <0.001

Dilated LA (%) 75 12 <0.001

Regurgitations (%) 75 18 <0.001

_N_S_ _–_ _n_o_t_ _s_ig_n_i_fi_c_a_n_t_ _(P__ >__0__.0_5__)_____________________________________________________________________________

Mani et al. Coexistence of Cardiomyopathy and Chronic Liver Disease in Non-Moderate Drinkers

JNMA I VOL 52 I NO. 5 I ISSUE 189 I JAN-MAR, 2013 221

In another analysis, the drinking parameters,

ultrasonographic features of liver and liver function

tests of subjects with HMD were compared with that

of without HMD (Table 3).

Table 3. Various parameters among subjects with HMD and without HMD.

Parameters HMD (n = 58) No HMD (n = 42) P value

Age (years) 47.7±5.9 41.6±8.4 <0.01

M:F 20:9 14:7 NS

Daily intake of alcohol (g/day) 78.6±31.3 45.5±18.3 <0.001

Duration of alcohol intake (years) 25.5±7.0 17.52±6.7 <0.001

Lifetime intake amount (kg) 706.1±289.2 272.4±101.5 <0.001

CLD (%) 83 19 <0.001

AST/ALT >2 (%) 40 50 NS

Serum albumin level (g/dl) 2.69±0.9 3.2±0.9 <0.05

Decreased albumin level (%) 82 55 <0.05

Prothrombine time (min) 4.9±3.0 5.3±4.1 NS

Raised prothrombine time (%) 62 50 NS

_N_S_ _–_ n_o_t_ s_ig_n_i_fi_c_a_n_t_ (_P_ >_0_._0_5_)___________________________________________________________________________________

The duration, daily intake, and life time intake amount

of alcohol were significantly higher among subjects

with HMD (25.5 vs 17.5 years, P<0.05, 78.6 vs 45.6

g/day, P <0.001 and 706.1 vs 272.4 kg, P<0.001

respectively). The proportion of subjects with CLD was

high among HMD subjects (83 vs 19%, P<0.001).

Markers of acute liver damage were raised in both

groups, but the statistically significant difference

was not seen. However, the markers more reflecting

chronic liver disease such as the serum albumin were

significantly lower among subjects with HMD. Nearly

82% subjects with HMD in comparison to 55% subjects

without HMD had decreased albumin level (P <0.001).

The prothrombine time was also raised in both groups

but there was no significant difference among them.

DISCUSSION

This is the first of its kind study from Nepal. The results

of our study are also at variance with the past-held

view of an inverse relationship between cirrhosis and

cardiomyopathy in chronic alcoholics,13,14 and supports

alternative views on this regard.15-18 Majority of the

alcoholics (56%) had chronic liver disease in the form

of cirrhosis or early cirrhosis, remaining had either fatty

liver or normal liver, whereas 58% alcoholics suffered

from HMD in the form of DCM or possible DCM. The

results of this study clearly indicate that HMD and CLD

not only may coexist, but that they often do so. In

one side, more than 85% subject with CLD also had

HMD; in another side more than 82% subjects with

HMD also had CLD. In contrast to this, only 19.05%

alcoholic subjects without HMD had CLD and only

22.72% subjects without CLD had HMD. These data

also suggest that alcoholics who are relatively resistant

to the effects of chronic alcohol intake on the heart also

manifest some degree of resistance in the liver as well.

In our study the cardiac dysfunction was common

in patients with CLD, and more than 85% subjects

with chronic liver disease had evidence of dilated

cardiomyopathy or possible DCM. The possibility of

cardiac impairment as a secondary effect of chronic liver

disease can also be raised, but it seems very unlikely.

Estruch et al,29 had studied the cardiac function in

non-alcoholic cirrhosis and had found entirely normal

cardiac function in all non-alcoholic cirrhotic subjects.

They also showed that the alcoholics with normal

cardiac function who had been drinking large amounts

of ethanol had a much lower incidence of cirrhosis than

did similar patients with documented alcohol-induced

heart muscle disease.

The demonstration of higher rates of DCM and possible

DCM in patients with CLD is in accord with previous

studies that have shown preclinical cardiac dysfunction

or latent cardiomyopathy in chronic alcoholics with

liver disease.16-18,29-32 Indeed, the low systemic vascular

resistance, especially in cirrhotic with ascites,33 may

mask the signs of cardiac dysfunction, which may be

apparent when the vascular resistance is increased

towards normal,30 or when the patient is subjected to

volume or pressure overload.16 In our study, significant

number of alcoholic subjects also had left ventricular

diastolic dysfunction which was more common among

the subjects without CLD. Its incidence had decreased

among subjects with CLD where the incidence of LV

Mani et al. Coexistence of Cardiomyopathy and Chronic Liver Disease in Non-Moderate Drinkers

222 JNMA I VOL 52 I NO. 5 I ISSUE 189 I JAN-MAR, 2013

systolic dysfunction was high. This could be because

of the pseudonormalization of diastolic function when

the systolic dysfunction is present.22

Although the pathogenesis of HMD including DCM,9

and CLD including cirrhosis,10 has not been clearly

defined, the correlation between cardiac and liver

diseases on the one hand and the dose-response

relationship between these disorders and ethanol

consumption on the other,11,12 suggest the possibility of

a common pathogenetic mechanism at the cellular level.

Cardiovascular death is an important cause of mortality

in alcoholics.34 In view of the substantial prevalence

of cardiomyopathy in alcoholics with liver disease,

the occurrence of sudden death in alcoholics with

cirrhosis or fatty liver,35,36 likely reflects an increased

susceptibility to fatal arrhythmias.

Some of the cardiovascular abnormalities in our alcoholic

subjects can also be a part of cirrhotic cardiomyopathy,

a clinical syndrome in patients with liver cirrhosis

characterized by an abnormal and blunted response to

physiologic, pathologic, or pharmacologic stress.37,38 It

is difficult to delineate which abnormalities are the part

of DCM and which the part of cirrhotic cardiomyopathy.

Although this was the beyond the scope of our study,

we assume that few of the findings could also be the

part of cirrhotic cardiomyopathy in some subjects and

this issue needs on further clarification and studies.

This study has some limitations; most of them were

inherent to its descriptive nature. In addition, the sample

size was very small and all the subjects were alcoholics

only; the conclusion on the extent of echocardiographic

abnormalities in non-alcoholic chronic liver disease

cannot be derived. Similarly we do not know the

incidence of these studied parameters such as DCM and

chronic liver disease in normal population. Therefore,

few of the conditions in liver and heart may not be

fully related to alcohol intake only or can also be a part

of cirrhotic cardiomyopathy. Moreover, our study of

alcoholic liver diseases and its classification is solely

dependent on ultrasonographic parameters only and

may not be acceptable to all.

CONCLUSIONS

A relationship exists between HMD and CLD. Nonmoderate

drinkers with HMD have a higher prevalence

of symptomatic and non-symptomatic CLD. Similarly

non-moderate drinkers with CLD show higher rates of

symptomatic or asymptomatic HMD. In other hand,

alcoholic subjects free from either heart or liver disease

are more likely to be free from toxic effects in another

organ too. Therefore, despite unknown pathogenesis

of HMD and CLD, the coexistence of cardiac and

liver diseases on the one hand and the dose-response

relationship between these disorders and alcohol

consumption on the other, suggest the possibility of

a common pathogenetic mechanism at the cellular

level. This study, despite its observational nature and

small size, is clearly successful to show the concurrent

existence of HMD and CLD in alcoholic subjects. A

more precisely designed prospective study with large

sample size will be crucial for further clarification and

strengthening the results of present study.

Mani et al. Coexistence of Cardiomyopathy and Chronic Liver Disease in Non-Moderate Drinkers