Open Journal of Gastroenterology, 2013, 3, 344-348 OJGas Published Online December 2013 (
Cirrhotic cardiomyopathy among patients with liver
Tilahun Belay1, Todd Gress1, Rameez Sayyed2
1Department of Internal Medicine, Marshall University, Huntington, USA
2Department of Cardiovascular Medicine, Marshall University, Huntington, USA
Received 8 November 2013; revised 8 December 2013; accepted 19 December 2013
Copyright © 2013 Tilahun Belay et al. This is an open access article distributed under the Creative Commons Attribution License,
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Introduction: Cirrhotic cardiomyopathy (CCM) is a
clinical syndrome in patients with liver cirrhosis
characterized by an abnormal and blunted response
in cardiac output and contractility to physiologic,
pathologic, or pharmacologic stress but a normal to
increased cardiac response at rest [1-4]. Information
on the epidemiology and natural history of CCM is
limited. Methods: All patients with a diagnosis of cir-
rhosis (N = 451) seen at gastroenterology clinic over
the four years were evaluated. CCM was defined us-
ing echocardiogram (ECHO) and electrocardiogram
(ECG) criteria [1]. Patients with structural or ische-
mic heart disease or incomplete information were
excluded (N = 220). Results: Among the 231 patients
with cirrhosis, 118 (51.1%) met criteria for CCM,
and no patient had this problem documented in their
medical record. Those with CCM were older (62.7 vs
57.8 years; p < 0.001) and more likely to be female
(55.8 vs 40.2%; p = 0.02) compared to those without
CCM. The likelihood of CCM increased with each
quartil e of age (OR 1.6 per quartile; 95% CI 1.2 - 2 .0).
Patients with alcoholic and unknown causes of cir-
rhosis are more likely to have CCM, (p < 0.001).
CCM was more commonly associated with alcohol
abuse in men than women (49.1 vs 21.3 %; p = 0.002).
Conclusion: CCM, a diagnosis of exclusion, defined
by ECHO and ECG criteria is a common problem
among cirrhotic patients attending a gastroenterology
practice. Advancing age and female gender were as-
sociated with a higher prevalence of CCM, but the
cause of cirrhosis was not possibly limited by smaller
sa mple size within cause-spe cific categories. CCM was
not recognized by our clinicians, and routine screen-
ing tests were not performed. Provider awareness of
CCM is needed since implementation of angiotensin
receptor blocker and beta-blocker therapy early in
the course of cirrhosis may modify the changes in car-
diac function [5 ,6].
Keywords: Cirrhosis; Cardiomyopathy
CCM is a clinical syndrome in patients with liver cirrho-
sis characterized by an abnormal and blunted response to
physiologic, pathologic, or pharmacologic stress but nor-
mal to increased cardiac output and contractility at rest
[7-19]. CCM is a diagnosis of exclusion and other causes
of cardiac dysfunction including valvular heart disease,
congenital heart disease, ischemic heart disease, Conduc-
tion abnormalities, and hypertrophic cardiomyopathy
should be excluded. Previous studies on liver transplant
candidates have estimated that up to 50% of patients with
advanced cirrhosis have features of cardiac dysfunction
and 7% - 21% of post-operative deaths were attributed to
heart failure [20,21].
The epidemiology and natural history of CCM is not
well defined. It is felt that the onset is insidious, latency
time is long, and it is often undiagnosed, or a diagnosis is
made late in the course of the disease [1-4]. Irrespective
of the etiology, symptoms range from mild diastolic
dysfunction with progressive exercise limitation, to par-
oxysmal atrial fibrillation and ventricular arrhythmias, to
fulminant heart failure with biventricular dilatation, and
ventricular hypokinesis which becomes evident under
increased circulatory demands. It is associated with the
hepatorenal syndrome [1,10].
The increase in cardiac output and circulatory in-
travascular plasma volume and the hyperdynamic state of
cirrhosis induces a volume overload in cardiac muscle
T. Belay et al. / Open Journal of Gastroenterology 3 (2013) 344-348 345
which subsequently contributes to the myocardial hyper-
trophy, left atrial enlargement, isovolumic relaxation
time prolongation and a decreased early to late diastolic
flow ratio (E/A ratio). However, the decreased left ven-
tricular afterload, due to peripheral vasodilation, con-
ceals the systolic dysfunction, which remains normal at
rest and becomes evident only during stress, in the form
of an impaired chronotropic and inotropic response [2,
CCM is diagnosed based on electrocardiographic and
echocardiographic criteria [1]. Electrocardiographic ab-
normalities in CCM include QT prolongation (corrected
QT interval > 0.44 s) or multiple extrasystoles due to
hyperdynamic state, as well as bundle branch block and
electromechanical dyssynergy during acute decompensa-
tion and hypotension [1,15,16,19,22-24].
Echocardiographic features of CCM include prolonged
isovolumic time (>80 msec), E/A ratio 1, and de-
creased pattern of contractility with preserved systolic
function (LVEF > 50%) during the hyperdynamic state,
as well as decreased wall motion, increased wall thick-
ness and enlarged atrium during acute decompensation
and hypotension [1,15,16,19].
Current management recommendations of CCM in-
clude nonspecific supportive measures, pharmacological
therapy and liver transplantation. Patients my benefit
from salt restriction (to prevent water and sodium reten-
tion), administration of loop diuretics (to decrease renal
reabsorption of sodium and water), spironolactone and
angiotensin receptor blockers (to inhibit the renin-an-
giotensin axis and prevent left ventricular remodeling),
beta-blockers and nitrates (beneficial effect on adrener-
gic receptor density, improve the coronary arteries and
have venodilatory effects leading to preload reduction).
The extent of CCM generally correlates to the degree of
liver insufficiency. Most of the humoral and hemody-
namic alterations in terminal stage liver disease are re-
stored with time after liver transplantation. However, the
exact prognosis remains unclear [1,24-27].
The study was conducted among patients who were seen
at the gastroenterology clinics of the department of in-
ternal medicine at Marshall University between Jan 2008
and Nov 2011. The study was approved by the institu-
tional review board at Marshall University. Records of
all patients with diagnosis of Cirrhosis seen in this period
were and reviewed. Patients who had electrocardiograph
and echocardiograph were identified and reports re-
viewed. Patients with valvular heart disease, congenital
heart disease, ischemic heart disease, paced rhythm,
bundle branch block, hypertrophic cardiomyopathy or
evidence of any other gross structural heart disease were
excluded from the study.
Out of the 451 patients who had cirrhosis, 241 had ei-
ther or both of echocardiograph and electrocardiograph
documented in their records, whereas 210 have neither
on file and excluded from the study. Ten patients who
had evidence of structural heart disease (valvular heart
disease, congenital shunts), ischemic heart disease (CAD)
or primary systolic dysfunction were eliminated from the
study making the total number of study subjects 231.
Patients who had features of diastolic heart failure, spe-
cifically, prolongation of resting QT interval (corrected
QT interval > 0.44 sec), or had E/A ratio < 1, prolonged
deceleration time, decreased pattern of contractility, in-
creased wall thickness, with resting LVEF 50% and
with no structural lesions were considered to have CCM.
A descriptive analysis was performed examining the
pertinent variables. The Student’s t-test was used for con-
tinuous variables, and the Pearson X2 test and the
Fisher’s test for categorical variables. Multivariate ana-
lysis was performed including, age, gender, and the
causes of cirrhosis. All p-values were two-tailed with a
p-value of <0.05 set a priori and used as the level of sig-
nificance. All statistical analyses were performed using
SPSS version 19 for Windows (SPSS Inc., Chicago, IL,
The age of the study subjects ranged from 27 to 93 with
mean age of 60 years. Women accounted to 44.2% (102)
of the study population and men accounted to 55.8%
(129). The single most common cause of cirrhosis was
attributed to unknown causes (39.4%, N = 91), followed
by alcohol abuse (27.3%, N = 63) and viral hepatitis
(6.1%, N = 14) (see Ta b l e 1 ). A combination of alcohol
and hepatitis virus infection was present in 22 (9.5%),
alcohol and autoimmune liver disease in one patient and
that of infectious hepatitis and autoimmune liver disease
in another. Whereas, cause of cirrhosis was not docu-
mented in 29 (12.6%) of the cases.
Table 1. Causes of cirrhosis.
Cause of cirrhosis Frequency Percent Cumulative
Unknown cause 91 39.4 39.4
Alcohol 63 27.3 66.7
Hepatitis B or C infection14 6.1 72.8
Autoimmune hepatitis 10 4.3 77.1
Alcohol and viral hepatitis22 9.5 86.6
No cause documented 29 1.6 99.2
Other combination 2 0.8 100.0
Total 231 100.00
Copyright © 2013 SciRes. OPEN ACCESS
T. Belay et al. / Open Journal of Gastroenterology 3 (2013) 344-348
One hundred ninety five patients (84.4%) had EKG on
file. Eighty of these patients (41.0%) meet the criteria for
CCM by EKG alone. One hundred fifty five patients
(67.1%) had echocardiography report on file. Eighty two
of these patients (52.9%) meet the criteria for CCM by
echocardiography alone. One hundred eighteen (51.1%)
patients have either EKG or Echocardiography evidence
for cardiomyopathy. Cirrhosis patients are at a significant
risk of developing cardiomyopathy; p = 0.0007.
There was increasing trend in prevalence of CCM
across all quartiles of age (OR 1.6; 95% CI 1.2 - 2.0).
The likelihood increased by 1.6 times for each quartile
increase in age, p < 0.001.Sixty one (59.8%) female and
57 (44.2%) male cirrhotic patients had cardiomyopathy.
The mean age of women with CCM was 62 years and
that of men was 59 years. Patients with CCM were older
(p < 0.001) and female (p = 0.02) compared to those
without CCM.
Over all, patients with alcoholic cirrhosis and those in
which the cause of cirrhosis was not known were more
likely to have CCM compared to other causes of cirrho-
sis. Fifty three (58.2%) of the patients with unknown
causes of cirrhosis are women and 38 (41.8%) were men
(see Table 2). Seventeen (27.0%) of the patients with
alcoholic cirrhosis were female and 46 (73.0%) were
men. CCM is more common amongst men with alcoholic
cirrhosis than women when compared to unknown cause
of cirrhosis (X2 = 14.7, level of significant p < 0.001).
The study was not statistically powered to detect a dif-
ference among other causes (infectious, autoimmune
causes of cirrhosis) if one exists.
Liver cirrhosis is associated with a wide range of car-
diovascular abnormalities. These abnormalities include
hyperdynamic circulation characterized by an increase in
cardiac output and a decrease in peripheral vascular re-
Table 2. CCM among various causes of Cirrhosis.
Characteristic All Patients
(N = 231)
(N = 118)
(N = 113)p-value
Age, mean (SD) 60.3 (11.2)62.7 (11.0) 57.8 (11.0)<0.001
Gender, % Female 44.2 (102)51.7 (61) 36.3 (41)0.02
Cause (%)
Idiopathic (%) 39.4 (91)44.1 (52) 34.5 (39)
Alcohol only (%) 27.3 (63)25.4 (30) 29.2 (33)
Viral only (%) 6.1 (14)7.6 (9) 4.4 (5)
Alcohol and Viral (%) 9.5 (22)9.3 (11) 9.7 (11)
Autoimmune (%) 5.2 (12)4.2 (5) 6.2 (7)
Incomplete Workup (%) 12.6 (29)9.3 (11) 15.9 (18)
sistance. Despite the increased cardiac output, decreased
beta-adrenergic responsiveness (impaired ventricular
contractility in response to both physiological and phar-
macological stimuli) has been described. Other cardiac
abnormalities include structural changes including en-
largement or hypertrophy of different cardiac chambers
and electrophysiological changes such as QT prolonga-
tion (impaired electric “recovery” ability of ventricular
myocardium) [1-4,7-19,25]. This constellation of cardiac
abnormalities is termed CCM.
In our study, one hundred eighteen (51.1%) had either
EKG or Echocardiography evidence for cardiomyopathy
(p = 0.0007). In a previous study it was found that as
many as 50% of cirrhotic patients undergoing liver trans-
plantation showed signs of cardiac dysfunction [10,28-
30]. It is possible that the clinicians may have had a
higher index of suspicion for cardiac disease on patients
who have had the diagnostic testing and the rates of ab-
normalities to be higher in this subset of patients .Older
patients with cirrhosis have a higher likelyhood of hav-
ing cardiomyopathy (increase by 1.6 per quartile of age,
p = 0.0009). The extent of CCM generally correlates to
the degree of liver insufficiency [1,18,21,24-26]. It is not
clear if the difference in age related prevalence in our
study is due to the duration and or severity of the disease.
Sudden changes of hemodynamic state (vascular filling,
surgical or transjugular intrahepatic porto-systemic shunts,
and peritoneo-venous shunts), myocardial contractility
(introduction of betablocker therapy), and shortly after
orthotopic liver transplantation, can unmask the presence
of CCM, converting latent to overt heart failure. On the
other hand, liver transplantation may revert cardiac dys-
function. CCM plays a major role in the pathogenesis of
hepatorenal syndrome [1,10].
Over all, male patients with alcoholic cirrhosis were
more likely to have cardiomyopathy than women with
unknown causes of cirrhosis, (X2 =14.7, p < 0.001). This
could be because alcohol abuse may contribute to direct
cardiac dysfunction, although CCM has been clearly
documented to occur even in the absence of alcohol in-
gestion [10].
Recognition of CCM depends on the awareness of the
presence of this syndrome, particularly in patients with
advanced cirrhosis who undergo significant surgical,
pharmacological or physiological stresses [7,8,10,21,31].
A large number of cirrhosis patients had no work up
tailored towards screening for cardiomyopathy. Even
those who had tests and fulfilled the criteria for CCM,
the diagnosis was not documented on their records. This
may be due to lack of awareness as to the presence and
the magnitude of the problem. Since the cardiac reserve
is borderline in patients with cirrhosis, cardiovascular
status should be carefully monitored [10]. Cirrhosis pa-
tients should have screening for cardiac function once
Copyright © 2013 SciRes. OPEN ACCESS
T. Belay et al. / Open Journal of Gastroenterology 3 (2013) 344-348 347
diagnosis is made and at least prior to a scheduled major
procedure that can unmask the dysfunction and lead to
serious morbidity or death [32]. Regarding the screening
method, it appears that echocardiography identifies a
larger proportion of patients with cardiomyopathy than
EKG. Additional studies should be conducted to identify
the number of patients that would require screening di-
agnose CCM, the cost effectiveness of undertaking the
diagnostic testing as well as how early to start and how
frequent to undertake screening evaluation.
CCM is a common problem, but often under diagnosed.
A higher prevalence of CCM in our study was noted
amongst patients with advancing age, female gender,
alcoholic cirrhosis and patients in whom the cause of
cirrhosis was not identified. While a higher prevalence of
CCM was evident among patients in whom the cause of
cirrhosis is unknown and alcoholic cirrhosis, the study
was not statistically powered to detect a difference among
other causes (infectious, autoimmune causes of cirrhosis)
if one exists. A large number of patients have not had
screenings for CCM. Awareness should be increased
among providers to increase recognition and target ther-
We are grateful to Natalie Hartley (RN, BSN) who was the clinical
allscripts support and Melissa Marcum, (BSN, CCRC), research coor-
dinator for University Cardiovascular Services at Marshall University,
Joan C. Edwards School of Medicine for their support at the initial
phase of the study. We would like to thank Dr. Larry Dial, chairman of
internal medicine department at Marshall University, Joan C. Edwards
School of Medicine for his steady support at all times of the study.
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