Journal of Cardiology 67 (2016) 140–146

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Journal of Cardiology
journal homepage: www.elsevier.com/locate/jjcc

Original article

A detailed evaluation of cardiac function in cirrhotic patients and its

alteration with or without liver transplantation
Yan Chen (MD)a,1, Albert C. Chan (MD)b,1, See-Ching Chan (MD)b, Siu-Ho Chok (MD)b,
William Sharr (MD)b, James Fung (MD)b, Ju-Hua Liu (MD)a, Zhe Zhen (MD)a,
Wai-Ching Sin (MBBS)a, Chung-Mau Lo (MD)b, Hung-Fat Tse (MD, PhD)a,c,*,
Kai-Hang Yiu (MD)a,c,*
a
Division of Cardiology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
b
Division of Surgery, The University of Hong Kong, Hong Kong, China
c
Research Centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

A R T I C L E I N F O A B S T R A C T

Article history: Background: Cirrhosis has been shown to be associated with left ventricular (LV) myocardial dysfunction,
Received 24 June 2015 but studies of right ventricular (RV) function in cirrhotic patients compared with controls are scarce.
Received in revised form 13 July 2015 Limited studies have prospectively evaluated the progression of myocardial function in patients with
Accepted 20 July 2015
cirrhosis and assessed changes in cardiac function following liver transplantation (LTx). So the aim of the
Available online 21 August 2015
study was to evaluate biventricular myocardial function in cirrhotic patients and its alteration with or
without liver transplantation.
Keywords:
Methods: A total of 103 patients with cirrhosis (age 55  7 years, male 75%) were recruited. Conventional
Cardiac function
and 2-dimensional speckle tracking echocardiography was performed to determine the presence of LV and
Cirrhosis
Liver transplantation RV (biventricular) dysfunction. For comparison, 48 matched control subjects were included. Follow-up
echocardiography was performed in 41 patients following LTx and in 26 patients who did not undergo LTx.
Results: Patients with cirrhosis had biventricular dilatation, increased LV mass, impaired LV diastolic
function, and biventricular systolic strain compared with controls. Following LTx, cirrhotic patients had
reduced biventricular dilatation, a smaller LV mass, and improved biventricular systolic strain after a
mean duration of 18.2  6.6 months. Patients who did not undergo LTx had a further increase in LV mass but
no significant change in biventricular dimensions or systolic strain (mean duration of 20.4  8.3 months).
Conclusions: The present study demonstrates that patients with cirrhosis had biventricular dilatation
and impaired biventricular systolic strain compared with controls. Following LTx, biventricular
dilatation reduced and biventricular systolic strain improved. In contrast, patients who did not undergo
LTx experienced a further increase in LV mass.
ß 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Introduction the use of advanced 2-dimensional (2D) speckle tracking derived

Patients with cirrhosis have been shown to have myocardial
dysfunction: a distinct entity termed cirrhotic cardiomyopathy has
been attributed to this phenomenon [1,2]. Previous studies using
echocardiography have demonstrated that patients with cirrhosis
have impaired left ventricular (LV) diastolic function [3,4]. With
* Corresponding authors at: Cardiology Division, Department of Medicine, The
University of Hong Kong, Room 1929B/K1931, Block K, Queen Mary Hospital, Hong
Kong, China. Tel.: +852 22553633/22553598; fax: +852 28186304.
E-mail addresses: hftse@hku.hk (H.-F. Tse), khkyiu@hku.hk (K.-H. Yiu).
1
Dr Chen and Dr Chan are considered to be co-first authors.
strain analysis that enables detection of subtle myocardial
dysfunction, a recent study has further shown that patients with
cirrhosis have impaired LV myocardial contractility [5]. Nonethe-
less these studies have been cross-sectional and the focus was on
degree of LV dysfunction in cirrhotic compared with non-cirrhotic
subjects.
Recently, right ventricular (RV) function has been shown to be
superior to LV function in the prediction of adverse clinical
outcome in patients with cirrhosis who undergo liver transplanta-
tion (LTx) [6]. Nonetheless studies of RV function in these patients
compared with controls are scarce. Further, only limited studies
have prospectively evaluated the altered myocardial function in
patients with cirrhosis and assessed the changes following LTx

http://dx.doi.org/10.1016/j.jjcc.2015.08.001
0914-5087/ß 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
 Y. Chen et al. / Journal of Cardiology 67 (2016) 140–146
[7,8]. Therefore the aim of the present study was to compare the LV
and RV (biventricular) function in cirrhotic patients with controls
and prospectively evaluate the difference in progression of
biventricular function in cirrhotic patients with and without LTx.
Patients and methods
Study population
From January 2011 to August 2013, a total of 103 consecutive
Chinese patients with cirrhosis, aged over 18 and referred to the
Department of Surgery at Queen Mary Hospital (the only center in
Hong Kong) for LTx were recruited. Patients with any one of the
following were excluded: documented history of cardiovascular
disease including coronary artery disease, myocardial infarction,
stroke or peripheral vascular disease, acute liver failure, and LTx
not related to liver cirrhosis. Patients with clinical and echocar-
diographic features of hepato-pulmonary syndrome and pulmo-
nary hypertension were also excluded. For comparison, 48 control
subjects recruited from a health screening program organized by
the Cardiology Division, Department of Medicine, The University of
Hong Kong, were matched with patients for age, sex, body mass
index (BMI), and cardiovascular risk factors.
The study was approved by the local institutional ethics board
and all subjects gave written informed consent.
Study protocols
Data on baseline demographics and clinical characteristics, and
blood sampling were obtained prospectively on the same day in all
study subjects after overnight fasting. BMI and conventional
cardiovascular risk factors such as history of diabetes mellitus
(defined as a serum fasting glucose 7.1 mmol/L or prescription of
anti-hyperglycemic medication), and hypertension (defined as
either resting systolic or diastolic blood pressure 140/90 mmHg
on two occasions or prescription of antihypertensive medication)
were documented. The use of medications, including beta blocker,
calcium channel blocker, angiotensin-converting enzyme inhibi-
tors/angiotensin receptor blockers, and diuretics were recorded in
patients. Clinical status was assessed by the Child-Pugh score and
the model for end-stage liver disease (MELD) score.
Conventional echocardiography
All patients with cirrhosis and controls were imaged in the left
lateral decubitus position using a commercially available echo-
cardiography system (Vingmed Vivid 7, General Electric Vingmed
Ultrasound, Milwaukee, WI, USA). A 3.5-MHz transducer was used
to obtain images that were digitally stored in cine-loop format
(3 cardiac cycles). Offline analysis was performed using EchoPAC
version 108.1.5 (General Electric – Vingmed, Horten, Norway). The
LV end-diastolic septal and posterior wall thickness, LV dimen-
sions, volumes, and ejection fraction were measured according to
the current recommendations [9]. LV mass was calculated using
Devereux’s Formula [10]. Evaluation of LV diastolic function was
based on the pulsed-wave Doppler of mitral valve inflow,
measuring peak early diastolic velocity (E), peak late (A) diastolic
velocity, and E/A ratio. Using tissue Doppler imaging, the early
diastolic velocity (E0 ) was measured at the level of the LV basal
lateral segment. In addition, E/E0 ratio was calculated as an
estimation of LV filling pressure [11]. LV diastolic dysfunction was
therefore categorized as previously described: normal; mild,
defined as LV impaired relaxation without evidence of increased
filling pressure; moderate, defined as LV impaired relaxation
associated with moderate elevation of filling pressure or pseudo-
normal filling; and severe, defined as restrictive LV filling [11].
141
Right ventricular end-diastolic area (RVEDA) and right ventric-
ular end-systolic area (RVESA) were measured by manually tracing
the RV endocardial border on the apical 4-chamber view; care was
taken to obtain a true non-foreshortened view oriented to obtain
the maximum RV dimension. The right ventricular fractional area
change (RVFAC) was calculated using the following equation:
(RVEDA  RVESA)/RVEDA  100% [9], with a lower reference valve
for normal RV systolic function of 35%. Tricuspid annular plane
systolic excursion (TAPSE) was measured from the apical 4-
chamber view: an M-mode cursor was placed through the
tricuspid annulus and the displacement of the base of the RV
free wall along the cursor from end-diastole and end-systole was
measured, with a lower reference value for impaired RV systolic
function of 1.6 cm. Finally, right ventricular systolic pressure
(RVSP) was determined from peak tricuspid regurgitation velocity
by continuous-wave Doppler using simplified Bernoulli equation
and combining this value with an estimate of the right atrial
pressure (RAP): RVSP = 4(V)2 + RAP. For conventional echocardi-
ography parameters, RV systolic function was quantified with
RVFAC and TAPSE.
Two-dimensional speckle tracking strain analysis
Two-dimensional speckle tracking strain analysis is an ad-
vanced imaging technique that provides detailed assessment of
myocardial deformation by tracking natural acoustic markers
(speckles) on a frame-to-frame basis within the cardiac cycle. The
speckles are detected on the standard gray-scale 2D images and are
distributed evenly within the myocardium.
Myocardial systolic strain of the LV can be assessed in three
orthogonal directions: longitudinal strain, circumferential strain,
and radial strain. The detailed measurement of LV systolic strain
was determined from the 3 apical (2-, 3-, and 4-chamber) views
and has been described in detail [12,13]. Global longitudinal and
circumferential strains are expressed as negative values, and a
lower strain is represented by a less negative value. Global radial
strain is expressed as a positive value, and a lower value indicates
lower strain.
The measurement of RV global longitudinal systolic strain using
2D speckle tracking analysis has been described previously
[14,15]. Briefly, from the apical 4-chamber view, a region of
interest (ROI) was manually traced along the endocardial border of
the RV free wall and septal wall, and the width was set to match
wall thickness. The tracked ROI was visually checked and adjusted
if necessary and the RV global longitudinal strain calculated
(Fig. 1). RV longitudinal strain is expressed as a negative value: a
lower strain is represented by a smaller negative value.
Follow-up echocardiography
During the study period, 41 patients underwent LTx and a
repeat echocardiography was performed after a mean duration of
18.2  6.6 months following LTx. A total of 62 patients remained on
the waiting list for LTx; 14 patients refused a follow-up echocardiog-
raphy evaluation and 22 patients died during the study period.
Accordingly, 26 patients who did not receive LTx underwent a follow-
up echocardiogram at 20.4  8.3 months as well as baseline
echocardiography.
Statistical analysis
Data are expressed as mean  standard deviation for continuous
variables and frequencies or proportions for categorical variables.
Continuous demographic variables of the two groups were compared
using independent sample Student’s t test. Categorical demographic
variables were compared using Pearson Chi-square test or the Fisher’s
142 Y. Chen et al. / Journal of Cardiology 67 (2016) 140–146

Fig. 1. An example of right ventricle (RV) systolic strain at longitudinal direction measured by 2-dimensional speckle tracking analysis from the apical 4-chamber view. Each
color denotes a regional segmental strain (a total of 6 segments) and the RV systolic strain is calculated as the average value for peak strain of the 6 segments. The white arrow
denotes the directions of longitudinal strain.

exact test if at least one cell had an expected cell count below five.
Comparison of changes for those who underwent LTx (pre-LTx and
post-LTx echocardiography) and those who did not (baseline and
follow-up echocardiography) were performed by paired Student t
tests. All statistical analyses were performed using the statistical
package SPSS for windows (Version 18.0, SPSS, Chicago, IL, USA). All
p-values reported are 2-sided for consistency. A p-value <0.05 was
considered statistically significant.
Results
Clinical characteristics
cirrhosis, creatinine level, BMI, the prevalence of hypertension,
diabetes, and current smoking were nonetheless similar between
the two groups (Table 2).
Biventricular echocardiographic parameters in patients and controls
Comparison of echocardiographic parameters in patients with
cirrhosis and controls is shown in Table 3. Patients with cirrhosis
had a larger LV dimension, increased LV end-diastolic septal
thickness, and greater LV mass. The prevalence of diastolic
dysfunction and E/E0 ratio was also larger in patients with

Table 2
The baseline characteristics of patients with cirrhosis and Clinical characteristics of patients with and without liver transplantation (LTx).
controls are shown in Table 1. The age, gender, BMI, and the
prevalence of hypertension, diabetes, and smoker status were Patients with Patients p
LTx (n = 41) without
similar between the two groups. Nonetheless patients with
LTx (n = 26)
cirrhosis had lower systolic blood pressure, diastolic blood
pressure, and higher heart rate than controls (Table 1). Age (years) 54.9  7.7 54.1  8.2 0.69
Male, n (%) 30 (71.4) 19 (73.1) 0.99
The majority of patients were male and in over 60% of cases Etiology
cirrhosis was due to viral hepatitis. Up to three quarters of patients Alcohol, n (%) 6 (14.6) 3 (11.5) 0.50
had a Child-Pugh grade B or higher degree of cirrhosis. For those Viral, n (%) 30 (73.2) 17 (65.4)
who underwent a second echocardiogram, patients who had Other causes, n (%) 5 (12.2) 6 (23.1)
Child-Pugh Grade
undergone LTx had worse Child-Pugh grade, higher MELD score,
A 7 (17.1) 12 (46.2) <0.01
bilirubin, international normalized ratio level, and lower albumin B 11 (26.8) 10 (38.5)
level than those without LTx (Table 2). The age, gender, etiology of C 23 (56.1) 4 (15.3)
MELD score 21.3  8.9 12.2  5.6 <0.01
Bilirubin (mg/dl) 225.5  231.0 60.2  100.0 <0.01
Table 1
Albumin (g/dl) 31.9  7.0 35.6  6.8 0.04
Clinical characteristics of patients with cirrhosis and controls.
Creatinine (mg/dl) 87.6  37.5 90.3  28.5 0.76
Cirrhosis Controls p International normalized ratio 1.7  0.5 1.3  0.3 <0.01
(n = 103) (n = 48) Body mass index (kg/m2) 24.1  4.3 24.9  5.9 0.50
Hypertension, n (%) 10 (24.4) 7 (26.9) 0.82
Age (years) 54.9  7.3 53.5  7.9 0.28 Diabetes mellitus, n (%) 7 (17.1) 7 (26.9) 0.33
Male, n (%) 77 (74.8) 32 (66.7) 0.30 Smoker, n (%) 3 (7.3) 5 (19.2) 0.14
Systolic blood pressure (mmHg) 118.3  17.0 127.3  12.1 0.02 Medications, n (%)
Diastolic blood pressure (mmHg) 67.3  11.2 84.0  8.8 <0.01 Beta blocker 13 (31.7) 11 (42.3) 0.26
Heart rate (beats/min) 70.0  14.1 62.9  9.3 <0.01 Calcium channel blocker 13 (31.7) 7 (26.9) 0.44
Body mass index (kg/m2) 24.7  4.4 23.5  2.5 0.10 ACEI/ARB 3 (7.3) 2 (7.7) 0.65
Hypertension, n (%) 26 (25.2) 7 (14.5) 0.14 Diuretics 14 (34.1) 11 (42.3) 0.50
Diabetes mellitus, n (%) 21 (20.4) 5 (10.4) 0.13
Smoker, n (%) 12 (11.7) 8 (16.7) 0.40 Except where indicated otherwise, values are the mean  SD or n (%). ACEI,
angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker;
Except where indicated otherwise, values are the mean  SD or n (%). MELD, model for end stage liver disease.
 Y. Chen et al. / Journal of Cardiology 67 (2016) 140–146 143

Table 3 Table 4
Echocardiography parameters in patients with cirrhosis and controls. Prospective echocardiography assessment in patients prior to and following liver
transplantation (LTx).
Cirrhosis Controls p
(n = 103) (n = 48) Pre-LTx Post-LTx p
(n = 41) (n = 41)
LV conventional parameters
LV end-diastolic septal thickness (cm) 1.1  0.2 1.0  0.1 <0.01 Systolic blood pressure (mmHg) 120.0  15.7 125.0  15.3 0.08
LV end-diastolic diameter (cm) 4.7  0.7 4.5  0.4 0.02 Diastolic blood pressure (mmHg) 68.0  12.9 79.6  15.7 <0.01
LV end-diastolic posterior 1.0  0.2 1.0  0.1 0.73 Body mass index (kg/m2) 25.0  4.1 24.1  4.5 0.11
wall thickness (cm) Creatinine (mg/dl) 87.6  37.5 97.4  24.2 0.11
LV mass (g) 208.5  57.5 175.6  42.8 <0.01 LV conventional parameters
LV end diastolic volume (ml) 94.0  29.2 74.0  16.0 <0.01 LV end-diastolic septal 1.1  0.2 1.2  0.2 0.03
LV end systolic volume (ml) 33.4  12.7 26.5  7.5 <0.01 thickness (cm)
LV ejection fraction (%) 65.1  4.8 64.1  4.4 0.19 LV end-diastolic diameter (cm) 4.8  0.6 4.4  0.5 <0.01
Heart rate (beats/min) 70.0  14.1 62.9  9.3 <0.01 LV end-diastolic posterior 0.9  0.2 1.0  0.1 0.07
LV diastolic function parameters wall thickness (cm)
E (m/s) 0.84  0.21 0.74  0.14 <0.01 LV mass (g) 214.0  55.1 195.8  54.5 0.049
A (m/s) 0.80  0.25 0.64  0.14 <0.01 LV end diastolic volume (ml) 91.4  27.1 71.3  16.9 <0.01
E/A ratio 1.13  0.42 1.20  0.30 0.22 LV end systolic volume (ml) 32.2  12.9 25.2  7.7 <0.01
LV diastolic function, n (%) LV ejection fraction (%) 66.1  4.6 65.2  4.7 0.30
Normal 60 (58.3) 35 (72.9) <0.01 Heart rate (beats/min) 71.5  15.1 70.5  11.0 0.67
Mild 40 (38.8) 13 (27.1) LV diastolic function parameters
Moderate 1 (1) 0 (0) E (m/s) 0.83  0.21 0.75  0.14 0.04
Severe 2 (1.9) 0 (0) A (m/s) 0.82  0.23 0.81  0.19 0.73
E/e0 – lateral 7.42  2.37 6.35  1.42 <0.01 E/A ratio 1.08  0.38 0.97  0.27 0.06
LV strain analysis LV diastolic function grade, n (%)
LS (%) 18.6  2.6 20.1  2.8 <0.01 Normal 23 (56.1) 17 (41.4) 0.38
CS (%) 16.6  2.4 21.6  3.6 <0.01 Mild 14 (34.1) 20 (48.8)
RS (%) 39.9  13.1 44.9  14.3 <0.04 Moderate 4 (9.8) 4 (9.8)
RV parameters Severe 0 (0) 0 (0)
RVEDA (cm2) 13.9  3.9 12.6  2.5 0.01 E/e0 – lateral 7.2  2.1 6.8  2.0 0.30
RVESA (cm2) 6.6  2.4 5.7  1.5 <0.01 LV strain analysis
RVFAC (%) 0.53  0.08 0.55  0.06 0.06 LS (%) 18.5  2.6 20.8  2.0 <0.01
TAPSE (cm) 2.3  0.4 2.3  0.2 0.77 CS (%) 16.5  2.4 18.7  2.3 <0.01
RVSP (mmHg) 25.3  7.8 15.6  6.7 <0.01 RS (%) 39.9  13.2 41.4  8.6 0.83
RV total longitudinal strain (%) 21.2  4.4 23.0  2.6 <0.01 RV parameters
RVEDA (cm2) 13.6  3.7 12.4  2.2 0.01
Except where indicated otherwise, values are the mean  SD or n (%). A, peak late
RVESA (cm2) 6.2  2.1 5.5  1.2 0.02
diastolic velocity of mitral inflow; CS, circumferential strain; E, peak early diastolic
RVFAC (%) 0.55  0.06 0.55  0.05 0.76
velocity of mitral inflow; e0 , early diastolic velocity at LV basal lateral segment; E/A
TAPSE (cm) 2.3  0.3 2.2  0.2 0.11
ratio, ratio of peak early diastolic velocity to late diastolic velocity of mitral inflow;
RVSP (mmHg) 25.3  8.1 23.2  7.5 0.14
E/e0 , ratio of peak early diastolic velocity to early diastolic velocity at LV basal lateral
RV total longitudinal strain (%) 21.0  4.8 23.2  2.5 <0.01
segment; LS, longitudinal strain; LV, left ventricular; RS, radial strain; RV, right
ventricular; RVEDA, right ventricular end-diastolic area; RVESA, right ventricular A, peak late diastolic velocity of mitral inflow; CS, circumferential strain; E, peak
end-systolic area; RVFAC, right ventricular fractional area change; RVSP, right early diastolic velocity of mitral inflow; e0 , early diastolic velocity at LV basal
ventricular systolic pressure; TAPSE, tricuspid annular plane systolic excursion. lateral segment; E/A ratio, ratio of peak early diastolic velocity to late diastolic
velocity of mitral inflow; E/e0 , ratio of peak early diastolic velocity to early
diastolic velocity at LV basal lateral segment; LS, longitudinal strain; LV, left
cirrhosis. Importantly, 2D speckle tracking-derived global LV ventricular; RS, radial strain; RV, right ventricular; RVEDA, right ventricular
systolic strains in all 3 orthogonal directions were impaired in end-diastolic area; RVESA, right ventricular end-systolic area; RVFAC, right
ventricular fractional area change; RVSP, right ventricular systolic pressure;
patients with cirrhosis compared with controls.
TAPSE, tricuspid annular plane systolic excursion.
With reference to right heart echocardiography parameters,
patients with cirrhosis had a larger RV end-diastolic and end-
systolic area, and higher RVSP than controls. Importantly, patients
with cirrhosis had an impaired RV systolic strain, compared with
controls, despite similar conventional RV function as determined Prospective echocardiography parameters of patients without LTx
by RVFAC and TAPSE.
Nonetheless patients with Child A, B, and C grade cirrhosis had a The comparison between baseline and follow-up echocardio-
similar global LV systolic longitudinal strain (17.7  2.4% vs. graphic parameters in patients who did not undergo LTx is
18.9  2.8% vs. 19.0  2.5%; p = 0.09), circumferential strain presented in Table 5. The LV wall thickness and LV mass were
(16.0  2.5% vs. 16.6  2.4% vs. 17.0  2.3%; p = 0.23), radial strain significantly increased on follow-up echocardiography. No signifi-
(37.9  13.7% vs. 40.2  12.2% vs. 39.9  13.1%; p = 0.62), and RV cant alteration to LV systolic and diastolic function and RV
systolic strain (19.7  4.7% vs. 21.8  3.7% vs. 21.7  4.5%; parameters was noted. The change in LV wall thickness and LV
p = 0.11). mass was nonetheless not related to age, gender, and use of
medications (p > 0.05).
Comparison of echocardiography parameters pre- and post-LTx
Discussion
The comparison of pre and post-LTx echocardiography param-
eters in 41 patients is shown in Table 4. Following LTx, there was a The present study demonstrates that patients with cirrhosis
significant reduction in LV dimension and volume, a lower LV have biventricular dilatation and impaired biventricular systolic
mass, and an improved LV global systolic longitudinal and strain compared with controls. Importantly, patients with cirrhosis
circumferential strain. There was also a reduced RV end-diastolic following LTx had reduced biventricular dilatation and improved
and end-systolic area, and improved RV systolic strain. The change biventricular systolic strain. For those who did not undergo LTx,
in biventricular strain and dimension was nonetheless not related follow-up echocardiography demonstrated a progressive increase
to age, gender, and use of medications (p > 0.05). in LV wall thickness and mass.
144 Y. Chen et al. / Journal of Cardiology 67 (2016) 140–146

Table 5 demonstrating LV systolic strain deformation in all three

Prospective echocardiography assessment in patients who did not receive LTx.
orthogonal directions that indicate transmural disease involve-
Baseline Follow up p ment of the myocardium in patients with cirrhosis.
(n = 26) (n = 26) RV function has now been recognized as an important predictor
Systolic blood pressure (mmHg) 119.4  16.9 121.4  18.9 0.54 of survival in patients with cardiac disease [20]. Recently, a study
Diastolic blood pressure (mmHg) 72.6  10.7 75.5  13.1 0.20 of 216 patients who underwent LTx demonstrated that for RV
Body mass index (kg/m2) 25.1  5.7 25.9  6.4 0.16 echocardiography parameters, the degree of tricuspid regurgita-
Creatinine (mg/dl) 90.3  28.5 91.6  31.6 0.78
tion in particular was most associated with adverse outcome
LV conventional parameters
LV end-diastolic septal 1.0  0.2 1.2  0.1 <0.01 [6]. This study thus highlighted the importance of assessment of RV
thickness (cm) in patients with cirrhosis. A previous post-mortem analysis
LV end-diastolic diameter (cm) 4.6  0.5 4.6  0.6 0.90 revealed a high rate of RV chamber dilatation in approximately
LV end-diastolic posterior 1.0  0.1 1.1  0.1 0.01 one-third of patients with cirrhosis [21]. Similar to the findings of
wall thickness (cm)
LV mass (g) 199.1  51.5 225.4  52.7 <0.01
the present study, others have demonstrated that patients with
LV end diastolic volume (ml) 88.2  21.1 85.7  32.6 0.53 cirrhosis have a larger RV dimension than controls when measured
LV end systolic volume (ml) 31.9  9.8 30.5  12.6 0.35 by echocardiography [16,22,23]. In the present study, the RV
LV ejection fraction (%) 64.3  4.0 64.4  6.8 0.97 dimension is significantly increased in patients with cirrhosis. This
Heart rate (beats/min) 65.2  11.0 65.6  11.0 0.88
could be explained by an increased venous return to the right heart
LV diastolic function parameters
E (m/s) 0.80  0.17 0.80  0.18 0.98 caused by the development of portosystemic collaterals to
A (m/s) 0.74  0.29 0.77  0.21 0.29 counterbalance the increased intrahepatic vascular resistance to
E/A ratio 1.23  0.48 1.13  0.46 0.27 portal blood flow [24]. Further, pulmonary arterial pressure is
LV diastolic function grade, n (%) increased that may further contribute to enlargement of RV
Normal 15 (57.7) 14 (53.9) 0.99
Mild 9 (34.7) 10 (38.5)
dimension. Upon liver transplantation, both the portosystemic
Moderate 1 (3.8) 1 (3.8) shunt and pulmonary arterial pressure will be reduced that may
Severe 1 (3.8) 1 (3.8) partly explain the reduction in RV dimension [25]. Future
E/e0 – lateral 7.2  2.3 7.2  3.1 0.89 prospective studies are nonetheless required to discern the
LV strain analysis
underlying mechanism for RV dimension reduction following
LS (%) 18.6  2.0 18.6  2.9 0.98
CS (%) 17.0  1.9 17.2  3.0 0.73 liver transplantation. Importantly, the present results provide
RS (%) 39.4  11.9 36.2  5.5 0.20 additional evidence that RV myocardial contractility, as evaluated
RV parameters by systolic strain, is impaired in patients with cirrhosis compared
RVEDA (cm2) 13.1  4.0 13.3  3.5 0.86 with controls. It is of note that although hepato-pulmonary
RVESA (cm2) 6.3  2.1 6.5  1.8 0.55
RVFAC (%) 0.52  0.06 0.51  0.06 0.52
syndrome and pulmonary hypertension may adversely affect RV
TAPSE (cm) 2.3  0.3 2.3  0.4 0.72 myocardial function, these conditions were excluded in the current
RVSP (mmHg) 24.2  6.3 24.1  6.7 0.94 population. As a result, the impaired RV function observed should
RV total longitudinal strain (%) 21.7  3.9 21.6  4.0 0.96 be related to cirrhosis per se and cannot be attributed to these
A, peak late diastolic velocity of mitral inflow; CS, circumferential strain; E, peak conditions.
early diastolic velocity of mitral inflow; e0 , early diastolic velocity at LV basal Theoretically, LTx may reverse cirrhotic cardiomyopathy.
lateral segment; E/A ratio, ratio of peak early diastolic velocity to late diastolic Indeed, a study involving 15 patients with cirrhosis showed a
velocity of mitral inflow; E/e0 , ratio of peak early diastolic velocity to early
reduction in LV mass 6–12 months following LTx [7]. This is
diastolic velocity at LV basal lateral segment; LS, longitudinal strain; LV, left
ventricular; RS, radial strain; RV, right ventricular; RVEDA, right ventricular confirmed by the present study. Nonetheless reversibility of
end-diastolic area; RVESA, right ventricular end-systolic area; RVFAC, right cardiac dysfunction following LTx has not been documented. By
ventricular fractional area change; RVSP, right ventricular systolic pressure; including a larger study population and using an advanced
TAPSE, tricuspid annular plane systolic excursion.
echocardiographic technique, the present study enables detection
of a reduced biventricular dilatation and improved biventricular
systolic strain following LTx. This finding provides firm evidence
Previous studies have consistently demonstrated that patients that LTx can reverse biventricular remodeling and improve
with cirrhosis have LV hypertrophy [4,16] that results in diastolic myocardial function in patients with cirrhosis.
dysfunction [3,4,16] and has been confirmed by our studies. In The 2005 World Congress of Gastroenterology in Montreal
contrast, resting LV systolic functional impairment is not apparent working party has defined cirrhotic cardiomyopathy as impaired
as measured by conventional methods such as LV ejection fraction, contractility with systolic and diastolic dysfunction together with
partly because of reduced afterload due to a low systemic vascular prolonged QT interval in the absence of other known causes of
resistance. Recently, 2D speckle-tracking strain analysis has been cardiac disease [26]. Nonetheless the current guidelines and
proposed as a sensitive and accurate method to evaluate recommendations do not comment on the progression of cirrhotic
subclinical systolic dysfunction in various groups of disease cardiomyopathy. The present study is the first to prospectively
[13,17,18]. It allows detection of LV dysfunction in three demonstrate that in patients with cirrhosis awaiting LTx, a
orthogonal directions, namely longitudinal, circumferential, and significant increase in LV wall thickness and LV mass is observed.
radial. The LV myocardial fiber architecture has a multilayer and Of note, up to 46% of patients were of Child-Pugh Grade A and had a
helical arrangement of myofibers that forms the multi-dimen- low MELD score indicative of early stage liver cirrhosis; progres-
sional deformation of LV during each cardiac cycle. Longitudinal sion of LV mass nonetheless remained significant. This further
direction deformation is usually the first to be affected in early suggests that cardiomyopathy can be progressive irrespective of
diseases of the myocardium and is suggestive of subendocardial the severity of cirrhosis. Future studies that encompass different
disease. Circumferential and radial strain is affected relatively late stages of cirrhosis are warranted to validate the current finding.
in the disease process and represents transmural damage
[19]. Using this technique, a recent study has demonstrated that Clinical implications
patients with cirrhosis have impaired LV systolic longitudinal
strain compared with controls, suggestive of subendocardial Previous studies have demonstrated that LV echocardiography
dysfunction [5]. The present study extends this finding by parameters such as LV hypertrophy [27] and diastolic function
 Y. Chen et al. / Journal of Cardiology 67 (2016) 140–146
[28–30] can predict outcome in patients with cirrhosis, although
others could not replicate these results [6,31]. In contrast, the right
heart is more sensitive to any alteration in preload and afterload
than the left heart [32]. Accordingly, accurate detection of cardiac
function, especially RV function, is key to risk stratify cardiac
complications for candidates awaiting LTx. The advent of advanced
2D speckle tracking derived strain analysis, as in the present study,
provides a sensitive and reliable method to accurately assess
biventricular function and predict outcomes in patients with
cirrhosis. Importantly, the present study demonstrated that LV
hypertrophy is progressive in patients with cirrhosis but can be
reversed upon LTx. The progressive nature of adverse LV
remodeling highlights the importance of regular assessment by
echocardiography to detect significant changes to cardiac function
in candidates awaiting LTx. The rate of adverse progression and its
clinical significance nonetheless require evaluation by a larger
study cohort.
Limitations
The present study did not perform invasive hemodynamic
measurements to assess for ventricular wall stress, cardiac output
and systemic vascular resistance and would require elaboration
from future studies. Further, the sequence of RV and LV dilatation
and dysfunction would require assessment by additional studies.
Patients with cirrhosis have prolonged QT interval that may
reverse upon liver transplantation [33]. Whether the reversal of QT
interval is related to biventricular dimension and function
improvement following liver transplantation would require
further evaluation. The present study did not include the
evaluation of clinical outcome. Future studies are therefore needed
to evaluate the prognostic value and to better define the frequency
of echocardiography assessment in patients with cirrhosis.
Furthermore, only 2-dimensional echocardiographic parameters
were used to evaluate both geometry and function. Novel 3-
dimensional echocardiography geometric assessment could be
used to confirm the present findings. The majority of cases of
cirrhosis were due to viral hepatitis; future studies in patients with
other etiologies (for example alcoholic cirrhosis) will be required.
Conclusion
This study demonstrates that patients with cirrhosis had
biventricular dilatation and impaired biventricular function
measured by systolic strain analysis that is not apparent on
conventional echocardiographic assessment. Reduced biventricu-
lar dilatation and improved biventricular systolic function was
detected following LTx. For those who did not undergo LTx, a
significant increase in LV mass was observed.
Funding
This research received no grant from any funding agency in the
public, commercial, or not-for-profit sectors.
Conflict of interest
The authors declare that there is no conflict of interest.
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