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TABLE 15.5 Studies analyzing outcomes of liver transplantation in patients with cardiac dysfunction.
First author,
year, country
Total
sample
size
Subjects
Age (x)
Sex (M/F)
Etiology
(ETOH/Viral/Other)
Child (A/B/C)
Meld (X)
Excluded known CVD
(Y/N)
Time post-
transplants Results
Cardiac
variable A
Cardiac variable
B
Comparison of
AvsB;P value
Dowsley et al.
[44] United
States
107 55
73/34
29/0/78
/
19.2
Yes
2.6 months (x )
Range: 06
months
1. Increased E/E’ predictor of HF after
LT (3.4x)
2. Increased LAVI predictor of HF after
LT (2.9x)
3. Low MAP predictor of HF after LT
(2.1x)
4. Increased LAVI associated with
decreased survival
c
No HF
E/E’: 7.1
LAVI:
41.0 mL/m
2
/
LAVI
(,40 mL/m
2
)
82% (1-year
survival)
71% (5 year
survival)
HF
E/E’: 9.1
31.4 mL/m
2
/
LAVI . 40 mL/m
2
54% (1-year
survival)
50% (5 year
survival)
.02
b
.05
b
.003
b
.01
.01
Josefsson et al.
[140] Sweden
a
234 52
162/72
85/55/94
28/104/102
16.5
No (8% with CVD)
4 years (x )
Range: 0.59
years
1. SD not associated with perioperative
HF
2. DD not associated with perioperative
HF
3. DD associated with late graft failure
mortality
No HF
NR
% DD: 21.5
HF
NR
% DD: 16
NR
NS
HR: 4.82
Mittal et al.
[141]
United States
a
970 53.2
333/634
167/471/332
/
21
No (2.3% with CAD)
5.3 years (x )
Range: NS
1. DD associated with acute cellular
graft rejection (ACR)
a. Grade 1 DD was not associated
with ACR
b. Grade 2 and 3 DD were associated
with ACR
2. DD associated with Graft failure
a. Grade 1 DD not associated with
graft failure
b. Grade 2 and 3 DD associated with
graft failure
3. DD associated with all-cause mortality
a. Grade 1 DD not associated with
all-cause mortality
b. Grade 2 and 3 DD associated with
all-cause mortality
HR: 3.38
HR: 1.11
(CI , 1)
HR: 10.97 and
13.31
HR: 2.09
HR: 1.26
(CI , 1)
HR: 1.38 and
HR 3.12
HR:1.52
HR: 0.93
HR: 1.58 and
1.73
Qureshi et al.
[142] United
States
a
970 53.2
333/634
Same
population
as above
167/471/332
/
18.3
No (5.8% with CAD)
5.3 years (x )
Range: NS
1. HF was non-ischemic in 59.2% of
patients
2. DD associated with post-LT HF
a. Grade 1 and 2 DD not associated
with post-LT HF
b. Grade 3 DD associated with post-
LT HF
HR: 1.52 and
1.75 (CI , 1)
HR: 1.89
Darstein et al.
[143] Germany
a
352 54.9
241/111
140/142/70
/
19
No (61.4% with HTN)
4.2 years (x )
Range: NS
1. LVH associated with decreased
survival
No LVH
23.5%
mortality
LVH
30.4% mortality
0.05
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Raevens et al.
[21] Belgium
173 57
111/62
69/33/71
/
17
Yes (presumed based
on use of CCM
criteria)
NS 1. DD not associated with short term
(,3mo) mortality (shown)
2. DD not associated with long term
( . 3mo) mortality (shown)
1. DD not associated with short term
CVC (shown)
2. DD not associated with long term CVC
(shown)
No DD
9%
15%
5%
1%
DD
14%
18%
4%
4%
NS
NS
NS
NS
Sonny et al.
[46]
United States
243
d
55
175/68
44/103/96
/
17
No (8% with CAD)
5.2 years (x ) 1. DD not associated with mortality,
MACE or graft failure [composite
outcome]
2. QTc prolongation associated with
composite outcome
/
/
/
/
HR: 1.47
(CI , 1) P 5 .17
a
HR: 1.01
P 5 .05
a
Sonny et al. [46]
United States
225 58.2
165/60
51/78.96
/
22.2
Yes
46 months (x ) 1. DD (shown) associated with new HF
post-LT (,6 months)
2. Higher LVEF associated with
decreased HF post- LT
3. New HF associated with graft failure
and/or 1-year mortality (shown)
4. New HF associated with all-cause 1
year mortality (shown)
No HF
58%
EF: 61%
16%
13%
HF
76%
EF: 59%
33%
33%
OR: 5.88,
P 5 .025
OR: 0.90,
P 5 .04
OR: 1.99,
P 5 .03
OR 2.33,
P .013
a
Studies e did not exclude previous cardiac disease (i.e., did not meet criteria for cirrhotic cardiomyopathy).
b
multivariate COX analysis.
c
Kaplan-Meier survival.
d
SD assessed in 92, DD in 78.
CCM, cirrhotic cardiomyopathy; CAD, coronary artery disease; CVD, cardiovascular disease; HTN, hypertension; E/E’, E/E’, ratio of early transmitral diastolic inflow to early mitral annular velocity; HF, heart
failure; LT, liver transplant; LAVI, left atrial volume index; MAP, mean arterial pressure; SD, systolic dysfunction; DD, diastolic dysfunction; CVC, cardiovascular complications; LVEF, left ventricle ejection
fraction; MACE , major adverse cardiac event; HR, Hazard Ratio; OR, odds ratio; CI, 95% confidence interval.
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TABLE 15.6 Studies assessing effect of β blockers in patients with CCM.
First author, year,
country
Total
sample
size
Subjects
Age (x )
Male/
female
Cirrhosis
Etiology
alcohol/viral/
other)
Child (A/B/C)
Meld score (x )
Drug
Dose
Time to analysis Results
Pre-
intervention
Post-
intervention
Comparison of
pre- vs post-
intervention;
P value
Henriksen et al.
[144] Denmark
Prospective
observation
17 60
15/2
17/0/0 2/10/5 Propranolol
80 mg; 1 dose
90 mins
1. Decreased QTc (x )
2. Decreased QTc (x ) on those with
prolonged QTc
3. No effect on those with normal
QTc
4. Response to Propranolol in 10/17
patients
0.460 Ms
0.488 Ms
0.429 ms
0.440 Ms
0.456 Ms
0.422 ms
, .005
, .05
NS
Zambruni et al.
[145] Italy
Prospective
observation
30 58.8
25/5
7/18/5 15/10/5
12.6
Nadolol
64 mg (x ); Daily
Range: 40160 mg
13 months
1. Decreased QTc (x ) using Bazetts
formula
2. No change or increased QTc using
Cirrhosis (shown), Fridericia,
Hodges, and Framingham formula
3. Decreased QTc in 90% of those
with prolonged QTc (x )
4. Increased QTc in 75% of those with
normal QTc (x )
5. Response to Nadolol in 17/30
patients
455.4 Ms
444.3 Ms
473.3 Ms
429.8 ms
440.0 Ms
445.7 Ms
458.4 Ms
439.3 ms
, .001
NS
.007
.01
Serste et al.
[146]
France Prospective
observation
151
a
60.4
122/29
85/47/19 0/49/102
18.8
Propranolol (77/151)
113 mg (x ); Daily
Range: 40160 mg
8 months (median)
Range: 147months
1. No change in HVPG
2. Decreased survival time (median)
in those using propranolol
3. Decreased probability of 1-year
survival in those using propranolol
No
propranolol
20.0 mmHg
20 months
64%
Propranolol
19.1 mmHg
5 months
19%
NS
.0001
.0001
Yilmaz et al.
[147]
Turkey Cross-
sectional
95 45.1
55/40
13/53/30 33/25/37
13.7
Propranolol (42/95)
4060 mg; Daily
/
Spironolactone (23/95)
100300 mg; Daily
Furosemide (23/95)
4080 mg; Daily
1. Higher BNP in those using
Propranolol
2. Higher BNP in those using
diuretics (Spironolactone or
furosemide or both)
No
propranolol
228.4 pg/mL
No diuretic
249.1 pg/mL
Propranolol
364.4 pg/mL
Diuretic
411.7 pg/mL
.005
.001
Gu
¨
nay et al.
[148]
Turkey Cross-
sectional
51
b
55.8
32/19
5/30/16 33/12/6
9 (median)
Propranolol (20/51)
/
/
Spironolactone (11/51)
/
/
1. Lower RV strain in those using
Metoprolol
a. apical free wall strain
b. basal free wall strain
2. No difference in RV morphology in
those using metoprolol
3. Lower lateral systolic velocity in
those using Spironolactone
No Metoprolol
2 24.74
2 22.23
No
Spironolactone
14.47 cm/s
Metoprolol
2 20.85
2 19.00
Spironolactone
12.43 m/s
.04
.03
.04
Silvestre et al.
[149]
Canada RCT
78 50.4
32/46
0/43/35 67(A 1 B)/11
12
Metoprolol (41/78)
120 mg(x ); Daily
6 months
1. No morphological changes in any
morphologic parameter: LAV
(shown), LVEDD, LVEDV, LVMI
26 mL
2/41
66.5%
26.5 mL
5/32
67%
NS
NS
NS
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2. No change in Diastolic Dysfunction
3. No change in Systolic Function
(LVEF shown)
4. No change in BNP (shown), NA,
Renin activity or Troponin
5. No difference in hospitalizations/
mortality
42 pg/mL
Placebo
8/2
42 pg/mL
Metoprolol
6/5
NS
NS
a
All patients had refractory ascites.
b
Patients did not have cardiac dysfunction.
QTc, Corrected QT interval; HVPG, hepatic venous pressure gradient; BNP, brain natriuretic peptide; RV, right ventricle; LAD, left atrial dimension; LVMI, left ventricular mass index, LVEF, Left ventricular ejection
fraction; NA, noradrenaline.
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Albumin
Besides the generation of oncotic pressure, Albumin has the capacity to bind many substances such as fatty
acid, pro-inflammatory cytokines, LPS, bilirubin, arachidonic acid, prostaglandins, thromboxanes, leukotrienes,
cooper, and iron. Albumin also traps multiple ROS and RNS and therefore modulates the intracellular levels of
this antioxidant system
[154]. Using bile duct ligation in rats, Bortoluzzi and colleagues found that albumin has
positive cardiac inotropic effect in cirrhotic cardiomyopathy. Albumin normalizes TNFα and inducible NO
synthase, MAD(P)H-oxidase activity, and nuclear translocation of NF-κB in cardiac tissue, indicating a decrease
of heart inflammation and oxidative stress. They confirmed that albumin improves cardiac function (
Table 15.7)
via two mechanisms: 1) by reducing the negative inotropic effect of the NF-κB-iNOS-NO pathway and 2) by
blunting the oxidative stress-mediated overexpression of Gi-proteins and downexpression of Adcy3
[155]. The
clinical study showed that intravenous albumin administration significantly improves cardiac function in cir-
rhotic patients with SBP
[156,157].
Antioxidant and antiinflammatory treatments
Erythropoietin is a hypoxia-induced hormone and a major regulator of erythropoiesis. Xanthos and coworkers
demonstrated that erythropoietin has antiapoptotic, antiinflammatory, and antioxidant properties
[160].
Congestive heart failure patients treated with erythropoietin showed reduction of left ventricular hypertrophy,
enhanced exercise performance, increased ejection fraction, decreased mortality, improve d cardiac function, and
shortened hospitalization
[161]. Erythropoietin is protective in many types of heart diseases, such as congestive
heart failure, myocarditis, cardiomyopathy, and ischemic injury
[162]. It also protects cardiomyocytes from ische-
mic injury, decreases oxidative stress, attenuates myocardial inflammation by suppression of tumor necrosis fac-
tor (TNFα), and improves cardiac contractile function
[162].
Our lab applied erythropoietin to a rat cirrhotic cardiomyopathy model and found that it significantly inhibits
proinflammatory cytokines such as TNFα and suppresses oxidative stress. It also significantly improved systolic
and diastolic function in cirrhotic heart
[162]. It is known that 75% of patients with chronic liver diseases have
anemia
[163], so in addition to its antiinflammatory and antioxidant features, erythropoietin may have potential
for the treatment of cirrhotic cardiomyopathy.
Mousavi and coworkers used taurine in bile duct ligated rats and found that it significantly reduces tissue
ROS, lipid peroxidation, protein carbonylation, and increased GSH/GSSG ratio, total antioxidant capacity, and
mitochondrial ATP content. Overall, taurine decreases oxidative stress and improves mitochondrial function in
the cirrhotic heart of rats
[164]. Furthermore, taurine alleviates liver injury (evidenced by decreased ALT and
AST) which is beneficial to cirrhosis-based cardiomyopathy. Taurine also decreases the level of creatine kinase
MB (CKMB), a marker of heart injury. Taurine is worth further investigation in patients with CCM.
Spermidine, a pleiotropic molecule, has antioxidant and antiinflammatory effects
[165]. Sheibani et al. in a cir-
rhotic rat model found that the level of heart oxidative stress, evidenced by increased malondialdehyde, and
decreased superoxide dismutase (SOD, a key antioxidant) and GSH is significantly increased. Cardiac inflamma-
tory markers such as TNFα, interleukin 1β (IL-1β), and P-NF-kB/NFkB ratio were significantly increased.
Spermidine significantly reduced these markers of cardiac oxidative stress and inflammation. Furthermore, the
QTc interval was significantly decreased in BDL 1 spermidine group compared with that in BDL controls (204.
6 4 vs 170 6 5 msec, P , .001). The contractility of papillary muscle from BDL 1 spermidine group was also sig-
nificantly increased compared with that from BDL rats (P , .001). This study again suggests a potential therapy
that merits further study in patients with CCM.
Liver transplantation
Liver transplantation is a double-edged sword in cirrhotic cardiomyopathy. On the one hand, liver transplan-
tation is the only effective cure for end-stage liver failure and is generally believed to eventually reverse cirrhotic
cardiomyopathy. On the other hand, liver transplantation is a significant challenge for cirrhotic patients as car-
diovascular dysfunction is a major risk factor for perioperative and postop erative mortality. A retrospective
cohort study analyzed 4265 liver transplant recipients and found that cardiovascular mortality accounted for
17.2% of deaths. Up to 40% of early postoperative deaths are due to cardiovascular causes
[166].
238 15. Cirrhotic cardiomyopathy
III. Cardiovascular system in liver failure
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TABLE 15.7 Studies assessing effects of aldosterone antagonists, albumin infusion, and TIPS.
First author
Year
Country
Total Sample
Size
Subjects
Age(X)
Sex (M/F)
Cirrhosis
Etiology
(ETOH/Viral/
Other)
Child (A/B/C)
Meld score (X)
Intervention
Dose
Time to analysis Results
Pre-
Intervention
Post-
Intervention P
Pozzi et al.
[153] USA
25 5862
17/8
0/25/0 25/0/0 K-Canrenoate
200 mg; Daily
6 months
1. Decreased HVPG
2. Decreased LVWT
3. Decreased LVEDV
4. No change in E/A ratio
5. No change in MSNA
15.3 mmHg
21.8 mm
99.2 mL
1.0
43 bs/min
13.8 mmHg
20.7 mm
86.4 mL
0.9
40 bs/min
, .05
, .02
, .01
NS
NS
Shasthry
et al.
[158]
India
99 50.9
86/13
44/14/41 5/53/41
15.9
Albumin infusion
1 g/kg for 4 hours
Variable
1. 30/99 patients developed volume
overload & patients with higher
BMI were associated with increased
risk of developing volume overload.
2. Increased HR
3. Decreased pO2
4. Increased A-a
5. Increased E/e’
6. Increased cardiac output
7. No change in MAP
8. No change in inferior vena cava
diameter
9. No change in Lved
10. No change in E/A
N/A
79.7 bpm
85.4 mmHg
24.5 mmHg
7.35
4.94 L/min
88.0 mmHg
19.5 mm
40.9 mm
1.21
N/A
84.4 bpm
78.4 mmHg
29.6 mmHg
7.99
5.86 L/min
88.2 mmHg
19.9 mm
41.4 mm
1.22
.34
, .001
, .01
, .015
, .15
, .001
NS
NS
NS
NS
Busk et al.
[159]
Denmark
25 58
20/5
23/1/1 0/14/11 TIPS
N/A
1 week/4 months
1. Increase in serum alanine
aminotransferase
2. Increase in serum bilirubin
3. No change in serum albumin
4. Decrease in serum creatinine
5. Increase in GFR
6. Decrease in HVPG
7. Increase in HR
8. No change in MAP
9. Increase in CO
10. Increase in SV
11. Decrease in TBV
12. Increase in CBV
13. Increase in PCWP
14. Increase in LVID
15. Increase in EA
25 U/L
17 μmol/L
29 g/L
86 umol/L
80 mL/min
18 mmHg
74bpm
87 mmHg
6.87 l/min
99 mL
5.98 L
1.73 L
10 mmHg
4.35 cm
0.9
36/29 U/L
28/32 μmol/L
27/28 g/L
75/75 umol/L
92/97 mL/min
6 mmHg/NA
74/85bpm
84/89 mmHg
7.92 l/min
110 mL/NA
5.58 L/NA
1.81 L/NA
14 mmHg/NA
4.72/5.03 cm
1.2/0.9
, .005/NS
, .005/ , 0.005
NS
, .05/ , 0.05
, .05/ , 0.05
, .0005/NA
NS/ , .005
NS/NS
, .005/NS
, .005/NS
, .05/NS
, .05
, .005/NS
, .05/ , .005
, .05/NS
HVPG, Hepatic venous pressure gradient; LVWT, left ventricle wall thickness; LVEDV, left ventricle end diastolic volume; E/A, peak velocity flow in early diastole/peak velocity flow in late diastole; MSNA, muscle
sympathetic nerve activity; HR, heart rate; pO
2
, partial pressure oxygen; A-a, alveolararterial gradient; MAP, mean arterial Pressure; LVED, left ventricular end diastolic diameter; GFR, glomerular filtration rate;
CO, cardiac output; SV, stroke volume; TBV, total blood volume; CBV, central blood volume; PCWP, pulmonary capillary wedge pressure; LVID, left ventricular internal dimension.
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It has been suggested that CCM shows complete resolution following liver transplantation. Myocardial recov-
ery following liver transplantation has been described as a triphasic model wh erein perioperative heart failure
(phase one) is followed by further decompensation lasting up to 3 months (phase two)
[167]. The third phase
describes resolution of functional, structural, and electrical abnormalities. Whether or not such recovery is rou-
tinely seen is still debated. There are several studies that examined the reversibility of functional parameters fol-
lowing liver transplantation.
CCM reversibility: QTc prolongation
There is good consensus that QTc prolongation improves after liver transplantation. We found nine studies
investigating this phenomenon
[3947], and a clear majority revealed overall improvement in QTc after liver
transplantation (
Table 15.5). A study by Torregrosa et al. demonstrated complete normalization of QTc at approx-
imately 9 months after liver transplantation in 15 patients for whom data was available
[40]. Studies from Bal
[39] and Adigun [41] and their coworkers demonstrated an overall improvement in QTc, but they also noted that
up to 14% patients actually had worsening of QTc at 6 and 9 months following transplant,. In children, QTc nor-
malized in a majority of patients after liver transplant
[168]. The reason for worsening of QTc in certain patients
remains unknown but may be related to posttransplant medication regimens. Overall, it appears that QTc values
normalize in a significant majority of individuals following transplantation.
CCM reversibility: Systolic and diastolic function
The literature to date shows nine studies which examined changes in systolic and diastolic function after LT
[40,44,46,47,130134]. Improvement of systolic function following liver transplantation was first shown in 2005
with Torregrosa et al. documenting improvements of baseline hemodynamic parameters as well as improvement
of the blunted systolic response to physiologic stress
[40]. More recently, Chen et al. using speckle echocardiogra-
phy demonstrated improvement in systolic strain pre- and posttransplantation
[133]. Posttransplant assessments
in these studies were done at 9 and 18 months, respectively. In a pediatric cohort, reversibility of biliary atresia-
associated cirrhotic cardiomyopathy was documented in 80% at a median postoperative time of 95 days
[52].
In contrast to these findings, three studies have shown that systolic function worsens following liver trans-
plant. Dowsley et al. documented that 26% of individuals with normal systolic function prior to transplant devel-
oped systolic dysfunction (LVEF , 50%) at a mean of 2.6 months posttransplant
[44]. Acosta et al. reported a
higher incidence of systolic dysfunction at 21 months posttransplant compared to pretransplant
[130]. Finally,
Sonny and colleagues reported the persistence of systolic dysfunction at 3.2 years in up to 42% of individuals,
who developed new systolic dysfunction posttransplant
[46]. It is certainly feasible and credible that systolic
function does not dramatically improve following transplantation, but how can we possibly explain these obser-
vations that systolic function actually deteriorates following transplantation? We believe that the explanation lies
in several possible factors. One is that, for example, in the Dowsley study above, cardiac function was examined
too early in the postoperative course (mean of 2.6 posttransplant), so that many of these patients may still have
been in a transient phase of mild deterioration of ventricular function in the immediate postoperative period, the
phase 2 described above
[167]. The major explanation for deterioration of systolic function observed much later,
as in the other two studies, likely re lates to the immunosuppressive drug regimens to prevent rejection. Many of
these drugs have adverse cardiovascular effects including worsening or precipitation of arterial hypertension as
well as increasing hyperlipidemia. These cardiovascular risk factors may aggravate the strain on cardiac perfor-
mance in these patients.
There are also several studies showing neither improvement nor deterioration of systolic function
[46,131,132].
Despite their findings of deteriorating systolic function, Dowsley and colleagues found an improvement in the
mean E/E’ ratio post-LT at 2.6 months but did not observe changes in the E/A ratio
[44]. Torregrosa et al. also
documented improvement in peak filling rate during ventricular stress and a decrease in left atrial diameter, a
surrogate for diastolic dysfunction, following transplantation
[40]. Chen and colleagues found a decrease in LV
end-diastolic volume but did not observe changes in E/A ratio and, in contrast to the Dowsley study, found no
change in E/E’
[133]. Junge et al. documented a decrease in LV end diastolic diameter and LV mass index at one
year post-LT in the pediatric population
[134]. Gajanana et al. reported a decrease in left atrial volume in addition
to the improvement in the grade of diastolic dysfunction in 85% of individuals [47]. However, the overall preva-
lence of diastolic dysfunction remained the same.
240 15. Cirrhotic cardiomyopathy
III. Cardiovascular system in liver failure
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Studies have also documented further deterioration of diastolic function after transplant. Therapondos and col-
leagues documented a decrease in the mean E/A ratio and an increase in IVRT at 3 months
[131]. Acosta et al.
found a higher incidence of diastolic dysfunction as well as a decrease in the mean E/A ratio at 21 months post-
LT
[130]. Sonny et al. found that the grade of diastolic dysfunction worsened following LT and this was accom-
panied with an increase in left ventricle mass index
[46]. Lastly, a few of the studies demonstrated neither
improvement nor deterioration of diastolic function after transplantation
[47,132].
Overall, the literature surrounding the impact of liver transplantation on CCM remain s unsettled. To date,
most studies show improvement of QTc prolongation and certain structural cardiac parameters. However, the
impact of transplantation on overall systolic or diastolic cardiov ascular function is mixed. Why some patients
show early reversibility within the first postoperative year whereas others do not, remains unknown. Indeed,
other cardiovascular abnormalities also do not fully resolve even within 2 years. Hadengue and colleagues
showed persistence of portosystemic collaterals and increased cardiac output despite normalization of portal
pressure in transplant recipients up to two years after transplantation
[169].
We believe that liver transplantation will eventually reverse cirrhotic cardiomyopathy if the liver remains
well-functioning and that a major factor underlying the conflicting results is the deteriorating of several cardio-
vascular risk factors due to immunosuppression regimens, particularly hypertension. Some immunosuppressives
even have either direct cardiodepressant properties or significant antioxidant actions
[170,171]. Patients following
transplantation generally fall into two major categories: those relatively healthy without major complications, and
those with chronic recurrent complications such as rejections, sepsis, and recurrence of their original liver dis-
ease. Patients in the former category feel much better and thus often gain weight and adiposity, and some resume
habits such as smoking so their cardiovascular risk profile worsens. Those patients in the latter category have
increased cardiovascular risk factors because of these recurrent complication episodes. For example, sepsis and
the resultant inflammatory phenotype is now identified as a major pathogenic mechanism of cardiodepression
and cirrhotic cardiomyopathy.
What is required to answer the question about reversibility after transplantation will be careful long-term
studies 23 years after transplantation in the subgroup of patients with good liver function and no cardiovascu-
lar risk factors engendered or aggravated by antirejection drugs, that is, no significant arterial hypertension. We
believe that this group will indeed show reversibility and normalization of cardiac function.
Conclusion
In conclusion, cirrhotic cardiomyopathy is latent because of vasodilatation. However, when challenged, the heart
may manifest overt congestive heart failure. Cirrhotic cardiomyopathy is a major cause of mortality and morbidity
when patients are challenged with procedures such as TIPS or liver transplantation. The definition and diagnosis
has recently been updated and needs further validation. There is currently no specific treatment. However,
β-adrenergic blockers, aldosterone antagonists, albumin, erythropoietin, and other antioxidant and antiinflamma-
tory agents should be investigated.
References
[1] Kowalski HJ, Abelmann WH. The cardiac output at rest in Laennec’s cirrhosis. J Clin Invest 1953;32(10):102533.
[2] Regan TJ, Levinson GE, Oldewurtel HA, Frank MJ, Weisse AB, Moschos CB. Ventricular function in noncardiacs with alcoholic fatty liver:
role of ethanol in the production of cardiomyopathy. J Clin Invest 1969;48(2):397407.
[3] Gould L, Shariff M, Zahir M, Di Lieto M. Cardiac hemodynamics in alcoholic patients with chronic liver disease and a presystolic gallop.
J Clin Invest 1969;48(5):8608.
[4] Limas CJ, Guiha NH, Lekagul O, Cohn JN. Impaired left ventricular function in alcoholic cirrhosis with ascites. Ineffectiveness of ouabain.
Circulation. 1974;49(4):75460.
[5] Lee SS. Cardiac abnormalities in liver cirrhosis. West J Med 1989;151(5):5305.
[6] Ma Z, Lee SS. Cirrhotic cardiomyopathy: getting to the heart of the matter. Hepatology. 1996;24(2):4519.
[7] Desai MS, Eblimit Z, Thevananther S, Kosters A, Moore DD, Penny DJ, et al. Cardiomyopathy reverses with recovery of liver injury, cho-
lestasis and cholanemia in mouse model of biliary fibrosis. Liver international 2013.
[8] Liu H, Jayakumar S, Traboulsi M, Lee SS. Cirrhotic cardiomyopathy: Implications for liver transplantation. Liver Transpl 2017;23
(6):82635.
[9] Cazzaniga M, Salerno F, Pagnozzi G, Dionigi E, Visentin S, Cirello I, et al. Diastolic dysfunction is associated with poor survival in
patients with cirrhosis with transjugular intrahepatic portosystemic shunt. Gut. 2007;56(6):86975.
241References
III. Cardiovascular system in liver failure
https://t.me/medicina_free
[10] Alexander J, Mishra P, Desai N, Ambadekar S, Gala B, Sawant P, et al. Cirrhotic cardiomyopathy: Indian scenario. J Gastroenterol
Hepatol 2007;22(3):3959.
[11] Raedle-Hurst, TM, Welsch C, Forestier N, Kronenberger B, Hess G, Herrmann E, et al. Validity of N-terminal propeptide of the brain
natriuretic peptide in predicting left ventricular diastolic dysfunction diagnosed by tissue Doppler imaging in patients with chronic liver
disease. Eur J Gastroenterol Hepatol 2008;80:86573.
[12] Rabie RN, Cazzaniga M, Salerno F, Wong F. The use of E/A ratio as a predictor of outcome in cirrhotic patients treated with transjugular
intrahepatic portosystemic shunt. Am J Gastroenterol 2009;104(10):245866.
[13] Kazankov K, Holland-Fischer P, Andersen NH, Torp P, Sloth E, Aagaard NK. Resting myocardial dysfunction in cirrhosis quantified by
tissue Doppler imaging. Liver Int 2011;31(4):53440.
[14] Merli M, Calicchia A, Ruffa A, Pellicori P, Riggio O, Giusto M, et al. Cardiac dysfunction in cirrhosis is not associated with the severity
of liver disease. Eur J Intern Med 2013;24(2):1726.
[15] Enache I, Oswald-Mammosser M, Woehl-Jaegle M-L, Habersetzer F, Di Marco P, Charloux A, et al. Cirrhotic cardiomyopathy and hepa-
topulmonary syndrome: prevalence and prognosis in a series of patients. Respir Med 2013;107(7):10306.
[16] Karagiannakis DS, Vlachogiannakos J, Anastasiadis G, Vafiadis-Zouboulis I, Ladas SD. Frequency and severity of cirrhotic cardiomyopa-
thy and its possible relationship with bacterial endotoxemia. Dig Dis Sci 2013;58(10):302936.
[17] Salari A, Shafaghi A, Ofoghi M, Saeidinia A, Mansour-Ghanaei F. Diastolic dysfunction and severity of cirrhosis in nonalcoholic cirrhotic
patients. Int J Hepatol 2013;2013:892876.
[18] Nazar A, Guevara M, Sitges M, Terra C, Sola
`
E, Guigou C. LEFT ventricular function assessed by echocardiography in cirrhosis: relation-
ship to systemic hemodynamics and renal dysfunction. J Hepatol 2013;58(1):517.
[19] Mao H, Jiang D, Huang L. The serum nT-proBnP in Patients with Cirrhosis: relationship to Cardiac dysfunction and liver function.
Infect Int 2013;2:3642.
[20] Sampaio F, Pimenta J, Bettencourt N, Fontes-Carvalho R, Silva AP, Valente J. Systolic and diastolic dysfunction in cirrhosis: a tissue-
Doppler and speckle tracking echocardiography study. Liver Int 2013;33(8):115865.
[21] Raevens S, Pauw D, Geerts A, Berrevoet F, Rogiers X, Troisi R, et al. Prevalence and outcome of diastolic dysfunction in liver transplanta-
tion recipients. Comparative Study Acta Cardiol 2014;69(3):27380.
[22] Somani PO, Contractor Q, Chaurasia AS, Rathi PM. Diastolic dysfunction characterizes cirrhotic cardiomyopathy. Indian Heart J 2014;66
(6):64955.
[23] Falletta C, Filı
`
D, Nugara C, Di Gesaro G, Mina
`
C, Baravoglia CMH, et al. Diastolic dysfunction diagnosed by tissue Doppler imaging in
cirrhotic patients: Prevalence and its possible relationship with clinical outcome. Eur J Intern Med 2015;26(10):8304.
[24] Celtik C, Durmaz O, Oner N, Yavuz T, Go
¨
kce S, Aydogan A, et al. Investigation of cardiomyopathy in children with cirrhotic and noncir-
rhotic portal hypertension O
¨
meroglu, Semra So
¨
ku
¨
cu
¨
. J Pediatr Gastroenterol Nutr 2015;60(2):17781.
[25] Voiosu AM, Daha IC, Voiosu TA, Mateescu BR, Dan GA, B
˘
aicu¸s CR, et al. Prevalence and impact on survival of hepatopulmonary syn-
drome and cirrhotic cardiomyopathy in a cohort of cirrhotic patients. Liver Int 2015;35(12):254755.
[26] Barbosa M, Guardado J, Marinho C, Rosa B, Quelhas I, Lourenc¸o A, et al. Cirrhotic cardiomyopathy: isn’t stress evaluation always
required for the diagnosis? World J Hepatol 2016;8(3):200.
[27] Merli M, Torromeo C, Giusto M, Iacovone G, Riggio O, Puddu P. Survival at 2 years among liver cirrhotic patients is influenced by left
atrial volume and left ventricular mass. Liver Int 2017;37(5):7006.
[28] Hammami R, Boudabbous M, Jdidi J, Trabelsi F, Mroua F, Kallel R, et al. Cirrhotic cardiomyopathy: is there any correlation between the
stage of cardiac impairment and the severity of liver disease? Libyan J Med 2017;12(1).
[29] Wiese S, Hove J, Mo S, Mookerjee RP, Petersen CL, Vester-Andersen MK, et al. Myocardial extracellular volume quantified by magnetic
resonance is increased in cirrhosis and related to poor outcome. Liver Int 2018;38(9):161423.
[30] Huang X, Thansamay S, Yang K, Luo T, Chen S. Measurement of Exhaled Nitric Oxide in Cirrhotic Patients with Esophageal and Gastric
Varices. Biomed Res Int 2019;2019:9673162.
[31] Shaaban A, Gangwani MK, Pendela VS, Vindhyal MR. StatPearls. Treasure Island (FL); 2021.
[32]
Cabac-Pogorevici I, Muk B, Rustamova Y, Kalogeropoulos A, Tzeis S, Vardas P. Ischaemic cardiomyopathy. Pathophysiological insights,
diagnostic management and the roles of revascularisation and device treatment. Gaps and dilemmas in the era of advanced technology.
Eur J Heart Fail 2020;22(5):78999.
[33] Diaz RA, Nihoyannopoulos P, Athanassopoulos G, Oakley CM. Usefulness of echocardiography to differentiate dilated cardiomyopathy
from coronary-induced congestive heart failure. Am J Cardiol 1991;68(11):12247.
[34] Kato K, Lyon AR, Ghadri JR, Templin C. Takotsubo syndrome: aetiology, presentation and treatment. Heart. 2017;103(18):14619.
[35] Chahal D, Liu H, Shamatutu C, Sidhu H, Lee SS, Marquez D. Review article: Comprehensive analysis of cirrhotic cardiomyopathy
Aliment Pharmacol Ther. 2021; 53:985998.
[36] Pozzi M, Carugo S, Boari G, Pecci V, De Ceglia S, Maggiolini S, et al. Evidence of functional and structural cardiac abnormalities in cir-
rhotic patients with and without ascites. Hepatology. 1997;26(5):11317.
[37] Bernardi M, Calandra S, Colantoni A, Trevisani F, Raimondo ML, Sica G, et al. Q-T interval prolongation in cirrhosis: prevalence, rela-
tionship with severity, and etiology of the disease and possible pathogenetic factors. Hepatology. 1998;27(1):2834.
[38] Yoon KT, Liu H, Lee SS. Cirrhotic cardiomyopathy. Curr Gastroenterol Rep 2020;22(9):19.
[39] Bal JS, Thuluvath PJ. Prolongation of QTc interval: relationship with etiology and severity of liver disease, mortality and liver transplan-
tation. Liver Int 2003;23(4):2438.
[40] Torregrosa M, Aguade
´
S, Dos L, Segura R, Go
´
nzalez A, Evangelista A, et al. Cardiac alterations in cirrhosis: reversibility after liver trans-
plantation. J Hepatol 2005;42(1):6874.
[41] Adigun AQ, Pinto AG, Flockhart DA, Gorski JC, Li L, Hall SD, et al. Effect of cirrhosis and liver transplantation on the gender difference
in QT interval. Am J Cardiol 2005;95(5):6914.
[42] Carey EJ, Douglas DD. Effects of orthotopic liver transplantation on the corrected QT interval in patients with end-stage liver disease.
Dig Dis Sci 2005;50(2):3203.
242 15. Cirrhotic cardiomyopathy
III. Cardiovascular system in liver failure
https://t.me/medicina_free
[43] Zurick III AO, Spier BJ, Teelin TC, Lorenze KR, Alberte C, Zacks S, et al. Alterations in corrected QT interval following liver transplant
in patients with end-stage liver disease. Clin Cardiol 2010;33(11):6727.
[44] Dowsley TF, Bayne DB, Langnas AN, Dumitru I, Windle JR, Porter TR, et al. Diastolic dysfunction in patients with end-stage liver dis-
ease is associated with development of heart failure early after liver transplantation. Transplantation. 2012;94(6):64651.
[45] Zahmatkeshan M, Fallahzadeh E, Najib SS, Amoozgar H, Malekhosseini SA, Nikeghbalian S. The relationship between QT interval dis-
persion and end-stage liver disease score in the patients undergoing orthotopic liver transplantation. Int Cardiovasc Res J 2013;7(4):135.
[46] Sonny A, Ibrahim A, Schuster A, Jaber WA, Cywinski JB. Impact and persistence of cirrhotic cardiomyopathy after liver transplantation.
Clin Transpl 2016;30(9):98693.
[47] Gajanana D, Gupta S, Koshkelashvili N, Rubio M, Bhalla V, Amanullah A. Electrocardiographic and echocardiographic changes in
patients undergoing liver transplant stratified by outcomes. Int J Cardiol 2016;223:699700.
[48] Izzy M, VanWagner LB, Lin G, Altieri M, Findlay JY, Oh JK, et al. Redefining cirrhotic cardiomyopathy for the Modern Era. Hepatology.
2020;71(1):33445.
[49] Mechelinck M, Hartmann B, Hamada S, Becker M, Andert A, Ulmer TF, et al. Global longitudinal strain at rest as an independent predic-
tor of mortality in liver transplant candidates: A retrospective clinical study. J Clin Med 2020;9(8).
[50] Carvalho MVH, Kroll PC, Kroll RTM, Carvalho VN. Cirrhotic cardiomyopathy: the liver affects the heart. Braz J Med Biol Res 2019;52(2):e7809.
[51] Desai MS, Zainuer S, Kennedy C, Kearney D, Goss J, Karpen SJ. Cardiac structural and functional alterations in infants and children
with biliary atresia, listed for liver transplantation. Gastroenterology. 2011;141(4):126472 72 e14.
[52] Gorgis NM, Kennedy C, Lam F, Thompson K, Coss-Bu J, Akcan Arikan A, et al. Clinical consequences of cardiomyopathy in children
with biliary atresia requiring liver transplantation. Hepatology. 2019;69(3):120618.
[53] Ma Z, Meddings JB, Lee SS. Cardiac plasma membrane physical properties and β-adrenergic receptor function are unaltered in portal-
hypertensive rats. Hepatology. 1995;22(1):18893.
[54] Finucci G, Desideri A, Sacerdoti D, Bolognesi M, Merkel C, Angeli P, et al. Left ventricular diastolic function in liver cirrhosis. Scand J
Gastroenterol 1996;31(3):27984.
[55] Braverman AC, Steiner MA, Picus D, White H. High-output congestive heart failure following transjugular intrahepatic portal-systemic
shunting. Chest. 1995;107(5):14679.
[56] Pozzi M, Ratti L, Redaelli E, Guidi C, Mancia G. Cardiovascular abnormalities in special conditions of advanced cirrhosis. The circulatory
adaptative changes to specific therapeutic procedures for the management of refractory ascites. Gastroenterol Hepatol 2006;29(4):26372.
[57] Wong F, Sniderman K, Liu P, Allidina Y, Sherman M, Blendis L. Transjugular intrahepatic portosystemic stent shunt: effects on hemody-
namics and sodium homeostasis in cirrhosis and refractory ascites. Ann Intern Med 1995;122(11):81622.
[58] Huonker M, Schumacher YO, Ochs A, Sorichter S, Keul J, Rossle M. Cardiac function and haemodynamics in alcoholic cirrhosis and
effects of the transjugular intrahepatic portosystemic stent shunt. Gut. 1999;44(5):7438.
[59] Wong F, Blendis L. The pathophysiologic basis for the treatment of cirrhotic ascites. Clin Liver Dis 2001;5(3):81932.
[60] Lee SS, Liu H. Cardiovascular determinants of survival in cirrhosis. Gut. 2007;56(6):7468.
[61] Vasatova M, Pudil R, Safka V, Fejfar T, Buchler T, Hulek P, et al. Elevated cardiac markers are associated with higher mortality in
patients after transjugular intrahepatic portosystemic shunt insertion. Ann Clin Biochem 2013;50(Pt 2):1226.
[62] Moller S, Krag A, Bendtsen F. Kidney injury in cirrhosis: pathophysiological and therapeutic aspects of hepatorenal syndromes. Liver
international 2014;34(8):115363.
[63] Ruiz-del-Arbol L, Urman J, Fernandez J, Gonzalez M, Navasa M, Monescillo A, et al. Systemic, renal, and hepatic hemodynamic
derangement in cirrhotic patients with spontaneous bacterial peritonitis. Hepatology. 2003;38(5):121018.
[64] Lee SS. Cardiac dysfunction in spontaneous bacterial peritonitis: a manifestation of cirrhotic cardiomyopathy? Hepatology. 2003;38(5):108991.
[65] Ruiz-del-Arbol L, Monescillo A, Arocena C, Valer P, Gines P, Moreira V, et al. Circulatory function and hepatorenal syndrome in cirrho-
sis. Hepatology. 2005;42(2):43947.
[66] Fede G, Spadaro L, Tomaselli T, Privitera G, Germani G, Tsochatzis E, et al. Adrenocortical dysfunction in liver disease: a systematic
review. Hepatology 2012;55(4):128291.
[67] Fontan Balestra E. Hepato-adrenal syndrome. Rev Clin Esp 1956;61(4):23744.
[68] Marik PE, Gayowski T, Starzl TE. The hepatoadrenal syndrome: a common yet unrecognized clinical condition. Crit Care Med 2005;33
(6):12549.
[69] Fede G, Spadaro L, Tomaselli T, Privitera G, Piro S, Rabuazzo AM, et al. Assessment of adrenocortical reserve in stable patients with cir-
rhosis. J Hepatol 2011;54(2):24350.
[70] Theocharidou E, Krag A, Bendtsen F, Moller S, Burroughs AK. Cardiac dysfunction in cirrhosis - does adrenal function play a role? A
hypothesis. Liver Int 2012;32(9):132732.
[71] D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 stud-
ies. J Hepatol 2006;44(1):21731.
[72] Suman A, Barnes DS, Zein NN, Levinthal GN, Connor JT, Carey WD. Predicting outcome after cardiac surgery in patients with cirrhosis:
a comparison of Child-Pugh and MELD scores. Clin Gastroenterol Hepatol 2004;2(8):71923.
[73] Krag A, Bendtsen F, Henriksen JH, Moller S. Low cardiac output predicts development of hepatorenal syndrome and survival in patients
with cirrhosis and ascites. Gut. 2010;59(1):10510.
[74] Yang YY, Liu H, Nam SW, Kunos G, Lee SS. Mechanisms of TNFalpha-induced cardiac dysfunction in cholestatic bile duct-ligated mice:
interaction between TNFalpha and endocannabinoids. J Hepatol 2010;53(2):298306.
[75] Liu H, Ma Z, Lee SS. Contribution of nitric oxide to the pathogenesis of cirrhotic cardiomyopathy in bile duct-ligated rats.
Gastroenterology. 2000;118(5):93744.
[76] Liu H, Song D, Lee SS. Role of heme oxygenase-carbon monoxide pathway in pathogenesis of cirrhotic cardiomyopathy in the rat. Am J
Physiol Gastrointest Liver Physiol 2001;280(1):G6874.
[77] Iwakiri Y. The molecules: mechanisms of arterial vasodilatation observed in the splanchnic and systemic circulation in portal hyperten-
sion. J Clin Gastroenterol. 2007;41(Suppl 3):S28894.
243References
III. Cardiovascular system in liver failure
https://t.me/medicina_free
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