Predictors of cardiac hepatopathy in patients with right heart failure.
ABSTRACT Some patients with right heart failure develop cardiac hepatopathy (CH). The pathophysiology of CH is thought to be secondary to hepatic venous congestion and arterial ischemia. We sought to define the clinical and hemodynamic characteristics associated with CH.
A retrospective cross sectional analysis was performed in which subjects were identified from our institutional cardiology database if echocardiography showed either right ventricular (RV) hypokinesis or dilatation, and was performed within 30 days of right heart catheterization. A chart review was then performed to identify patient clinical characteristics and to determine if the patients had underlying liver disease. Subjects with non-cardiac causes for hepatopathy were excluded.
In 188 included subjects, etiology for right heart dysfunction included left heart failure (LHF), shunt, pulmonary hypertension, mitral- tricuspid- and pulmonic valvular disease. On multivariate analysis, higher RV diastolic pressure and etiology for RV dysfunction other than LHF were both associated with CH. Low cardiac output was associated with CH only amongst those without LHF.
CH is most often seen in subjects with elevated RV diastolic pressure suggesting a congestive cause in most cases. CH associated with low cardiac output in patients without LHF suggests that low flow may be contributing to the patophysiology in some cases.
Article: Ischemic hepatitis.[show abstract] [hide abstract]
ABSTRACT: Seven patients with cardiovascular disease had clinical episodes and marked transaminase elevations that suggested viral hepatitis, but all had morphologic evidence (from liver biopsy or autopsy specimens) that documented centrilobular necrosis (ischemic hepatitis) with no evidence of viral or drug injury. Several also had moderate or marked passive congestion of the liver so the liver biopsies of 15 additional patients were retrospectively reviewed. In this latter group congestion alone was associated with normal or minimal elevation in transaminases while all patients with notable (greater than 5 times normal) transaminase elevations had centrilobular necrosis. Congestion alone, no matter how severe or prolonged, seems to do little if any damage to the liver. Centrilobular necrosis, or ischemic hepatitis, correlates with significant hypertransaminasemia, appears to result from failure of hepatic perfusion (with or without preceding hypotension), and presents with clinical and laboratory manifestations that suggest viral hepatitis.Digestive Diseases and Sciences 03/1979; 24(2):129-35. · 2.26 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: The prevalence and importance of liver function test (LFT) abnormalities in a large contemporary cohort of heart failure patients have not been systematically evaluated. We characterized the LFTs of 2679 patients with symptomatic chronic heart failure from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity program (CHARM). We used multivariable modelling to assess the relationships between baseline LFT values and long-term outcomes. Liver function test abnormalities were common in patients with chronic heart failure, ranging from alanine aminotransferase elevation in 3.1% of patients to low albumin in 18.3% of patients; total bilirubin was elevated in 13.0% of patients. In multivariable analysis, elevated total bilirubin was the strongest LFT predictor of adverse outcome for both the composite outcome of cardiovascular death or heart failure hospitalization (HR 1.21 per 1 SD increase, P<0.0001) and all-cause mortality (HR 1.19 per 1 SD increase, P<0.0001). Even after adjustment for other variables, elevated total bilirubin was one of the strongest independent predictors of poor prognosis (by global chi-square). Bilirubin is independently associated with morbidity and mortality. Changes in total bilirubin may offer insight into the underlying pathophysiology of chronic heart failure.European Journal of Heart Failure 02/2009; 11(2):170-7. · 5.25 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Serial liver function tests were performed in 175 patients with right-sided heart failure of diverse etiology. The cases were classified as acute or chronic depending on the duration and severity of congestive failure. The indices of liver function studied and the incidence of abnormal values obtained were as follow. Excretory function: serum bilirubin (31 per cent), bromsulfalein retention (80 per cent), alkaline phosphatase (10 per cent). Parenchymal cell destruction: serum glutamic oxalacetic transaminase (33 per cent), serum glutamic pyruvic transaminase (11 per cent). Abnormal serum protein production: serum globulins (51 per cent), thymol turbidity (2 per cent). Biosynthetic functions: plasma prothrombin concentration (80 per cent), serum albumin (30 per cent), cephalin flocculation (19 per cent), cholinesterase activity (48 per cent), cholesterol (46 per cent), cholesterol esters (37 per cent).The causes of the right heart failure did not appear to influence the pattern of altered liver function as much as whether failure was acute or chronic. The liver indices reflecting parenchymal cell destruction and excretory activity were most affected during acute failure. Elevated levels of transaminase (up to 1,200 units) and bilirubin (up to 8 mg. per cent) were obtained in half of the patients with acute failure, in the absence of myocardial or pulmonary infarction. A much greater incidence of elevated transaminase levels was found in acute failure (49 per cent) than in chronic failure (5 per cent). These changes correlated with the presence of centrilobular hepatocellular necrosis.The majority of indices of hepatic function returned to normal within one to two weeks following cardiac compensation, except for those reflecting biosynthesis by the liver, which improved more slowly, and hyperglobulinemia, which tended to persist. Repeated attacks of failure (as in rheumatic heart disease) were associated with more severe impairment in liver function.The American Journal of Medicine 03/1961; 30:211-25. · 4.77 Impact Factor
Predictors of cardiac hepatopathy in patients with
right heart failure
Sherry Megalla1ABCDEF, Dvorah Holtzman1ABCDEF, Wilbert S. Aronow2DEF,
Reza Nazari1ABCDEF, Svetlana Korenfeld1ABCDEF, Aron Schwarcz1ABCDEF,
Ythan Goldberg1ABCDEF, Daniel M. Spevack1ABCDEFG
1 Department of Medicine, Cardiology Division, Montefiore Medical Center, Albert Einstein College of Medicine,
Bronx, NY, U.S.A.
2 Department of Medicine, Cardiology Division, New York Medical College, Valhalla, NY, U.S.A.
Source of support: Departmental sources
Background: Some patients with right heart failure develop cardiac hepatopathy (CH). The pathophysiology of
CH is thought to be secondary to hepatic venous congestion and arterial ischemia. We sought to
define the clinical and hemodynamic characteristics associated with CH.
Material/Methods: A retrospective cross sectional analysis was performed in which subjects were identified from our
institutional cardiology database if echocardiography showed either right ventricular (RV) hypo-
kinesis or dilatation, and was performed within 30 days of right heart catheterization. A chart re-
view was then performed to identify patient clinical characteristics and to determine if the patients
had underlying liver disease. Subjects with non-cardiac causes for hepatopathy were excluded.
Results: In 188 included subjects, etiology for right heart dysfunction included left heart failure (LHF),
shunt, pulmonary hypertension, mitral- tricuspid- and pulmonic valvular disease. On multivariate
analysis, higher RV diastolic pressure and etiology for RV dysfunction other than LHF were both
associated with CH. Low cardiac output was associated with CH only amongst those without LHF.
Conclusions: CH is most often seen in subjects with elevated RV diastolic pressure suggesting a congestive cause
in most cases. CH associated with low cardiac output in patients without LHF suggests that low flow
may be contributing to the patophysiology in some cases.
Author’s address: Wilbert S. Aronow, Cardiology Division, New York Medical College, Macy Pavilion, Room 138, Valhalla, NY 10595,
U.S.A., e-mail: email@example.com
A Study Design
B Data Collection
C Statistical Analysis
D Data Interpretation
E Manuscript Preparation
F Literature Search
G Funds Collection
© Med Sci Monit, 2011; 17(10): CR537-541
Current Contents/Clinical Medicine • IF(2010)=1.699 • Index Medicus/MEDLINE • EMBASE/Excerpta Medica • Chemical Abstracts • Index Copernicus
Right heart failure causing cardiac hepatopathy (CH) is a
distinct clinical entity in which the clinical and hemody-
namic features are poorly defined [1–3]. Hepatocellular
necrosis and dysfunction in the setting of right heart fail-
ure have been attributed to both hepatic congestion and
hepatic ischemia . The histopathologic appearance
of a congested “nutmeg” liver is distinctive and well de-
scribed. Microscopic examination shows sinusoidal con-
gestion in the early stages; with subsequent hemorrhagic
necrosis, hepatocyte degeneration, fatty changes and even-
tually fibrosis [2,4]. In hepatic ischemia, cardiac output
and hence oxygen delivery is impaired . Histological
examination may reveal centrilobular fibrosis and subse-
quent portal fibrosis [4,6].
The finding of hepatopathy in patients with cardiac dysfunc-
tion has important clinical implications. Increased mortality
has been demonstrated when transaminitis or hyperbiliru-
binemia [7,8] are present in patients with cardiac dysfunc-
tion. Since most patients with right heart dysfunction do not
develop CH, we sought to define the clinical and hemody-
namic characteristics associated with this entity.
Material and Methods
A retrospective cross sectional analysis was performed. Our
hospital cardiology database was queried to identify all sub-
jects who had right ventricular (RV) hypokinesis or dilata-
tion on echocardiography. Patients were included if they
also had right heart catheterization performed within 30
days of their echocardiograms. Charts were reviewed for
demographic data, comorbid conditions, medications and
serologic assessment of hepatic function. Subjects were ex-
cluded from analysis if potential causes of hepatic dysfunc-
tion other than cardiac disease were identified on chart
review (Figure 1). Subjects with acute shock were exclud-
ed, namely those patients who presented with hypotension
and/or cardiac arrest. Thereby, this excluded severe acute
RV dysfunction and acute left ventricular (LV) dysfunction.
Furthermore, subjects with malignancy, autoimmune dis-
ease, complex congenital cardiac disease, human immu-
nodeficiency virus, substance abuse, and hemochromatosis
were also excluded and labeled as other in Figure 1. These
subjects were excluded because of the higher likelihood of
noncardiac causes of hepatic dysfunction.
CH was defined as an aspartate aminotransferase
>100 U/L, an alkaline phosphatase >200 U/L, or a se-
rum total bilirubin >2.0 mg/dL. These markers were cho-
sen because they are often abnormal in CH. [9,10]. The
cutoffs chosen represent values approximately twice the
upper limit of normal. The chosen cutoffs also corre-
sponded approximately with the 95th percentile observed
in our study sample.
The etiology of right heart dysfunction was classified by a
study cardiologist based on the clinical, echocardiograph-
ic, and hemodynamic data. This assessment was made while
blinded to CH status. Etiology was classified as being due to
one of the following: left heart failure, pulmonary arterial
hypertension, shunt, tricuspid regurgitation, pulmonic re-
gurgitation, or other etiology. Subjects were classified based
on their primary cardiac pathology that was most likely to
cause right heart dysfunction.
322 subjects in total
188 included subjects
Alcohol abuse (n=35)
Viral hepatitis (n=23)
Heart transplant (n=9)
Shock – including cardiogenic and
Other – including cancer,
complex congenital cardiac disease,
HIV, substance abuse,
Figure 1. Inclusions and exclusions.
Clinical Research Med Sci Monit, 2011; 17(10): CR537-541
The study selection included patients who had evidence of
right ventricular dilatation or hypokinesis who had both a
cardiac catheterization and an echocardiogram within one
month of each other during the period of December, 2000
through July, 2006. The criteria for the study were justified.
Patients were included only with evidence of right heart dys-
function in our study population in order to evaluate the he-
patic derangements seen with this type of cardiomyopathy.
Statistical analysis was done using Stata software, version 9.1
(College Station, TX). Normally distributed data were pre-
sented as the mean ± standard deviation (SD). Non-normal
data were presented as the median [interquartile range (IR)].
Comparison of means was performed using the two-sample
t-test. Comparison of categorical data was performed using
c2. Comparison of medians was performed using the Mann-
Whitney or Kruskal Walllis tests as appropriate. Logistic re-
gression analysis was used to examine for clinical, echocar-
diographic and hemodynamic variables associated with CH.
From the study sample of 188 patients, 56 (30%) were found
to have CH. Demographics and clinical variables are dis-
played in Table 1. No difference was seen in age, sex, body
surface area, medication use, and prevalence of hyperten-
sion and diabetes between those with and without congestive
hepatopathy. Renal function was similar between those with
and without CH. Etiologies for RV dysfunction are shown in
Table 2, stratified by the presence or absence of CH. Having
left heart failure as the etiology for RV dysfunction was less
common in the CH group, p=0.002.
Echocardiographic and invasively measured data are shown
in Table 3. Those with CH had similar LV ejection fraction,
left atrial diameter, RV systolic pressure, and wedge pressure
compared to those without CH. Prevalence of severe tricus-
pid regurgitation, RV hypokinesis and dilated RV were also
similar in each group. Those with CH had a higher RV dia-
stolic pressure than those without CH, p<0.001.
In a multivariate logistic regression model, the only variables
found to be independent predictors of CH were etiology
for RV dysfunction other than left heart failure, odds ratio
(OR) 2.94 [95% confidence interval (CI): 1.51, 5.72] and in-
creased RV diastolic pressure, OR 2.47 [95% CI: 1.11, 5.51].
The relationship of cardiac output and congestive hepatop-
athy was complex. Overall, the cardiac output was similar
in those with CH compared to those without CH, p=0.08,
(Table 3). In the whole study sample, cardiac output was
not an independent predictor of CH (OR 1.44 [95% CI:
0.73, 2.83], p=0.3). However, within the group of subjects
whose RV dysfunction was not caused by left heart failure,
low cardiac output was a significant predictor of CH (OR
2.74 [95% CI: 1.08, 6.95]). Accordingly, the prevalence of
No cardiac hepatopathy
Age (years)62±17 0.97
Male (%)5550 57 0.39
Body surface area (m2) 1.9±0.3 1.8±0.21.9±0.3 0.32
Hypertension (%)81 8679 0.26
Diabetes (%)413942 0.73
Creatinine 1.1 [1, 1.5] 1.2 [1, 1.7] 1.1 [1, 1.5] 0.09
Statin use (%)3423 39 0.07
Anti-platelet use (%) 4446 43 0.72
ACEI or ARB use (%)4646 45 0.90
Beta blocker use (%) 6160 61 0.90
Loop diuretic use (%) 6158 62 0.63
Amiodarone use (%)251 0.14
Warfarin use (%)24 1727 0.22
AST >100 mg/dL (%) 13 450 <0.001
Alk-phos >200 mg/dL (%)14 480 <0.001
Total bilirubin >2.0 mg/dL (%)
Normal data are presented as the mean ± standard deviation. Non-normal data are presented as the median [interquartile range].
ACEI – angiotensin-converting enzyme inhibitor; ARB – angiotensin receptor blocker; AST – aspartate aminotransferase; Alk-phos – alkaline
Table 1. Patient demographics and clinical variables.
Med Sci Monit, 2011; 17(10): CR537-541 Megalla S et al – Predictors of cardiac hepatopathy in patients with right heart failure
CH in those with left heart failure was 21%, as compared to
42% in those without left heart failure with preserved cardi-
ac output and 56% in those without left heart failure with
reduced cardiac output (Figure 2).
The main findings of our study were that CH was associated
with increased RV diastolic pressure and with etiology for
RV dysfunction not secondary to left heart failure. Reduced
cardiac output was associated with CH only amongst those
without left heart failure. This in contrast to the findings
reported by Kubo, et al in which they found that patients
with a lower cardiac index from left heart failure had wors-
ening levels of liver function tests . In their study, how-
ever, only patients with left heart failure were included. In
addition, their study cohort had lower cardiac output com-
pared with our study sample. This may account for the dif-
ferences seen in those patients with left heart failure .
Furthermore, the finding of increased RV diastolic pressure
in those with CH supports the hypothesized pathophysiolo-
gy of hepatic congestion suggested from histological series.
Increased RV diastolic pressure implies increased right atri-
al, central venous and hepatic venous pressure. This is sim-
ilar to findings reported by Van Deursun whereby higher
CVP was associated with liver function abnormalities .
Increased hepatic venous pressure is therefore a plausible
explanation for sinusoidal congestion often observed in his-
tological specimens of patients with CH .
It is not intuitively obvious that the etiology for RV dysfunc-
tion should be associated with CH. This finding was found
to be independent of RV diastolic pressure and cardiac out-
put on multivariate analysis. The cross-sectional nature of
our study makes it impossible to draw conclusions regard-
ing causality. We therefore cannot conclude that those with
RV dysfunction who do not have left heart failure are at in-
creased risk for developing CH independent of RV diastolic
pressure and cardiac output. Our snapshot, one-time mea-
surement of RV diastolic pressure may not reflect pressures
No cardiac hepatopathy
Left heart failure (%) 5841 650.002
Mitral valve disease (%) 21 2718 0.18
Shunt (%)555 0.99
Pulmonary hypertension (%)8 135 0.09
Primary TR or PR (%)2220.89
Other etiology (%)7 1350.05
Table 2. Etiology of right heart dysfunction.
TR – tricuspid regurgitation; PR – pulmonic regurgitation.
No cardiac hepatopathy
LV ejection fraction (%)
LA diameter (mm)
Severe TR (%)
RV hypokinesis (%)
RV dilated (%)
30 [25, 50]
48 ± 9
30 [25, 50]
30 [25, 50]
RV systolic pressure (mmHg)
RV diastolic pressure (mmHg)
Cardiac output (Liters/min)
Wedge pressure (mmHg)
Normal data are presented as the mean ± standard deviation. Non-normal data are presented as the median [interquartile range]. LV – left
ventricular; LA – left atrial; TR – tricuspid regurgitation; RV – right ventricular.
3.9 [3.1, 4.7]
22 [16, 28]
4.0 [3.3, 5.0]
24 [16, 28]
3.7 [3.0, 4.6]
22 [16, 28]
Table 3. Echocardiographic and catheterization variables.
Clinical Research Med Sci Monit, 2011; 17(10): CR537-541
chronically. This association should therefore be investigated
further. Furthermore, the severity of tricuspid regurgitation
was not found to be associated with CH. This is in contrast to
previous reports by Lau showing an association between the
severity of TR and liver function abnormalities .
The finding that lower cardiac output is associated with CH
only in those without left heart failure is also intriguing. It is
sensible that the measured cardiac output more truly reflects
RV function when there is isolated RV dysfunction with nor-
mal LV output. When left heart dysfunction is also present, the
measured cardiac output reflects the joint pathology of both
chambers. Low cardiac output would be expected in those
with chronic hepatic ischemia. Lack of association between
low cardiac output and CH in both our whole cohort and in
the group with left heart failure argues that hepatic ischemia
was not often the cause of CH in our study. Since transient
ischemic insult with hypotension or shock prior to right heart
catheterization were excluded from this study, low cardiac out-
put probably reflected a more chronic process.
Patients with cirrhotic cardiomyopathy have both elevat-
ed levels of NT-proBNP and LV diastolic dysfunction .
Using a value of 1000 pg/ml, the sensitivity of serum NT-
proBNP in distinguishing ascites due to cirrhosis from asci-
tes due to heart failure was 100% . Most patients with
acute decompensated heart failure have high liver stiffness
values which, like NT-proBNP levels tend to decrease with
clinical improvement . Gamma-glutamyltransferase is
also independently associated with an adverse outcome in
patients with chronic heart failure .
Our study has some limitations. As previously mentioned,
the cross sectional and retrospective nature of our investiga-
tion, limit inferences about causal relationships. Therefore,
findings of associations between various parameters and CH
do not imply that the parameters are the cause or the ef-
fect of CH. Further investigation into such mechanisms is
warranted. It is also important to note that measurement of
parameters on catheterization, serology and echocardiog-
raphy were not simultaneous. This may have particular im-
portance in congestive heart failure patients whose hemo-
dynamics may vary substantially from day to day. Lastly, our
study sample excluded those with acute RV or LV dysfunction
and thereby limiting our analysis to chronic RV dysfunction.
Evolving technology in echocardiography has allowed for
more sophisticated measures of right heart function. RV
strain, strain rate and tricuspid annular plane systolic excur-
sion are measures of RV contractility. 3-dimensional echo-
cardiography may improve quantification of RV size, shape
and function. Association between these parameters and
CH may be an area for future investigation.
In conclusion, we found that CH was associated with higher
RV diastolic pressure and etiology for RV dysfunction oth-
er than left heart failure. Low cardiac output was associated
with CH only in those who did not have left heart failure.
These findings help us to better understand the relation-
ship between right heart dysfunction and CH.
Conflicts of interest
None of the authors have any conflicts of interest pertain-
ing to this article.
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Figure 2. Prevalence of cardiac hepatopathy in those with and
without left heart failure (LHF) divided amongst different
cardiac output (CO) subgroups.
Med Sci Monit, 2011; 17(10): CR537-541Megalla S et al – Predictors of cardiac hepatopathy in patients with right heart failure