Pediatric Cirrhotic Cardiomyopathy:
Impact on Liver Transplant Outcomes
Norman Junge ,
* Claudia Junge,
* Julian Schr€oder,
and Ulrich Baumann
Paediatric Gastroenterology and Hepatology;
Paediatric Cardiology and Intensive Medicine, Hannover Medical School,
In adults, cirrhotic cardiomyopathy (CCM) has a signiﬁcant incidence and impact on liver transplantation. For pediatric
liver transplantation (pLT), data on liver-induced cardiac changes are scarce, and in particular, the comparison between
cirrhotic and noncirrhotic liver disease has not been investigated. We retrospectively evaluated cardiac changes associated
with CCM by echocardiography and 12-lead electrocardiogram in 198 pLT-candidates (median age 4.1 years) 4.2 before
and 12 months after pLT. Results were correlated with the stage of liver ﬁbrosis and cholestasis before transplantation.
The left ventricular end-diastolic diameter (LVIDd) z score, left ventricular mass z score, and left ventricular mass index
were signiﬁcantly higher in cirrhotic patients (-0.10 versus 0.98, P < 0.001; -1.55 versus -0.42, P 5 0.001; 78.99 versus
, P 5 0.001, respectively) compared with children with noncirrhotic liver disease. Pathological z scores
(>2SDS) for the LVIDd occurred more frequently in cirrhotic patients compared with patients with noncirrhotic liver dis-
ease (31/169 versus 1/29; P 5 0.03) and were signiﬁcantly associated with cholestasis. All observed cardiac changes were
reversible 1 year after pLT. Pathological LVIDd z scores correlated highly with intensive care unit (ICU) stay (9.6 days
versus 17.1 days, respectively, P 5 0.002) but not with patient survival pre-LT or post-LT. In contrast to other studies,
prolonged QTc time was not associated with liver cirrhosis in our patients. In conclusion, CCM-associated cardiac
changes in pLT candidates with cirrhotic liver disease are frequent, mild, and associated with cholestasis and reversible
after pLT. They may impact peritransplant care and posttransplant hospitalization time. Further prospective evaluation is
warranted. In particular, for QTc time prolongation etiological factors, possible protective effects of ursodeoxycholic acid
treatment and the use as a screening parameter for CCM should be veriﬁed.
Liver Transplantation 24 820–830 2018 AASLD.
Received December 18, 2017; accepted March 28, 2018.
The impact of liver dysfunction on other organs, such
as the kidneys, lungs, and adrenal glands, is well-rec-
ognized. Cirrhotic cardiomyopathy (CCM) as
impaired cofunction between the liver and heart has
more recently gained attention and was ﬁrst described
CCM in adults is deﬁned by systolic and/or
diastolic dysfunction, left ventricular hypertrophy, and/
or QTc interval prolongation.
The underlying mech-
anism of diastolic dysfunction in cirrhosis is likely due
to the increased myocardial wall stiffness caused by
myocardial hypertrophy, ﬁbrosis, and subendothelial
edema, which subsequently results in high ﬁlling pres-
sures of the left ventricle and atrium. Recent ﬁndings
suggest that bile acids (cholestasis) play a key role in
the development of CCM.
Several studies described cardiac abnormalities using
echocardiography and electrocardiogram (ECG)
examinations of cirrhotic patients. Raevens et al.
found a CCM incidence of 43% in 173 adult liver
transplant candidates but could not detect any impact
on outcome, and further studies
could not identify
an effect of diastolic dysfunction on survival. Few stud-
ies demonstrated a signiﬁcantly elevated mortality in
patients with CCM after liver transplantation (LT).
Abbreviations: aF, advanced ﬁbrosis; AILD, autoimmune liver disease;
ALF, acute liver failure; ALT, alamine aminotransferase; ARPKD,
autosomal recessive polycystic kidney disease; AST, aspartate aminotrans-
ferase; BMI, body mass index; CCM, cirrhotic cardiomyopathy; ECG,
electrocardiogram; FS, ﬁbrosis score; GALD, gestational alloimmune
liver disease; GGT, gamma-glutamyl transferase; IVSd, interventric-
ular septum; ICU, intensive care unit; LBMD, liver-based metabolic
disease; LT, liver transplantation; LVIDd, left ventricular end-
diastolic diameter; LVM, left ventricular mass; LVMI, left ventricu-
lar mass index; LVPWTd, left ventricular posterior wall thickness;
naF, nonadvanced ﬁbrosis; PFIC, progressive familial intrahepatic
cholestasis; pLT, pediatric liver transplantation; POT1, point of time
1; POT2, point of time 2; re-LT, re-liver transplantation.
Address reprint requests to Norman Junge, M.D., Paediatric Gastroenter-
ology and Hepatology, Hannover Medical School, Carl- Neuberg-Str 1,
30625 Hannover, Germany. Telephone: 1 49 511 532 3233; FAX : 1
49 511 532 3294 ; E-mail : junge.Norman@mh-hannover.de
JUNGE ET AL.