Background: It is still difficult to predict the outcome in patients requiring Fontan Revisions and in those who have evidence of congestive hepatopathy and probable cirrhosis requiring major cardiac surgery including heart transplant. Over the years, many prognostic indices have been derived from laboratory results of blood tests, clinical and physiological variables (or some combination thereof), from liver imaging to liver histology, which has issues of sampling error, medical risks and technical difficulty. None of these have proved entirely satisfactory. Predicting morbidity or survival is particularly important when deciding about Fontan revisions versus the need for heart transplantation. What is needed here is a truly reliable test of liver function that can help predict outcome, on the basis of a single measurement within few days of a planned revision. For this purpose, it is desirable that the chosen tests of liver performance be safe, non-invasive, easy to perform, have a rapid turnaround for results, and be readily repeatable.

Tests of hepatic elimination of various exogenous substances have been described, such as galactose elimination capacity (GEC), indocyanine green (ICG) clearance, lidocaine metabolism to monoethylglycinexylidide (MEGX), and other tests that rely on liver metabolic capacity. None of these metabolic or clearance tests achieved widespread acceptance or use, mostly because their performance and analyses were cumbersome.

HepQuant,LLC has developed a platform of tests of liver function which include Systemic Hepatic Filtration Rate (HFR), Portal HFR, SHUNT, and Disease Severity Index (DSI)1,2. HepQuant tests specifically target the hepatic uptake of cholate and use a single noninvasive test of 90 minutes duration to quantify the systemic circulation, portal circulation, and portal-systemic shunt and to derive a DSI in intact human subjects. HepQuant tests can assess all stages and etiologies of liver disease. In chronic HCV patients HepQuant testing can predict which patients will respond to antiviral therapy and can measure the improvement in hepatic function that occurs after successful antiviral therapy. Patients who did not respond were followed for an average of 5 years and up to 8 years, and baseline HepQuant testing could predict clinical outcomes (CTP progression, variceal bleeding, encephalopathy, ascites, liver-related death) with 87% sensitivity and 71% specificity.

Hypothesis The results of HepQuant in patients with CHD will correlate with outcomes of cardiac surgery (namely morbidity as defined by complications such as ischemic hepatitis, survival, need for heart transplantation, improvement of liver function post revision), and thus can be used for prognosis in this condition, either alone or in conjunction with other clinical, physiological, and laboratory prognostic scores, thereby giving clinical guidance concerning the need for heart transplantation and simultaneous liver transplantation..

Primary Aim To assess the relationship between HepQuant testing results and clinical outcomes in patients with liver disease secondary to congenital heart disease (CHD) undergoing Fontan revisions.

To assess the clinical outcomes of patients with liver disease secondary to acquired cardiomyopathy or valvular disease that will undergo extensive heart surgery or heart transplantation.

Secondary Aim To assess whether HepQuant testing predicts clinical outcome in patients with Liver Disease and CHD when used in conjunction with other diagnostic tests, such as MELD, Child-Turcotte-Pugh (CTP), liver stiffness measurement (US with ARFI), and Fibrotest (Fibrosure).

Study population Male and female Subjects (age 18 to 70 years) with liver disease secondary to congenital heart disease or cardiomyopathy.

Inclusion Criteria:

1. Written informed consent obtained prior to any study-specific assessments.
2. Liver disease secondary to congenital heart disease or cardiomyopathy.
3. Male and female subjects (age 18 to 70 years of age).

Exclusion Criteria:

1. Male and female subjects < 18 or > 70 years of age.
2. Female subjects of child-bearing potential that are pregnant or breast feeding.
3. Subjects on both beta blockers and ACE inhibitors.