"Do Serum and Stool Biochemical and Hematopoietic Biomarkers Predict Low Cardiac Index in Patients with Fontan Physiology?”

Doctor's Name: 
Bradley Marino MD
Cincinnati Children’s Hospital

"Do Serum and Stool Biochemical and Hematopoietic Biomarkers Predict Low Cardiac Index in Patients with Fontan Physiology?”

“ JH is a 21 year old woman who was born with tricuspid valve atresia in which the entire right side of her heart was significantly underdeveloped, thereby leaving her left ventricle as the only pumping chamber to the body. She had 3 major cardiac operations by the time she was 4 years old including a Fontan operation. After her Fontan operation she did “alright” with no subsequent hospitalizations while in grade school, although she was noticeably smaller than the other children and wasn’t allowed to compete in competitive sports.  In high school she began to "slow down" a bit, and had an exercise stress test that was "OK for a Fontan patient, though not normal." She and her cardiologist discussed possible placement of a pacemaker, but no decision was reached.  During her first semester of nursing school she had a viral syndrome and developed a pleural effusion which was treated with diuretics. More medications were added recently to improve her heart function and a pacemaker was implanted, but she now appears to have heart failure, with liver and kidney problems. Her cardiologist is talking about the possibility of more heart surgery; maybe even a heart transplant.  JH and her family want to know: why didn't we (and our doctors) see this coming? Could something less drastic have been done sooner?”

The Fontan operation is used to treat patients like JH with complex congenital heart defects where there is only one pumping chamber.  Death rates for  patients undergoing the Fontan operation have decreased over time with a majority of these patients surviving to adolescence and adulthood.  Fontan survivors suffer from decreased heart function, which worsens over time leading to chronic heart failure.  Patients with “failing Fontan” physiology cannot pump enough blood to the body’s major organs, resulting in poor kidney function, short stature due to lack of bone growth, low blood cell counts, cirrhosis of the liver, and poor intestinal function.  In order to prevent, or delay the onset of such multi-system organ failure, doctor’s need to have a simple, yet comprehensive surveillance method is needed to identify patients who are in the earliest stages of “failing Fontan” physiology.

Blood, urine, and stool tests are universally available and minimally invasive, making them an attractive way of serially monitoring organ function in Fontan survivors.  What is not known is: 1) which organ-specific tests best identify Fontan survivors with worsening heart function prior to the “failing Fontan” physiology; and 2) if earlier initiation of therapies to improve heart function based on blood and stool test assessment will abolish, or postpone “failing Fontan” physiology.  These gaps in knowledge leave medical caregivers without guidance regarding how to best screen for early heart dysfunction that may be reversible with timely and appropriate therapeutic interventions. Our long-term goal is to move care for children and adults who have undergone the Fontan operation beyond the essential but narrow pursuit of improving early survival to a new paradigm that enables doctors to identify declining heart function and begin treatment before irreversible multi-system organ damage has occurred.  By providing earlier treatment to maximize heart function, we hope to improve both quality of life and long-term survival in the Fontan population.

In a retrospective study, our multi-center Fontan Research Consortium has recently shown for the first time that some blood tests for the kidney, liver, and bone marrow are associated with precise Magnetic Resonance Imaging measures of heart function. The objectives of this application are: 1) to test in a prospective manner whether there are blood, urine, and stool tests that are associated with heart function in Fontan survivors; and 2) to identify a set of organ-specific blood, urine, and/or stool tests that detect poor heart function in Fontan survivors.  These initial data, combined with the expertise of our multidisciplinary investigative team in our Fontan Research Consortium and supportive research environments, place us in an ideal position to achieve the following Specific Aim: To assess whether blood and/or urine and/or stool tests related to 6 major organs (heart, kidney, bone, bone marrow, liver, small intestine) known to be affected by Fontan physiology can predict worse heart function in Fontan survivors.  Primary Hypotheses:  We believe that there is an association between organ-specific blood, urine, and stool tests and heart function in Fontan survivors.

To maximize outcomes in Fontan survivors through effective targeted interventions to maximize heart function, scientific data must first characterize the association between important organ-specific tests and declining heart function.  The proposed study will fill key gaps in knowledge by efficiently capitalizing on our previous work, our pre-existing Fontan Research Consortium, and the expertise of our multidisciplinary team.  The findings from this study will provide critical data that will inform future evidence-based targeted stratification, evaluation, and intervention programs for Fontan survivors that allow healthcare providers to better prevent and/or treat heart failure that is associated with organ-specific Fontan complications and poorer quality of life in the growing population of Fontan survivors.


Award Date 1: 
Award Amount 1: 
Award Date 2: 
Award Amount 2: 
$100,000 (Ann & Robert H Lurie Children's Hospital)