University of Utah
Shaji Menon, MD, Primary Investigator
Division of Pediatrics
Salt Lake City, UT
Research project: Effect of Sildenafil on Exercise Capacity in Pediatric Fontan Patients
Funding requested: $24,106
About 35,000 infants are born with congenital heart disease each year in the United States. In the 1940’s, many of these children failed to survive to adulthood. Tremendous progress has been made in the management of even the most complex forms of congenital heart disease and there are now 1,300,000 adults with congenital heart disease in the United States. As more and more children born with congenital heart disease survive in to adulthood, we are seeing a myriad of complex medical issues in the survivors that has skyrocketed the resource utilization and cost of health care. This is particularly true for patients born with single ventricle (essentially “half a heart”) who continue to have the highest morbidity, mortality and health care costs.
The standard treatment for single ventricle patients requires several surgeries with the final stage being the Fontan operation. The Fontan operation allows the only ventricle the child has to pump blood to the body. Venous blood must flow into the lungs without a pump. The Fontan procedure is largely responsible for the improvement in survival of these patients. Along with the improvement in survival, however, Fontan patients are at risk for developing multiple medical problems and this risk increases with age. One of the main health problems that interfere with the patients’ quality of life is the progressive decrease in the ability to perform exercise or work. There are several factors responsible for this but two main causes: 1) absence of a pump to push blood into the lungs and 2) poor pump function that tends to develop over time.
In Fontan patients, one ventricle is missing so there is no pump to push the blood through the lungs where the blue blood gets oxygenated. Blood has to passively flow through the lungs. In many Fontan patients, the resistance to flow of blood through lungs is higher than in normal people. This combination of higher resistance and absence of a pump to push blood through lungs results in decreased filling of heart. The amount of blood the heart ejects during pumping is limited by its filling. Reduced filling in a Fontan heart results in low output during ejection leading to decreased ability of a person with a Fontan to work. This is especially true during exercise when more blood is needed to meet the increased oxygen demands of the body. Because the problem only becomes worse with aging, many patients with a Fontan will suffer from progressive difficulty with exercise performance, deterioration in quality of life, and eventually need heart transplantation or will die prematurely
Sildenafil is a drug that is known to significantly reduce the resistance to blood flow through lungs and improve ventricular filling in children with other conditions that also have high lung resistances. In a recent study of adults who have had the Fontan operation, a single dose of Sildenafil significantly improved their exercise performance. Because of these promising results, we propose a study to see if Sildenafil will improve exercise tolerance in children with the Fontan circulation. We expect this study to provide insight into the effectiveness of Sildenafil for improving the exercise performance of children with the Fontan circulation. Data from this pilot study will contribute to the design of a large multicenter trial to answer the question of whether this drug will help patients who have had the Fontan. Our long-term goals in treatment of these patients are to improve the efficiency of heart function, which will improve the quality of life and delay or avoid the need for cardiac transplantation and death.
