Sildenafil After the Fontan Operation (SAFO)

• Change in maximal oxygen consumption from baseline testing to post-medication/placebo testing [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ] [ Designated as safety issue: No ]
  

• Oxygen pulse [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ] [ Designated as safety issue: No ]
  
• Ventricular function [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ] [ Designated as safety issue: No ]
  
• Atrioventricular valvar regurgitation [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ] [ Designated as safety issue: No ]
  
• Myocardial performance index [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ] [ Designated as safety issue: No ]
  
• E:E (passive ventricular inflow/diastolic myocardial velocity) [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ] [ Designated as safety issue: No ]
  
• Fontan flow pattern [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ] [ Designated as safety issue: No ]
  
• Mesenteric artery pulsatility index [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ] [ Designated as safety issue: No ]
  
• PedsQL 4.0 - a generic quality of life assessment [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ] [ Designated as safety issue: No ]
  
• PCQLI - a disease specific quality of life assessment [ Time Frame: 6 weeks for each arm of the study (12 weeks total) ] [ Designated as safety issue: No ]
  

The Fontan physiology is the end result of staged reconstruction of the heart and the major blood vessels in patients who have a single ventricle. After completion of the reconstruction, the great veins which usually bring blood back to the heart are connected directly to the pulmonary arteries, allowing blood from the body to bypass the heart and flow directly into the lungs. In this system, blood flow through the lungs is passive (not pumped) and the efficiency of flow through the cardiovascular system is related to the resistance to blood flow in the vessels of the lungs.

There are two potential problems that arise in this scenario, as a result of the resistance to blood flow in the vessels of the lungs. First, the amount of blood flow returning to the heart from the lungs may not be sufficient to allow the heart to function at maximum efficiency, compromising the heart's ability to keep up with the demands of the body. Second, if the resistance to blood flow in the lungs is high, pressure may be transmitted back into the great veins themselves and secondarily into the organs of the body causing mild, or sometimes significant, organ dysfunction. Not all patients with the Fontan physiology develop these problems, but we know that even in patients without obvious problems, the ability to keep up with an increased metabolic demand, as during exercise, in compromised.

Improving the efficiency of blood flow through the lungs should improve the return of blood to the heart and thereby diminish the pressure transmitted back to the vessels which passively deliver blood to the lungs. We believe that this change may manifest as diminished symptoms in those patients with known difficulties, or may allow for an increased ability to walk, run, or participate in sports in those without any overt symptoms. Most importantly, we speculate that improved efficiency of flow through the lungs, and the resulting improved cardiac output (blood flow through the body) will make patients more energetic and will make them feel better.

Sildenafil is an oral medication that has been used to treat patients with pulmonary hypertension, a disease in which there is abnormally elevated pressure in the vessels of the lung. In this disease, the resistance in the lungs is abnormally high, severely limiting the ability of the heart to keep up with the demands of the body. Sildenafil lowers the resistance in the vessels of the lungs and has been shown to improve exercise performance in patients with this disease. We believe that Sildenafil may have a similar benefit for our patients after Fontan operation in whom cardiac output is also limited by resistance of the blood vessels in the lungs.

In our study, we will compare the exercise capacity, echocardiographic measures of cardiac function, and the overall quality of life in patients with the Fontan before and after a six-week period of sildenafil administration. As a control, the same group of patients will take a placebo for a six-week period, also with before and after testing. We hypothesize that oral sildenafil will result in significant improvements in exercise capacity, energy levels, and echocardiographic measures of cardiac function and output in our study participants. We are hopeful that the findings of this investigation will directly help children and young adults with Fontan physiology.