Sildenafil After the Fontan Operation
Condition: Hypoplastic Left Heart Syndrome; Tricuspid Atresia
MeSH terms: Hypoplastic Left Heart Syndrome; Tricuspid Atresia
Study type: Interventional
Phase: Phase 2

Summary: 
      In this study, the investigators will evaluate the effect of sildenafil on exercise tolerance
      in patients with a single cardiac ventricle who have undergone the Fontan operation. The
      investigators will also evaluate echocardiographic measures of ventricular function and
      measure quality of life changes using two validated quality of life measures. The hypothesis
      is that sildenafil will result in increased exercise tolerance in patients who have had the
      Fontan operation as compared to placebo.
    

Detailed description: 
      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.
    

Intervention name(s): Sildenafil; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): One 20 mg capsule of sildenafil will be taken by mouth three times-a-day.; One placebo capsule will be taken by mouth three times-a-day.
Other intervention name(s): Revatio; Viagra
Intervention MeSH terms: Sildenafil Citrate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Other Single Ventricle Anatomy; Hypoplastic Left Heart Syndrome; Tricuspid Atresia