• change in flow mediated dilation (during reactive hyperemia); evaluate endothelial function at baseline and 4-5 weeks after initial study. [ Time Frame: 4-5 weeks after initial study ] [ Designated as safety issue: No ]
  

• change in BNP [ Time Frame: drawn at baseline and 4-5 week visit ] [ Designated as safety issue: No ]
  
• change in Form assay [ Time Frame: drawn at baseline and 4-5 week visit ] [ Designated as safety issue: No ]
  
• change in TNF alpha [ Time Frame: drawn at baseline and 4-5 week visit ] [ Designated as safety issue: No ]
  
• change in cytotkine panels [ Time Frame: drawn at baseline and 4-5 week visit ] [ Designated as safety issue: No ]
  
• change in 6 minute walk test [ Time Frame: performed at first and last visit to determine toleration of daily activity ] [ Designated as safety issue: No ]
  
• drawn and conducted at baseline and 4-5 weeks after initial study. [ Time Frame: baseline and 4-5 weeks after initial study ] [ Designated as safety issue: No ]
  

Drug: Spironolactone (drug)
1 mg/kg/day; afer 2 weeks doubled to 2/mg/kg/day. Patient's with endothelium-dependent brachial artery vasodilation and single-ventricle should show improvement within 4-8 weeks. Patients and their labs who are receiving Spironolactone will be followed.

Spironolactone The starting dose of spironolactone is 1 mg/kg/day. After two weeks this dose will be doubled to the same maximum dose (2/mg/kg/day) as in RALES. If side effects occur or plasma urea and electrolytes became deranged the dose will be halved. Patients unable to tolerate the minimum dose will be withdrawn. Measurement of serum electrolytes will occur at baseline, at two weeks, and at time of repeat evaluation.

Endothelial Function

Subjects with single ventricle will have an evaluation of endothelial function:

1. At baseline
2. On spironolactone- 4-5 weeks after initial study.

Imaging protocol:

The diameter of the brachial artery will be measured from two-dimensional ultrasound images, using a 12 MHz linear array transducer and an Accuson Sequoia system (Accuson, Mountainview, California). Measurements of the brachial artery will be obtained:

1. In a resting state
2. During limb ischemia
3. In response to reactive hyperemia
4. At rest

Reactive hyperemia will be induced by inflating a standard blood pressure cuff to 50 mm Hg above the systolic blood pressure for 4.5 minutes and then deflating the cuff.

After data collection, the DICOM-formatted images will be transferred to a PC for investigator-blinded measurement of brachial artery diameter using image analysis software (Brachial Tools 3.1, Medical Imaging Applications, Iowa).

Measurement of prognostic markers:

Blood samples

Plasma beta-type natriuretic peptide, form assay, TNF alpha and a Cytokine panel will be drawn at base line and at the final 4-5 week visit for this study.

Samples will be collected between 11 am and 1 pm after 30 minutes' supine rest. The samples will be centrifuged and plasma stored at -70°C (peptides) or -20°C (other samples). Plasma [beta]-type natriuretic peptide (BNP) samples will be collected into EDTA and aprotonin and measured by radioimmunoassay 6-minute walk test.

A 6-minute walk test will be performed at the first visit and the last visit. During this test, signs and symptoms will be recorded (i.e. chest pain and shortness of breath) to determine toleration of daily activity. A doctor or nurse will conduct this test and the patient will be provided the opportunity to stop or rest if symptoms become severe.

Outcome measures

The primary outcome measure will be the change in flow mediated dilation (during reactive hyperemia). This will be expressed as a percentage.

Secondary outcome measures will include changes in BNP, Form assay, TNF alpha, Cytokine panels and the 6-minute walk test.

Statistical analysis

We and others have previously shown that asymptomatic patients with the Fontan operation have a mean flow-mediated dilation of approximately 4% compared to 8-9% in controls. In order to detect a 25% change in FMD, with a power of 0.80, the current study would require a patient population of 13 cases. There are currently over 40 patients with single ventricle who are followed in the adult congenital clinic at Emory University.

We plan on enrolling 20 patients into this study.