Detection of Diffuse Scar in Patients With Diabetes

This study will be conducted in TWO (2) PHASES:

Phase 1: Prospective cohort study of patients with diabetes mellitus, in which index cardiac
MRI will be done after screening to determine FIBROTIC INDEX. Patients are subsequently
followed for 5 years for a primary endpoint (composite cardiovascular event).

Phase 2: Of the patients with "HIGH" FIBROTIC INDEX, 50 patients will be randomly selected
and randomized 1:1 to placebo:eplerenone 25 mg daily for 6 months, and a repeat cardiac MRI
will be done to assess the fibrotic index post-treatment.

Phase 2 is a PILOT study of 50 patients.

The inclusion/exclusion criteria for the different phases is shown below.

For PHASE I (Prospective Cohort Study to determine prognostic value of fibrotic index)

Inclusion Criteria:

- Diabetes mellitus, type II

- Age >= 40 years

- UKPDS 10 year Risk Score > 15%

- Low risk stress test (defined explicitily in our protocol)

Exclusion Criteria:

- suspected or confirmed myocarditis or infiltrative disease (including
hemochromatosis, sarcoid, or amyloid)

- history of prior MI or coronary revascularization (by Q waves on electrocardiogram in
2 contiguous leads or by clinical history)

- clinical HF (with prior hospital admission for HF or documentation of reduced LV
ejection fraction after index CMR)

- metallic hazards

- hematocrit < 30% (within 1 year of nuclear stress test) or history of active bleeding
(within 3 months of stress test)

- estimated GFR (by Modified Diet in Renal Disease) < 45 ml/min/1.73m2 (within 2 weeks
of planned CMR)

- pregnancy

- severe non-cardiac illness that or prognosis (e.g., end stage liver disease,
malignancy, advanced HIV/AIDS)

For PHASE 2:

Inclusion Criteria:

- Included in Phase I

- Systolic blood pressure > 140 mmHg on two occasions (at the initial nuclear stress
test and at the index cardiac MRI)

Exclusion criteria:

1. Concomitant cytochrome P450 (CYP3A4) inhibitors or inducers;

2. Concomitant potassium supplementation or potassium sparing diuretics;

3. Concomitant use of both ACE inhibitor and ARB therapy (at any dose);

4. Renal dysfunction (GFR < 50 ml/min or serum creatinine > 1.5 mg/dL (as assessed at
time of index CMR);

5. Any urine microalbuminuria (as assessed at time of index CMR);

6. Baseline (pre-therapy) serum potassium > 5.0 mEq/L;

7. Lack of reliable telephone contact number for relaying results or the need to
discontinue drug therapy;

8. Age > 75 years (given the tendency toward renal insufficiency not captured by GFR,
dehydration and/or concomitant illness)

9. Women able to become pregnant (given the undefined risk of eplerenone therapy in
pregnant women and newborns).