concern over safety of rosiglitazone in heart failure

This study will investigate the effects of rosiglitazone, a medicine commonly used to treat type 2 diabetes, on the utilization of glucose by the heart in patients with heart failure which is not due to heart attacks. The primary purpose of the study is to determine whether treatment with an insulin-sensitizing medication will improve the heart's ability to metabolize glucose (sugar).

Nondiabetic patients with nonischemic cardiomyopathy who are insulin-resistance or insulin-sensitive based on a fasting homeostasis model assessment (HOMA) value are eligible for the trial. At baseline, a 6-minute walk test is performed, followed by assessment of coronary flow reserve with ammonia-PET imaging before/after adenosine infusion. Subjects are then given an oral glucose load (75g), followed by PET imaging with F-18-fluoro-2-deoxyglucose (FDG). Subjects then begin taking rosiglitazone 4 mg qd x 12 weeks, after which the 6-minute walk test & PET imaging is repeated.

Inclusion Criteria:

• Diagnosis of nonischemic dilated cardiomyopathy, current NYHA class I-II congestive heart failure
• History of Stage C-D heart failure with EF ≤ 40% during the course of the disease
• Treatment with a stable comprehensive heart failure regimen for at least 3 months (including beta-blockers and ACE-inhibitors or angiotensin receptor blockers unless intolerant)
• Age > 18 yrs

Exclusion Criteria:

• Cardiomyopathy due to one of the following:

  • Ischemic heart disease
  • Primary valvular lesion
  • Hypertrophic cardiomyopathy

• Cardiac resynchronization within the last 3 months

• Transaminase values > 2.5 x upper limit of normal or history of liver disease

• Diagnosis of diabetes mellitus by:

  • Diabetes previously diagnosed per patient history
  • 2 or more fasting glucose values > 125 mg/dl

• Current NYHA class III or IV heart failure

• Serum creatinine > 1.6 mg/dl

• History of heart transplantation

• Pregnancy or active breast feeding

• Hospitalization for decompensated heart failure within 30 days prior to enrollment.