Conditions: Idiopathic Dilated Cardiomyopathy
Keywords: ejection fraction beta-blocker carvedilol metoprolol myocardial gene expression human heart ventricular remodeling wall stress adrenergic signaling myosin heavy chain
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 56
Healthy volunteers: no

Brief summary:
The primary goal of the study is to measure in the intact human heart, the alterations in gene expression over time that are associated with reverse remodeling in response to β-blockade. The second goal is to investigate the signaling mechanisms which in turn are responsible for these changes in gene expression, and the third goal is to determine the relationship between intrinsic systolic dysfunction and remodeling of the left ventricle. This will be accomplished by measuring ventricular size, function, and gene expression in myocardial tissue samples obtained by percutaneous biopsy prior to initiation of β-blockade and at 3 and 12 months after start of therapy. The specific Aims and Hypotheses to be tested are:

1. Aim: Determine the changes in gene expression associated with changes in intrinsic systolic function and with functional decompensation in the intact, failing human heart.

   a. Hypothesis: Changes in the expression of select genes precede or accompany changes in left ventricular systolic function in humans with idiopathic dilated cardiomyopathy (IDC).
2. Aim: Identify signaling mechanisms responsible for alterations in expression of key genes involved in mediation of ventricular hypertrophy or contractile dysfunction.

   a. Hypothesis: Myocardial-failure-associated regulation of select messenger ribonucleic acids and proteins are related to left ventricular wall stress and neurohormonal signaling.
3. Aim: In the relationship between contractile dysfunction and dilatation/remodeling, determine the relationship between contractile dysfunction and structural remodeling.

   b. Hypothesis: the contractile dysfunction is primary and structural remodeling secondary.

Detailed description:

Arms:
arm 1: Patients with normal ejection fraction who underwent a single myocardial biopsy and received no β-blocker therapy arm 2: Idiopathic dilated cardiomyopathy patients randomized to metoprolol succinate titrated to a goal of 200 mg by mouth daily for 18 months arm 3: Idiopathic dilated cardiomyopathy patients who were randomized to receive metoprolol succinate and doxazosin titrated to a goal of 200 mg and 8 mg by mouth daily for 18 months arm 4: Idiopathic dilated cardiomyopathy patients who were randomized to receive carvedilol titrated to a goal of 25 mg by mouth twice daily for 18 months

Interventions: intervention 1: Carvedilol intervention 2: Metoprolol succinate intervention 3: Metoprolol succinate + doxazosin
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol document: