Effect of Beta-blockers on Structural Remodeling and Gene Expression in the Failing Human Heart
Status:
Completed
Trial end date:
2009-03-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 4
Details
Lead Sponsor:
University of Colorado, Denver
Collaborators:
AstraZeneca GlaxoSmithKline National Heart, Lung, and Blood Institute (NHLBI)