Abstract 14639: Changes In Expression of Cholesteryl Ester Transfer Protein (CETP) Are Correlated with Improvement in Left Ventricular Function in Patients with Heart Failure and Reduced Ejection Fraction Who Respond to β-blocker Therapy
Introduction: The ability to predict likelihood of LVEF improvement in patients with heart failure-reduced ejection fraction (HFREF) treated with β-blockers using clinical features is limited. Our objective was to use myocardial gene expression profiling to identify genes that may predict response to β-blockade and may be involved in LV reverse-remodeling in HFREF patients.
Methods: 51 patients with non-ischemic dilated cardiomyopathy and LVEF ≤ 40% underwent endomyocardial biopsy and radionuclide ventriculography at 0, 3, and 12 months of β-blocker therapy with either carvedilol or metoprolol CR/XL. Response was defined as an increase in EF of ≥8% at 12 months or if not available, ≥5% at 3 months. Myocardial biopsies were taken from the distal right ventricular septum via a percutaneous approach. Total RNA was extracted and gene expression was quantified using the Affymetrix HGU133_plus_2 chip. Data were normalized controlling for batch effect, and low variance probesets were removed. The remaining 16,383 probesets were analyzed by repeated-measures ANOVA in responders or non-responders at all three timepoints. Tukey post-hoc tests were used to determine pairwise differences.
Results: There were a total of 33 responders and 18 nonresponders. The mRNA transcript encoding cholesteryl ester transfer protein (CETP) was higher in responders than in nonresponders at baseline (Figure, p < 0.05). Transcript levels in nonresponders did not change at 3 or 12 months (p = 0.63, p = 0.91), but CETP expression in responders decreased significantly at 3 and 12 months (p < 0.05, p < 0.0001).
Conclusion: CETP mRNA levels in cardiac tissue may predict which HFREF patients will respond to beta-blocker treatment, and progressive decrease of CETP expression was associated with LV reverse remodeling. Little is known about the function of CETP in the myocardium, and further study is needed regarding the role of CETP in heart failure and implications for drugs that inhibit CETP.
- © 2012 by American Heart Association, Inc.