Author + information
- Michael Albert Hinterberg,
- David Kao,
- Anis Karimpour-Fard,
- Kika Sucharov,
- Lawrence E. Hunter,
- David Port and
- Michael Bristow
Congestive heart failure has a varying degree of responsiveness to treatment with β- blocking agents. Given that microRNAs are known to be involved in regulation of cardiac hypertrophy and remodeling, we hypothesized that their differential expression may be predictive of prognosis and treatment response. To test this hypothesis, improvement in left ventricular ejection fraction (LVEF) over the course of one-year of β-blocker treatment was correlated with baseline myocardial microRNA expression in heart failure patients.
Patients with idiopathic dilated cardiomyopathy and an LVEF of <40%, were randomized to treatment with metoprolol, metoprolol + doxazosin, or carvedilol. Subjects underwent radionuclide ventriculography and endomyocardial biopsy at baseline, 3, and 12 months. Treatment response was defined as an improvement in LVEF of ≥ 8% at twelve months or ≥ 5% at three months. Myocardial microRNA expression was quantified using the Affymetrix GeneChip miRNA array comprising 7816 microRNA probesets. Baseline microRNA expression levels were analyzed using non-parametric correlation testing and used to build decision trees in Weka, an open-source data-mining tool, in order to form predictive classifiers.
Of the 34 patients enrolled who had at least one follow-up microRNA sample, 24 (71%) were men, and the average age was 46.2±13.5 years. In total 19/34 (55.8%) met criteria for treatment response. Baseline levels of several miRNAs were found to be associated with LVEF response. Using the C4.5 decision tree algorithm, one probe, corresponding to the microRNA dre-mir-133a-5p was identified to be most highly predictive of LVEF response in this cohort with a sensitivity of 94.7%, specificity of 66.7%, and PPV of 78.2%.
Dre-mir-133a-5p, which is similar in sequence to mmu-mir-133a-3p, was moderately expressed in heart tissue of heart failure patients and associated with LVEF improvement. Dre-mir-133a-5p is a passenger strand to mir-133, which has been implicated in cardiac hypertrophy and remodeling, and it may serve as a diagnostic predictor of LVEF improvement in response to β-blocker therapy.
Oral Contributions South, Room 104
Sunday, March 10, 2013, 11:30 a.m.-11:45 a.m.
Session Title: Joint Session of the Heart Failure Society of America and American College of Cardiology
Abstract Category: 17. Heart Failure: Therapy
Presentation Number: 925-6
- 2013 American College of Cardiology Foundation