Abstract 16023: Plasma Levels of MicroRNA-133a Predict Complete Regression of Left Ventricular Hypertrophy After Valve Replacement in Patients With Aortic Stenosis
Background: Increasing evidence supports the key regulatory role of micro-RNAs in various cardiac pathological conditions, including LV hypertrophy. In aortic stenosis (AS) patients, we have reported that the myocardial expression of microRNA-133a (miR-133a) at surgery, together with some remodeling related genes and clinical parameters, predicts the amount and completeness of LV reverse remodeling 1 year after aortic valve replacement (AVR). Based on these data, we hypothesized that the expression levels of plasma circulating miR-133a in the same cohort of patients could be also a marker of hypertrophy reversibility.
Objectives: To establish the value of preoperative circulating miR-133a, in conjunction with other clinical and echocardiographic parameters, as a predictor of LV mass (LVM) regression 1 year after valve replacement in a surgical cohort of AS patients.
Methods: In 46 patients with AS, total RNA was isolated from plasma using TRIzol. Spiked-in C. elegans-miR-39 was used as control. Reverse transcription was performed using miR-133a and cel-miR-39 specific primers. qRT-PCR was performed with Taqman assays. miR-133a levels were normalized to cel-miR-39. Multiple linear regression analysis was used for predicting absolute LVM reduction 1 year after surgery. The probability of LVM normalization 1 year after surgery was assessed by means of logistic regression analysis (PASW Statistics 18, SPSS Inc).
Results: The predictive equation of absolute LVM reduction 1 year after surgery (adjusted R2=0.64; p<0.001) was: ΔLVM = -16.3 + 6.9 plasma miR-133a** + 0.4 LVM*** + 1.5 Age* - 4.9 Body mass index** The predictive equation of LVM normalization 1 year after surgery (sensitivity 85.0; specificity 70.6; overall correct 78.4%) was: P=1/[1+ e -(17.78 + 0.57 plasma miR-133a* - 0.47 BMI* - 0.02 LVM*)].
Conclusions: Our results further support the role of miR-133a as a key element of the reverse remodeling process. We provide the first evidence that the level of circulating miR-133a could be a bedside clinical biomarker of LV hypertrophy reversibility that might be helpful for the indication and timing of surgery in asymptomatic patients with severe AS.
- © 2011 by American Heart Association, Inc.