Abstract 18952: Differential Cardiac Gene Expression at the Time of VAD Placement Differentiates Eventual VAD-Recovery From VAD-Dependence

Introduction: Only ~5% of Ventricular assist device (VAD) supported end stage heart failure (HF) patients recover enough cardiac function to allow VAD removal. VAD use introduces significant risks, yet it is difficult to identify patients with the greatest recovery potential and who may benefit from VAD removal. The RECOVER trial ( NCT00687856 ) seeks novel functional and molecular markers to identify those patients that may recover sufficient cardiac function to allow successful VAD removal. Hypothesis: Gene expression analysis of the ventricular core recovered at the time of VAD placement can differentiate those patients who eventually develop VAD-independence ( R) from those remaining VAD-dependent ( D ). Methods: Two groups of VAD-supported patients with non-ischemic HF were studied; R group (n=9 patients) and D (n=14). R group patients (8/9) had >6mo freedom from HF after VAD removal. R vs D did not differ (p=NS) in age (30.0+-/9 vs 36.4+/-11 yrs); sex (6M/3F vs 10M/4F), pre-VAD EF (18.6+/-4 vs17.6+/-5%) or LVEDD (6.24+/-0.4 vs 6.54 +/- 0.8 cm). RNA was isolated from VAD-implant core and analyzed on Agilent GE60K arrays. After log2-transformation and cyclic LOESS normalization, expression analysis was performed (GeneSpring). Results: Uncorrected t-test revealed 302 transcripts that differed between R and D groups by >1.5 fold (p<0.05). Relative to D , R had 81 transcripts lower and 220 higher. Euclidean Ward’s clustering (Figure) of 45 transcripts with >1.5X differential expression and p<0.005 segregated most R (blue) from D (red) patients. Conclusions: In a small group of patients, gene expression analysis performed at the time of VAD placement showed potential differences between patients with eventual recovery versus those remaining VAD-dependent. The results may reflect differences in underlying in heart failure severity, and reveal those with potential for functional recovery. More cases will be required to confirm these preliminary observations.