Abstract 3257: Myocardial Expression of Extracellular Matrix Genes during LVAD Combination Therapy - Relevance to Recovery
Background - Clinical recovery from heart failure can be achieved using combined LVAD support and pharmacologic therapy. The extracellular matrix (ECM) plays a major role in heart failure and we sought to examine whether decreased expression of ECM genes would be a feature of myocardial recovery in patients.
Methods - Real-time quantitative RT-PCR analysis of collagen I (COLI), collagen III (COLIII), fibronectin (FN), TGFβ1 and the fibroblast marker Thy1 was performed on myocardial samples from end-stage DCM patients at the time of implant (n = 16), at the time of LVAD explant in patients who recovered (n = 11) or at transplant in patients who failed to recover (n = 5).
Results - At the time of implant, overall expression of the profibrotic markers, COL I, COL III and Thy1, was higher in patients who subsequently failed to recover compared to recovery patients (2.43, 2.62 and 5.34-fold, respectively, p < 0.05). However, in patients who subsequently recovered, expression was variable at implant with two groups distinguishable. One group had higher expression of COLI, COLIII, TGFβ1, FN and Thy1 levels at implant and showed a trend to decrease expression during treatment (0.41 ± 0.50, 0.46 ± 0.25, 0.82 ± 0.33, 0.73 ± 0.50 and 0.51 ± 0.38-fold). A second group had low expression levels at implant and showed a significant increase during treatment (5.19 ± 2.77, 4.02 ± 1.98, 2.33 ± 1.25, 2.05 ± 0.58 and 11.56 ± 11.25-fold respectively, p < 0.02). Similar complex expression patterns were observed for TGFβ1, FN, MMPs and TIMPs. Interestingly, lower expression levels of COL1, COLIII and Thy1 at explant correlated with higher ejection fraction measured at explant and 1, 2 and 5 years post-explant (R = −0.365, R = −0.365, R = −0.3303 respectively p < 0.05,).
Conclusion - Our data reveal complex patterns of ECM genes during LVAD therapy. Overall expression of pro-fibrotic markers was higher at implant in patients who subsequently failed to recover. However, descreased expression during treatment was not essential for recovery and a subset of recovery patients showed a significant increase. Regardless of overall expression pattern, lower levels of pro-fibrotic markers at explant was associated with improved function following recovery.