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Combined left ventricular assist device (LVAD) support and pharmacological management of the failing heart can induce reversal of maladaptive cardiac remodelling leading to normalisation of cardiac structure and recovery of cardiac function. The purpose of this study was to compare the gene expression profiles of recovered and non-recovered LVAD patients in order to identify mechanisms underlying the recovery process and differences which may determine outcome. Myocardial expression of 54 genes chosen for their potential role in heart failure and tissue repair was measured using quantitative PCR at the time of LVAD implantation and again at explantation (recovery, n = 13) or transplantation (non-recovery, n = 5). Patients who went on to recover had higher levels of Giα2, EPAC2 and lower levels of IGF2 at the time of LVAD implant compared to patients who failed to recover. During recovery, expression of BNP, IL-1β, VWF and SFRP1 was decreased whilst RGS4 increased. Expression of IGF1 and pro-fibrotic genes was coordinated during recovery. Correlation analysis identified a novel co-regulation of SFRP1 and βMHC in myocardium. In summary, the gene expression profile underlying recovery is complex and comprises both regression and exacerbation of elements of the pathological gene program. Modulation of Giα2, EPAC2, RGS4 and SFRP1 indicates that inhibition of cAMP signalling may potentiate recovery prior to treatment whilst enhanced cAMP and Wnt signalling may underlie recovery during LVAD support.

Background: The UK Government funds ventricular assist device (VAD) implantation as bridge to transplantation (BTT) at three centers. Results from this program have not been published., Methods: All 70 VAD implants for BTT, 71 inotrope-dependent and 179 non-VAD transplant candidates, accepted for transplantation between April 2002 and December 2004, were prospectively monitored for survival to transplantation, survival overall and quality of life., Results: Of the 70 VAD patients, 31 (44%) survived to heart transplantation, 4 (6%) were bridged to recovery and 5 remained on support at the end of the study. Thirty patients (43%) died while on support. Overall survival from VAD implant was 52% at 1 year. Ten percent of non-VAD inotrope-dependent patients and 9% of routine transplant candidates died while on the waiting list. For transplant recipients, 12-month post-operative survival was 84%, 85% and 84%, respectively, for VAD, inotrope-dependent and routine transplant candidates. VAD and non-VAD patients had similar post-transplant adverse event rates., Conclusions: There was a role for VAD bridge to transplant for selected patients in the UK, despite the availability of an effective urgent transplant list. VAD patients who underwent transplantation had survival rates similar to other transplant candidates.