A Prospective Multicentre Study of Myocardial Recovery Using Left Ventricular Assist Devices (REmission from Stage D Heart Failure: RESTAGE-HF): Medium Term and Primary Endpoint Results.

Background: Left ventricular assist device (LVAD) unloading and hemodynamic support in patients with advanced chronic heart failure can result in significant improvement in cardiac function allowing LVAD removal, however the rate of this is generally considered to be low. This prospective multicenter non-randomized study (RESTAGE-HF) investigated whether a protocol of optimized LVAD mechanical unloading, combined with standardized specific pharmacological therapy to induce reverse remodeling and regular testing of underlying myocardial function, could produce a higher incidence of LVAD explantation. Methods: Forty patients with chronic advanced heart failure from non-ischemic cardiomyopathy receiving the Heartmate II LVAD were enrolled from 6 centers. LVAD speed was optimized with an aggressive pharmacological regimen and regular echocardiograms were performed at reduced LVAD speed (6000rpm, no net flow) to test underlying myocardial function. The primary endpoint was the proportion of patients with sufficient improvement of myocardial function to reach criteria for explantation within 18 months with sustained remission from HF (freedom from transplant/VAD/death) at 12 months. Results: Prior to LVAD age was 35.1±10.8 years, 67.5% were male, heart failure mean duration was 20.8±20.6 months, 95% required inotropic and 20% temporary mechanical support, left ventricular ejection fraction (LVEF) was 14.5±5.3%, end-diastolic diameter (LVEDD) 7.33±0.89cm, end-systolic diameter (LVESD) 6.74±0.88cm, PA saturations were 46.7±9.2% and pulmonary capillary wedge pressure (PCWP) was 26.2±7.6mmHg. Four enrolled patients did not undergo the protocol due to medical complications unrelated to the study procedures. Overall 40% of all enrolled (16/40) patients achieved the primary endpoint, p<0.0001, with 50% (18/36) of patients receiving the protocol being explanted within 18 months (pre-explant LVEF 57±8%; LVEDD 4.81±0.58cm; LVESD 3.53±0.51cm; PCWP 8.1±3.1mmHg; PA sats 63.6±6.8% at 6000rpm). Overall 19 patients were explanted (19/36, 52.3% of those receiving the protocol). The fifteen ongoing explanted patients are now 2.26±0.97years post explant. Post-explantation survival free from LVAD or transplantation was 90% at 1-year and 77% at 2 and 3 years. Conclusions: In this multicenter prospective study, this strategy of LVAD support combined with a standardized pharmacologic and cardiac function monitoring protocol resulted in a high rate of LVAD explantation and was feasible and reproducible with explants occurred in all six participating sites.