A bridge far enough?

T he publication in this issue of Circulation of the Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure (ADVANCE) trial by Aaronson, Slaughter, and colleagues 1 tracks continuing advance in the rapidly expanding field of mechanical circulatory support. As implantable device technology and the clinical learning curve have supported better outcomes over time, the journey is leaving the critically ill patients behind and moving into populations with less imminent risk of death, and will soon include more ambulatory patients for whom pivotal outcomes extend beyond stroke-free survival. The success of this trial stimulates questions about routes to new device approval, the length of our bridges, and the directions for travel beyond a bridge. The ADVANCE trial demonstrated that the new continuous flow centrifugal device serves as an effective bridge for patients awaiting a donor heart for transplantation. 1 Previous devices approved for this indication include several configurations of pulsatile pumps and most recently a continuous flow axial pump. Approval for the bridging indication has required progressively more rigorous data but has never been supported by a randomized trial, because randomization to death or to device support is not reasonable in the face of progressive organ compromise and anticipated death from native heart collapse. Of the first 3 devices approved for the bridging indication, 2 offered no control population and 1 included a small historical control of patients in the same institutions who, for various reasons, did not receive a device. 2,3 The present report raises the standard for bridging device approval, offering the first prospective comparison of outcomes with the new device with outcomes without it during the same time period, in this case with other devices currently available for left ventricular support. The control data population was drawn from the Inter-agency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Registry, which chronicles the progress of durable mechanical circulatory support throughout the United States, growing from Ϸ1000 patients in 60 sites at the initiation of the ADVANCE trial in 2008 to 3500 patients at the conclusion of this trial 4 and 5500 in 150 sites at the time of this publication. The original registry design included detailed characterization of measured baseline characteristics and the INTERMACS profiles, which are descriptors of clinical disease severity that include the time dimension of increasing acuity 5 (Figure). These require experienced clinical assessment and are quantitatively less rigorous than …