Destination mechanical circulatory support: proposal for clinical standards

Mechanical circulatory support device (MCSDs) have evolved during the past 2 decades to become accepted bridging therapy for patients with irreversible hemodynamic deterioration while awaiting cardiac transplantation. More recently, based on the results of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) study, MCSD therapy has become available as permanent or destination therapy for a restricted population of patients with advanced heart failure (AHF) not thought to be appropriate transplant candidates. The potential proliferation of new devices and the possible expansion of the target populations bring new responsibilities. Unlike pharmaceutical trials that have included thousands of patients, trials with MCSDs will continue to be performed on a relatively small scale because equipoise for randomization can be undermined by the unmasked nature of mechanical support, the logistics of study finances, and the continuous device improvements—all of which constrain trial size and duration. Currently, insufficient evidence beyond REMATCH criteria exists for refining potential long-term MCSD therapy candidate cohorts, and application of this challenging therapy is complicated further by the degree of institutional commitment, surgical expertise, multidisciplinary skills, available devices, and overall experience required for the successful application of mechanical circulatory support.

The REMATCH trial was a landmark study that demonstrated the benefit of MCSDs in patients with AHF not eligible for transplantation. Patients supported with MCSDs had significantly better survival at 1 year than did patients with advanced end-stage heart failure who were treated medically (many with long-term parenteral inotropes). Although a survival benefit was clear, it was only over a 2-year time period, and morbidity was substantial, particularly with respect to infections, neurologic events, and pump malfunctions.

These observations force us to consider carefully patient selection and the infrastructure of centers with strategies developed to provide this type of care. In the United States, the Food and Drug Administration (FDA) approval of the HeartMate device for chronic therapy occurred on November 25, 2002. Based on previous experience with newly marketed devices, procedures, and surgical techniques, 2 trends are likely after FDA approval: First, centers will begin to place devices into patients with a less dismal prognosis than the prognosis of those randomized in REMATCH. Second, the expansion of centers will lead to establishment of startup MCSD programs with less experience than established long-term MCSD centers and will lead to centers without on-site heart transplantation capabilities. Indeed, although the vast majority of implantable MCSD currently are placed in patients admitted to heart transplant centers, in time new “permanent MCSD” centers without these more expanded services may develop. These trends may decrease the survival benefit from destination MCSD therapy. In the worst case scenario, a detectable survival benefit may no longer exist in post-approval long-term MCSD implant practice, implying that destination MCSD therapy results only in switching the mode of death. Instead of dying of refractory heart failure, transplant-ineligible patients with AHF who receive mechanical support would die of infection, coagulopathies, neurologic events, or catastrophic device malfunction. Although observation of 129 patients in the REMATCH trial provided definitive evidence of benefit for this specific population, the trial neither adequately identified subsequent target populations nor defined centers in which the next phase of implementation should occur. The most appropriate suggestion may be that “destination MCSD centers” should resemble those participating in REMATCH. The immediate risks of uncritically generalizing REMATCH results may be device implantation in patients less likely to benefit.

Viewing this potential development within a social science perspective, it is important to avoid repeating history. We have to bear in mind the problems that led to a moratorium on cardiac transplantation in the 1970s and on artificial heart implantation in the 1980s, after an initial series of Jarvik-7 total artificial heart implantations.

To ensure high-quality and maximally effective destination MCSD services, a systematic strategy should be developed including 1) documentation of all destination MCSD implantations in an appropriate registry to facilitate risk-factor identification and the development of predictive models; 2) translational research on the impact of MCSD therapy on innate and adaptive immune responses, infection, coagulopathies, neurologic dysfunction, and nutritional status; 3) expeditious and coordinated improvement of management practices; and 4) development of reimbursement rules and development of center standards for hospitals desiring to perform long-term MCSD therapy by regulatory bodies, such as the Centers for Medicare and Medicaid Services in the United States. Given the multidimensional challenge of the post-REMATCH era, a continuous collaborative strategy is in the best long-term interest of MCSD centers, manufacturers, regulatory agencies, and payors/insurers.

Since approval of the HeartMate device for long-term therapy occurred on November 5, 2002, decisions regarding reimbursement strategies are beginning to be established. Because such decisions will significantly influence which centers perform chronic MCSD implantation and will affect the overall health care impact of this therapy, it is appropriate for expert societies such as the International Society for Heart and Lung Transplantation (ISHLT) to provide funding agencies, such as the Centers for Medicare and Medicaid Services, in the United States with recommendations for selecting centers to perform destination MCSD implantation and to receive reimbursement. The ISHLT is uniquely positioned to develop recommendations because it provides an international framework with many diverse medical and surgical experts available for consultation who are involved in AHF and MCSD therapy. In collaboration with other professional societies, such recommendations could be tailored to the individual requirements of different countries. By their nature, any set of guidelines will somewhat limit use of this technology, especially in the early implementation phase. Although limited deployment of destination MCSD technology may seem counterproductive to those interested in more immediate expansion of this new technology, consistent optimization of outcomes from the start and appropriate patient selection eventually will provide the highest likelihood for acceptance by the public, by regulatory bodies, and by the cardiology community at large.

In suggesting policies for identifying centers that would qualify for long-term MCSD implantation programs, our over-riding commitment is to the protection and benefit of the individual patient. In this regard, the patient could most obviously receive harm from this complex therapy if the medical and surgical personnel and the institutional team did not have sufficient expertise. However, given the limited mid- and long-term efficacy data, it also is important to prevent the use of this therapy in patients with AHF who could be treated more appropriately with medical therapy, heart transplantation, or other surgical therapies short of MCSD. If institutions or individuals make decisions for implantation who are not truly experienced and expert in the allocation of therapies for patients with AHF failure, proliferation of this therapy may result in the inappropriate use of MCSDs in patients who are “too well” (needlessly subjecting them to expensive and unproven long-term therapy) or “too ill” (those with multisystem dysfunction and a decreased probability of successful outcome).