Left Ventricular Assist Devices for Adults

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Left Ventricular Assist Devices for Adults
Since the first widespread clinical application of left ventricular assist devices (LVADs) for patients with end-stage heart failure in the late 1980s, major advances have been seen in their development and design, and the indications for their use have increased substantially. LVADs have evolved towards being permanent implants, providing so-called destination therapy. Several trials unveiled both the clinical promise and the current technical barriers of widespread application of LVADs as destination therapy. Undoubtedly, the future of LVADs for adults will involve changes in LVAD technology and patient selection and, ultimately, a paradigm shift in the reception of this modality by the medical community.

While the designs of currently available LVADs have demonstrated impressive achievements—textured surfaces that largely resist thrombosis and pump designs that minimize heat generation (please see Supplementary Figures 1-3 online)—no feature has demonstrated the durability required of destination therapy. Furthermore, the extended bridging time to transplantation resulting from more widespread availability of transplantation and the growing transplantation waiting list means that future pumps will need to be substantially more durable than their predecessors.

Axial flow pumps and centrifugal pumps offer some promise of improved device longevity and smaller size and are therefore applicable for increasing numbers of patients. Notably, neither design produces pulsatile flow, a characteristic that, while intuitively desirable, might not be physiologically mandatory for long-term function. A lack of requirement for pulsatility should render these devices inherently more durable, but studies with long enough follow-up to analyze either design for destination support remain incomplete. Ultimately, successful LVADs will have to demonstrate excellent durability, be user-friendly and, unquestionably, cost-effective.

Paradoxically, the design of successful devices will have to demonstrate both divergence and convergence from current design. LVADs should continue to evolve (diverge) from the simple designs of the 1980s to more-complex designs, and must range from minimally invasive (e.g. intravascular ventricular assistance) to fully invasive devices (e.g. total artificial hearts). Only by providing a wide spectrum of devices that mirror and thereby address many patients' needs will LVAD therapy succeed. Concurrently, however, device technology must itself converge; if widespread application is to be realized, LVAD therapy cannot be so divergent as to be available only at a limited number of centers of excellence. Several different LVADs should be available so that the most appropriate design can be matched to individual patients' needs.

A seminal lesson learned during the initial peak in LVAD implantation was that early device insertion before severe multiorgan failure presaged superior outcomes. Various screening scales based on perioperative mortality have been developed so that clinicians can predict the outcome of potential LVAD candidates. As experience with LVADs for destination therapy grows, a similar scale will undoubtedly emerge, especially for the initial cohort (nontransplant candidates), who tend to be older with more medical comorbidites than their bridge-to-transplant predecessors.

The first reports of so-called reverse remodeling after LVAD implantation appeared in the mid-1990s. Since then, the concept of active reverse remodeling following device implantation, possibly as a bridge to recovery, has attracted widespread interest. Active reverse remodeling aims to improve ventricular recovery (as measured by gene expression, humoral factors, physiologic indices and serial echocardiograms) throughout the support period. Proposed strategies suggest adjunctive therapies in conjunction with simple ventricular decompression by LVAD support, but these are as yet only anecdotal. For example, adding β2-adrenergic receptor agonists to LVAD therapy to stimulate left ventricular hypertrophy has had encouraging early results. The application of cell transplantation and gene therapy to alter apoptotic pathways promulgated by heart failure seems to have some potential use in mechanical ventricular decompression. The accurate delineation of stem cells and their method of delivery, however, remain significant obstacles.

Since the FDA approved LVAD implantation as destination therapy 2 years ago, far fewer patients than anticipated have entered destination therapy trials. Some of this shortfall is probably related to reluctance on the part of physicians to consider LVAD support for nontransplant candidates as anything other than end-of-life care. Yet, REMATCH and other studies comparing quality of life during device support with that during maximum pharmacologic therapy indicate that LVAD patients' results are superior. Furthermore, if the lessons learned in the 1990s were applied, use of LVADs as destination therapy in healthier patients would probably improve long-term morbidity and mortality. Thus, just as LVAD implantation evolved from support available only to those dying from cardiogenic shock, destination therapy must be viewed as treatment for heart failure patients other than those for whom pharmacologic therapy has reached its limits.

Could patients in NYHA class III be considered as candidates for LVAD implantation? Here, perhaps, one needs to concede that a paradigm shift is required. Ultimately, if device durability issues can be overcome, the distinction between patients being bridged to transplantation and those undergoing device implantation as destination therapy will become less clear. Indeed, the 2-year survival of patients supported by mechanical ventricular assistance has been reported as approaching that of high-risk patients after transplantation. Like patients with end-stage renal disease on dialysis, all those with end-stage heart failure on device support could be considered as a group—some will receive a transplant; those who are not transplant candidates could remain on device support indefinitely; and others, with adjunctive therapies such as cell transplantation or improved pharmacologic augmentation, might recover myocardial function sufficiently for device removal.

This paradigm shift, however, requires several steps. Device manufacturers need to make available several durable, reliable, user-friendly and relatively inexpensive LVADs. Heart failure cardiologists need to broaden their perspective of for whom and for what indications LVAD implantation should be considered. Surgeons need to continue their vigilance toward development of a facile, minimally invasive approach to minimize surgical risk and long-term morbidity.

The success of LVAD therapy will generate previously unforeseen ethical dilemmas. What will be the fiscal and epidemiologic impact of extending the lifespan of the elderly who might otherwise have succumbed earlier to heart failure? What defines palliative care in this circumstance, in which cardiovascular support has limitless potential? If device support is to be discontinued, should it be carried out in hospital or at home, and by whom? We have historically followed a strict preoperative protocol to discuss with LVAD recipients our plans to withdraw LVAD support should meaningful survival become a remote likelihood. Similarly, in the future, establishing an appropriate more-detailed care directive prior to long-term or destination LVAD implantation will be an ethical imperative.

LVAD therapy, like the organ transplantation community for whom it was established, will challenge the medical community and society in a variety of as yet unfathomable ways. Most of the technological barriers to the goals outlined here are surmountable; obstacles requiring the alteration of therapeutic strategies could require substantially more effort. In summary, with correct convergence and divergence of device design and availability, and appropriate selection and management of patients, the widespread application of mechanical circulatory assistance for heart failure is imminent.

Supplementary information is available on the Nature Clinical Practice Cardiovascular Medicine website.


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