VIEWPOINT
Same Bridge, New Destinations
Rethinking Paradigms for Mechanical Cardiac Support in Heart Failure
G. Michael Felker, MD, MHS, FACC* and
Joseph G. Rogers, MD, FACC
Duke University School of Medicine, Durham, North Carolina
Manuscript received August 30, 2005;
accepted September 29, 2005.
* Address reprint requests: Dr. G. Michael Felker, Duke Clinical Research Institute, 2400 Pratt Street, Room 0311 Terrace Level, Durham, North Carolina 27705
(Email: michael.felker{at}duke.edu).
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Abstract
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Mechanical cardiac support with ventricular assist devices is an established therapy for a variety of clinical scenarios, including postcardiotomy shock, "bridge to transplant," and "destination therapy." At present, device development, clinical trial design, regulatory approval, and reimbursement decisions for the clinical application of mechanical cardiac support devices continue to be considered in the context of these clinical indications. Although understandable from a historical perspective, these arbitrary divisions are inconsistent with the clinical realities of advanced heart failure therapy. By narrowly focusing on transplant eligibility at a static point in the clinical course, current guidelines impede the broader application of ventricular assist device technology to the growing population of patients who may benefit from this therapy.
The concept of replacing the function of the failing human heart with a mechanical pump is now in its fifth decade. This fledgling field was bolstered by the original request for proposals from the National Institutes of Health in 1976, which challenged investigators to develop a pump capable of supporting the circulation for up to two years without external venting (1). The use of ventricular assist devices (VADs) to provide relatively short-term hemodynamic support to patients awaiting heart transplant, initially approved by the Food and Drug Administration in 1994, has been a major therapeutic advance and led to improvements in survival to transplant and post-transplant outcomes (2). The favorable experience with VAD therapy for postcardiotomy shock as well as extended durations of support when applied as a "bridge to transplant" provided important insights into the feasibility of VAD implantation as a long-term therapy in patients who were not transplant candidates, a so-called "destination therapy." The efficacy of this concept was tested in the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial, evaluating the use of VAD support as long-term therapy in patients with end-stage heart failure deemed ineligible for heart transplant (3). On the basis of the favorable results of REMATCH, the HeartMate XVE device (Thoratec, Pleasanton, California) was approved for use as destination therapy in selected patients not eligible for cardiac transplant and who met REMATCH entry criteria.
Treatment paradigms for using VAD support have paralleled the historical development of this therapy. A variety of short-term assist devices currently are in use for postcardiotomy shock, and this continues to represent the most common indication for VAD support in the U. S. (4). For patients with hemodynamic deterioration not due to postcardiotomy shock, a "two-track" paradigm has evolved in which patients are assigned to either "bridge to transplant" or "destination therapy" based on their perceived transplant candidacy at the time of implantation. This two-track paradigm has become integrated into the way that device therapy is viewed by clinicians, regulatory agencies, and third-party payers. Additionally, the focus on transplant eligibility is perpetuated in the design of clinical trials, which continue to be performed separately for "bridge to transplant" and "destination therapy" indications. This dichotomy, in which clinicians are required to assign patients to "bridge to transplant" or "destination therapy" before device implantation, is inconsistent with the realities of clinical care of patients with advanced heart failure.
Prolonged device support is associated with the reversal of many aspects of the end stage heart failure state. At the molecular level, device support results in an improved neurohormonal profile, decreased myocardial expression of inflammatory cytokines, and reversal of some aspects of the molecular phenotype of heart failure (5–7). These cellular changes often are accompanied by substantial clinical improvements, such as improvement in renal function, resolution of pulmonary hypertension, and improvement in overall functional status (8,9). Given that renal dysfunction, increased pulmonary vascular resistance, and overall debilitation are among the most common relative contraindications to heart transplant, it is clear that VAD support may convert some patients with contraindications to transplant into appropriate transplant candidates. Recent data from Young et al. (9) provide support for this contention. In this cohort of patients supported with VADs with at least one relative contraindication to transplant, both survival to transplant and post-transplant outcomes were similar to those of patients with no relative contraindications. This was true despite the fact that 95% of the cohort with relative contraindications would have been rejected for transplant listing by at least one high-volume center at the time of study entry. These data clearly demonstrate that many patients can be successfully "bridged to transplant candidacy" by VAD support.
In clinical practice, the evaluation of eligibility for transplant requires a complex multidisciplinary effort, involving medical, immunological, psychological, and financial evaluation. Frequently, clinical deterioration may preclude complete transplant evaluation before VAD support is required, making it impossible to fully judge transplant candidacy before implantation of a device. As suggested previously, some patients initially implanted as "destination therapy" because of renal dysfunction or pulmonary hypertension may subsequently become acceptable transplant candidates after prolonged device support and rehabilitation. Alternatively, some patients initially implanted as a "bridge to transplant" may subsequently experience either recovery of ventricular function or complications during VAD support (such as a disabling stroke) that may make them inappropriate or ineligible for transplant. These examples underscore the fact that transplant eligibility is a dynamic rather than a static consideration and must be continually reevaluated with changes in the patient's clinical condition.
At present, the aforementioned clinical realities are misaligned with regulatory and reimbursement guidelines for VAD support. Patients who currently are not suitable for cardiac transplantation (and therefore are not eligible for VAD implantation as a "bridge to transplant") but who do not currently meet accepted criteria for destination therapy may be left in a "coverage gap" that requires them to experience further life-threatening deterioration before third-party payers will provide coverage for VAD support. A glaring example of this coverage gap is the patient with an acute myocardial infarction and cardiogenic shock who is ineligible for transplantation. According to current Center for Medicare and Medicaid Services guidelines, such a patient would not qualify for a VAD because eligible patients must have New York Heart Association functional class IV symptoms that failed to respond to optimal medical therapy for at least 60 of the previous 90 days (10). Another "loophole" in the current system is with regard to patients undergoing cardiac surgery who may be provided VAD support (under a postcardiotomy shock indication) whereas otherwise-similar patients with the same degree of left ventricular dysfunction and hemodynamic compromise are not eligible for VAD therapy unless they are listed for transplantation or meet criteria for destination therapy.
Medical decision making should be based on an appropriate assessment of the risks and benefits of a given therapy, not on whether patients fit into a care pathway based on future clinical events that may be impossible to predict. Linking reimbursement and approval to the ultimate "destination" of the patient makes no more sense for VAD therapy than for other expensive, invasive therapies, such as cardiac resynchronization. In light of these considerations, we suggest that it is inappropriate and clinically unreasonable for patients to be assigned to an ultimate destination when initiating mechanical cardiac support. Instead, mechanical cardiac support should be used with a primary focus on the likely duration of support required and the clinical condition of the patient, rather than being narrowly focused on future transplant eligibility. For patients with acute hemodynamic deterioration, such as postcardiotomy shock, acute myocardial infarction, or fulminant myocarditis, short-term hemodynamic support with VADs is a viable therapeutic option regardless of transplant eligibility. Similarly, in patients with progressive chronic heart failure, longer-term VAD therapy may be an appropriate therapeutic option regardless of future transplant eligibility. Decision making about the appropriateness of subsequent therapies (such as eligibility for cardiac transplantation) should be evaluated once patients have recovered from the initial device implantation and undergone appropriate rehabilitation. The combination of progressive improvements in device technology and the growing population of patients with advanced heart failure, estimated at between 300,000 and 800,000 in the United States alone, will necessitate the transition of VADs from a "niche therapy" used only at tertiary heart failure centers into the mainstream of cardiovascular care (11,12). Such a transformation will require clinicians, researchers, device manufacturers, regulatory agencies, and third-party payers to rethink traditional paradigms for using mechanical cardiac support. Only by moving beyond the narrow focus on transplant eligibility will the medical community be prepared to address both the challenges and the opportunities created by the broader applicability of mechanical cardiac support moving into the 21st century.
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References
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1. Frazier OH, Delgado RM. Mechanical circulatory support for advanced heart failure: where does it stand in 2003? Circulation 2003;108:3064-3068.[Free Full Text]2. Aaronson KD, Eppinger MJ, Dyke DB, Wright S, Pagani FD. Left ventricular assist device therapy improves utilization of donor hearts J Am Coll Cardiol 2002;39:1247-1254.[Abstract/Free Full Text] 3. Rose EA, Gelijns AC, Moskowitz AJ, et al. Long term use of left-ventricular assist device for end-stage heart failure N Engl J Med 2001;345:1435-1443.[Abstract/Free Full Text] 4. Stevenson LW, Kormos RL, Barr ML, et al. Mechanical cardiac support 2000: current applications and future trial design: June 15 and 16, 2000 Bethesda, Maryland Circulation 2001;103:337-342.[Free Full Text] 5. Bruckner BA, Stetson SJ, Perez-Verdia A, et al. Regression of fibrosis and hypertrophy in failing myocardium following mechanical circulatory support J Heart Lung Transplant 2001;20:457-464.[CrossRef][Web of Science][Medline] 6. Torre-Amione G, Stetson SJ, Youker KA, et al. Decreased expression of tumor necrosis factor-alpha in failing human myocardium after mechanical circulatory support: a potential mechanism for cardiac recovery Circulation 1999;100:1189-1193.[Abstract/Free Full Text] 7. Vatta M, Stetson SJ, Perez-Verdia A, et al. Molecular remodelling of dystrophin in patients with end-stage cardiomyopathies and reversal in patients on assistance-device therapy Lancet 2002;359:936-941.[CrossRef][Web of Science][Medline] 8. Petrofski JA, Hoopes CW, Bashore TM, Russell SD, Milano CA. Mechanical ventricular support lowers pulmonary vascular resistance in a patient with congential heart disease Ann Thorac Surg 2003;75:1005-1007.[Abstract/Free Full Text] 9. Young JB, Rogers JG, Portner PM, et al. Bridge to eligibility: LVAS support in patients with relative contraindications to transplantation J Heart Lung Transplant 2005;24:S75. 10. NCD for Artificial Hearts and Related Devices. Medicare National Coverage Determinations Manualhttp://new.cms.hhs.gov/manuals/downloads/ncd103c1_Part1.pdf 2005Accessed August 29, 2005. 11. Adams KF, Zannad F. Clinical definition and epidemiology of advanced heart failure Am Heart J 1998;135:S204-S215.[CrossRef][Web of Science][Medline] 12. Stevenson LW, Rose EA. Left ventricular assist devices: bridges to transplantation, recovery, and destination for whom? Circulation 2003;108:3059-3063.[Free Full Text]
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Abstract
References