Author + information
- aCardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
- bDivision of Cardiac Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Sunu S. Thomas, Cardiology Division, Massachusetts General Hospital Heart Center, 55 Fruit Street, GRB 800, Boston, Massachusetts 02114.
- cardiac allograft vasculopathy
- ejection fraction
- heart transplant
- left ventricular systolic dysfunction
- primary graft failure
Cardiac transplantation remains the gold standard for heart replacement therapy for patients with end-stage heart disease. Although the absolute numbers of heart transplant procedures performed in the United States has grown in recent years, this modest increase has little epidemiological impact on the increasing prevalence of heart failure in a growing and aging population. Despite a record number of >3,000 transplants in 2016, >20,000 patients of the 3 million with advanced heart failure could potentially be eligible for heart replacement therapy (1,2).
The donor organ shortage continues to limit cardiac transplantation’s therapeutic impact. Consequently, tremendous attention has been paid to finding ways to expand the donor pool. Efforts have included public awareness campaigns to increase the absolute number of potential donors, increased use of marginal donors, and, most recently, use of donor hearts following circulatory death. New industries are emerging focused on donor organ assessment and resuscitation.
Ultimately, the greatest opportunity may lie in improving our selection criteria among the available donors deemed marginal. Consensus guidelines have been introduced to help guide clinicians, although supporting evidence is limited. Donor organs are commonly rejected for coronary atherosclerosis, ventricular hypertrophy, valvular disease, or the presence of prognostically unfavorable risk factors such as older age, diabetes, and substance abuse (3). Daunting, however, is the dilemma that arises in the evaluation of the potential donor heart where left ventricular systolic dysfunction manifests in the absence of such concomitant comorbidities. How does the transplant provider tasked with donor selection identify left ventricular systolic dysfunction that is both reversible and durable post-transplantation? Fundamentally, is the initial presentation of significant left ventricular dysfunction a marker of potentially irrecoverable injury? To what extent is the use of inotropes or pressors during donor organ resuscitation an opportunity to gauge myocardial reserve or, rather, a declaration of vasoactive dependence in a heart that may not fully recover? The implications are stark given that nearly one-fourth of all available donor organs are initially rejected because of poor left ventricular ejection fraction (LVEF) or regional ventricular wall motion abnormalities (4).
In this issue of the Journal, Madan et al. (5) present a large clinical outcomes analysis on cardiac transplantation that is derived from donor hearts with left ventricular systolic dysfunction at the time of initial donor screening. Using the nationwide multicenter Organ Procurement and Transplant Network (OPTN) database, these investigators compared the outcomes of transplant recipients who had donors with significant cardiac dysfunction (LVEF ≤40%; n = 472) that normalized before organ procurement (LVEF ≥50%), defined as “Improved Donor LVEF,” with the outcomes of transplant recipients with “Normal Donor LVEF” (LVEF ≥55%; n = 11,233) on an initial transthoracic echocardiogram. Madan et al. (5) did not observe any statistically significant post-transplant differences in recipients’ survival at 30 days or at 1 and 3 years; in the incidence of primary graft failure at 90 days; or in the diagnosis of cardiac allograft vasculopathy at 5 years. These findings remained steadfast following propensity matching between both groups.
The implications of this study cannot be understated regarding their potential impact on liberating providers’ behavior toward donor candidate screening. Of the 472 donors in the “Improved Donor LVEF” group, the initial median LVEF at the time of listing was only 35%. This included 130 donors with an LVEF ≤ 25%. Although overall inotropic use and peak dosage were higher in this patient group, 43 (9.1%) of these donors recovered their intrinsic ventricular function without concomitant vasoactive therapy, and another 166 (35.2%) were weaned off inotropes at the time of cardiac transplantation. Time to achieve the obligate improvement in LVEF to ≥50% on a follow-up echocardiogram was relatively rapid over a median time of 18.0 h following the initial evaluation. The analysis also demonstrated a near doubling in the cardiac transplantation use of improved LVEF-type donors from 2010 to 2014. A greater proportion of these organs were allocated outside of their primary listing region, a finding likely reflecting the more aggressive selection behaviors of higher-volume transplantation centers.
Interestingly, 97% of all patients in the study group who demonstrated improved donor LVEF had an underlying cerebral mechanism for death, including brain anoxia, head trauma, central nervous system tumor, and cerebrovascular event or stroke. Brain death has well-recognized physiological consequences including cardiac dysfunction (6). Experienced cardiac transplantation practitioners understand that even severe cardiac dysfunction in a brain-dead donor warrants further scrutiny. Donor organ procurement organizations often have well-established protocols including thyroid replacement and/or inotropic challenges to increase organ use. Such therapies, in addition to a “tincture of time,” often result in significant improvement if not normalization of cardiac function. In fact, one could argue that such hearts at the time of transplantation are no longer marginal.
In the absence of a primary neurological cause for death, the durability of donor left ventricular function recovery cannot be assumed. The current analysis was predicated on the requirement of serial echocardiograms of the potential donor organ. However, the 472 donors with an initial marginal LVEF with follow-up echocardiograms constitute only 3% of the 15,853 adult heart transplants registered over the study period. Systematic sonographic evaluation of the donor heart is a nonstandardized practice across organ procurement organizations. Cardiac investigations, including coronary angiography and right-sided heart catheterization, are motivated by specific transplantation center practices and often the obligate vetting of a donor already provisionally accepted for a recipient pending serial testing. Moreover, the opportunity for further evaluation of a marginal donor is influenced by the donor family’s willingness, resource availability for study equipment and expert personnel, and even competing surgical timetables involving the procurement of noncardiac organs from the same donor. Although these issues may reflect potential bias, the current study should motivate further research and protocolization for donor organ evaluation and management.
Ultimately, the new horizon in thoracic organ transplantation will undoubtedly increasingly use ex vivo perfusion systems to assess and perhaps optimize donor organs. The currently enrolling EXPAND Heart Trial (sponsored by TransMedics Inc., Andover, Massachusetts) is exploring the outcomes of transplant recipients whose donor hearts were outside of standard acceptance criteria. This type of perfusion platform may facilitate the aggressive assessment of donor organs without placing recipients at undue risk.
Heart transplantation will remain the gold standard for end-stage heart disease for the foreseeable future. Because the overall numbers are quite small, well-designed retrospective analyses remain important for the assessment of current practices and to use a scarce but invaluable resource most efficiently and effectively. We would like to congratulate Madan et al. (5) for a pivotal study that draws attention to the challenges of donor evaluation and for inspiring a greater investment toward further delineating the potential for marginal donor heart use through diagnostic and therapeutic algorithms that may assist in an increasingly challenging donor selection process.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the author and do not necessarily represent the views of JACC or the American College of Cardiology.
Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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