Author + information
- Jennifer A. Cowger, MD, MS∗ ()
- ↵∗Address for correspondence:
Dr. Jennifer A. Cowger, Advanced Heart Failure, Transplant, and MCS, St. Vincent Heart Center of Indiana, 8333 Naab Road, Suite 400, Indianapolis, Indiana 46260.
In 2016, 3,191 individuals in the United States were fortunate enough to receive a cardiac transplant (1). Although the number of patients who received transplants in 2016 was the highest in Organ Procurement and Transplantation Network (OPTN) history, heart failure (HF) practitioners and their patients are keenly aware of the ongoing marked imbalance between organ demand and supply—an imbalance that is growing because more patients are surviving stage D HF with the advancement of mechanical circulatory support (MCS). In 2005, there were 2,712 patients listed for transplantation, of whom 138 (5.1%) had MCS in place at the time of listing (2). In 2015, the number of candidates on the wait list rose to 3,791, and 31% were on MCS at listing (2). Simultaneously, the numbers of individuals delisted due to progressive illness are also increasing. In 2005, 3.3% of all delisted patients (n = 3,018) were removed due to progressive sickness compared with 9.3% of delisted patients (n = 4,099) in 2015 (1). Currently, modifications to the adult transplantation allocation system within the United States are underway as a means of improving organ allocation to the sickest of listed patients (3). However, such modifications do not necessarily address the accelerating demand for donor organs.
To address the U.S. donor−recipient imbalance, at least 1 of 3 interventions must take place: 1) the duration of survival on MCS technology must markedly increase, thereby reducing the need for transplantation; 2) the size of the wait list for transplantation must be reduced; or 3) the size of the donor pool needs to be expanded. Although survival on MCS support has improved substantially with the evolution of continuous flow left ventricular assist device (LVAD) technologies, the present average survival is still ∼3.7 years, paling in comparison to the 10- to 13-year mean survival following transplantation (4,5). Device technological advancement and regulatory approval take considerable time; thus, it is not reasonable to expect survival gains commensurate with that of transplantation averages in the near future. In a previous editorial, Stevenson (6) proposed that 1 means of trimming the wait list was to restrict transplantation to patients younger than age 65 years. Presently, patients age 65 years or older make up ∼17% of the transplantation wait list, and the median recipient age and proportion of patients aged 65 years or older who receive a cardiac transplant (∼17% in 2016 vs. 9.8% in 2005) are increasing (1,4). In this age group, even modest improvements in LVAD survival (by an average of 2 to 3 additional years) could help reduce the need for transplantation and trim the wait list. Until this occurs, ethical discussions are warranted regarding the benefits and detriments of placing age restrictions on U.S. transplant recipients.
Equally daunting is addressing the U.S. donor organ shortage. The impediments to successful cardiac donation are composed of both societal and medical facets. Unwillingness to donate organs in the United States is shrouded in years of distrust of the medical system, a lack of understanding of the difference between brain death versus cardiac death, as well as cultural and religious beliefs (7). On the medical side, the United Network for Organ Sharing (UNOS) and transplantation centers go through great efforts to match donors with recipients, aiming to achieve the best transplant recipient survival and donor organ use in an era of growing donor demand (3). Simultaneously, transplantation centers need to ensure that their institutional Scientific Registry of Transplant Recipients (SRTR) risk-adjusted transplant survival meets Medicare Conditions of Participation benchmarks. As such, programs often institute additional center-specific, donor−recipient matching criteria (e.g. donor−recipient size and sex, donor echocardiographic and/or hemodynamic characteristics), leading to marked variations in U.S. donor use and the potential for rejection of decent donor hearts. In the last SRTR report, an increase in the rate of hearts recovered for transplantation but not used was noted, especially in the 35- to 49-year donor age group (2). In an era of lengthening donor lists and death from MCS complications, there is a question if a better means of matching donor hearts in a select group of transplantation candidates exists to improve donor use and HF patient access to transplantation.
The Donor Risk Index (DRI) was derived and internally validated by Weiss et al. (8) using multivariable modeling of OPTN data from adult patients who underwent transplantation between 1997 and 2007. Survival at 1 year was 89%, 87%, 82%, and 81% in low, low-medium, medium-high, and high DRI groups, respectively (8). Even in the high-risk donor group, 1 year recipient survival was on par with average 1 year LVAD survival (80%) in INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) and was much better than survival after LVAD exchange (survival <65%) or for those living on biventricular VAD support (survival <60%) (5). At 5 years, survival in patients who received transplants from high-risk donors (∼62% at 5 years) was also superior to that of LVAD (<40%) (5,8). In this issue of the Journal, Nguyen et al. (9) applied the DRI to a contemporary group of OPTN patients (2006 to 2015) and compared recipient outcome after transplantation with that of survival with continued transplantation listing. This analysis again revealed a survival benefit with transplantation compared with continued waiting on the list, even in those recipients who had higher risk donors according to the DRI (9). Importantly, the overall survival benefit of transplantation versus waiting appeared to occur at different time frames for different DRI risk groups. For recipients with low and low-medium risk DRI scores, the survival advantage of transplantation versus continued waiting occurred early (<6 months) after transplantation (9). For those with high-risk DRI scores, the benefit of transplantation versus waiting came after 2 years. This implies that there is an upfront cost of higher mortality with transplantation in recipients from higher risk donors, which is likely due to the operative risk and complications from high levels of immunosuppression. However, transplantation with a higher risk donor match, compared with waiting, still offered an overall longer term survival reward.
On a more granular level, Nguyen et al. (9) showed that patients with initial UNOS 1A and 1B listings derived a statistically and clinically significant survival benefit (mortality hazard ratio [HR] 0.37 to 0.52 in UNOS 1A and HR 0.41 to 0.66 in UNOS 1B) from transplantation compared with waiting, even if a recipient received the transplant from a high-risk donor (9). A delayed survival advantage was also seen for those who were status 1A at the time of transplantation. In patients who were listed status 1B or status 2 at the time of transplantation, demonstration of a clear benefit from a higher risk donor transplant was lacking. As Nguyen et al. pointed out, many patients currently waiting as a status 1B are stable on home inotropes or LVAD support. Thus, the upfront risks of the transplantation operation are higher than the benefits of staying listed. However, for many MCS patients, this “stability” is transient because the hazard rates for most MCS complications rise with support duration (5). This was suggested in Figure 4 of the study (9), which showed an intersection of the hazard curves for the low/low-medium DRI groups with that of those who were still waiting at 24 to 36 months. In UNOS 2 listed patients, escalation to sicker listing statuses is also common (10). Thus, there may still be a longer term survival advantage from transplantation in these UNOS groups.
The concept of accepting higher risk donors for transplantation is likely to be met with much angst in the U.S. transplantation community. Some may argue that reducing the average U.S. cardiac transplant survival even slightly with higher risk donors leads to unjust organ use. Although UNOS aims to standardized allocation, the transplantation center ultimately provides final organ acceptance. Because centers do not follow a standardized donor−recipient matching process, we really do not know if what we are currently doing is optimal. It is possible that a standardized matching process, with improved donor organ use, could improve outcomes for a larger percentage of listed HF patients. Alternatively, one may identify, through clinical study, a subset of listed patients (e.g., older patients, those with MCS complications) who gain a marked survival benefit from higher risk transplantation versus waiting. Many donor−recipient matching tools like the DRI exist, and it is not clear which tool, if any, provides the best short- and long-term risk discrimination (6,9,11). A well powered, prospective clinical study with short- and long-term mortality endpoints will be required for an alternative donor list and/or higher risk donor matching protocol to be fully embraced by U.S. transplantation cardiologist and surgeons.
Like many malignancies, we have not found a cure for end-stage HF. MCS has been our profession’s palliative chemotherapy, extending survival, but not curing the disease. Each of us is faced with the patients who improve markedly after MCS only to die in 2 to 4 years because they lost the window for transplantation. As a transplantation community, in which recent research has been lacking, it is time to embrace a clinical study on the usefulness of accepting higher risk donors for carefully selected recipients.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Cowger has reported that she has received research-related travel support from Abbott.
- 2017 American College of Cardiology Foundation
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