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Since 2005, the United States donor heart allocation system assigned patients awaiting transplantation with measurably distinct outcomes into a single high urgency priority status. In this old system, patients in cardiogenic shock as well as ambulatory stable patients with complications of a left ventricular assist device (LVAD) were allocated to a similar status of highest urgency (referred to as United Network for Organ Sharing [UNOS] Status 1A) and competed equally for donor organs. This led to overcrowding of the list within this high urgency status category with consequent prolongation of waiting times and concerns of inequity in allocation across several geographic regions.
In response to this issue, and to provide greater opportunity for candidates disadvantaged by the allocation system (such as those with congenital heart disease or restrictive cardiomyopathy syndromes), the donor heart allocation system was redesigned in the United States on October 18, 2018.
One principal alteration to the new system was the breakdown of the previous single highest urgency status (1A) into 3 separately ranked statuses deemed to be in descending order of sickness (new status 1, 2, and 3). In this system, patients in cardiogenic shock and supported with therapy such as extracorporeal membrane oxygenation (ECMO) or other non-dischargeable biventricular mechanical circulatory support were assigned to the highest urgency status, whereas those with lesser degrees of support were distributed into a descending rank order of priority in urgency. It was envisioned that such a system would allow more equitable organ allocation and likely provide overall net benefit to the community of patients awaiting heart transplantation. We now report on early outcomes of this transition to the new 2018 allocation system within the United States.
The data were acquired from the publicly available UNOS registry, and because it contains no patient identifiers, was deemed exempt from Institutional Review Board review. The analysis was limited to adult (age ≥18 years old at listing) undergoing a first time, single-organ heart transplantation. Patients listed and transplanted in the 3 years before the UNOS allocation change (prior system, October 18, 2015–October 18, 2018) were compared with those listed and transplanted under the new system (after October 18, 2018–March 31, 2019). Outcomes for the new system were available up to June 6, 2019. The methodology for identifying durable or temporary support with mechanical circulatory devices is outlined in the Supplementary Material available online at www.jhltonline.org. The principal outcome of interest was death or retransplantation following heart transplantation. Analyses were performed using Stata version 16 (Stata Corp., College Station, TX). Baseline characteristics among the 2 patient groups were compared with Student's t-test for normally distributed and Wilcoxon-Mann-Whitney test for non-normally distributed variables. Chi-square tests were used for comparison of categorical variables. To assess association between the allocation system era and the primary outcome, Cox proportional hazards regression analysis was used. Potential confounders influencing post-transplantation survival, including recipient age, race, recipient sex, prior sternotomy, cardiomyopathy type, diabetes mellitus, ischemic time, waitlist time, donor age, presence or absence of an LVAD, and sex mismatch (female donor to male recipient), were then forced in the models and tested for significance in a univariate exploratory analysis (p < 0.2). These were then incorporated in a forward and backward stepwise fashion using the likelihood ratio test for significance to arrive at a final adjusted model. All comparisons were two-sided and a p-value < 0.05 was considered significant. A Fine-Gray competing risk analysis was performed to assess the impact of the new allocation system on waitlist mortality. Modeling of net losses and gains (defined as the differences in wait list survival gains and post-transplant losses) in the prior system vs the new system is described in the Supplementary Material online. We performed 2 separate sensitivity analyses to examine robustness of the primary result (Supplementary Material online).
Baseline characteristics of patients by allocation system group are in Table 1. Patients listed and transplanted in the new system were more likely to be on temporary mechanical circulatory support and with worse hemodynamics (higher pulmonary vascular resistance, lower cardiac output, and higher mean pulmonary capillary wedge pressures). A significant decrease in patients bridged to transplant with durable LVADs and median wait times in the new system was noted, whereas ischemic time was longer. The use of ECMO support was 4-fold greater in the new system. The urgency status at listing and the last status before transplantation is in the Supplementary Material online (Supplementary Table 1). In the new system, most transplants occurred in urgency status 1, 2, or 3 (83%). The 90-day survival estimates are 87.6% vs 94.5% in the new system and the prior system, respectively (log rank p < 0.0001). The 180-day survival estimates are 77.9% vs 93.4 % in the new system and the prior system, respectively (log rank p < 0.0001). In the multivariate models, patients listed and transplanted in the new system experienced a higher hazard rate for death or retransplantation (unadjusted hazard ratio [HR] 2.1, 95% confidence interval [CI] 1.5–3.0, p < 0.001; adjusted HR 2.1, 95% CI 1.4–2.9, p < 0.001). The final Cox model included recipient age, recipient sex, ischemic time, prior sternotomy, wait time, donor age, and presence or absence of an LVAD. Each 30-minute increase in ischemic time was associated with an 8% increase in the hazard rate of post–cardiac transplant death or retransplantation (HR 1.08, 95% CI 1.04–1.12, p < 0.001). Figure 1B provides outcomes for those within each group comparing patients in the highest urgency status 1A in the previous system and status 1, 2, and 3 in the new system (adjusted HR 2.1, 95% CI 1.4–3.2). Survival on the waitlist 180 days in the previous system was 95.0% (95% CI 94.5–95.5%). Survival at 180 days in the new system was 96.1% (95% CI 94.2–97.3 %, log rank p = 0.08). In a competing risk analysis, the new system was protective against waitlist mortality (adjusted HR 0.43, 95% CI 0.31–0.60, p < 0.001, adjusted for recipient age, presence of an LVAD at listing, temporary support, and diabetes mellitus). The net impact of the allocation system change on number of lives saved on the waitlist and the increase in post-transplant mortality or retransplantation is modeled in Supplementary Table 2 online.
Table 1Baseline Characteristics of Patients Listed and Transplanted in the Prior System vs the New System
Baseline characteristic
Prior system
New system
p-value
n = 6,001
n = 539
Recipient characteristics
Age
54 ± 13
54 ± 13
0.43
Men
4,318 (72)
385 (72)
0.80
White
3,858 (64)
350 (65)
0.76
LVAD at transplant
2,510 (42)
122 (23)
<0.0001
Temporary mechanical support
596 (10)
221 (41)
<0.0001
ECMO at listing or at transplant
98 (1.6)
35 (6.5)
<0.0001
Ischemic cardiomyopathy
1,800 (30)
160 (30)
0.61
Prior sternotomy
2,305 (38)
188 (35)
0.11
Body mass index (kg/m2)
27.4 ± 4.8
26.7 ± 5.2
0.003
History of diabetes mellitus
1,537 (26)
123 (23)
0.16
Serum creatinine (mg/dl)
1.2
1.2
0.24
Blood group
0.65
O
2,180 (36)
192 (36)
A
2,508 (42)
219 (41)
B
934 (15)
87 (16)
AB
379 (6)
41 (8)
Recipient hemodynamics
Pulmonary vascular resistance (wood units)
2.4 ± 1.6
2.8 ± 2.0
<0.0001
Pulmonary capillary wedge pressure (mm Hg)
18.3 ± 8.8
19.9 ± 9.0
<0.001
Cardiac output (liters/min)
4.2 ± 1.4
4.1 ± 1.5
<0.01
Donor characteristics
Ischemic time (hours)
3.0 ± 1.0
3.4 ± 0.96
<0.0001
Donor age (years)
32.1 ± 10
33.1 ± 11
0.0600
Sex mismatch
852 (14)
70 (13)
0.44
Wait time (all patients)
68 [22, 177]
14 [6, 34]
<0.001
Median wait times for those transplanted, by initial status
Median wait times represent the times calculated from listing to transplantation for patients in the 2 time periods examined, but does not include nor account for the wait times of those that remain on the list.
Prior system status
1A
28 [11, 84]
na
1B
77 [29, 192]
na
2
134 [56, 279]
na
New system status
1
na
3 [2, 6]
2
na
7 [4, 13]
3
na
13 [8, 26]
4
na
26 [13, 58]
6
na
33 [15, 52]
Abbreviations: ECMO, extracorporeal membrane oxygenation; LVAD, left ventricular assist device; na, not applicable.
Normally distributed continuous variables are displayed as mean ± standard deviation. Non-normally distributed variables are displayed as median and interquartile range. Binary or categorical variables are displayed as number and percent.
a Median wait times represent the times calculated from listing to transplantation for patients in the 2 time periods examined, but does not include nor account for the wait times of those that remain on the list.
Figure 1 AFreedom from death or retransplantation: prior system vs new system. Kaplan-Meier curves demonstrating death or retransplantation in prior system vs new system. Associated adjusted hazard ratio from the multivariate model is displayed. CI, confidence interval. (B) Freedom from death or retransplantation: prior system 1A vs new system status 1, 2, and 3. Kaplan-Meier curves demonstrating death or retransplantation in prior system 1A vs new system status 1, 2, and 3. Associated adjusted hazard ratio is displayed. CI, confidence interval.
The findings of our early analysis into the implications of the current change in the US allocation system for donor heart organs suggest that although waitlist mortality has been reduced, post-transplantation outcomes may have worsened considerably. As waitlist mortality in the previous system was relatively low,
The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: thirty-sixth adult heart transplantation report - 2019; focus theme: donor and recipient size match.
the absolute impact of this reduction in waitlist mortality is small compared with the increase in death or graft loss after transplantation, as is being observed in this early examination of the new system. The analysis also demonstrates important epidemiological shifts in the bridging strategies that are now predominantly focused on temporary mechanical circulatory support devices. The allocation system and the strategies employed have resulted in a decrease in wait list times for those transplanted in the new system, which has reduced the need for transitioning patients to durable LVAD therapy. Importantly, increased severity of illness as suggested by the higher acuity and worse hemodynamic profiles coupled with the increased use of temporary circulatory support devices with their antecedent post-transplantation risks for optimal outcome may partly explain these observations of a reduced post-transplant survival.
The longer ischemic times reported under the operation of the current allocation system suggest either a wider regional availability of donors and/or a greater propensity for accepting donors with longer distance transit times likely because of the increased acuity of the recipients. This analysis lacks robustness for sub-stratifying outcomes within the hierarchal categories of status 1, 2, or 3 within the current allocation system. These early trends in short-term survival are sufficiently concerning because a limited number of heart transplantations occur in the US each year. In addition, transplantation programs in the US are subject to rigorous regulatory scrutiny, and declining outcomes set into motion a cascade of efforts at high cost and personnel time at afflicted centers, which may detract from direct patient care. Our analysis was not powered to assess regional or center heterogeneity in these observed findings. Whether these trends persist over the longer period of observation remains uncertain. Given the short duration of follow-up in the new system, the confidence around the survival probabilities start to widen in the later post-transplant survival times. It should be emphasized that these estimates represent an early look, and we are hopeful that as more data is recorded and experience accrues in the new system, these trends will show partial or complete reversal. It is quite possible that early trends will facilitate initiation of center-based programs to refine their candidate selection (to avoid transplanting those patients with clear evidence of high risk) as well as improve donor organ choices. Thus, we believe that there is a reasonable chance that a larger and longer experience will reverse these early troubling trends.
Our intention in highlighting these early trends under the new allocation system in the United States are principally designed to draw the community into a suitable debate to ensure that more comprehensive details and refinements to the system or at the center level are instituted rapidly and uniformly. A better understanding of the factors underlying these findings will likely serve to improve the outcomes for our patients undergoing heart transplantation in the United States.
Disclosure statement
Dr Cogswell reports no direct conflicts pertinent to the development of this manuscript. Other general conflicts include consulting relationships with Abbott and Medtronic. Dr Cogswell is on the Advisory Board for Medtronic and her spouse is a Medtronic employee. Dr John reports no direct conflicts pertinent to the development of this manuscript. Other general conflicts include consulting relationships with Abbott and Medtronic. Dr John also has research grants from Abbott and Medtronic. Dr Estep reports no direct conflicts pertinent to the development of this manuscript. Other general conflicts include a consulting relationship with Abbott and Advisory Board work for Medtronic. Dr Tedford reports no direct conflicts pertinent to the development of this manuscript. Other general conflicts include consulting relationships with Medtronic, Arena Pharmaceuticals, and United Therapeutics. Dr Tedford is on the steering committee for Medtronic and the research advisory board for Abiomed. He also does hemodynamic core lab work for Acetlion and Merck. Dr Pagani reports no direct conflicts pertinent to the development of this manuscript. Dr Martin reports no direct conflicts pertinent to the development of this manuscript. Dr Mehra reports no direct conflicts pertinent to the development of this manuscript. Other general conflicts include consulting relationships with Abbott (paid to Brigham and Women's Hospital), Medtronic, Janssen, Mesoblast, Portola, Bayer, NupulseCV, FineHeart, Leviticus, Triple Gene, and Baim Institute for Clinical Research. Dr Mehra is also Editor in Chief of the Journal of Heart and Lung Transplantation; however, the writing does not constitute the official stance of the journal nor the society that it represents, the International Society of Heart and Lung Transplantation. This study was funded by University of Minnesota Departmental Funds.
Supplementary data
Supplementary data associated with this article can be found in the online version at www.jhltonline.org.
The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: thirty-sixth adult heart transplantation report - 2019; focus theme: donor and recipient size match.
Years of research of candidates for heart transplantation led to crafting the recent donor heart allocation system in the United States, implemented in October 2018, which was designed to allow more equitable organ allocation of patients awaiting heart transplantation, to reduce mortality in the waiting list, and to preserve excellent outcomes post–heart transplant. In their study, Cogswell et al.1 examine key changes in patient characteristics and post-transplant outcomes in the period of 3 years before and 5.4 months after the change of the US allocation algorithm.
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