Heart transplantation (HTx) is greatly limited by organ shortage. To address this crisis, donation after circulatory death (DCD) is an emerging alternative to the traditional donation after brain death (DBD). Unfortunately, there is scarce data on HTx outcomes for this donation type, particularly within the United States; our investigation seeks to address this knowledge gap. As part of this study, the UNOS thoracic database was analyzed for first-time, adult, isolated orthotopic HTx recipients between 2019 and 2023. Patients were stratified into 3 groups: DBD, DCD III, and DCD IV. Further subgroup analysis for DCD III donors was conducted based on the procurement method, direct procurement and perfusion (DPP) or normothermic regional perfusion (NRP). After creating the sample cohort, a total of 14,035 HTx recipients were included in our analysis (DBD 86.5%, DCD III 6.9%, DCD IV 6.5%). There was an exponential increase in the number of DCD III cases and HTx centers that offer this donation type during the study period. DCD III recipients had a higher incidence of postoperative dialysis use; otherwise, all 3 groups shared similar rates of postoperative permanent pacemaker placement and stroke, acute rejection, and mortality. Within DCD III recipients, DPP and NRP procurement techniques had similar survival. To conclude, although DCD III was associated with an increased incidence of postoperative dialysis use, both DCD type III and IV had comparable morbidity and survival as the standard of care DBD donors. Overall, our investigation provides encouraging data to support DCD use as a safe option to increase the limited donor pool in the United States.
Graphical abstract
Heart transplantation (HTx) is significantly limited by an ongoing organ shortage. In 2022 alone, over 7,500 adult patients in the United States were on the HTx waitlist, yet only 3,652 hearts were donated and ultimately transplanted. In addressing this grave donor shortage, many transplant centers have expanded their donor eligibility criteria. In the 21st century, an active area of research and strategy to further expand the donor pool is through donation after circulatory death (DCD). In contrast to donation after brain death (DBD), DCD is highly versatile and includes direct procurement and perfusion (DPP) or normothermic regional perfusion (NRP). However, one unique challenge with DCD is the inevitable warm ischemic time (WIT) period following cardiocirculatory collapse, thereby leading to ischemia and subsequent ischemic-reperfusion injury. Despite this obstacle, with the advent of perfusion technology, DCD utilization has become a practical and safe alternative to DBD. Current results from solid abdominal organ transplant outcomes using DCD, including liver, kidney, and pancreas, describe comparable results to their DBD counterpart. Similarly, preliminary data from international HTx studies suggest that DCD utilization is a safe alternative to DBD. , In the United Kingdom where DCD procurement was adopted early, this practice allowed for a reported 48% increase in HTx rates; in the United States, it is projected to increase HTx volume by as much as 30%. However, further investigation into potential differences in clinical outcomes between DBD and DCD HTx in the United States is needed. Notably, in this population, the subacute implications of DCD use after 1-year of HTx is unknown. Therefore, we sought to address this gap in knowledge by comparing the national outcomes between DCD and DBD use.
Methodology
Study population
The United Network for Organ Sharing (UNOS) thoracic database was queried for first-time, adult orthotopic HTx recipients in the United States. As the first recorded DCD HTx occurred in 2019, the investigation’s review period was limited to patients who were transplanted between January 2019 and September 2023. Recipients who received multiorgan transplants were excluded from the analysis.
Classification of donation type and procurement methods
Once the final cohort was established, patients were categorized into groups based on their donor Maastricht classification. Under this system, 4 DCD categories are described: Type I: dead on arrival at the hospital, Type II: dead after unsuccessful resuscitation efforts, Type III: awaiting cardiac arrest, often in a controlled setting following life-support withdrawal, and Type IV: cardiac arrest following brain death. For the current investigation, using the above classifications, recipients were stratified into 3 groups: DBD, DCD Type III (DCD III), and DCD Type IV (DCD IV).
As part of this study, further subgroup analyses were performed in the DCD III group based on their procurement method: DPP or NRP. As the UNOS database does not directly include these modalities as explicit variables, assumptions were made based on methodologies described in previous investigations to indirectly categorize patients into DPP or NRP groups. ,, Specifically, the period between donor death to aortic cross-clamping was used to categorize the groups: DPP was considered to be the procurement technique when the interval time was less than 30-minutes, whereas NRP was defined as an interval greater than 30-minutes. ,
Statistical analysis
Continuous variables were reported as mean ± standard deviation if normally distributed, or median (interquartile range) if skewed. Groups were compared using analysis of variance (ANOVA) or Kruskal-Wallis nonparametric testing as appropriate. Categorical variables were presented as a percentage and compared using the Chi-squared test. Kaplan-Meier curves were used to present the survival probabilities of participants separated according to strata of donation type and procurement methods and compared using the log-rank test. Univariable and multivariable Cox proportional hazard methods were utilized to quantify mortality risk for the previous predefined variables. Clinically relevant variables, as listed in the Supplementary Materials , with a univariable p-value of less than or equal to 0.10 in the overall sample were eligible for entry into both multivariable models. The final model for donation type assessment was created using a backward stepwise elimination method that retained covariables with a p-value of less than 0.05. Given the smaller sample size of the DCD III cohort, no further elimination methodology was conducted to obtain the final model for procurement methods mortality assessment.
For the entirety of the study, a p-value less than 0.05 was considered statistically significant. All statistical analyses were performed using JMP Pro 16 software (SAS Institute Inc., Cary, NC). The Institutional Review Board at the University of California Davis deemed that this investigation did not meet the definition of human research, therefore, institutional review was not required.
Results
A total of 14,035 HTx recipients were included in our study. DBD recipients made up approximately 86.5% of the cohort, DCD III 6.9%, and DCD IV 6.5%. Figure 1 illustrates the temporal trends for each group. There was a clear increase in the proportion of DCD III recipients over the years, culminating in 14.6% of all HTx in the year 2023, while the DCD IV group was mostly stagnant. As shown in Figure 2 , the geographic distribution for most DCD III HTx occurred in the New England (Region 1), South-West (Region 5), and South Mid-Atlantic (Region 11) regions. Transplant center practices have also changed significantly during the review period. Figure 3 displays the exponential growth of HTx institutions that offer DCD III transplantation. Similarly, as illustrated in Supplementary Figure S1 , the majority of cases come from high-volume centers, although medium-volume HTx institutions showed a similar increase in DCD. Conversely, this donation type has only recently been utilized at low-volume centers, and their contribution to date makes up less than 5% of the yearly DCD III volume.
Yearly trends in the incidence of HTx donation type within the United States between 2019 and 2023. DBD = donation after brain death; DCD = donation after circulatory death; HTx = heart transplantation.
Geographical distribution of DCD III HTx in the United States. DCD = donation after circulatory death; HTx = heart transplantation; UNOS = United Network for Organ Sharing.
Yearly trends in the number of heart transplant centers that accept DCD III between 2019 and 2023. DCD = donation after circulatory death; HTx = heart transplant.
Patient demographic and medical data is presented in Table 1 across donation types. Those who had DCD III donors were generally White and male, and were least likely to require inotropic, ECMO, IABP, or ventilatory support at the time of listing. However, they had the highest incidence of VAD/TAH use at listing. Ultimately, this group had the greatest proportion of low-acuity status at listing, and similarly the lowest incidence of high-acuity status. All 3 groups had similar rates of diabetes, cigarette use, heart failure etiology, and pulmonary vascular resistance values. Donor and donor-recipient matching data are presented in Table 2 . DCD III donors were more likely to be White and male and were also generally lower risk compared to other groups: they were on average younger, and less likely to have a history of hypertension, diabetes, or cigarette use greater than 20 pack years. Apart from DCD III, DCD IV donors were found to have the greatest incidence of CPR use and were most likely to have anoxia as their primary cause of death. Overall, DBD and DCD IV groups were generally found to share similar donor and recipient traits, whereas the DCD III cohort typically had lower risk features.
Table 1
Characteristics of study participants according to donation type
|
DBD
(n = 12,147) |
DCD III
(n = 974) |
DCD IV
(n = 914) |
p – value | |
|---|---|---|---|---|
| Age (years) | 57 (46-63) | 57 (46-64) | 57 (46-63) | 0.516 |
| Sex (M) | 72.6% | 79.7% | 73.2% | <0.001 |
| Weight (kg) | 84.3 ± 18.2 | 88.8 ± 18.6 | 84.5 ± 18.4 | <0.001 |
| BMI (kg/m 2) | 27.8 ± 5.0 | 28.6 ± 4.9 | 27.9 ± 4.9 | <0.001 |
| Race | <0.001 | |||
|
White
Black Hispanic Asian |
60.0%
24.5% 10.3% 3.9% |
68.4%
20.0% 10.0% 1.5% |
57.9%
24.2% 13.0% 3.8% |
|
| History of diabetes | 28.4% | 29.4% | 25.9% | 0.200 |
| History of cigarette use | 41.3% | 44.4% | 39.7% | 0.093 |
| Primary etiology | 0.368 | |||
|
NIDCM
ICM HCM RCM |
57.4%
27.7% 3.4% 4.4% |
55.1%
28.9% 4.5% 4.4% |
55.4%
27.8% 3.7% 5.8% |
|
| Hemodynamics | ||||
|
Mean PAP (mm Hg)
PCWP (mm Hg) CO (L/min) PVR (wood units) |
28.1 ± 10.5
18.9 ± 9.0 4.2 ± 1.3 2.5 ± 1.6 |
27.1 ± 10.4
17.7 ± 9.0 4.3 ± 1.3 2.4 ± 1.5 |
28.6 ± 10.3
19.3 ± 8.7 4.2 ± 1.3 2.5 ± 1.6 |
0.004
<0.001 0.014 0.071 |
| Highest educational level | 0.120 | |||
|
High school or below
College or above |
41.6%
58.4% |
38.2%
61.8% |
40.9%
59.1% |
|
| Insurance type | 0.016 | |||
|
Medicaid or donation
Medicare or other govt. sponsored Private or self-funded |
15.2%
35.2% 49.6% |
14.1%
38.4% 47.5% |
18.1%
31.8% 50.1% |
|
| ECMO | 3.8% | 0.7% | 5.7% | <0.001 |
| IABP | 16.0% | 9.2% | 17.4% | <0.001 |
| Inotrope use | 34.7% | 27.1% | 33.9% | <0.001 |
| VAD/TAH | 28.3% | 33.6% | 25.0% | <0.001 |
| Ventilator | 1.9% | 0.5% | 2.3% | <0.001 |
| Acuity status | <0.001 | |||
|
Low
Medium High |
19.2%
33.6% 47.3% |
26.6%
40.0% 33.4% |
19.0%
31.7% 49.3% |
|
| Annual HTx center volume | <0.001 | |||
|
Low (<15)
Medium (15-35) High (>35) |
12.5%
46.7% 40.8% |
2.6%
23.7% 73.7% |
9.7%
42.8% 47.5% |
|
| Total days on WL | 29 (9-142) | 32 (9-154) | 30 (9-156) | 0.761 |
BMI = body mass index; ECMO = extracorporeal membrane oxygenation; HCM = hypertrophic cardiomyopathy; IABP = intra-aortic balloon pump; ICM = ischemic cardiomyopathy; NIDCM = nonischemic dilated cardiomyopathy; PVR = pulmonary vascular resistance; RCM = restrictive cardiomyopathy; TAH = total artificial heart; VAD = ventricular assist device; WL = waitlist.
Table 2
Donor characteristics and donor-recipient matching data across donation types
|
DBD
(n = 12,147) |
DCD III
(n = 974) |
DCD IV
(n = 914) |
p-value | |
|---|---|---|---|---|
| Age (years) | 32.8 ± 10.3 | 30.5 ± 8.4 | 32.7 ± 10.2 | <0.001 |
| Sex (male) | 71.3% | 85.9% | 70.8% | <0.001 |
| Race | <0.001 | |||
|
White
Black Hispanic Asian |
61.8%
17.1% 18.0% 1.6% |
76.9%
9.8% 11.2% 1.1% |
62.7%
15.9% 17.6% 2.7% |
|
| Weight (kg) | 84.8 ± 20.0 | 86.7 ± 20.5 | 85.9 ± 20.3 | 0.008 |
| BMI (kg/m 2) | 28.1 ± 6.3 | 27.7 ± 6.5 | 28.3 ± 6.3 | 0.102 |
| History of hypertension | 15.8% | 12.6% | 15.1% | 0.022 |
| History of cigarette use (>20PY) | 12.5% | 9.7% | 14.4% | 0.008 |
| History of diabetes | 4.1% | 2.3% | 3.6% | 0.008 |
| History of CAD | 0.2% | 0.1% | 0.3% | 0.509 |
| History of MI | 1.1% | 1.1% | 2.6% | 0.003 |
| Cause of death | <0.001 | |||
|
Anoxia
Head trauma CVA |
45.6%
39.1% 12.7% |
49.0%
40.8% 6.5% |
63.8%
25.8% 8.8% |
|
| CPR given? | 55.1% | 56.1% | 98.3% | <0.001 |
| CPR duration (min) | 20 (10-30) | 15 (9-22) | 16 (9-30) | <0.001 |
| Ischemic time (hours) | 3.5 ± 1.1 | 5.0 ± 2.2 | 3.4 ± 1.1 | <0.001 |
| Agonal time (min) * | N/A | 2 (1-4) | N/A | N/A |
| Functional warm ischemic time (min) † | N/A | 28 (21-81) | N/A | N/A |
| Total warm ischemic time (min) ‡ | N/A | 32 (24-84) | N/A | N/A |
| Procurement technique | N/A | N/A | N/A | |
|
66.3%
33.8% |
||||
|
DPP
NRP |
||||
| Organs recovered | 5 (4-6) | 4 (3-4) | 4 (4-6) | <0.001 |
| Organs transplanted | 4 (4-6) | 4 (3-4) | 4 (4-6) | <0.001 |
| ABO blood type matching | 0.256 | |||
|
Compatible
Identical |
13.9%
86.1% |
13.1%
86.9% |
15.7%
84.4% |
|
| HLA mismatch | 0.371 | |||
|
0-3
4-6 |
14.1%
85.9% |
12.5%
87.5% |
14.8%
85.2% |
|
| PHM ratio | 1.04±0.17 | 1.04±0.18 | 1.04±0.17 | 0.746 |
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