Huntley GD, Danford DA, Menachem J, Kutty S, Cedars AM. Donor Characteristics and Recipient Outcomes After Heart Transplantation in Adult Congenital Heart Disease. J Am Heart Assoc. 2021 Jul 20;10(14):e020248. doi: 10.1161/JAHA.120.020248. Epub 2021 Jul 9. PMID: 34238025; PMCID: PMC8483491.
Take Home Points:
- Volume and proportion of patients with adult congenital heart disease (ACHD) requiring heart transplantation (HTx) is rising rapidly, while donor availability remains low
- Registry data has shown longer wait times for HTx in ACHD patients compared to those without ACHD (non-ACHD), a lower probability of high-priority listing status, and a lower likelihood of transplantation
- This current large retrospective analysis of data from Scientific Registry of Transplant Recipients in the USA between 2000 – 2016 has identified very few differences in donor characteristics between HTx recipients with ACHD and non-ACHD, but longer waitlist times for Status 1A-listed ACHD patients
- Post-transplant outcomes demonstrated worse early mortality (days 0 – 30) in ACHD HTx recipients, similar intermediate mortality (31 days – 4 years) and superior late mortality (> 4 years); no donor characteristics were found to be associated with mortality
- Unique donor selection criteria in ACHD are not indicated based on the findings from this retrospective analysis.
Commentary from Dr. Timothy Roberts (Melbourne, Australia), section editor of ACHD Journal Watch:
There is a persistent shortage of cardiac allografts for ACHD and NCHD patients awaiting HTx, resulting in considerable time spent on waitlists and high waitlist mortality. Despite this, a low donor heart acceptance rate has been observed across all patients which may suggest an increasing avoidance of risk. The refusal of a donor heart may be due to various reasons, although evidence to support refusal is limited to only a few factors including increasing age, ischaemia time, history of stroke, diabetes mellitus, coronary artery disease, substance abuse, and in some cases age, sex and weight mismatch.
The current study group hypothesized that greater donor selectivity does not improve post-HTx outcomes for patients with ACHD awaiting HTx, but rather may lengthen waitlist times and worsen post-HTx outcomes.
The Scientific Registry of Transplant Recipients (USA) was utilized to perform a retrospective analysis of adult patients listed for HTx between 2000 and 2016. Patients were separated according to their underlying disease being ACHD or NCHD and further subcategorized into candidates (pre-HTx) and recipients (post-HTx). The primary outcome was waitlist time for candidates and posttransplant survival for recipients. All candidate variables were considered, as were all donor and recipient variables provided in the SRTR Database.
A total of 1649 patients with ACHD were listed for HTx during the study period, of which 903 underwent HTx; for NCHD patients 35274 of 54330 listed patients proceeded to HTx. Key significant differences between ACHD and NCHD HTx candidates were:
- Smaller proportion of ACHD patients initially listed as Status 1A (45% vs. 52%; p<0.001)
- Longer time on waitlist for ACHD patients (253 +/- 391 vs. 199 +/- 316 days; p<0.001)
Key significant differences in donor characteristics to ACHD vs. NCHD HTx recipients were younger age, shorter height, lower weight, more female sex, lower INR, and higher LV ejection fraction (see Table 2, below).
Survival curves demonstrated worse 30-day mortality for ACHD HTx recipients, similar survival rates to 4 years, and superior survival beyond 4 years (Figure 1, below).
Multivariable models were constructed to identify donor characteristics associated with post-HTx mortality in each risk period including HTx recipients with ACHD or NCHD, followed by models of post-HTx mortality for only ACHD HTx recipients in each risk period. No donor characteristics were associated with early or intermediate mortality in ACHD. Donor prerecovery steroid use and meeting high-risk donor criteria according to the Centers for Disease Control and Prevention were associated with late mortality (HR 2.891 [95% CI 1.189-7.029, p=0.006]; and HR 2.612, [95% CI 1.327-5.142, p=0.006], respectively). Donor history of other drug use was associated with late survival (HR 0.46, 95% CI 0.248-0.850, p=0.013).
Analysis was also limited to patients with a final listing status of 1A given patients with ACHD listed as 1A experience longer waitlist times and worse waitlist outcomes. Candidate, recipient and donor characteristics were largely similar to the total cohort. Survival curves suggested a similar 3-period, time-dependent difference in mortality risk. Multivariable models did not identify any difference in donor-specific risk factors that were significantly associated with early, intermediate or late mortality.
Donor characteristics associated with waitlist time in ACHD patients listed as status 1A identified Epstein-Barr virus nuclear antigen negative donor, a donor without an alcohol use disorder, and a cytomegalovirus (CMV) negative donor as being associated with longer waitlist times. Interestingly, none of these three variables were significantly associated with mortality irrespective of listing status.
The authors conclude that the absence of donor characteristics associated with early or intermediate mortality, and minimal factors associated with late mortality, provide support against the need to create unique donor selection criteria in ACHD HTx candidates. The high early perioperative mortality in ACHD HTx recipients but superior long term survival mirrors that of other registry data, the latter thought to be due to lower comorbidity burden.
It should be noted that the retrospective nature of this study, missing data points and absence of congenital anatomy or prior congenital operations limit the statistical accuracy and strength of the data provided, although certainly shines a light on the potential for HTx teams to liberalise donor criteria.