CTS Newsletter 4:2020: Influence of donor age in heart transplantation

CTS Collaborative Transplant Study

Newsletter 4:2020

November 1, 2020

Transplantation of organs from expanded criteria donors has become a major issue in organ transplantation. Therefore, we dedicated two of this year’s CTS Newsletters to the impact of donor age on kidney and liver transplant outcomes (1:2020 and 3:2020). For this Newsletter we analyzed the influence of donor age in heart transplant recipients. Heart transplantations make up the third largest part of the Collaborative Transplant Study (CTS) database after kidney and liver transplantations with, however, only 8% of all registered transplants.

In total, 43,535 orthotopic heart transplantations performed in adult recipients of first grafts from ≥18-year-old deceased donors during 1985–2019 were evaluated. Patients with combined organ transplants were excluded.

**Figure 1.** Distribution of (A) recipient and (B) donor age in adult recipients of first orthotopic heart transplants in different transplant periods.

Figure 1 demonstrates the changes in the distribution of recipient and donor age from 1985 to 2019. Recipient age showed an increase until 1999 but remained with an average of 51 years approximately constant during 2000–2019. Donor age, in contrast, showed a continuous increase over the whole time period. Between 1985–1989 and 2010–2019, the proportion of 18–29-year-old young donors decreased from 55.7% to 21.7% and the proportion of ≥50-year-old donors increased from 2.2% to 30.6%. However, the average increase in donor age since 2000 has been, with approximately 5 years, only half as high as in kidney and liver transplantation.

The strong correlation between recipient and donor age illustrated in Figure 2 indicates that age matching is frequently practiced in allocation of heart allografts.

**Figure 2.** Correlation between recipient and donor age in first orthotopic heart transplantations performed between 2000 and 2019.

Apart from donor and recipient age, important factors that significantly influence heart transplant outcomes are original disease leading to transplantation, cold ischemia time, geographical region, recipient race, pre-transplant antibodies, cause of donor death, donor history of hypertension, and urgency. In addition to transplant period or donor age, some of these factors (e.g. original disease) show also correlations with recipient age, making multivariable Cox regression analyses essential for the assessment of the influence of donor age on survival of heart transplants.

**Figure 3.** Hazard ratios (red) with 95% confidence intervals (blue) of multivariable Cox regression analysis for the influence of donor age on 5-year graft survival. Donor age category 18–24 years served as reference.

As illustrated in Figure 3, there is an approximately linear influence of donor age on graft survival, while an additional substantial increase in the risk of graft loss becomes apparent in recipients of hearts from ≥60-year-old donors. In contrast, "The International Society of Heart and Lung Transplantation" indicates in its "Guidelines for the care of heart transplant recipients" from 2010 55 years as a critical donor age threshold (doi: 10.1016/j.healun.2010.05.034) and Daniel et al. report in their recent paper from 2019 an even lower donor age of 50 years as a critical limit in ≥60-year-old recipients (doi: 10.1016/j.athoracsur.2018.06.085). Therefore, we analyzed the influence of donor age in the recipient age groups 18–39 (7,195 patients), 40–49 (9,812), 50–59 (17,222), and ≥60 years (9,306) separately (Figure 4).

**Figure 4.** Influence of donor age on graft survival during the first five post-transplant years after first orthotopic heart transplantation in four different categories of recipient age.

CTS data indicate that the influence of donor age is strongly dependent on recipient age and it is difficult to define a “critical” donor age limit without considering the recipient age. In all age groups, graft survival is best with hearts from <30-year-old donors, while this “good outcome” limit is slightly shifted towards <35 years in ≥60-year old recipients. For the remaining donor age groups, the analysis provides strong arguments in favor of strict age matching. In 18–39-year old recipients, hearts from <40-year-old donors should be preferred whereas hearts from 55–59-year-old donors also appear to be acceptable for 50–59-year old recipients. The less pronounced increase in the risk of graft failure with organs from ≥60-year-old donors is observed in ≥60-year old recipients.

Unfortunately, the Covid-19 pandemic has gained a new momentum. Many patients with a history of SARS-CoV-2 infection will soon have access to transplantation and an increasing number of previously transplanted patients will be hospitalized for SARS-CoV-2. Therefore, we planned a pre- and post-transplant serum study involving SARS-CoV-2 infected patients and will soon contact you about the details. With the Collaborative Transplant Study, we have a unique opportunity to collect reliable information on the impact of SARS-CoV-2 infection on transplant outcomes. Please support us with your participation in the serum studies and do not miss to fill out the information on hospitalizations for SARS-CoV-2 in CTS follow up forms.