Heart transplantation remains the gold-standard therapy for end-stage heart failure patients; yet the number of heart transplants performed annually in the United States has remained stagnant because of shortage of donor organs. Although listed, many patients will not survive to even get the opportunity to undergo heart transplantation. Currently, the crude annual mortality on heart transplant waiting list is approximately 11%, which has improved compared with previous years because of increasing use of ventricular assist devices, rhythm correction devices, and more advanced heart failure centers.1
Because of the donor shortage and deaths on the waiting list, there has been a push to use marginal or high-risk donors to increase the number of heart transplants performed. Previous studies have described the risk factors responsible for high-risk donor organs and their outcomes posttransplant.2–4 Many studies have shown suboptimal early posttransplant outcomes with the use of high-risk donor organs but advocate their cautious use to increase the availability of transplant therapy to more patients.5,6 By using the United Network for Organ Sharing (UNOS) thoracic organ transplant database, we aimed to establish a quantitative scoring system to identify the risk profiles of recipients and donors to predict their mid-term and long-term survival. We also aimed to assess posttransplant survival of these patients after combining various risk profiles between the recipient and the donor groups. The ultimate goal is to match the donor and the recipient to achieve the best possible outcomes with a scarce resource and potentially improve the utilization and outcome of the high-risk donor.
Study Population and Data
The UNOS thoracic organ transplant database was requested after local institutional review board approval. The available database was queried for patients aged ≥18 years who underwent heart transplantation from January 2005 to December 2013. The UNOS data were further assessed for demographic, clinical, and posttransplant survival information for both recipients and donors.
Based on the available demographic and risk factor data, two separate multivariate cox-proportional hazard models were created one each for recipients and donors. Risk factors from the cox-proportional hazard model with p < 0.1 were included in a scoring system and assigned a score based on the hazard ratio. For recipients, all patients in the database were assigned a score for each of the recipient scoring variable. For donors, all patients in the database were assigned a score for each of the donor scoring variable. Total recipient score was calculated for each patient by addition of scores assigned to the individual recipient scoring variables for that patient. Similarly total donor score was calculated for each patient by addition of scores assigned to individual donor scoring variables for that patient. Table 1 shows all the recipient scoring variables included in the scoring system with assigned scores. We included total artificial hearts, biventricular devices, intraaortic balloon pumps, and pulsatile-flow ventricular assist devices as non-continuous-flow (CF) ventricular assist devices. Table 2 shows all the donor scoring variables included in the scoring system with assigned scores.
On the basis of the total score, recipients were divided into 5 groups: very low-risk (VLR) group (score = 0, n = 3,353), low-risk (LR) group (score = 1, n = 4,168), intermediate-risk (IR) group (score = 2, n = 3,822), high-risk (HR) group (score = 3, 4, n = 4,425), and very high-risk (VHR) group (score ≥ 5, n = 1,349). On the basis of the total score, donors were divided into 3 groups: low-risk (LD) group (score = 0, n = 9,105), intermediate-risk (ID) group (score = 1, 2, n = 6,695), and high-risk (HD) group (score ≥ 3, n = 1,327). Table 3 shows recipient and donor risk groups based on the scoring system.
Primary endpoint of the study was the actuarial survival based on the recipient and donor risk groups. Kaplan–Meier survival curves were generated to assess the differences in survival between the risk groups. We then assessed survival outcomes for each recipient group stratified by the three donor groups. All statistical analysis was done using SAS software 9.3 (SAS Inc., Cary, NC).
A total of 17,131 patients underwent heart transplant during the study period. Major factors within the HR and VHR groups were body mass index > 30 kg/m2 (46%), mean pulmonary artery pressure >30 mmHg (65%), creatinine > 1.5 mg% (63%), bilirubin > 1.5 mg% (54%), and pulsatile left ventricular assist device (LVAD)/biventricular assist device/total artificial heart (45%). Major factors within the high-risk donor group were gender mismatch (81%) and ischemia time >4 hours (88%).
Survival in VLR, LR, IR, HR, and VHR groups at 1 year was 93, 92, 90, 85, and 76%, respectively, and at 5 years was 81, 79, 75, 71, and 64%, respectively (Figure 1). Survival in LD, ID, and HD groups at 1 year was 90, 87, and 84%, respectively, and at 5 years was 78, 74, and 67%, respectively (Figure 2). Patients with lower risk have significantly improved survival in both recipient and donor groups (p < 0.0001 for both recipients and donors).
When very low-risk and low-risk recipients received organs from high-risk donors, their 1 year survival was 89 and 88%, respectively, and 5 year survival was 74 and 70%, respectively. When the high-risk and very high-risk recipients received organs from high-risk donors, their 1 year survival was 83 and 62%, respectively, and 5 year survival was 65 and 49%, respectively. Table 4 shows combination survival estimates for recipient and donor groups at 30 days, 1 year, and 5 years. Figure 3 shows combination survival between very low-risk and very high-risk recipients stratified by the donor risk groups. We merged the recipient and donor scores and divided the sum of scores in three groups of low, intermediate, and high risk. Table 5 shows the division of sum of scores used to determine the low-, intermediate-, and high-risk patients as well as their 30 day, 1 year, and 5 year survival estimates.
The prevalence of heart failure in Unites States is estimated to be 6.6 million in year 2012, and its relentless progression to end-stage refractory disease is associated with 50% mortality within 5 years of diagnosis.7 Heart transplant as a primary therapy to treat advanced heart failure is limited because of a persistent shortage of donor organs and has led to use of high-risk or marginal organs in certain instances; however, there is no consensus document on definition of donor heart risk profile and guidelines on the use of high-risk or marginal donor organs.
Various studies have shown recipient and donor risk factors predicting adverse post-heart transplant outcomes; however, only few studies have described an objective risk scoring methodology to predict 1 year posttransplant outcomes, independently using recipient and donor risk factors.4,8 We have shown that increased recipient and donor risk scores are associated with adverse post-heart transplant survival at 1 and 5 years. The risk scoring model described in our study not only corroborates findings of previous studies but is also supportive in predicting mid-term and long-term survival after heart transplant. Our study also indicates that recipient risk factors are more relevant in predicting posttransplant survival compared with donor factors. This could be because of stringent donor selection criteria by individual programs and geographical limitation in organ sharing resulting in stagnant donor pool.9 We have also shown that high-risk recipients have worse early outcomes compared with low-risk recipients, and this can influence the donor organ allocation. Various individual clinical factors play role in increasing the risk profile of recipients, and using a multivariate regression model can account for several such interactions and provide independent risk factors predicting posttransplant outcomes.
Donor organ allocation is critical to maximize the option of heart transplant as a therapy and achieve optimum posttransplant survival in the milieu of donor organ shortage. Our research showed that transplanting a high-risk organ to a very low-risk recipient is associated with 1 and 5 year survival of 89 and 74%, respectively. It also demonstrated that transplanting a low-risk organ in a very high-risk recipient is associated with 1 and 5 year survival of 80 and 67%, respectively. The combination survival shows that use of high-risk organs in low-risk recipients is associated with better survival than use of low-risk organs in very high-risk recipients. This is suggestive that matching high-risk organs to low-risk recipients is associated with the best possible posttransplant survival at 1 and 5 years and can increase the availability of low-risk organs for high-risk recipients.
Donor organ allocation is multifactorial, and regional variations play significant role in organ distribution along with individual recipient factors. Thus, matching donors and recipients by their risk profiles may not be achievable every time.9,10 The high-risk recipient population may have an increased urgency for transplant that could prompt acceptance of high-risk donor organs in many circumstances. However, more recent studies have shown that early and mid-term survival of patients with CF LVAD on the waiting list is similar to the posttransplant survival of patients transplanted with high-risk donor organs.11 The use of CF LVADs could potentially improve the survival of patients awaiting heart transplant, but they will spend significantly more time on the waiting list compared with non-LVAD candidates.12,13 It is possible that the use of CF LVADs can allow more patients to stay stable and longer on waiting list to increase their chances of being offered a suitable organ that leads to optimum posttransplant survival. We argue that waiting list patients eligible for CF LVAD implant should receive CF LVAD, so that they can stay stable on waiting list and the suitable donor organs should be prioritized for waiting list patients who are not eligible for CF LVAD implant.
This is a retrospective study; hence, several donor factors such as donor heart hemodynamic data, donor troponin values, and breakdown of total ischemia time were not available to be included in the scoring system. Validating the scoring system on a cohort of patients transplanted in the year 2014 and after is essential, and we propose to validate it by using data from several large transplant centers. The UNOS database does not contain information that would allow the determination of the circumstances that led to acceptance of high-risk donor organs for high-risk recipients.
An objective scoring system can be generated independently using recipient and donor risk factors to predict post-heart transplant survival. An increased risk score in both recipients and donors is associated with decreased post-heart transplant survival. Use of high-risk donor organs in low-risk recipients is associated with acceptable survival at 5 years but use of high-risk donor organs in very high-risk recipients is associated with 5 year survival of only 49%. Combining recipient and donor risk profiles can predict post-heart transplant survival that can be very useful in determining donor organ allocation.
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