Combining donor derived cell free DNA and gene expression profiling for non-invasive surveillance after heart transplantation.

BACKGROUND: Donor-derived cell free DNA (dd-cfDNA) and gene expression profiling (GEP) offer noninvasive alternatives to rejection surveillance after heart transplantation; however, there is little evidence on the paired use of GEP and dd-cfDNA for rejection surveillance. METHODS: A single center, retrospective analysis of adult heart transplant recipients. A GEP cohort, transplanted from January 1, 2015 through December 31, 2017 and eligible for rejection surveillance with GEP was compared to a paired testing cohort, transplanted July 1, 2018 through June 30, 2020, with surveillance from both dd-cfDNA and GEP. The primary outcomes were survival and rejection-free survival at 1 year post-transplant. RESULTS: In total 159 patients were included, 95 in the GEP and 64 in the paired testing group. There were no differences in baseline characteristics, except for less use of induction in the paired testing group (65.6%) compared to the GEP group (98.9%), P < .01. At 1-year, there were no differences between the paired testing and GEP groups in survival (98.4% vs. 94.7%, P = .23) or rejection-free survival (81.3% vs. 73.7% P = .28). CONCLUSIONS: Compared to post-transplant rejection surveillance with GEP alone, pairing dd-cfDNA and GEP testing was associated with similar survival and rejection-free survival at 1 year while requiring significantly fewer biopsies.

Impact of diabetes mellitus on clinical outcomes after heart transplantation.

PURPOSE: Diabetes mellitus (DM) is common among recipients of heart transplantation (HTx) but its impact on clinical outcomes is unclear. We evaluated the associations between pretransplant DM and posttransplant DM (PTDM) and outcomes among adults receiving HTx at a single center. METHODS: We performed a retrospective study (range 01/2008 - 07/2018), n = 244. The primary outcome was survival; secondary outcomes included acute rejection, cardiac allograft vasculopathy, infection requiring hospitalization, macrovascular events, and dialysis initiation post-transplant. Comparisons were performed using Kaplan-Meier and multivariable Cox regression analyses. RESULTS: Pretransplant DM was present in 75 (30.7%) patients and was associated with a higher risk for infection requiring hospitalization (p < 0.05), but not with survival or other outcomes. Among the 144 patients without pretransplant DM surviving to 1 year, 29 (20.1%) were diagnosed with PTDM at the 1-year follow-up. After multivariable adjustment, PTDM diagnosis at 1-year remained associated with worse subsequent survival (hazard ratio 2.72, 95% confidence interval 1.03-7.16). Predictors of PTDM at 1-year included cytomegalovirus seropositivity and higher prednisone dose (> 5 mg/day) at 1-year follow-up. CONCLUSIONS: Compared to HTx recipients without baseline DM, those with baseline DM have a higher risk for infections requiring hospitalization, and those who develop DM after HTx have worse survival.

Trends in heart transplant outcomes for patients over the age of 70 years in the United States: An analysis of the scientific registry of transplant recipients database.

BACKGROUND: Patients of advanced age are often considered to be poor candidates for heart transplant (HT). As the U.S. population continues to age, it is important for clinicians to understand how best to select patients for advanced therapies. METHODS: This was a retrospective analysis of the U.S. Scientific Registry of Transplant Recipients data from 2006 to August 2022 in adult recipients. Patients were excluded if they were multiorgan transplant, re-do transplants, or less than 1 year post transplant. RESULTS: Recipients ≥70 had a 1-year survival of 87.5%, compared to 91.1% for <60%, and 88.4% for 60-69 years (p < 0.001). Survival improved numerically, but not significantly, as transplant eras progressed for those ≥70 years. Survival by Kaplan-Meier analysis was greatest at 5 years for <60 years (80.6%), compared to 60-69 years (78.2%) and ≥70 years (77.1%). When comparing 60-69 years to ≥70 years by this same metric, there was significant difference (p = 0.12). One year survival for those ≥70 years has improved from 2000-2009 (80.7%) to 88.5% since October 2018 (p < 0.001). As recipients increased in age, they were more likely to be male, and less likely to be Black or Hispanic/Latino (p < 0.001). CONCLUSION: Overall, HT outcomes are excellent for carefully selected patients ≥70 years, and transplanting patients in this age cohort can be considered.

Primary Graft Dysfunction Is Associated With Development of Early Cardiac Allograft Vasculopathy, but Not Other Immune-mediated Complications, After Heart Transplantation.

BACKGROUND: We investigated associations between primary graft dysfunction (PGD) and development of acute cellular rejection (ACR), de novo donor-specific antibodies (DSAs), and cardiac allograft vasculopathy (CAV) after heart transplantation (HT). METHODS: A total of 381 consecutive adult HT patients from January 2015 to July 2020 at a single center were retrospectively analyzed. The primary outcome was incidence of treated ACR (International Society for Heart and Lung Transplantation grade 2R or 3R) and de novo DSA (mean fluorescence intensity >500) within 1 y post-HT. Secondary outcomes included median gene expression profiling score and donor-derived cell-free DNA level within 1 y and incidence of cardiac allograft vasculopathy (CAV) within 3 y post-HT. RESULTS: When adjusted for death as a competing risk, the estimated cumulative incidence of ACR (PGD 0.13 versus no PGD 0.21; P = 0.28), median gene expression profiling score (30 [interquartile range, 25-32] versus 30 [interquartile range, 25-33]; P = 0.34), and median donor-derived cell-free DNA levels was similar in patients with and without PGD. After adjusting for death as a competing risk, estimated cumulative incidence of de novo DSA within 1 y post-HT in patients with PGD was similar to those without PGD (0.29 versus 0.26; P = 0.10) with a similar DSA profile based on HLA loci. There was increased incidence of CAV in patients with PGD compared with patients without PGD (52.6% versus 24.8%; P = 0.01) within the first 3 y post-HT. CONCLUSIONS: During the first year after HT, patients with PGD had a similar incidence of ACR and development of de novo DSA, but a higher incidence of CAV when compared with patients without PGD.

The Impact of the COVID-19 Pandemic on the Transplant Pharmacist Workforce.

Background: The COVID-19 pandemic has placed an unprecedented strain on the US healthcare system, greatly impacting transplant centers. Objective: The purpose of this survey was to evaluate the impact of the COVID-19 pandemic on the transplant pharmacist workforce. Methods: A survey was disseminated electronically to assess the impact of the COVID-19 pandemic on the transplant pharmacist workforce. Respondents were asked to give background regarding transplant center, patient, population, and departmental staffing. Results: There were 67 total respondents from 56 transplant centers. In response to the COVID-19 pandemic, 55% of centers reported stopping non-life saving transplants, and a majority (89%) stopped living donor transplants altogether. The banning of caregivers on-site during education, reduction of bedside education teaching, and cancelling of group teaching classes occurred at 46%, 40%, and 22% of centers, respectively. Consequently, 42% of pharmacists surveyed felt that their confidence in patient and caregiver's understanding of medications had decreased since these changes have been implemented. Conclusions: Pharmacist perception of patient and caregiver understanding of transplant medications has decreased since before the COVID-19 pandemic. As health systems strategize resource allocation throughout the pandemic, the importance of patient education must be prioritized to sustain and improve transplant outcomes.

Impact of using higher-risk donor hearts for candidates with pre-transplant mechanical circulatory support.

BACKGROUND: We evaluated post-heart transplant (HTx) outcomes after use of higher-risk donor hearts for candidates supported with pre-HTx mechanical circulatory support (MCS). METHODS: In this retrospective analysis of the national United Network for Organ Sharing registry, a total of 9,915 adult candidates on MCS underwent HTx from January 1, 2010 to March 31, 2019. Multi-organ, re-transplant, and congenital heart disease patients were excluded. Higher-risk donor organs met at least one of the following criteria: left ventricular ejection fraction <50%, donor to recipient predicted heart mass ratio <0.86, donor age >55 years, or ischemic time >4 hours. Primary outcome was 1 year post-transplant survival. RESULTS: Among HTx recipients, 3688 (37.2%) received higher-risk donor hearts. Candidates supported with pre-HTx extracorporeal membrane oxygenation or biventricular assist device (n = 374, 3.8%) who received higher-risk donor hearts had comparable 1 year survival (HR: 1.14, 95% CI: [0.67-1.93], p = 0.64) to recipients of standard-risk donor hearts, when adjusted for recipient age and sex. In candidates supported with intra-aortic balloon pump (n = 1391, 14.6%), transplantation of higher-risk donor hearts did not adversely affect 1 year survival (HR: 0.80, 95% CI: [0.52-1.22], p = 0.30). Patients on durable left ventricular assist devices (LVAD) who received higher-risk donor hearts had comparable 1 year survival to continued LVAD support on the waitlist, but mortality was increased compared to those who received standard-risk donor hearts (HR: 1.37, 95% CI: [1.11-1.70], p = 0.004). CONCLUSIONS: Patients requiring pre-HTx temporary MCS who received higher-risk donor hearts had comparable 1 year post-transplant survival to those who received standard-risk donor hearts. Stable patients on durable LVADs may benefit from waiting for standard-risk donor hearts.