Race and Ethnic Differences in Donor-Derived Cell-Free DNA and Gene Expression Profiling in Heart Transplant Recipients in a Negative Biopsy Cohort AHA Conference Repository

American Heart Association

Final ID: MDP103

Race and Ethnic Differences in Donor-Derived Cell-Free DNA and Gene Expression Profiling in Heart Transplant Recipients in a Negative Biopsy Cohort

Abstract Body (Do not enter title and authors here): Introduction: The Donor-Derived Cell-Free DNA-Outcomes AlloMap Registry (D-OAR) study has highlighted the significant capability of dd-cfDNA, showcasing a 97% negative predictive value (NPV) for identifying both acute cellular rejection (ACR) and antibody-mediated rejection (AMR) at a dd-cfDNA threshold of 0.20%. This development has greatly enhanced the range of biomarkers available to clinicians, confirming dd-cfDNA as a reliable clinical biomarker for monitoring heart transplant (HT) recipients. Short and long-term outcomes for African American HT recipients are worse. Given these findings, our study aims to investigate baseline differences in the levels and positivity rates of dd-cfDNA stratified by race in a negative biopsy cohort.
Methods: We conducted a single-center retrospective review of all HT recipients from 2019 to 2023 with at least one valid combined dd-cfDNA sample drawn between April 2019 and July 2023. Multiorgan transplant recipients and those without a paired biopsy result were excluded. A positive biopsy result was defined as >= ISHLT grade 1R/1B or pAMR>0. Dd-cfDNA (AlloSure, AS) result was considered positive if ≥0.12%, and as a sub-analysis using a threshold ≥0.20%. A positive peripheral GEP (pGEP, AlloMap, AM) test was defined as >30 in the first five months post-transplant and >34 afterward. Samples associated with a positive biopsy result were excluded. We further stratified our cohort based on race.
Results: Of 643 paired dd-cfDNA/GEP samples from 227 patients, the median age was 55 years, and 27% were female. The cohort was stratified into four categories: 53% were white, 18.8% were AA, 20.4% were Hispanic/Latino, and 7.8% were of other races. We observed no baseline differences in the positive dd-cfDNA levels (p=0.39) and positivity rates of dd-cfDNA at a threshold of 0.12% and 0.20% (p=0.08, p=0.06) or GEP positivity rates (p=0.52) between the 4 race categories in our surveillance cohort (Figure 1). Further comparison of patients treated for rejection based on non-invasive monitoring did not reveal a difference.
Conclusions: In our surveillance cohort, dd-cfDNA levels and positivity rates were not different between AA and white HT recipients. Further prospective randomized trials are needed to elucidate potential race-related differences in dd-cfDNA levels.

Oren, Daniel ( NYP-BMH, Weill Cornell Medicine , New York , New York , United States )
Yunis, Adil ( Columbia University Medical Center , New York City , New York , United States )
Raikhelkar, Jayant ( Columbia university medical center , New York , New York , United States )
Clerkin, Kevin ( Columbia university medical center , New York , New York , United States )
Peterson, Stephen J ( NYP-BMH, Weill Cornell Medicine , New York , New York , United States )
Parikh, Manish ( NYP-BMH, Weill Cornell Medicine , New York , New York , United States )
Latif, Farhana ( Columbia Univerisity Medical Center , New York , New York , United States )
Sayer, Gabriel ( Columbia University Medical Center , New York , New York , United States )
Uriel, Nir ( Columbia University Medical Center , New York City , New York , United States )
Moeller, Cathrine ( Columbia University , New York , New York , United States )
Fernandez Valledor, Andrea ( Columbia University , New York , New York , United States )
Rahman, Salwa ( Columbia university medical center , New York , New York , United States )
Rubinstein, Gal ( Columbia University , New York , New York , United States )
Baranowska, Julia ( Columbia University , New York , New York , United States )
Lotan, Dor ( Columbia University Medical Center , New York City , New York , United States )
Defilippis, Ersilia ( Columbia University Medical Center , New York , New York , United States )
Fried, Justin ( Columbia University Medical Center , New York , New York , United States )

Author Disclosures:

Daniel Oren:

DO NOT have relevant financial relationships

Adil Yunis:

DO NOT have relevant financial relationships

Jayant Raikhelkar:

No Answer

Kevin Clerkin:

No Answer

Stephen J Peterson:

No Answer

Manish Parikh:

No Answer

Farhana Latif:

DO NOT have relevant financial relationships

Gabriel Sayer:

DO have relevant financial relationships

Nir Uriel:

No Answer

Cathrine Moeller:

No Answer

Andrea Fernandez Valledor:

DO NOT have relevant financial relationships

Salwa Rahman:

DO NOT have relevant financial relationships

Gal Rubinstein:

No Answer

Julia Baranowska:

DO NOT have relevant financial relationships

Dor Lotan:

DO have relevant financial relationships

Ersilia DeFilippis:

DO have relevant financial relationships

Justin Fried:

DO NOT have relevant financial relationships

Meeting Info:

Scientific Sessions 2024

2024

Chicago, Illinois

Session Info:

Hyping Up Heart Transplant

Saturday, 11/16/2024 , 09:30AM - 10:55AM

Moderated Digital Poster Session

More abstracts from these authors:

Incidence and Characteristics of Peri-Procedural Complications of Cardiac Implantable Electrical Devices in Breast Cancer Survivors

Keller Eleanor, Uriel Nir, Yarmohammadi Hirad, Raikhelkar Jayant, Noteware Laura, Accordino Melissa, Connolly Eileen, Saluja Deepak, Goldberg Anne, Wan Elaine, Sayer Gabriel, Biviano Angelo

Sex differences in cardiac allograft rejection states using Tissue gene-expression profiling (MMDx)

Fernandez Valledor Andrea, Regan Matthew, Yunis Adil, Salazar Ruben, Hennecken Carolyn, Fried Justin, Raikhelkar Jayant, Clerkin Kevin, Latif Farhana, Sayer Gabriel, Uriel Nir, Moeller Cathrine, Oren Daniel, Rahman Salwa, Baranowska Julia, Lotan Dor, Rahman Afsana, Elad Boaz, Defilippis Ersilia

American Heart Association