Citations 2
Everolimus and Low-Dose Tacrolimus After Heart Transplant in Children
Almond, Christopher S. , Alejos, Juan , Ameduri, Rebecca , Barkoff, L., Barnes, Aliessa, Butto, Arene , Carlo, Waldemar F. , Chrisant, Maryanne , Dreyer, William J. , Everitt, Melanie D. , Gonzales, S., Hollander, Seth A. , Kindel, Steven J. , Klein, Gloria L., Lamour, Jacqueline M. , Lee, Joanne , Lü, Minmin , Lytrivi, Irene D. , Miyamoto, Shelley D. , Pahl, Elfriede , Peng, David M. , Sutcliffe, David , Ybarra, A., Zangwill, Steven , Rossano, Joseph W. , Investigators, TEAMMATE Trial, Choi, Jua , Wilber, Jared, Sutherland, Scott M. , Feng, Dana, Lagerborg, Kendra, Burns, Julia, Nikolli, Kledja, Twombly, Adrianna, Massey, Linda K., Wartick, Jennifer, Yohannes, Kifle, Gupta, Akanksha , Major, Melissa , Blume, Elizabeth D. , Esteso, Paul , VanderPluym, Christina , Bastardi, Heather , MacLean, Matthew T. , Haschke, Paul, Gibbons, Taylor , Vu, Courtney , Reilly, Sydney, Ha, Lynne, Boyle, Carley, Robie, Sharon L., Ogata, Kay, Knecht, Carlos, Browne, Lorna P. , Malone, LaDonna J. , Gordon, Megyn, Molina, Kimberly , Cabrera, Antonio G. , Lambert, Linda, Fullerton, Chase, Thompson, Kate J., Cardon, Michelle, Timmer, Amanda, Nelson, Michelle , Ramstack, Dani, Heyrend, Carly, Benefield, Emily C., Roberson, Teresa, Butts, Ryan J. , Martinez, Maria , Pottorre, Simi, Burgardt, Laura, Armstrong, Blake, Zamberlan, M. , McCormick, Amanda D. , Bartsch, Jaynee, Mahle, William T. , Burnett, Meilssa, Pietra, Biagio A. , Breault, Leah, Friedland‐Little, Joshua , Prakash, Ranjini, Lee, Anne CC , Brody, Linnea, Huberts, Avery, Noon, Kelli, Guadiz, Donna, Garcia, Allison, Addonizio, Linda J. , Repp, Arielle, Cornelius, C.E. , Abraham, Margaret, Rose-Felker, Kristen, Moninger, Allison, Huston, Allison, Berman, Pamela, Ploutz, Michelle , Wisotzkey, Bethany , Grohall, Stacey, Colon, April, Churosh, Jenny, Cordova, Renee, Smith, Paulette, Kornetsky, Susan , Mitchell, Anna, Alderson, Daniel, Dominguez, R Blanco, Gawlowicz, Kennan, Lipsitz, Stuart R. , Eisen, Howard J. , Jeewa, Aamir , Uber, Patricia A., Thakar, Rahul, Ellsworth, Darrell L. , McCormick, A , Peng, D M , Daly, Kevin P , Albers, Erin L. , Auerbach, Scott R. , Bock, Matthew J. , Castleberry, Chesney , Deshpande, Shriprasad R. , Feingold, Brian , Lal, Ashwin K. , Ryan, Thomas D. , Singh, Tajinder P. , Su, Jennifer A. , Sleeper, Lynn A. , Investigators, TEAMMATE Trial, Wilber, Jared, Nikolli, Kledja, Massey, Linda, Wartick, Jennifer, Major, Melissa, MacLean, Matthew, Lee, JungWoo, Joong, Anna , Reilly, Sydney, Kuhn, Michael, Ogata, Kay, Knecht, Carol, Gordon, Megyn, Hansen, Lisa, May, Lindsay J. , Lambert, Linda, Fullerton, Chase, Thompson, Kate, Timmer, Amanda, Heyrend, Carly, Martinez, Maria, Schumacher, Kurt R. , Lim, Heang M. , Bartsch, Jaynee, Burnett, Meilssa, Prakash, Ranjini, Lee, Anne CC , Brody, Linnea, Huberts, Avery, Noon, Kelli, Guadiz, Donna, Repp, Arielle, Bansal, Neha , Hsu, Daphne T. , Cornelius, Chelsea, Padilla, Luz A. , Churosh, Jenny, Cordova, Renee, Mitchell, Anna, Alderson, Daniel, Dominguez, Robleinscky, KOBASHIGAWA, JON A. , Wightman, Aaron G.
JAMA | September 17, 2025 | Volume: 334 | Issue: 15 | Pages: 1339
ImportanceStudies suggest that everolimus may reduce the risk of rejection, cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), and cytomegalovirus (CMV) after heart transplant. Everolimus use is controversial because of data demonstrating higher infection deaths when everolimus is introduced de novo after transplant. It is unclear whether everolimus is safe and effective when initiated at 6 months posttransplant in children, a population in which median graft survival is limited to 15 years and randomized clinical trials are lacking.ObjectiveTo evaluate the safety and efficacy of everolimus combined with low-dose tacrolimus to prevent major adverse transplant events (MATEs) in children after heart transplant.Design, Setting, and ParticipantsMulticenter, randomized, open-label, clinical trial enrolling 211 patients who were alive 6 months after pediatric heart transplant at 25 US sites from February 2018 to August 2020. The last date of follow-up was April 17, 2023.InterventionsParticipants were randomized to receive everolimus and low-dose tacrolimus (n = 107) or standard-dose tacrolimus and mycophenolate mofetil (n = 104) for 30 months.Main Outcomes and MeasuresThe primary efficacy end point was the MATE-3 score at 30 months, a validated composite ordinal end point including acute cellular rejection, CAV, and CKD. The primary safety end point was the MATE-6 score, encompassing the MATE-3 score plus antibody-mediated rejection, infection, and posttransplant lymphoproliferative disorder.ResultsAmong 211 children randomized, the mean age was 8.2 (SD, 6.3) years, 97 (46%) underwent transplant for congenital heart disease, and 49 (23%) were treated for rejection before 6 months. At 30 months, the mean MATE-3 score did not differ between the 2 treatment groups (mean difference, −0.32; 95% CI, −0.90 to 0.20; P = .16). The mean MATE-6 score was no higher in the everolimus group than in the mycophenolate group (baseline-adjusted mean difference, −0.40; 95% CI, −1.81 to 0.93), meeting the success criterion for safety (noninferiority margin <3). There were no differences in graft survival, MATE-free survival, or freedom from any individual MATE. Everolimus was associated with greater improvement in estimated glomerular filtration rate at 12 months (mean difference, 10.5 mL/min/1.73 m2; 95% CI, 1.09-19.91 mL/min/1.73 m2) and a lower incidence of CMV infection (hazard ratio, 0.50; 95% CI, 0.26-0.93).Conclusions and RelevanceAmong 6-month pediatric heart transplant survivors, everolimus and low-dose tacrolimus did not differ from tacrolimus and mycophenolate in preventing the composite of cellular rejection, CAV, and CKD at 30 months. However, everolimus and low-dose tacrolimus appear to be safe based on the total burden of 6 MATEs and may be associated with improved kidney function and less CMV infection.Trial RegistrationClinicalTrials.gov Identifier: NCT03386539
High-Sensitivity Cardiac Troponin I Assay to Screen for Acute Rejection in Patients With Heart Transplant
Patel, Parag C. , Hill, Douglas A., Ayers, Colby , Lavingia, Bhavna, Kaiser, Patricia A., Dyer, Adrian, Barnes, Aliessa, Thibodeau, Jennifer T. , Mishkin, Joseph D., Markham, David W. , Šťastný, Peter , Ring, W. Steves, Ayers, Colby R, Kaiser, Patricia, Dyer, Adrian K, Barnes, Aliessa P, Mammen, Pradeep P A, de Lemos, James A, Drazner, Mark H. , Mammen, Pradeep P.A. , Lemos, James A. de
Circulation: Heart Failure | April 14, 2014 | Volume: 7 | Issue: 3 | Pages: 463-469
10.1161/circheartfailure.113.000697
Background— A noninvasive biomarker that could accurately diagnose acute rejection (AR) in heart transplant recipients could obviate the need for surveillance endomyocardial biopsies. We assessed the performance metrics of a novel high-sensitivity cardiac troponin I (cTnI) assay for this purpose. Methods and Results— Stored serum samples were retrospectively matched to endomyocardial biopsies in 98 cardiac transplant recipients, who survived ≥3 months after transplant. AR was defined as International Society for Heart and Lung Transplantation grade 2R or higher cellular rejection, acellular rejection, or allograft dysfunction of uncertain pathogenesis, leading to treatment for presumed rejection. cTnI was measured with a high-sensitivity assay (Abbott Diagnostics, Abbott Park, IL). Cross-sectional analyses determined the association of cTnI concentrations with rejection and International Society for Heart and Lung Transplantation grade and the performance metrics of cTnI for the detection of AR. Among 98 subjects, 37% had ≥1 rejection episode. cTnI was measured in 418 serum samples, including 35 paired to a rejection episode. cTnI concentrations were significantly higher in rejection versus nonrejection samples (median, 57.1 versus 10.2 ng/L; P <0.0001) and increased in a graded manner with higher biopsy scores ( P trend <0.0001). The c -statistic to discriminate AR was 0.82 (95% confidence interval, 0.76–0.88). Using a cut point of 15 ng/L, sensitivity was 94%, specificity 60%, positive predictive value 18%, and negative predictive value 99%. Conclusions— A high-sensitivity cTnI assay seems useful to rule out AR in cardiac transplant recipients. If validated in prospective studies, a strategy of serial monitoring with a high-sensitivity cTnI assay may offer a low-cost noninvasive strategy for rejection surveillance.