Failing to Make the Grade: Conventional Cardiac Allograft Rejection Grading Criteria Are Inadequate for Predicting Rejection Severity.

Autor:	Arabyarmohammadi S; Department Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (S.A., C.Y., V.S.V.)., Yuan C; Department Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (S.A., C.Y., V.S.V.)., Viswanathan VS; Department Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (S.A., C.Y., V.S.V.)., Lal P; Department of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania (P.L.), Perelman School of Medicine, University of Pennsylvania, Philadelphia., Feldman MD; Department of Pathology and Laboratory Medicine, School of Medicine, Indiana University, Indianapolis (M.D.F.)., Fu P; Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH (P.F.)., Margulies KB; Cardiovascular Research Institute, Department of Medicine (K.B.M., E.G.P.), Perelman School of Medicine, University of Pennsylvania, Philadelphia., Madabhushi A; Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (A.M.).; Atlanta Veterans Affairs Medical Center, Decatur, GA (A.M.)., Peyster EG; Cardiovascular Research Institute, Department of Medicine (K.B.M., E.G.P.), Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Jazyk:	angličtina
Zdroj:	Circulation. Heart failure [Circ Heart Fail] 2024 Feb; Vol. 17 (2), pp. e010950. Date of Electronic Publication: 2024 Feb 13.
DOI:	10.1161/CIRCHEARTFAILURE.123.010950
Abstrakt:	Background: Cardiac allograft rejection is the leading cause of early graft failure and is a major focus of postheart transplant patient care. While histological grading of endomyocardial biopsy samples remains the diagnostic standard for acute rejection, this standard has limited diagnostic accuracy. Discordance between biopsy rejection grade and patient clinical trajectory frequently leads to both overtreatment of indolent processes and delayed treatment of aggressive ones, spurring the need to investigate the adequacy of the current histological criteria for assessing clinically important rejection outcomes. Methods: N=2900 endomyocardial biopsy images were assigned a rejection grade label (high versus low grade) and a clinical trajectory label (evident versus silent rejection). Using an image analysis approach, n=370 quantitative morphology features describing the lymphocytes and stroma were extracted from each slide. Two models were constructed to compare the subset of features associated with rejection grades versus those associated with clinical trajectories. A proof-of-principle machine learning pipeline-the cardiac allograft rejection evaluator-was then developed to test the feasibility of identifying the clinical severity of a rejection event. Results: The histopathologic findings associated with conventional rejection grades differ substantially from those associated with clinically evident allograft injury. Quantitative assessment of a small set of well-defined morphological features can be leveraged to more accurately reflect the severity of rejection compared with that achieved by the International Society of Heart and Lung Transplantation grades. Conclusions: Conventional endomyocardial samples contain morphological information that enables accurate identification of clinically evident rejection events, and this information is incompletely captured by the current, guideline-endorsed, rejection grading criteria. Competing Interests: Disclosures Dr Feldman is an equity holder and has technology licensed to both Elucid Bioimaging and Inspirata Inc. Dr Feldman is a scientific advisory consultant for Inspirata Inc and is on its scientific advisory board. Dr Feldman is also a consultant for Phillips Healthcare, XFIN, and Verbio. Dr Margulies holds research grants from Amgen and serves as a scientific consultant/advisory board member of Bristol Myers Squibb. Dr Madabhushi is an equity holder in Elucid Bioimaging, Inspirata Inc, and Picture Health. He has served as a scientific advisory board member of Picture Health, SimbioSys, and Aiforia Inc. He also has sponsored research agreements with AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, and Eli Lilly. His technology has been licensed to Elucid Bioimaging and Picture Health. He is also involved in 3 different National Institutes of Health R01 grants with Inspirata Inc.
Databáze:	MEDLINE
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