Non-invasive cardiac allograft rejection surveillance: reliability and clinical value for prevention of heart failure

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Non-invasive cardiac allograft rejection surveillance: reliability and clinical value for prevention of heart failure Michael Dandel 1,2

&

Roland Hetzer 2

Accepted: 31 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Allograft rejection-related acute and chronic heart failure (HF) is a major cause of death in heart transplant recipients. Given the deleterious impact of late recognized acute rejection (AR) or non-recognized asymptomatic antibody-mediated rejection on short- and long-term allograft function improvement of AR surveillance and optimization of action strategies for confirmed AR can prevent AR-related allograft failure and delay the development of cardiac allograft vasculopathy, which is the major cause for HF after the first posttransplant year. Routine non-invasive monitoring of cardiac function can improve both detection and functional severity grading of AR. It can also be helpful in guiding the anti-AR therapy and timing of routine surveillance endomyocardial biopsies (EMBs). The combined use of EMBs with non-invasive technologies and methods, which allow detection of subclinical alterations in myocardial function (e.g., tissue Doppler imaging and speckle-tracking echocardiography), reveal alloimmune activation (e.g., screening of complement-activating donor-specific antibodies and circulating donor-derived cell-free DNA) and help in predicting the imminent risk of immune-mediated injury (e.g., gene expression profiling, screening of non-HLA antibodies, and circulating donor-derived cell-free DNA), can ensure the best possible surveillance and management of AR. This article gives an overview of the current knowledge about the reliability and clinical value of non-invasive cardiac allograft AR surveillance. Particular attention is focused on the potential usefulness of non-invasive tools and techniques for detection and functional grading of early and late ARs in asymptomatic patients. Overall, the review aimed to provide a theoretical and practical basis for those engaged in this particularly demanding up-to-date topic. Keywords Heart transplantation . Acute cellular rejection . Antibody-mediated rejection . Cardiac rejection surveillance . Echocardiography . Ventricular function . Cardiac imaging . Immune monitoring . Therapeutic decision-making

Introduction Histological and immunopathological analysis of endomyocardial biopsy (EMB) specimens is the “gold standard” technique for acute rejection (AR) diagnosis, and routine EMB screenings at pre-defined time intervals are standard procedures for AR surveillance after heart transplantation (HTx). However, EMBs are distressing (particularly for children) and potentially risky for patients (tricuspid valve damage, myocardial perforation, radiation exposure, etc.) [1–4]. Additionally, due to differences in the interpretation of EMB

* Michael Dandel [email protected] 1

German Centre for Heart and Circulatory Research (DZHK), Partner Site Berlin, Berlin, Germany

2

Cardio Centrum Berlin, 10117 Berlin, Germany