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

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.