Abstract

Cardiac allograft rejection following heart transplantation is challenging to diagnose. Tissue biopsies are the gold standard in monitoring the different types of rejection. The last decade has seen an increased emphasis on identifying non-invasive methods to improve rejection diagnosis and overcome tissue biopsy invasiveness. Liquid biopsy, as an efficient non-invasive diagnostic and prognostic oncological monitoring tool, seems to be applicable in heart transplant follow-ups. Moreover, molecular techniques applied on blood can be translated to tissue samples to provide novel perspectives on tissue and reveal new diagnostic and prognostic biomarkers. This review aims to provide a comprehensive overview of the state-of-the-art of the new methodologies in cardiac allograft rejection monitoring and investigate the future perspectives on invasive and non-invasive rejection biomarkers identification. We reviewed literature from the most used scientific databases, such as PubMed, Google Scholar, and Scopus. We extracted 192 papers and, after a selection and exclusion process, we included in the review 81 papers. The described limitations notwithstanding, this review show how molecular biology techniques and omics science could be deployed complementarily to the histopathological rejection diagnosis on tissue biopsies, thus representing an integrated approach for heart transplant patients monitoring.

Highlights

  • Monitoring Endomyocardial biopsies (EMBs) for heart transplants is important for post-transplanted patients, who are subjected to about 14 EMBs during the first year post-transplant [2]

  • EMBs, systemiDue to these drawbacks, numerous attempts have recently been made to explore cally used for surveillance during the first year after heart transplantation, represent an theexpensive possibility of identifying a sensitive and non-invasive approach that might be used in medical procedure

  • EMBs remain the gold standard for cardiac allograft monitoring; the perceived need to complement the histological examination of the tissue with molecular approaches has led to the development of several molecular approaches to implementing diagnosis

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Summary

A Changing Paradigm in Heart Transplantation

Alessia Giarraputo 1 , Ilaria Barison 1 , Marny Fedrigo 1 , Jacopo Burrello 2 , Chiara Castellani 1 , Francesco Tona 3 , Tomaso Bottio 3 , Gino Gerosa 3 , Lucio Barile 2,4,5,† and Annalisa Angelini 1, *,†. Paradigm in Heart Transplantation: An Integrative Approach for Invasive and Non-Invasive Allograft Rejection. Faculty of Biomedical Sciences, Università Svizzera Italiana, 6900 Lugano, Switzerland. These authors have contributed to this work as senior authors

Introduction
Liquid Biopsy
Gene Expression Profiling of the Peripheral Blood Leucocytes
Cell-Free DNA
High-Sensitive Troponins
T-Cell Function
Donor-Specific Antibodies
Emerging Biomarkers
Extracellular Vesicles
Tissue Biopsy for Molecular Tests
MicroRNA on Tissue
Molecular Microscope
MRI for Non-Invasive Monitoring in Tissue
Gene Expression Profile in the Tissue
Findings
Conclusions

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