Insight into Noninvasive Radiological Modalities to Detect Heart Transplant Rejection

Purpose Patients with end-stage heart failure who remain symptomatic even with exemplary medical and device therapy are treated with heart transplantation. Multitudes of endeavor have been contrived during the last decennium in the field of noninvasive tests to rule out heart transplant rejection (HTR). In spite of having supportive literature, noninvasive imaging techniques lack acceptable documentation of clinical robustness, and endomyocardial biopsy (EMB) still remains the gold standard. The aim of this review is to shed light on the existing noninvasive radiological modalities to detect rejection among heart transplant recipients. Methods A comprehensive search was conducted for this review article on the basis of literature available including scientific databases of PubMed, Embase, and Google Scholar, using keywords of “Heart transplantation,” “Acute allograft rejection,” “Arrhythmias,” “Echocardiography,” “Speckle tracking echocardiography,” and “Cardiac magnetic resonance imaging” from inception until September 2020. Results After preliminary screening of the databases, details regarding existent noninvasive radiological modalities to detect HTR were gathered and compiled in this review article. Currently, deformation imaging using speckle tracking and T2 time using cardiac magnetic resonance imaging can serve as screening tools based on which further invasive investigations can be planned. Standardization of blood-based and imaging modalities as screening and possible diagnostic tools for rejection would have obvious clinical and financial benefits in the care of growing number of post heart transplant recipients in our country. Conclusion Diagnosis of allograft rejection in heart transplant recipients through noninvasive techniques is demanding. To unravel the potential of noninvasive radiological modalities that can serve as a standard-of-care test, a prospective multicentric study randomizing noninvasive modality as first strategy versus current EMB-based gold standard of care is the need of the hour.

MiR-146a regulates regulatory T cells to suppress heart transplant rejection in mice

Regulatory T cells (Tregs), which characteristically express forkhead box protein 3 (Foxp3), are essential for the induction of immune tolerance. Here, we investigated microRNA-146a (miR-146a), a miRNA that is widely expressed in Tregs and closely related to their homeostasis and function, with the aim of enhancing the function of Tregs by regulating miR-146a and then suppressing transplant rejection. The effect of the absence of miR-146a on Treg function in the presence or absence of rapamycin was detected in both a mouse heart transplantation model and cell co-cultures in vitro. The absence of miR-146a exerted a mild tissue-protective effect by transiently prolonging allograft survival and reducing the infiltration of CD4+ and CD8+ T cells into the allografts. Meanwhile, the absence of miR-146a increased Treg expansion but impaired the ability of Tregs to restrict T helper cell type 1 (Th1) responses. A miR-146a deficiency combined with interferon (IFN)-γ blockade repaired the impaired Treg function, further prolonged allograft survival, and alleviated rejection. Importantly, miR-146a regulated Tregs mainly through the IFN-γ/signal transducer and activator of transcription (STAT) 1 pathway, which is implicated in Treg function to inhibit Th1 responses. Our data suggest miR-146a controls a specific aspect of Treg function, and modulation of miR-146a may enhance Treg efficacy in alleviating heart transplant rejection in mice.