Heart Transplant Recipients with pAMR1(H+) and pAMR2 Rejection Have the Same Amount of Myocardial Injury by Allosure

Abstract

<h3>Purpose</h3> Circulating cell free DNA (cfDNA) rises in response to cell apoptosis and necrosis. The cell damage that occurs in rejection or myocardial injury results in a release of donor DNA into the circulation of the recipient and an increase in the level of dd-cfDNA (donor derived cell free DNA) making it a biomarker for myocardial injury that occurs in heart transplant rejection. Allosure®measures dd-cfDNA and has been validated in heart transplant recipients using histologic diagnosis of myocardial rejection. Transplant Cardiologists treat grade pAMR2 rejection or above per ISHLT guidelines. Using Allosure®we assessed the antibody mediated rejection dd-cfDNA levels in pAMR1(H+) and pAMR2 histologic endomyocardial biopsies (EMB) to evaluate if there is a difference in the amount of myocardial injury. <h3>Methods</h3> Prospectively unselected heart transplant recipients who underwent an EMB after transplant from 6/2019 to 8/2020 at our center and had a concomitant Allosure®were reviewed. We compared the Allosure®value in histologic pAMR0, pAMR1(H+) and pAMR2 rejection. <h3>Results</h3> 95 recipients had a concomitant EMB and Allosure®. 63 recipients had a grade pAMR0 with a Allosure®of 0.14 ±0.04 %, 22 recipients a grade pAMR1(H+) rejection with a Allosure®of 2.06 ±1.39 % and 10 recipients a grade pAMR2 rejection with a Allosure®of 2.03 ±1.58 %. The difference in Allosure®between pAMR0 and pAMR1(H+) was significant at p<0.001, as was the Allosure®difference between pAMR0 and pAMR2 at p<0.001. There was no significant difference in the Allosure®between pAMR1(H+) and pAMR2 rejection p=0.998. <h3>Conclusion</h3> Allosure®level indicates that the amount of myocardial injury or cell death in pAMR1 (H+) rejection is the same as grade pAMR2 rejection. Despite the difference in the histologic findings between the two endomyocardial AMR grades, pAMR1(H+) should be treated.