Alleviating Chaos Utilizing A Multidisciplinary Approach To Incorporate Heart Molecular Microscope Diagnostic System® Into Practice

Abstract

Background A new technology known as Molecular Microscope Diagnostic System® (MMDx) uses microarrays to analyze RNA transcripts of transplanted heart tissue and provides sophisticated differentiation amongst cellular mediated rejection (TCMR), antibody mediated rejection (ABMR), injury and healthy tissue. Yet, incorporation of this new data into practice can be challenging. We report the results from our single center experience. Methods Endomyocardial biopsies (EMB) and corresponding MMDx results from 65 adult heart transplant patients from our single center were retrospectively reviewed. Rejection by EMB was defined as TCMR greater than 1R and/or ABMR greater than pAMR0 utilizing ISHLT grading schematics. Results A total of 97 specimen results were reviewed. There was concordant findings between the EMB and MMDx in 83.5% (81/97) of the specimens. Of the 81 specimens, 76 of those were negative for rejection on both tests and 5 had positive EMB for ABMR/TCMR with correlating MMDx suggestive of rejection. There was a discordance in 16.5% (16/97) of specimens reviewed. Of the 16 specimens, 15 had negative EMB with the MMDx concerning for rejection. One of the 16 patients had a positive EMB however the MMDX was consistent with healthy tissue. These complex cases with discordant data were reviewed during our multi-disciplinary meeting which includes transplant cardiologists, coordinators, APPs, pharmacists, pathologists and immunology partners to adjudicate further management. The team approached each case individually, reviewing other factors such clinical symptoms, graft function by TTE, hemodynamics, cell-free DNA and donor specific antibodies when available. For five discordant patients with negative EMB and concerning MMDx, the team favored treatment for rejection if there were other corresponding factors present such as high cell-free DNA or clinical symptoms. For one patient admitted with clinic concerns for rejection aggressive treatment had already been initiated prior to positive EMB and negative MMDx being available. For the remaining patients with negative EMB and positive MMDx we advocated for a second round of data, including repeat biopsy and continued surveillance, before deciding on course of treatment for rejection. Conclusion MMDx is an additional tool to provide potentially more accuracy in patient diagnoses but should be utilized in combination with all other diagnostic data. In the cases of conflicting findings, a multi-disciplinary approach should be used to discuss further steps. Larger studies are needed to validate these preliminary findings.