Utilizing A Multidisciplinary Approach To Incorporate Heart Molecular Microscope Diagnostic System Into Clinical Practice

Abstract

Background The Molecular Microscope Diagnostic System (MMDx) utilizes microarrays to analyze RNA transcripts of transplanted heart tissue and provide sophisticated differentiation amongst cellular mediated rejection (TCMR), antibody mediated rejection (ABMR), injury and healthy tissue. However, incorporation of this into practice can be challenging. We report the continued results from our single center experience. Methods Endomyocardial biopsies (EMB) and corresponding MMDx results from 130 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 215 specimen results were reviewed (Table 1). There were concordant findings between the EMB and MMDx in 83.7% (180/215) of the specimens. Of these 180 specimens, 162 were negative for rejection on both tests and 18 had positive EMB for ABMR/TCMR with correlating MMDx suggestive of rejection. There was a discordance in 16.3% (35/215) of specimens reviewed. Of these 35 specimens, 30 had a negative EMB with the MMDx concerning for rejection. Five of the 35 specimens had a positive EMB however the MMDx was consistent with healthy tissue. These complex cases with discordant data were reviewed in a multi-disciplinary meeting including transplant cardiologists, coordinators, advanced practice providers, pharmacists, pathologists and immunologists to adjudicate further management. The team approached each case individually reviewing factors such clinical symptoms, graft function by echocardiography, hemodynamics, cell-free DNA and donor specific antibodies when available. For patents with discordant results 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 clinical 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, additional data including repeat biopsy and continued surveillance was often pursued before deciding on treatment for rejection. Conclusion MMDx is a tool to potentially provide added accuracy in patient diagnoses but should be utilized in combination with other diagnostic data. In cases of discordant results, a multi-disciplinary approach should be used to discuss further steps. Larger studies are needed to validate these preliminary findings. The Molecular Microscope Diagnostic System (MMDx) utilizes microarrays to analyze RNA transcripts of transplanted heart tissue and provide sophisticated differentiation amongst cellular mediated rejection (TCMR), antibody mediated rejection (ABMR), injury and healthy tissue. However, incorporation of this into practice can be challenging. We report the continued results from our single center experience. Endomyocardial biopsies (EMB) and corresponding MMDx results from 130 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. A total of 215 specimen results were reviewed (Table 1). There were concordant findings between the EMB and MMDx in 83.7% (180/215) of the specimens. Of these 180 specimens, 162 were negative for rejection on both tests and 18 had positive EMB for ABMR/TCMR with correlating MMDx suggestive of rejection. There was a discordance in 16.3% (35/215) of specimens reviewed. Of these 35 specimens, 30 had a negative EMB with the MMDx concerning for rejection. Five of the 35 specimens had a positive EMB however the MMDx was consistent with healthy tissue. These complex cases with discordant data were reviewed in a multi-disciplinary meeting including transplant cardiologists, coordinators, advanced practice providers, pharmacists, pathologists and immunologists to adjudicate further management. The team approached each case individually reviewing factors such clinical symptoms, graft function by echocardiography, hemodynamics, cell-free DNA and donor specific antibodies when available. For patents with discordant results 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 clinical 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, additional data including repeat biopsy and continued surveillance was often pursued before deciding on treatment for rejection. MMDx is a tool to potentially provide added accuracy in patient diagnoses but should be utilized in combination with other diagnostic data. In cases of discordant results, a multi-disciplinary approach should be used to discuss further steps. Larger studies are needed to validate these preliminary findings.