RESUMO
Right ventricular (RV) dysfunction (RVD) after orthotopic heart transplantation (OHT) is a common cause of morbidity and mortality. Impella RP Flex was recently approved for RV support as a temporary mechanical circulatory device. We present the first case of its use in managing RVD in a patient after OHT. Here, a 40 year old male patient with familial dilated cardiomyopathy and factor V Leiden mutation presented with Society for Cardiovascular Angiography & Interventions (SCAI) stage B cardiogenic shock. Hemodynamics at admission were indicative of need for intra-aortic balloon pump (IABP) support. Hemodynamics improved and patient underwent OHT. Postoperative day (POD) 1, IABP support was changed to 1:2 and eventually removed. Hemodynamics deteriorated quickly, requiring pharmacologic RV support and diuresis, but refractory RV failure persisted. Impella RP Flex was chosen due to the patient's small size and was placed via the right internal jugular vein on POD 12. The procedure was well tolerated, with the patient ambulatory the following day (POD 13). Impella was removed on POD 25 after 13 days of support. Patient achieved normal kidney, intrinsic rhythm improved sinus rhythm, and ultimately discharged on POD 50. Impella RP flex has emerged as a promising future indication as single or biventricular support postcardiac transplantation.
RESUMO
BACKGROUND: Endomyocardial biopsy (EMB)-based traditional microscopy remains the gold standard for the detection of cardiac allograft rejection, despite its limitation of inherent subjectivity leading to inter-reader variability. Alternative techniques now exist to surveil for allograft injury and classify rejection. Donor-derived cell-free DNA (dd-cfDNA) testing is now a validated blood-based assay used to surveil for allograft injury. The molecular microscope diagnostic system (MMDx) utilizes intragraft rejection-associated transcripts (RATs) to classify allograft rejection and identify injury. The use of dd-cfDNA and MMDx together provides objective molecular insight into allograft injury and rejection. The aim of this study was to measure the diagnostic agreement between dd-cfDNA and MMDx and assess the relationship between dd-cfDNA and MMDx-derived RATs, which may provide further insight into the pathophysiology of allograft rejection and injury. METHODS: This is a retrospective observational study of 156 EMB evaluated with traditional microscopy and MMDx. All samples were paired with dd-cfDNA from peripheral blood before EMB (up to 9 days). Diagnostic agreement between traditional histopathology, MMDx, and dd-cfDNA (threshold of 0.20%) was compared for assessment of allograft injury. In addition, the relationship between dd-cfDNA and individual RAT expression levels from MMDx was evaluated. RESULTS: MMDx characterized allograft tissue as no rejection (62.8%), antibody-mediated rejection (ABMR) (26.9%), T-cell-mediated rejection (TCMR) (5.8%), and mixed ABMR/TCMR (4.5%). For the diagnosis of any type of rejection (TCMR, ABMR, and mixed rejection), there was substantial agreement between MMDx and dd-cfDNA (76.3% agreement). All transcript clusters (group of gene sets designated by MMDx) and individual transcripts considered abnormal from MMDx had significantly elevated dd-cfDNA. In addition, a positive correlation between dd-cfDNA levels and certain MMDx-derived RATs was observed. Tissue transcript clusters were correlated with dd-cfDNA scores, including DSAST, GRIT, HT1, QCMAT, and S4. For individual transcripts, tissue ROBO4 was significantly correlated with dd-cfDNA in both nonrejection and rejection as assessed by MMDx. CONCLUSIONS: Collectively, we have shown substantial diagnostic agreement between dd-cfDNA and MMDx. Furthermore, based on the findings presented, we postulate a common pathway between the release of dd-cfDNA and expression of ROBO4 (a vascular endothelial-specific gene that stabilizes the vasculature) in the setting of antibody-mediated rejection, which may provide a mechanistic rationale for observed elevations in dd-cfDNA in AMR, compared to acute cellular rejection.