Purpose Assays detecting donor-derived cell-free DNA (dd-cfDNA) are increasingly utilized as a non-invasive marker for rejection in solid organ transplantation. Expected baseline values and trends in multiorgan transplants (MOT) have not been reported. We describe our experience with dd-cfDNA in heart multiorgan transplantations. Methods This is a retrospective cohort of 26 MOT recipients who underwent concomitant endomyocardial biopsy and dd-cfDNA between 2016 and 2021. The results of the first dd-cfDNA assay and biopsy readouts for rejection of all 26 patients were assessed. The indications for dd-cfDNA assay were constraints to elective biopsies during the pandemic, receiving full-dose anti-coagulation, and center inaccessibility. Results Our cohort consisted of 6 heart/liver transplant (HLTx) and 20 heart/kidney transplant (HKTx) recipients. The cohort's median age was 59.5 years (95% CI, 46-64) and predominantly Caucasians (42.3%) (Table 1). The median time from transplant to dd-cfDNA was 5 months (IQR 3.0-9.0). The median dd-cfDNA was higher in the HLTx group, 0.6%; IQR (0.3-0.8)] compared to the HKTx group, 0.2%; IQR (0.1-0.3)]. One case of acute cellular rejection was recorded in the HKTx group with a corresponding dd-cfDNA of 0.28% with no antibody-mediated rejection detected. Conclusion In the largest single-center MOT cohort to date, we describe baseline values for dd-cfDNA in HLTx and HKTx. Prospective multicenter studies will be necessary to establish the role of dd-cfDNA in predicting MOT rejection.
Purpose Early insertion of an RVAD may help to mitigate post-LVAD implantation morbidity and mortality. We hypothesize that concomitant RVAD insertion at time of LVAD implantation improves 1-year mortality in comparison to post-operative insertion. Methods A multi-center retrospective study of 826 consecutive patients who received either a HeartMate2 or HVAD between 1/2007 an 12/2017. We identified 91 patients who either had an unplanned or planned early RVAD on index admission. A Cox proportional hazard model was constructed to identify predictors of 1-year mortality. Results There were 91 patients (11%) who required an RVAD after LVAD implantation with 51 (56%) receiving a concomitant RVAD and 40 (43%) post-operatively (Table 1). Concomitant RVAD with LVAD insertion was associated with lower mortality (HR 0.45 [0.27, 0.76], p-value = 0.002, Figure 1). Our multivariable model (which included age, BMI, and ACE-i use) found receiving transplant (HR 0.04 [0.01, 0.29], p = 0.001) and concomitant RVAD (HR 0.51 [0.29, 0.90], p = 0.004) to be independent predictors of 1-year mortality with a final model C-statistic of 0.77. Stratifying concomitant RVAD by intended approach, planned versus unplanned RVAD insertion had a similar survival rate as unplanned approach at 1 year (42.8% versus 28.6%, p-value = 0.08). Conclusion We show in a continuous-flow and multi-institutional cohort that concomitant RVAD insertion at time of LVAD is associated with improved survival at 1 year compared to post-operative insertion.
Purpose Deciding which patients can be weaned from an RVAD placed after LVAD implantation could help triage advanced heart failure device strategy. Therefore, we set out to determine the predictors of RVAD weaning. Methods A multi-center retrospective study of 826 consecutive patients who received either a HeartMate2 or HVAD between 1/2007 an 12/2007. We identified 91 patients who received an early RVAD insertion during their LVAD implant index admission. A Cox Proportional hazard model was constructed to identify predictors of RVAD weaning. Results There were 91 patients (11%) who required an RVAD after LVAD with 48 (52%) weaned from RVAD support and 43 (48%) not weaned. Patients who were weaned had a lower prevalence of hypertension, higher pre-operative ACE-inhibitor use, and lower pre-operative transpulmonary gradient (TPG), RA-PCWP ratio, and RVSWI; they were also more likely to receive concomitant RVAD at time of LVAD insertion and ultimately transplanted more often (Table 1). Our multivariable model for predictors of RVAD weaning included pre-operative creatinine (HR 0.32 [0.15, 0.70], p = 0.004), PVR (HR 1.23 [1.02, 1.48], p = 0.03), non-white ethnicity (HR 2.56 [1.19, 5.54], p = 0.02), COPD (HR 4.63 [1.32, 16.25], p = 0.02), and concomitant RVAD insertion (HR 2.87 [1.00, 8.21], p-value = 0.05) with a model c-statistic of 0.84. The survival curve demonstrates that patients who are weaned from RVAD have significantly improved 1-year mortality (Figure 1, p < 0.001). Conclusion In a multi-institutional continuous-flow LVAD cohort, we show novel predictors of RVAD weaning that can help triage mechanical support strategy.
Our results demonstrate that the highest VIS score within the first 48 hours after LVAD implantation correlates with severe RVF.