Association between AT1R Autoantibody with Adverse Outcomes in Patients Bridged to Heart Transplant Using Continuous Flow Ventricular Assist Device

Abstract

Purpose Antibody to angiotensin-II type 1 receptor (AT1R-Ab) may be implicated in allograft dysfunction in patients who are bridged to heart transplant (BTT) with a continuous flow left ventricular assist device (VAD). We studied AT1R-Ab level following VAD implantation on event-free survival in BTT patients and whether AT1R-Ab elevation is independent from inflammation as measured through C-reactive protein (CRP). Methods Sera of 77 BTT patients from 2009 to 2017 were tested for AT1R-Ab and CRP prior to and after VAD placement. Elevated AT1R-Ab level was defined as greater than 10.0 U/mL. For statistical analysis, the value of 40 U/mL was assigned to AT1R-Ab level greater than 40 U/mL. Events were defined as acute cellular rejection, antibody-mediated rejection, cardiac allograft vasculopathy, reduced EF, and death. Results Median follow-up time after transplant was 3.3 years (range 0.4-9.0 years). After VAD implantation, AT1R-Ab was increased as compared to baseline (Fig 1A). Univariate regression analysis revealed that age, female gender, African-American race, time to transplant, type of VAD, HLA sensitization, and positive donor specific antibodies were not risk factors for AT1R-Ab sensitization. The elevated post-VAD AT1R-Ab cohort had more events than the normal AT1R-Ab group (61% vs 29%, Fig 1B). On Kaplan Meier analysis, there was a statistically decrease in 5-year event-free survival in patients who had elevated AT1R-Ab levels (Fig 1C). Multivariate Cox regression analysis showed increased post-VAD AT1R-Ab as an independent risk factor for developing events. Though CRP was high before and after VAD implantation, CRP had no statistically significant correlation with AT1R-Ab level (Fig 1D). Conclusion Increase in AT1R-Ab was seen in BTT patients after VAD implantation and was associated with adverse outcomes after heart transplant. The AT1R-Ab elevation does not appear to be an epiphenomenon related to CRP, a marker of inflammation.