Citations

Background: Heart transplantation (HT) remains the definitive therapy for end-stage heart failure, yet rejection and cardiac allograft vasculopathy (CAV) continue to limit long-term outcomes. Beyond donor-specific HLA antibodies, non-HLA antibodies, particularly anti-angiotensin II type 1 receptor antibodies (AT1R-Abs), have been implicated in allograft injury, but published findings are heterogeneous. Aim: The aim of this study is to systematically evaluate the evidence linking AT1R gene expression and anti-AT1R antibodies with key post-heart transplant outcomes. Methods: We conducted a systematic review in accordance with PRISMA guidelines. Scopus, PubMed, Web of Science, and the Cochrane Library were searched (December 2025) for cohort and case–control studies evaluating AT1R gene expression and/or AT1R-Ab status in HT recipients and their association with post-transplant outcomes. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the NIH Quality Assessment Tool. Results: Twelve studies encompassing 951 recipients met the inclusion criteria. Five studies evaluated AT1R mRNA expression, reporting variable patterns: several observed reduced AT1R/AT2R transcription after transplantation without clear clinical correlation, whereas others associated higher donor or recipient AT1R expression with transplant coronary artery disease and recurrent rejection. AT1R-Ab prevalence varied widely and appeared to increase after mechanical circulatory support, with substantial seroconversion reported during LVAD support in initially antibody-negative patients. Associations between AT1R-Ab and acute cellular rejection and antibody-mediated rejection were inconsistent across studies, and survival findings were inconclusive; however, some reports linked elevated AT1R-Abs to poorer long-term freedom from adverse events. Evidence regarding CAV was mixed, with signals of increased vasculopathy risk in some cohorts but not others. Conclusions: Current evidence suggests a potential role for AT1R expression and AT1R-Abs in cardiac allograft dysfunction, including rejection phenotypes and vasculopathy. Larger prospective studies with harmonized testing strategies are needed to define clinically meaningful AT1R-Ab cutoffs and clarify their utility in risk stratification and targeted therapeutic trials.

AbstractCardiac allograft rejection and failure may require mechanical circulatory support as bridge‐to‐retransplantation. Prognosis in this patient group is poor and implantable ventricular assist devices have had limited success due to organ failure associated with the high dose immunosuppression required to treat ongoing rejection. We present a case from our institution and the world‐wide experience utilizing the SynCardia CardioWest Total Artificial Heart (TAH‐t; SynCardia Systems, Inc., Tucson, AZ, USA) for replacement of the failing graft, recovery of patient and end‐organ failure with ultimate bridge to retransplantation. We present our experience and review of world‐wide experience for use of TAH‐t in this type patient.

Antibody-mediated rejection (AMR) (humoral rejection) of cardiac allografts remains difficult to diagnose and treat. Interest in AMR of cardiac allografts has increased over the last decade as it has become apparent that untreated humoral rejection threatens graft and patient survival. An international and multidisciplinary consensus group has formulated guidelines for the diagnosis and treatment of AMR and established that identification of circulating or donor-specific antibodies is not required and that asymptomatic AMR, that is, biopsy-proven AMR without cardiac dysfunction is a real entity with worsened prognosis. Strict criteria for the diagnosis of cardiac AMR have not been firmly established, although the diagnosis relies heavily on tissue pathological findings. Therapy remains largely empirical. We review an unfortunate experience with one of our patients and summarize recommended criteria for the diagnosis of AMR and potential treatment schemes with a focus on current limitations and the need for future research and innovation.