Background The aim was to evaluate the association of molecular‐level human leukocyte antigen (HLA) mismatching with post‐transplant graft survival, rejection and cardiac allograft vasculopathy (CAV). Methods We retrospectively analysed all primary cardiac transplant recipients between 01/1984‐06/2016. 1,167 patients fulfilled inclusion criteria and had HLA typing information available. In 312 donor‐recipient pairs, typing at serological split antigen level was available. We used the Epitope MisMatch Algorithm to calculate the number of amino acid differences in antibody‐verified HLA eplets (amino acid mismatch‐load (AAMM)) between donor and recipient. Results Patients with a higher HLA‐DR AAMM load had inferior 1‐year graft survival (hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.01‐1.28). The HLA‐AB AAMM load showed no impact on graft survival. In the subgroup with available split‐level information, we observed an inferior graft survival for a higher HLA‐DR AAMM load 3 months after transplantation (HR, 1.22; 95% CI, 1.04‐1.44) and a higher risk for rejection for an increasing HLA‐AB (HR, 1.70; 95% CI, 1.29‐2.24) and HLA‐DR (HR, 1.32; 95% CI, 1.09‐1.61) AAMM load. No impact on the development of CAV was found. Conclusions Molecular‐level HLA mismatch analysis could serve as a tool for risk stratification after heart transplantation and might take us one step further into precision medicine.
Background: Because of improved long-term survival after heart transplantation (HTx), late graft pathologies such as valvular disease or cardiac allograft vasculopathy (CAV) might need surgical intervention to enhance longer survival and ensure quality of life. To this date, there exist no guidelines for indication of cardiac surgery other than retransplantation after HTx. Methods: In this retrospective, single-center study, we evaluated patients who underwent cardiac surgery after HTx at our institution. Results: Between March 1984 and October 2016, 17 (1.16%) of 1466 HTx patients underwent cardiac surgery other than retransplantation after HTx. Indication were valvular disease (n = 7), CAV (n = 6), and other (n = 4). Of these, 29.4% (n = 5) were emergency procedures and 70.6% were elective cases. Median age at time of surgery was 61 years (interquartile range, 52-66 years); 82.4% (n = 14) were male. Median time to surgery after HTx was 9.3 years (2.7-11.1 years). In-hospital, mortality was 11.8% (n = 2); later need of retransplantation was 11.8% (n = 2) due to progressing CAV 3 to 9 months after surgery. One-year survival was 82.35%; overall survival was 47.1% (n = 8) with a median follow-up of 1477 days (416-2135 days). Overall survival after emergency procedures was 209 days (36-1119.5 days) whereas, for elective procedures, it was 1583.5 days (901.5-4319 days). Conclusions: Incidence of cardiac surgery after HTx in our cohort was low (1.16%) compared with that of other studies. In elective cases, long-term survival was good.
1 May 2018 in The Journal of Heart and Lung Transplantation
This brief overview discusses recent data on the use of mammalian target of rapamycin (mTOR) inhibitors in heart transplantation. Trials on de novo use have shown good efficacy of mTOR inhibitors; however, adverse events are often seen. Conversion protocols in long-term patients are mainly used in patients with renal insufficiency. Calcineurin inhibitor minimization and conversion to calcineurin inhibitor–free protocols have proven to stabilize renal function in recent trials. Lastly, beneficial effects of mTORs against the development of graft vasculopathy, cytomeglovirus infection and malignancy have been shown. Nevertheless, lower tolerability of the drug has affected the long-term use in patients. Future consideration of using mTORs will be individualized protocols in special subpopulation after heart transplantation.