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Vascular rejection and its relationship to allograft coronary artery disease
E H Hammond1, R L Yowell, G D Price
1Utah Transplantation Affiliated Hospitals Cardiac Transplant Program, LDS Hospital, University of Utah School of Medicine, Salt Lake City 84143.
Insights
Vascular rejection after heart transplant significantly worsens allograft survival and accelerates the development of allograft coronary artery disease. Mixed rejection shows intermediate outcomes between cellular and vascular rejection patterns.
Area of Science:
- Cardiology
- Immunology
- Transplantation
Background:
- Endomyocardial biopsy with immunofluorescence is crucial for monitoring heart transplant rejection.
- Allograft coronary artery disease (ACAD) is a major cause of late graft loss.
- Different rejection patterns may influence ACAD development and outcomes.
Purpose of the Study:
- To assess the relationship between rejection patterns and the development of allograft coronary artery disease (ACAD).
- To evaluate the impact of rejection patterns on allograft survival.
- To analyze the influence of sensitization to murine monoclonal CD3 antibody (OKT3).
Main Methods:
- Prospective monitoring of 268 heart transplant patients using endomyocardial biopsy immunofluorescence.
- Retrospective review of coronary angiograms to assess ACAD.
- Histopathological and immunofluorescence analysis of explanted/postmortem hearts.
- Monitoring for sensitization to OKT3 and separate analysis of sensitized patients.
Main Results:
- 141 patients had cellular, 76 vascular, and 52 mixed rejection patterns.
- Vascular rejection was associated with significantly worse allograft survival compared to cellular or mixed rejection.
- A significant difference in time to ACAD development was observed based on rejection pattern, with mixed rejection being intermediate.
Conclusions:
- Rejection pattern significantly impacts allograft survival and ACAD development after heart transplantation.
- Vascular rejection poses a higher risk for ACAD and poorer outcomes.
- Early identification and management of rejection patterns are critical for improving long-term graft function.
Abstract:
We have prospectively monitored 268 patients by our previously described method of routine immunofluorescence of endomyocardial biopsy specimens. We have classified these patients according to their rejection pattern: cellular, vascular, and mixed. The criteria for these designations have been previously described. In this study we retrospectively reviewed coronary angiograms of these patients to assess the presence and time-course of developing allograft coronary artery disease. All available explanted hearts and postmortem hearts were also assessed by light microscopic examination for acute coronary vasculitis and allograft coronary artery disease and by immunofluorescent microscopy for vascular immune complex deposition in a manner identical to immunofluorescent microscopic examination of endomyocardial biopsy specimens. Patients were also monitored for sensitization to immunoprophylactically administered murine monoclonal CD3 antibody (OKT3) and those demonstrated to be sensitized were separately analyzed. Clinical features and treatment of patients were retrospectively reviewed. We found that 141 patients could be classified as having cellular rejection, 76 as having vascular rejection, and 52 as having a mixed rejection pattern. The allograft survival in vascular rejection patients was significantly worse than in allografts of patients with cellular or mixed rejection, confirming our earlier results. Most importantly, we found a significant difference in the time to the development of allograft coronary artery disease based on the rejection pattern. This difference existed whether or not patients sensitized to OKT3 were excluded from evaluation. Patients with mixed rejection had an intermediate time to the development of allograft coronary artery disease between that of patients with cellular and vascular rejection.(ABSTRACT TRUNCATED AT 250 WORDS)