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Risk factors for chronic rejection in heart and lungs--why do hearts and lungs rot?
1Papworth Hospital, Cambridge, England.
Insights
Progressive coronary occlusive disease is the main cause of graft loss after heart transplantation. Early diagnosis and new therapies are crucial for preventing or delaying this condition and improving transplant outcomes.
Area of Science:
- Cardiology
- Transplantation Immunology
- Vascular Biology
Background:
- Progressive coronary occlusive disease (PCOD) is the primary cause of graft loss and mortality within the first year post-heart transplantation.
- PCOD affects both small and large coronary vessels, likely stemming from chronic immune responses leading to smooth muscle proliferation and atheromatous plaque formation.
Purpose of the Study:
- To identify significant risk factors for PCOD after heart transplantation.
- To explore strategies for preventing or delaying PCOD to improve long-term transplant survival.
- To investigate the causes of graft loss in lung transplantation, specifically obliterative bronchiolitis.
Main Methods:
- Multivariate analysis was employed to identify risk factors associated with PCOD.
- Clinical data from heart and lung transplant recipients were analyzed.
- Risk factor analysis was performed for obliterative bronchiolitis following lung transplantation.
Main Results:
- Significant risk factors for PCOD include preoperative diagnosis of ischemic heart disease, recipient age, and donor age.
- Cytomegalovirus (CMV) infection was not found to be an independent risk factor for PCOD in this series.
- Obliterative bronchiolitis, a cause of late graft loss in lung transplants, is associated with severe or persistent rejection in the initial months.
Conclusions:
- Early diagnosis of PCOD and the development of novel therapeutic strategies are essential for improving heart transplant outcomes.
- Obliterative bronchiolitis in lung transplants appears to be a final common pathway for lung injury, often mediated by rejection.
- Managing rejection is critical for preventing late graft loss in lung transplantation.
Abstract:
The major cause of graft loss and patient death during the 1st yr after heart transplantation is progressive coronary occlusive disease. All survival curves show progressive and persistent graft loss over time. To improve the overall results of heart transplantation, attention must be directed to the etiology, prevention, and treatment of coronary occlusive disease. This condition affects both small and large vessels, and most probably results from a continuous immune insult that generates smooth muscle proliferation and subsequent development of atheromatous plaque. Multivariate analysis suggests that highly significant risk factors for the development of coronary occlusive disease include preoperative diagnosis of ischemic heart disease, age of recipient, and age of donor. Other risk factors, notably cytomegalovirus (CMV) infection, have not proved to be independent causes of coronary occlusive disease in our series. Diagnosis before the occlusive disease sets in, as well as the development of new therapeutic strategies, may prevent or delay the onset of coronary artery disease, thereby improving overall results of heart transplantation. Graft loss from lung transplantation after the 1st yr is associated with obliterative bronchiolitis. This final end-stage progressive loss of small airways can be seen not only in transplanted lungs but in lungs with chronic infection. It appears to be a final common pathway for lung injury, but following transplantation it is most likely to be mediated by rejection. Risk factor analysis in our series indicates that severe or persistent rejection in the first few months is associated with the subsequent development of obliterative bronchiolitis.(ABSTRACT TRUNCATED AT 250 WORDS)