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Severe primary graft failure: Are there lasting impacts? Analysis from the PHTS Database
Jennifer Conway1, Tara Pidborochynski2, James K Kirklin3
1Stollery Children's Hospital, Edmonton, Alberta, Canada.
Insights
Primary graft failure (PGF) after heart transplantation (HTx) predicts early mortality but not long-term outcomes. Further research is needed to understand the impact of milder PGF on survival and long-term results.
Area of Science:
- Cardiovascular Surgery
- Transplantation Immunology
- Pediatric Cardiology
Background:
- Primary graft failure (PGF) is a major cause of early morbidity and mortality following heart transplantation (HTx).
- PGF arises from graft ischemia and subsequent ischemia-reperfusion injuries to the donor heart's cardiomyocytes and vasculature.
- Longer-term outcomes for patients experiencing PGF after HTx remain understudied.
Purpose of the Study:
- To investigate the long-term outcomes and survival rates of patients who experience primary graft failure (PGF) after heart transplantation (HTx).
- To identify predictors of PGF and its impact on graft survival, rejection, and coronary allograft vasculopathy (CAV).
Main Methods:
- Retrospective analysis of 4,982 patients undergoing primary HTx between January 1, 2010, and June 30, 2022, using the Pediatric Heart Transplant Society registry.
- PGF defined as death, retransplantation, or need for mechanical circulatory support within 72 hours of HTx.
- Kaplan-Meier analysis and Cox proportional hazard modeling were employed to assess survival and risk factors.
Main Results:
- 5.4% of patients (n=269) experienced PGF, characterized by younger age, higher prevalence of congenital heart disease, longer bypass and ischemic times, and increased pre-transplant support.
- PGF was associated with significantly lower overall survival at 1 year (54% vs. 94%) and predicted early graft loss and conditional survival up to 90 days.
- No significant differences in freedom from rejection or coronary allograft vasculopathy (CAV) were observed between PGF and non-PGF groups beyond 90 days.
Conclusions:
- Severe PGF independently predicts early mortality post-HTx but does not adversely affect long-term survival, rejection rates, or CAV.
- Further investigation into the impact of milder forms of PGF on patient outcomes is warranted.
- Developing strategies to mitigate PGF risk, such as improved preservation techniques, may reduce early post-HTx mortality.
Background:
Primary graft failure (PGF) is a leading cause of early morbidity and mortality after heart transplantation (HTx). PGF is secondary to graft ischemia and ischemia-reperfusion injuries to the cardiomyocytes and vasculature of the donor heart after transplantation. Longer-term outcomes after PGF are not well studied.
Methods:
Patients with an HTx (January 1, 2010 to June 30, 2022) were identified using the Pediatric Heart Transplant Society registry. PGF was defined as death, retransplantation, or need for mechanical circulatory support within 72 hours of HTx. Kaplan-Meier analysis and Cox proportional hazard modeling were utilized.
Results:
Of the 4,982 patients with a primary HTx, 5.4% (n = 269) met criteria for PGF. Patients with PGF were younger, with higher proportion of congenital heart disease, longer cardiopulmonary bypass and ischemic times (IT), and more likely to be on extracorporeal membrane oxygenation or ventilator at HTx (all p < 0.0001, IT p = 0.0006). PGF resulted in lower overall survival (1 year: 54% vs 94%, p < 0.001). This remained true when conditional survival was examined at 30 and 90 days but not at 1 year (p = 0.1143). Freedom from rejection did not differ between the groups at overall or conditional on 30 days but was slightly higher for those with PGF at 90 and 365 days. There was no difference in freedom from coronary allograft vasculopathy (CAV). PGF was an independent predictor of overall graft loss (hazard ratios [HR] 4.7, p < 0.0001) and conditional survival to 30 days (HR 2.47, p < 0.0001) and 90 days (HR 1.6, p = 0.012) but not beyond 1 year.
Conclusions:
Severe PGF is an independent predictor of early mortality post-HTx but subsequently does not further impact long-term survival, overall risk of rejection, or CAV. Understanding the impact of milder forms of PGF on survival and long-term outcomes is still needed. Methods to decrease the risk of PGF, such as alternative preservation and storage techniques, may impact early mortality post-HTx.
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