Are the Results of Late Heart Re-Transplantation Influenced by the Time Interval from Primary Transplantation?

Background: Heart re-transplantation represents an effective option in selected patients with graft failure. Although the results of heart re-transplantation have improved in recent years, little is known about the outcomes in patients requiring late (>1 year) re-transplantation or about the effects of prolonged exposure to immunosuppression on multiorgan function. Methods: Among all the heart re-transplantations performed, from November 1988 to April 2025, a total of 30 patients underwent late re-transplantation. Since literature data on late re-HTx are generally limited to those performed within 20 years, patients were divided according to the interval from primary to re-transplantation: <20 (Group A) or ≥20 years (Group B). Results: Group A included 17 patients re-transplanted after a median time of 15 years, and Group B 13 patients after a median time of 23 years. Group B patients were more commonly affected by severe chronic kidney disease and received more combined heart and kidney transplantation. Overall survival at 1, 5 and 10 years was 80%, 68% and 60%, and did not differ between Groups A and B (p = 0.5). However, Group B recipients were more commonly affected by malignancies (p < 0.01). Compared to primary heart transplantation in the same population, re-transplantation was associated with higher, albeit not statistically significantly, rates of infections, grade ≥ 2 rejections and malignancies. Conclusions: Late heart re-transplantation is associated with satisfactory outcomes and could be effectively considered in patients with late graft dysfunction. However, the prolonged exposure to immunosuppression requires particular attention in early pharmacological management as well as a close follow-up, especially in patients requiring heart re-transplantation after >20 years.