Canadian Journal of Cardiology


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      Standard immunosuppression for pediatric heart transplant recipients includes at least two immunosuppressive drugs (ISDs). Some patients are maintained on a single ISD if they have suffered complications or adverse drug reactions, but the outcomes of these patients have not been systematically studied. Our aim was to determine whether patients on a single ISD have equivalent graft survival (non-inferior hypothesis of a hazard ratio (HR) < 1.1) compared to those on ≥2 ISDs.


      For this retrospective, observational cohort study, we used the Pediatric Heart Transplant Society dataset (1999-2019). We assessed outcomes in a cohort of consecutive patients < 18 years of age on a single ISD after the first year post-transplant compared to patients on ≥2 ISDs. Re-transplanted children were excluded. The primary outcome was a composite of death or retransplantation (i.e., graft survival). Secondary outcome measures included treated rejection, coronary artery vasculopathy (CAV), malignancy and infection. Cox proportional models were used to assess survival after adjustments for baseline risk factors. We used a time-to-event analysis that accounted for changes in therapy and post-transplant lymphoproliferative disease (PTLD) status over time. Our analysis included 2,605 heart transplant recipients (median follow-up time of 5.7 years, total of 23,255 patient-years). Of these, 888 (34%) were on a single ISD for a median of 4.2 years, and 458 (18%) patients died or were retransplanted at a median of 4.8 years post-transplant. Patients on a single ISD were younger at transplant and more likely to have myocarditis at listing. Compared to patients on ≥2 ISDs, patients on a single ISD had improved graft survival (HR 0.70 CI 0.52-0.94). Patients without PTLD on a single ISD also had improved graft survival (HR 0.61 CI 0.45-0.84). For patients with PTLD, we found improved graft survival, but lacked power to prove non-inferiority (HR 0.58 CI 0.29-1.16). Being on a single ISD was associated with a decreased rate of CAV (HR 0.58 CI 0.46-0.75), but was not associated with increased rates of infection, rejection or malignancy.


      Use of immunosuppressive therapy with a single ISD beyond the first year post-heart transplant in children was associated with medium-term outcomes that were equivalent or improved compared to children on more than a single agent. Whether monotherapy would be effective as a first-line treatment in carefully selected patients and would be sufficient longer term requires further study.
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