Abstract 4141230: Systemic Sirolimus Therapy is Associated with Reduced Intervention Frequency in Pediatric Pulmonary Vein Stenosis

Background: Pediatric pulmonary vein stenosis (PVS) has a guarded prognosis and often necessitates repeated interventions. Small retrospective studies suggest benefits to adjunctive enteral systemic sirolimus therapy (SST) for PVS, including improved survival, slowed progression of in-stent stenosis, and reduced frequency of catheterization procedures. Hypothesis: We hypothesized patients undergo PVS interventions less frequently while receiving SST compared to pre-SST. Aims: The principal aim was to determine the impact of systemic sirolimus therapy on PVS intervention frequency. Methods: We retrospectively identified 45 patients treated at Texas Children’s Hospital who completed >1 month of SST for PVS between 2015-2022. First course of SST was analyzed. Primary endpoint was PVS intervention frequency (number of surgical or transcatheter PVS interventions/year), calculated for two intervals per patient: pre-SST (PVS diagnosis until start of SST) and on-SST (start of SST until cessation or follow-up if no interruptions >1 month). Generalized Poisson mixed linear models were fit to test the impact of SST on intervention frequency, accounting for paired intervals within each patient. A multivariable model also included age at interval start, PVS type (primary/post-repair), sex, prematurity, and concurrent antiproliferative medications. Mean cumulative functions were also compared. Results: Median per-patient PVS intervention rate (interventions/year) was 5 (IQR 2.3-10.6) pre-SST and 1.7 (0.8-2.8) on-SST. PVS intervention rate was significantly lower on-SST compared to pre-SST by the univariable and multivariable Poisson models (P<.0001, both). Patients accrued an increased mean cumulative number of interventions over time pre-SST compared to on-SST (P<.0001, Figure). Median duration of SST was 1.7 years and follow-up time from SST initiation was 2.7 years. There were 6 mortalities with 90% (95% CI 75-96%) Kaplan-Meier estimated survival 2 years from SST initiation. Conclusions: SST was associated with a reduction in PVS intervention frequency. Prospective studies are warranted to determine potential causality, delineate patient and vein-level outcomes, and determine optimal therapeutic duration.