Systemic Sirolimus Therapy Is Associated With Reduced Intervention Frequency in Pulmonary Vein Stenosis

Early clinical outcomes data for adjunctive systemic sirolimus therapy (SST) for moderate to severe pediatric pulmonary vein stenosis (PVS) are promising but limited.

The authors aimed to characterize a cohort of patients treated with SST to determine if SST was associated with a reduction in frequency of PVS interventions.

Medical records of 45 patients with PVS treated with SST for ≥1 month from 2015 to 2022 were retrospectively reviewed. PVS intervention rates pre-SST and on-SST were compared using generalized Poisson mixed models, accounting for paired intervals within each patient. In addition to an unadjusted model, an adjusted model accounted for age at interval start, PVS type, sex, prematurity, and concurrent antiproliferative therapy. Mean number of PVS interventions per patient over time (mean cumulative function) were also compared for these intervals in an unpaired fashion. Kaplan-Meier estimates were used to quantify survival over time.

Median per-patient PVS intervention rate (interventions/year) was 5 pre-SST and 1.7 on-SST, significantly lower on-SST in the unadjusted and adjusted models (P < 0.001, both). Patients accrued an increased cumulative number of interventions over time pre-SST compared to on-SST by mean cumulative function (P < 0.001). Median duration of SST was 1.7 years and median follow-up time from SST initiation was 2.7 years. There were 6 mortalities at a median of 1.1 years (range, 4.4 months-6.5 years) following SST initiation.

SST was associated with a reduction in frequency of PVS interventions. Prospective studies are warranted to determine potential causality, delineate patient- and vein-level outcomes, and determine optimal therapeutic duration.