1. Systemic Sirolimus Therapy for Infants and Children With Pulmonary Vein Stenosis.
- Author
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Patel, Jay D., Briones, Michael, Mandhani, Mansi, Jones, Shannon, Suthar, Divya, Gray, Rosemary, Pettus, Joelle, McCracken, Courtney, Thomas, Amanda, and Petit, Christopher J.
- Subjects
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PULMONARY stenosis , *PULMONARY veins , *RAPAMYCIN , *INFANTS , *DIAGNOSIS , *SURVIVAL analysis (Biometry) , *HEART valve prosthesis implantation , *ANTINEOPLASTIC antibiotics , *RETROSPECTIVE studies - Abstract
Background: Anatomic interventions for pulmonary vein stenosis (PVS) in infants and children have been met with limited success. Sirolimus, a mammalian target of rapamycin inhibitor, has demonstrated promise as a primary medical therapy for PVS, but the impact on patient survival is unknown.Objectives: The authors sought to investigate whether mTOR inhibition with sirolimus as a primary medical therapy would improve outcomes in high-risk infants and children with PVS.Methods: In this single-center study, patients with severe PVS were considered for systemic sirolimus therapy (SST) following a strict protocol while receiving standardized surveillance and anatomic therapies. The SST cohort was compared with a contemporary control group. The primary endpoint for this study was survival. The primary safety endpoint was adverse events (AEs) related to SST.Results: Between 2015 and 2020, our PVS program diagnosed and treated 67 patients with ≥moderate PVS. Of these, 15 patients were treated with sirolimus, whereas the remaining patients represent the control group. There was 100% survival in the SST group compared with 45% survival in the control group (log-rank p = 0.004). A sensitivity analysis was completed to address survival bias using median time from diagnosis of PVS to SST. A survival advantage persisted (log-rank p = 0.027). Two patients on sirolimus developed treatable AEs. Patients in the SST group underwent frequent transcatheter interventions with 3.7 catheterizations per person-year (25th to 75th percentile: 2.7 to 4.4 person-years). Median follow up time was 2.2 years (25th to 75th percentile: 1.2 to 2.9 years) in the SST group versus 0.9 years (25th to 75th percentile: 0.5 to 2.7 years) in the control group.Conclusions: The authors found a survival benefit associated with SST in infants and children with moderate-to-severe PVS. This survival benefit persisted after adjusting the analysis for survival bias. There were 2 mild AEs associated with SST during the study period; both patients were able to resume therapy without recurrence. [ABSTRACT FROM AUTHOR]- Published
- 2021
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