Systemic Sirolimus Therapy for Infants and Children With Pulmonary Vein Stenosis
| Autor: | Rosemary Gray, Amanda S. Thomas, Christopher J. Petit, Shannon Jones, Jay D. Patel, Divya Suthar, Joelle Pettus, Michael Briones, Courtney McCracken, Mansi Mandhani |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Percentile Georgia 030204 cardiovascular system & hematology 03 medical and health sciences 0302 clinical medicine Median follow-up Internal medicine Clinical endpoint Medicine Humans 030212 general & internal medicine Adverse effect Pulmonary vein stenosis Retrospective Studies Sirolimus Antibiotics Antineoplastic business.industry Sirolimus therapy Infant Stenosis Pulmonary Vein Child Preschool Cohort cardiovascular system Female Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | Journal of the American College of Cardiology. 77(22) |
| ISSN: | 1558-3597 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|