PMID- 34082911
OWN - NLM
STAT- MEDLINE
DCOM- 20211119
LR  - 20211119
IS  - 1558-3597 (Electronic)
IS  - 0735-1097 (Linking)
VI  - 77
IP  - 22
DP  - 2021 Jun 8
TI  - Systemic Sirolimus Therapy for Infants and Children With Pulmonary Vein Stenosis.
PG  - 2807-2818
LID - S0735-1097(21)01235-3 [pii]
LID - 10.1016/j.jacc.2021.04.013 [doi]
AB  - 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.
CI  - Copyright (c) 2021 American College of Cardiology Foundation. Published by Elsevier 
      Inc. All rights reserved.
FAU - Patel, Jay D
AU  - Patel JD
AD  - Department of Pediatrics, Division of Cardiology, Emory University and Children's 
      Healthcare of Atlanta, Atlanta, Georgia, USA.
FAU - Briones, Michael
AU  - Briones M
AD  - Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory 
      University and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
FAU - Mandhani, Mansi
AU  - Mandhani M
AD  - Department of Pediatrics, Division of Cardiology, Emory University and Children's 
      Healthcare of Atlanta, Atlanta, Georgia, USA.
FAU - Jones, Shannon
AU  - Jones S
AD  - Department of Pediatrics, Division of Cardiology, Emory University and Children's 
      Healthcare of Atlanta, Atlanta, Georgia, USA.
FAU - Suthar, Divya
AU  - Suthar D
AD  - Department of Pediatrics, Division of Cardiology, Emory University and Children's 
      Healthcare of Atlanta, Atlanta, Georgia, USA.
FAU - Gray, Rosemary
AU  - Gray R
AD  - Department of Pediatrics, Division of Cardiology, Emory University and Children's 
      Healthcare of Atlanta, Atlanta, Georgia, USA.
FAU - Pettus, Joelle
AU  - Pettus J
AD  - Department of Pediatrics, Division of Cardiology, Emory University and Children's 
      Healthcare of Atlanta, Atlanta, Georgia, USA.
FAU - McCracken, Courtney
AU  - McCracken C
AD  - Department of Pediatrics, Division of Cardiology, Emory University and Children's 
      Healthcare of Atlanta, Atlanta, Georgia, USA.
FAU - Thomas, Amanda
AU  - Thomas A
AD  - Department of Pediatrics, Division of Cardiology, Emory University and Children's 
      Healthcare of Atlanta, Atlanta, Georgia, USA.
FAU - Petit, Christopher J
AU  - Petit CJ
AD  - Department of Pediatrics, Division of Cardiology, Emory University and Children's 
      Healthcare of Atlanta, Atlanta, Georgia, USA. Electronic address: 
      cjp2196@cumc.columbia.edu.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Am Coll Cardiol
JT  - Journal of the American College of Cardiology
JID - 8301365
RN  - 0 (Antibiotics, Antineoplastic)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
CIN - J Am Coll Cardiol. 2021 Jun 8;77(22):2819-2821. PMID: 34082912
MH  - Antibiotics, Antineoplastic/*therapeutic use
MH  - Child, Preschool
MH  - Female
MH  - Georgia/epidemiology
MH  - Humans
MH  - Infant
MH  - Male
MH  - Retrospective Studies
MH  - Sirolimus/*therapeutic use
MH  - Stenosis, Pulmonary Vein/*drug therapy/mortality
OTO - NOTNLM
OT  - myofibroblastic proliferation
OT  - pulmonary vein stenosis
OT  - systemic sirolimus therapy
COIS- Funding Support and Author Disclosures The authors have reported that they have 
      no relationships relevant to the contents of this paper to disclose.
EDAT- 2021/06/05 06:00
MHDA- 2021/11/20 06:00
CRDT- 2021/06/04 05:46
PHST- 2021/02/01 00:00 [received]
PHST- 2021/04/01 00:00 [revised]
PHST- 2021/04/02 00:00 [accepted]
PHST- 2021/06/04 05:46 [entrez]
PHST- 2021/06/05 06:00 [pubmed]
PHST- 2021/11/20 06:00 [medline]
AID - S0735-1097(21)01235-3 [pii]
AID - 10.1016/j.jacc.2021.04.013 [doi]
PST - ppublish
SO  - J Am Coll Cardiol. 2021 Jun 8;77(22):2807-2818. doi: 10.1016/j.jacc.2021.04.013.