JTCVS Open (Apr 2024)
Bilateral remote ischemic conditioning in children: A two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgeryCentral MessagePerspective
- Nigel E. Drury, PhD, FRCS(CTh),
- Carin van Doorn, MD, FRCS(CTh),
- Rebecca L. Woolley, MSc,
- Rebecca J. Amos-Hirst, MSc,
- Rehana Bi, BSc(Hons),
- Collette M. Spencer, BSc(Hons),
- Kevin P. Morris, MD, FRCPCH,
- James Montgomerie, MD, FRCA,
- John Stickley, BSc,
- Adrian Crucean, MD,
- Alicia Gill, MSc,
- Matt Hill, MSc,
- Ralf J.M. Weber, PhD,
- Lukas Najdekr, PhD,
- Andris Jankevics, PhD,
- Andrew D. Southam, PhD,
- Gavin R. Lloyd, PhD,
- Osama Jaber, MD,
- Imre Kassai, PhD,
- Giuseppe Pelella, MD,
- Natasha E. Khan, MD, FRCS(CTh),
- Phil Botha, PhD, FRCS(CTh),
- David J. Barron, MD, FRCS(CTh),
- Melanie Madhani, PhD,
- Warwick B. Dunn, PhD,
- Natalie J. Ives, MSc,
- Paulus Kirchhof, MD,
- Timothy J. Jones, MD, FRCS(CTh),
- Edmund D. Carver,
- Alistair J. Cranston,
- Fraser Harban,
- Vasco Laginha Rolo,
- Ritchie Marcus,
- Anthony Moriarty,
- Raju Reddy,
- Susanna N. Ritchie-McLean,
- Monica A. Stokes,
- Ayngara Thillaivasan,
- Nandlal Bhatia,
- Carol Bodlani,
- Wendy Lim,
- Joe Mellor,
- Jutta Scheffczik
Affiliations
- Nigel E. Drury, PhD, FRCS(CTh)
- Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom; Department of Paediatric Cardiac Surgery, Birmingham Children's Hospital, Birmingham, United Kingdom; Address for reprints: Nigel E. Drury, PhD, FRCS(CTh), Institute of Cardiovascular Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom.
- Carin van Doorn, MD, FRCS(CTh)
- Department of Congenital Cardiac Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
- Rebecca L. Woolley, MSc
- Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom; Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
- Rebecca J. Amos-Hirst, MSc
- Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom; Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
- Rehana Bi, BSc(Hons)
- Department of Paediatric Cardiac Surgery, Birmingham Children's Hospital, Birmingham, United Kingdom
- Collette M. Spencer, BSc(Hons)
- Department of Congenital Cardiac Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
- Kevin P. Morris, MD, FRCPCH
- Department of Paediatric Intensive Care, Birmingham Children's Hospital, Birmingham, United Kingdom
- James Montgomerie, MD, FRCA
- Department of Paediatric Cardiac Anesthesia, Birmingham Children's Hospital, Birmingham, United Kingdom
- John Stickley, BSc
- Department of Paediatric Cardiac Surgery, Birmingham Children's Hospital, Birmingham, United Kingdom
- Adrian Crucean, MD
- Department of Paediatric Cardiac Surgery, Birmingham Children's Hospital, Birmingham, United Kingdom
- Alicia Gill, MSc
- Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom; Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
- Matt Hill, MSc
- Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom; Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
- Ralf J.M. Weber, PhD
- Phenome Centre Birmingham, School of Biosciences, University of Birmingham, Birmingham, United Kingdom
- Lukas Najdekr, PhD
- Phenome Centre Birmingham, School of Biosciences, University of Birmingham, Birmingham, United Kingdom
- Andris Jankevics, PhD
- Phenome Centre Birmingham, School of Biosciences, University of Birmingham, Birmingham, United Kingdom
- Andrew D. Southam, PhD
- Phenome Centre Birmingham, School of Biosciences, University of Birmingham, Birmingham, United Kingdom
- Gavin R. Lloyd, PhD
- Phenome Centre Birmingham, School of Biosciences, University of Birmingham, Birmingham, United Kingdom
- Osama Jaber, MD
- Department of Congenital Cardiac Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
- Imre Kassai, PhD
- Department of Congenital Cardiac Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
- Giuseppe Pelella, MD
- Department of Congenital Cardiac Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
- Natasha E. Khan, MD, FRCS(CTh)
- Department of Paediatric Cardiac Surgery, Birmingham Children's Hospital, Birmingham, United Kingdom
- Phil Botha, PhD, FRCS(CTh)
- Department of Paediatric Cardiac Surgery, Birmingham Children's Hospital, Birmingham, United Kingdom
- David J. Barron, MD, FRCS(CTh)
- Division of Cardiovascular Surgery, Hospital for Sick Children, Toronto, Canada; Department of Surgery, University of Toronto, Toronto, Canada
- Melanie Madhani, PhD
- Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom
- Warwick B. Dunn, PhD
- Phenome Centre Birmingham, School of Biosciences, University of Birmingham, Birmingham, United Kingdom; Department of Biochemistry and Systems Biology, Institute of Systems, Molecular, and Integrative Biology, University of Liverpool, Liverpool, United Kingdom
- Natalie J. Ives, MSc
- Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom; Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
- Paulus Kirchhof, MD
- Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom; Department of Cardiology, University Heart and Vascular Centre, UKE Hamburg, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany
- Timothy J. Jones, MD, FRCS(CTh)
- Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom; Department of Paediatric Cardiac Surgery, Birmingham Children's Hospital, Birmingham, United Kingdom
- Edmund D. Carver
- Alistair J. Cranston
- Fraser Harban
- Vasco Laginha Rolo
- Ritchie Marcus
- Anthony Moriarty
- Raju Reddy
- Susanna N. Ritchie-McLean
- Monica A. Stokes
- Ayngara Thillaivasan
- Nandlal Bhatia
- Carol Bodlani
- Wendy Lim
- Joe Mellor
- Jutta Scheffczik
- Journal volume & issue
-
Vol. 18
pp. 193 – 208
Abstract
Objective: The study objective was to determine whether adequately delivered bilateral remote ischemic preconditioning is cardioprotective in young children undergoing surgery for 2 common congenital heart defects with or without cyanosis. Methods: We performed a prospective, double-blind, randomized controlled trial at 2 centers in the United Kingdom. Children aged 3 to 36 months undergoing tetralogy of Fallot repair or ventricular septal defect closure were randomized 1:1 to receive bilateral preconditioning or sham intervention. Participants were followed up until hospital discharge or 30 days. The primary outcome was area under the curve for high-sensitivity troponin-T in the first 24 hours after surgery, analyzed by intention-to-treat. Right atrial biopsies were obtained in selected participants. Results: Between October 2016 and December 2020, 120 eligible children were randomized to receive bilateral preconditioning (n = 60) or sham intervention (n = 60). The primary outcome, area under the curve for high-sensitivity troponin-T, was higher in the preconditioning group (mean: 70.0 ± 50.9 μg/L/h, n = 56) than in controls (mean: 55.6 ± 30.1 μg/L/h, n = 58) (mean difference, 13.2 μg/L/h; 95% CI, 0.5-25.8; P = .04). Subgroup analyses did not show a differential treatment effect by oxygen saturations (pinteraction = .25), but there was evidence of a differential effect by underlying defect (pinteraction = .04). Secondary outcomes and myocardial metabolism, quantified in atrial biopsies, were not different between randomized groups. Conclusions: Bilateral remote ischemic preconditioning does not attenuate myocardial injury in children undergoing surgical repair for congenital heart defects, and there was evidence of potential harm in unstented tetralogy of Fallot. The routine use of remote ischemic preconditioning cannot be recommended for myocardial protection during pediatric cardiac surgery.