Bilateral Remote Ischemic Conditioning in Children: a two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgery

Bilateral Remote Ischemic Conditioning in Children Trial Investigators; Nigel E. Drury; Carin Van Doorn; Rebecca L. Woolley; Rebecca J. Amos-Hirst; Rehana Bi; Collette M. Spencer; Kevin P. Morris; James Montgomerie; John Stickley; Adrian Crucean; Alicia Gill; Matt  Hill; Ralf J. M. Weber; Lukas Najdekr; Andris Jankevics; Andrew D. Southam; Gavin R. Lloyd; Osama Jaber; Imre Kassai; Giuseppe Pelella; Natasha E. Khan; Phil Botha; David J. Barron; Melanie Madhani; Warwick B. Dunn; Natalie J. Ives; Paulus Kirchhof; Timothy J. Jones

doi:10.1016/j.xjon.2024.02.018

Bilateral Remote Ischemic Conditioning in Children: a two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgery

Bilateral Remote Ischemic Conditioning in Children Trial Investigators, Nigel E. Drury^*, Carin Van Doorn, Rebecca L. Woolley, Rebecca J. Amos-Hirst, Rehana Bi, Collette M. Spencer, Kevin P. Morris, James Montgomerie, John Stickley, Adrian Crucean, Alicia Gill, Matt Hill, Ralf J. M. Weber, Lukas Najdekr, Andris Jankevics, Andrew D. Southam, Gavin R. Lloyd, Osama Jaber, Imre KassaiGiuseppe Pelella, Natasha E. Khan, Phil Botha, David J. Barron, Melanie Madhani, Warwick B. Dunn, Natalie J. Ives, Paulus Kirchhof, Timothy J. Jones

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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 (p_interaction = .25), but there was evidence of a differential effect by underlying defect (p_interaction = .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.

Original language	English
Pages (from-to)	193-208
Journal	The Journal of Thoracic and Cardiovascular Surgery
Volume	18
Early online date	5 Mar 2024
DOIs	https://doi.org/10.1016/j.xjon.2024.02.018
Publication status	Published - 16 Apr 2024

Keywords

clinical trial
cyanosis
myocardial protection
pediatric cardiac surgery
remote ischemic preconditioning
tetralogy of Fallot

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10.1016/j.xjon.2024.02.018Licence: Creative Commons: Attribution (CC BY)

DruryNE2024BilateralFinal published version, 1.92 MBLicence: Creative Commons: Attribution (CC BY)

Remote Ischaemic Preconditioning for myocardial protection in young children undergoing heart surgery: a double-blind, randomised controlled trial in normoxic and hypoxic patients
Drury, N., Kirchhof, P., Dunn, W. & Madhani, M.
British Heart Foundation
1/01/16 → 30/09/22
Project: Research

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Bilateral Remote Ischemic Conditioning in Children Trial Investigators, Drury, N. E., Doorn, C. V., Woolley, R. L., Amos-Hirst, R. J., Bi, R., Spencer, C. M., Morris, K. P., Montgomerie, J., Stickley, J., Crucean, A., Gill, A., Hill, M., Weber, R. J. M., Najdekr, L., Jankevics, A., Southam, A. D., Lloyd, G. R., Jaber, O., ... Jones, T. J. (2024). Bilateral Remote Ischemic Conditioning in Children: a two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgery. The Journal of Thoracic and Cardiovascular Surgery, 18, 193-208. https://doi.org/10.1016/j.xjon.2024.02.018

@article{7b9f08e07933404bb6e0e468a2cc2a1f,

title = "Bilateral Remote Ischemic Conditioning in Children: a two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgery",

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.",

keywords = "clinical trial, cyanosis, myocardial protection, pediatric cardiac surgery, remote ischemic preconditioning, tetralogy of Fallot",

author = "{Bilateral Remote Ischemic Conditioning in Children Trial Investigators} and Drury, {Nigel E.} and Doorn, {Carin Van} and Woolley, {Rebecca L.} and Amos-Hirst, {Rebecca J.} and Rehana Bi and Spencer, {Collette M.} and Morris, {Kevin P.} and James Montgomerie and John Stickley and Adrian Crucean and Alicia Gill and Matt Hill and Weber, {Ralf J. M.} and Lukas Najdekr and Andris Jankevics and Southam, {Andrew D.} and Lloyd, {Gavin R.} and Osama Jaber and Imre Kassai and Giuseppe Pelella and Khan, {Natasha E.} and Phil Botha and Barron, {David J.} and Melanie Madhani and Dunn, {Warwick B.} and Ives, {Natalie J.} and Paulus Kirchhof and Jones, {Timothy J.}",

year = "2024",

month = apr,

day = "16",

doi = "10.1016/j.xjon.2024.02.018",

language = "English",

volume = "18",

pages = "193--208",

journal = "The Journal of Thoracic and Cardiovascular Surgery",

issn = "0022-5223",

publisher = "Elsevier",

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Bilateral Remote Ischemic Conditioning in Children Trial Investigators, Drury, NE, Doorn, CV, Woolley, RL, Amos-Hirst, RJ, Bi, R, Spencer, CM, Morris, KP, Montgomerie, J, Stickley, J, Crucean, A, Gill, A, Hill, M, Weber, RJM, Najdekr, L, Jankevics, A, Southam, AD , Lloyd, GR, Jaber, O, Kassai, I, Pelella, G, Khan, NE, Botha, P, Barron, DJ, Madhani, M, Dunn, WB, Ives, NJ , Kirchhof, P & Jones, TJ 2024, 'Bilateral Remote Ischemic Conditioning in Children: a two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgery', The Journal of Thoracic and Cardiovascular Surgery, vol. 18, pp. 193-208. https://doi.org/10.1016/j.xjon.2024.02.018

Bilateral Remote Ischemic Conditioning in Children: a two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgery. / Bilateral Remote Ischemic Conditioning in Children Trial Investigators ; Drury, Nigel E.; Doorn, Carin Van et al.
In: The Journal of Thoracic and Cardiovascular Surgery, Vol. 18, 16.04.2024, p. 193-208.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Bilateral Remote Ischemic Conditioning in Children

T2 - a two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgery

AU - Bilateral Remote Ischemic Conditioning in Children Trial Investigators

AU - Drury, Nigel E.

AU - Doorn, Carin Van

AU - Woolley, Rebecca L.

AU - Amos-Hirst, Rebecca J.

AU - Bi, Rehana

AU - Spencer, Collette M.

AU - Morris, Kevin P.

AU - Montgomerie, James

AU - Stickley, John

AU - Crucean, Adrian

AU - Gill, Alicia

AU - Hill, Matt

AU - Weber, Ralf J. M.

AU - Najdekr, Lukas

AU - Jankevics, Andris

AU - Southam, Andrew D.

AU - Lloyd, Gavin R.

AU - Jaber, Osama

AU - Kassai, Imre

AU - Pelella, Giuseppe

AU - Khan, Natasha E.

AU - Botha, Phil

AU - Barron, David J.

AU - Madhani, Melanie

AU - Dunn, Warwick B.

AU - Ives, Natalie J.

AU - Kirchhof, Paulus

AU - Jones, Timothy J.

PY - 2024/4/16

Y1 - 2024/4/16

N2 - 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.

AB - 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.

KW - clinical trial

KW - cyanosis

KW - myocardial protection

KW - pediatric cardiac surgery

KW - remote ischemic preconditioning

KW - tetralogy of Fallot

U2 - 10.1016/j.xjon.2024.02.018

DO - 10.1016/j.xjon.2024.02.018

M3 - Article

SN - 0022-5223

VL - 18

SP - 193

EP - 208

JO - The Journal of Thoracic and Cardiovascular Surgery

JF - The Journal of Thoracic and Cardiovascular Surgery

ER -

Bilateral Remote Ischemic Conditioning in Children Trial Investigators, Drury NE, Doorn CV, Woolley RL, Amos-Hirst RJ, Bi R et al. Bilateral Remote Ischemic Conditioning in Children: a two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgery. The Journal of Thoracic and Cardiovascular Surgery. 2024 Apr 16;18:193-208. Epub 2024 Mar 5. doi: 10.1016/j.xjon.2024.02.018

Bilateral Remote Ischemic Conditioning in Children: a two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgery

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Remote Ischaemic Preconditioning for myocardial protection in young children undergoing heart surgery: a double-blind, randomised controlled trial in normoxic and hypoxic patients

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