Disease severity, arrhythmogenesis, and fibrosis are related to longer action potentials in tetralogy of Fallot.
Arrhythmias
Congenital heart disease
Electrophysiology
Fibrosis
Journal
Clinical research in cardiology : official journal of the German Cardiac Society
ISSN: 1861-0692
Titre abrégé: Clin Res Cardiol
Pays: Germany
ID NLM: 101264123
Informations de publication
Date de publication:
May 2024
May 2024
Historique:
received:
05
03
2023
accepted:
16
08
2023
medline:
19
4
2024
pubmed:
19
9
2023
entrez:
19
9
2023
Statut:
ppublish
Résumé
Arrhythmias may originate from surgically unaffected right ventricular (RV) regions in patients with tetralogy of Fallot (TOF). We aimed to investigate action potential (AP) remodelling and arrhythmia susceptibility in RV myocardium of patients with repaired and with unrepaired TOF, identify possible correlations with clinical phenotype and myocardial fibrosis, and compare findings with data from patients with atrial septal defect (ASD), a less severe congenital heart disease. Intracellular AP were recorded ex vivo in RV outflow tract samples from 22 TOF and three ASD patients. Arrhythmias were provoked by superfusion with solutions containing reduced potassium and barium chloride, or isoprenaline. Myocardial fibrosis was quantified histologically and associations between clinical phenotype, AP shape, tissue arrhythmia propensity, and fibrosis were examined. Electrophysiological abnormalities (arrhythmias, AP duration [APD] alternans, impaired APD shortening at increased stimulation frequencies) were generally present in TOF tissue, even from infants, but rare or absent in ASD samples. More severely diseased and acyanotic patients, pronounced tissue susceptibility to arrhythmogenesis, and greater fibrosis extent were associated with longer APD. In contrast, APD was shorter in tissue from patients with pre-operative cyanosis. Increased fibrosis and repaired-TOF status were linked to tissue arrhythmia inducibility. Functional and structural tissue remodelling may explain arrhythmic activity in TOF patients, even at a very young age. Surprisingly, clinical acyanosis appears to be associated with more severe arrhythmogenic remodelling. Further research into the clinical drivers of structural and electrical myocardial alterations, and the relation between them, is needed to identify predictive factors for patients at risk.
Sections du résumé
BACKGROUND
BACKGROUND
Arrhythmias may originate from surgically unaffected right ventricular (RV) regions in patients with tetralogy of Fallot (TOF). We aimed to investigate action potential (AP) remodelling and arrhythmia susceptibility in RV myocardium of patients with repaired and with unrepaired TOF, identify possible correlations with clinical phenotype and myocardial fibrosis, and compare findings with data from patients with atrial septal defect (ASD), a less severe congenital heart disease.
METHODS
METHODS
Intracellular AP were recorded ex vivo in RV outflow tract samples from 22 TOF and three ASD patients. Arrhythmias were provoked by superfusion with solutions containing reduced potassium and barium chloride, or isoprenaline. Myocardial fibrosis was quantified histologically and associations between clinical phenotype, AP shape, tissue arrhythmia propensity, and fibrosis were examined.
RESULTS
RESULTS
Electrophysiological abnormalities (arrhythmias, AP duration [APD] alternans, impaired APD shortening at increased stimulation frequencies) were generally present in TOF tissue, even from infants, but rare or absent in ASD samples. More severely diseased and acyanotic patients, pronounced tissue susceptibility to arrhythmogenesis, and greater fibrosis extent were associated with longer APD. In contrast, APD was shorter in tissue from patients with pre-operative cyanosis. Increased fibrosis and repaired-TOF status were linked to tissue arrhythmia inducibility.
CONCLUSIONS
CONCLUSIONS
Functional and structural tissue remodelling may explain arrhythmic activity in TOF patients, even at a very young age. Surprisingly, clinical acyanosis appears to be associated with more severe arrhythmogenic remodelling. Further research into the clinical drivers of structural and electrical myocardial alterations, and the relation between them, is needed to identify predictive factors for patients at risk.
Identifiants
pubmed: 37725108
doi: 10.1007/s00392-023-02288-z
pii: 10.1007/s00392-023-02288-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
716-727Informations de copyright
© 2023. The Author(s).
Références
Pflugers Arch. 2020 Dec;472(12):1783-1791
pubmed: 32794054
Cells. 2021 Nov 17;10(11):
pubmed: 34831426
Int J Cardiol. 2016 Nov 1;222:422-429
pubmed: 27505328
Heart Rhythm. 2016 Jun;13(6):1303-8
pubmed: 26829112
Heart. 2014 Feb;100(3):247-53
pubmed: 24179163
Circulation. 1997 Jan 21;95(2):401-4
pubmed: 9008456
Int J Cardiovasc Imaging. 2019 Jan;35(1):143-151
pubmed: 30094564
Circ Arrhythm Electrophysiol. 2019 Jun;12(6):e007141
pubmed: 31113235
Physiol Rev. 2021 Jul 1;101(3):1083-1176
pubmed: 33118864
Europace. 2021 Mar 4;23(23 Suppl 1):i38-i47
pubmed: 33404047
Eur Heart J Cardiovasc Imaging. 2019 Sep 1;20(9):990-1003
pubmed: 30993335
Clin Med Insights Cardiol. 2015 Mar 23;8(Suppl 1):93-8
pubmed: 25861226
Front Physiol. 2020 Dec 10;11:519951
pubmed: 33362569
Pediatr Radiol. 2014 Apr;44(4):403-9
pubmed: 24419492
Circ J. 2018 Mar 23;82(4):1149-1154
pubmed: 29353862
Circulation. 1995 Jul 15;92(2):231-7
pubmed: 7600655
Pediatr Res. 1985 Dec;19(12):1263-7
pubmed: 4080443
Pediatr Cardiol. 2015 Oct;36(7):1523-31
pubmed: 25981566
Interact Cardiovasc Thorac Surg. 2020 Jul 1;31(1):129-137
pubmed: 32243531
Heart Rhythm. 2004 Oct;1(4):460-8
pubmed: 15851200
Congenit Heart Dis. 2014 Sep-Oct;9(5):407-14
pubmed: 24314315
JACC Clin Electrophysiol. 2018 Oct;4(10):1308-1318
pubmed: 30336877
Cardiovasc Res. 1998 May;38(2):424-32
pubmed: 9709403
Heart. 2017 Mar;103(5):347-354
pubmed: 28051771
J Thorac Cardiovasc Surg. 2006 Aug;132(2):270-7
pubmed: 16872949
Circulation. 2009 Mar 17;119(10):e235-40
pubmed: 19228822
Can J Cardiol. 2020 Nov;36(11):1815-1825
pubmed: 32416063
Heart Rhythm. 2009 Feb;6(2):251-9
pubmed: 19187920
Heart Rhythm. 2018 Apr;15(4):503-511
pubmed: 29170144
Circ Cardiovasc Imaging. 2017 Mar;10(3):
pubmed: 28292861
Heart. 2017 May;103(9):666-671
pubmed: 27803032
Eur Heart J. 2017 Jan 21;38(4):268-276
pubmed: 28182233
Cardiovasc Pathol. 2016 May-Jun;25(3):225-231
pubmed: 26938796
Acta Cardiol. 2020 Feb;75(1):20-25
pubmed: 30513267
Cardiol Young. 2004 Aug;14(4):360-6
pubmed: 15680040
Cardiovasc Res. 1999 Aug 1;43(2):332-43
pubmed: 10536663