Projects per year
Abstract
BACKGROUNDGenomic and experimental studies suggest a role for PITX2 in atrial fibrillation (AF). To assess if this association is relevant for recurrent AF in patients, we tested whether left atrial PITX2 affects recurrent AF after AF ablation.METHODSmRNA concentrations of PITX2 and its cardiac isoform, PITX2c, were quantified in left atrial appendages (LAAs) from patients undergoing thoracoscopic AF ablation, either in whole LAA tissue (n = 83) or in LAA cardiomyocytes (n = 52), and combined with clinical parameters to predict AF recurrence. Literature suggests that BMP10 is a PITX2-repressed, atrial-specific, secreted protein. BMP10 plasma concentrations were combined with 11 cardiovascular biomarkers and clinical parameters to predict recurrent AF after catheter ablation in 359 patients.RESULTSReduced concentrations of cardiomyocyte PITX2, but not whole LAA tissue PITX2, were associated with AF recurrence after thoracoscopic AF ablation (16% decreased recurrence per 2-(ΔΔCt) increase in PITX2). RNA sequencing, quantitative PCR, and Western blotting confirmed that BMP10 is one of the most PITX2-repressed atrial genes. Left atrial size (HR per mm increase [95% CI], 1.055 [1.028, 1.082]); nonparoxysmal AF (HR 1.672 [1.206, 2.318]), and elevated BMP10 (HR 1.339 [CI 1.159, 1.546] per quartile increase) were predictive of recurrent AF. BMP10 outperformed 11 other cardiovascular biomarkers in predicting recurrent AF.CONCLUSIONSReduced left atrial cardiomyocyte PITX2 and elevated plasma concentrations of the PITX2-repressed, secreted atrial protein BMP10 identify patients at risk of recurrent AF after ablation.TRIAL REGISTRATIONClinicalTrials.gov NCT01091389, NL50069.018.14, Dutch National Registry of Clinical Research Projects EK494-16.FUNDINGBritish Heart Foundation, European Union (H2020), Leducq Foundation.
Original language | English |
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Article number | e139179 |
Journal | JCI Insight |
Volume | 5 |
Issue number | 16 |
DOIs | |
Publication status | Published - 20 Aug 2020 |
Keywords
- Arrhythmias
- Cardiology
ASJC Scopus subject areas
- General Medicine
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Dive into the research topics of 'Reduced left atrial cardiomyocyte PITX2 and elevated circulating BMP10 predict atrial fibrillation after ablation'. Together they form a unique fingerprint.Projects
- 8 Finished
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Investigating regulatory pathways for intracellular sodium in the atria
Pavlovic, D. (Principal Investigator) & Thomas, S. (Co-Investigator)
1/10/19 → 30/04/23
Project: Research
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Scarred by kidney disease: FGF23 as a key mediator of cardiac fibrosis in patients with chronic kidney disease
Weston, C. (Co-Investigator), Pavlovic, D. (Co-Investigator), McGettrick, H. (Co-Investigator) & Gough, R. (Principal Investigator)
1/08/19 → 28/02/23
Project: Research
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BHF Research Accelerator Award
Bicknell, R. (Co-Investigator), Watson, S. (Co-Investigator), Rainger, E. (Co-Investigator), Senis, Y. (Co-Investigator), Fabritz, L. (Co-Investigator) & Kirchhof, P. (Principal Investigator)
1/04/19 → 30/09/24
Project: Research
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Cardiotonic steroids in patients with atrial fibrillation and heart failure: Quantification, functional effects and personalisation of digoxin therapy
Arlt, W. (Co-Investigator), Pavlovic, D. (Principal Investigator), Taylor, A. (Co-Investigator), Kotecha, D. (Co-Investigator) & Kirchhof, P. (Co-Investigator)
1/06/18 → 30/05/21
Project: Research
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Impact of chronic intermittent hypoxia on atrial resting membrane potential and Na 1.5 channel function: A new mechanism for causing atrial fibrillation
Kirchhof, P. (Principal Investigator) & Holmes, A. (Co-Investigator)
1/10/17 → 18/07/21
Project: Research
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H2020_COLLAB(IMI-JU)_BIGDATA@HEART
Kotecha, D. (Principal Investigator) & Kirchhof, P. (Co-Investigator)
1/03/17 → 28/02/23
Project: Research
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H2020_COLLAB_CATCH ME_(LEAD)
Kirchhof, P. (Principal Investigator), Fabritz, L. (Co-Investigator), Hemming, K. (Co-Investigator) & Deeks, J. (Co-Investigator)
1/05/15 → 30/04/19
Project: EU