Research ExplorerPublicationsReduced left atrial cardiomyocyte PITX2 and elevated circula...

Reduced left atrial cardiomyocyte PITX2 and elevated circulating BMP10 predict atrial fibrillation after ablation

Standard

Reduced left atrial cardiomyocyte PITX2 and elevated circulating BMP10 predict atrial fibrillation after ablation. / Reyat, Jasmeet S; Chua, Winnie; Cardoso, Victor R; Witten, Anika; Kastner, Peter M; Kabir, S Nashitha; Sinner, Moritz F; Wesselink, Robin; Holmes, Andrew P; Pavlovic, Davor; Stoll, Monika; Kääb, Stefan; Gkoutos, Georgios V; de Groot, Joris R; Kirchhof, Paulus; Fabritz, Larissa.

In: JCI INSIGHT, Vol. 5, No. 16, e139179, 20.08.2020.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Reyat, JS, Chua, W, Cardoso, VR, Witten, A, Kastner, PM, Kabir, SN, Sinner, MF, Wesselink, R, Holmes, AP, Pavlovic, D, Stoll, M, Kääb, S, Gkoutos, GV, de Groot, JR, Kirchhof, P & Fabritz, L 2020, 'Reduced left atrial cardiomyocyte PITX2 and elevated circulating BMP10 predict atrial fibrillation after ablation', JCI INSIGHT, vol. 5, no. 16, e139179. https://doi.org/10.1172/jci.insight.139179

APA

Reyat, J. S., Chua, W., Cardoso, V. R., Witten, A., Kastner, P. M., Kabir, S. N., Sinner, M. F., Wesselink, R., Holmes, A. P., Pavlovic, D., Stoll, M., Kääb, S., Gkoutos, G. V., de Groot, J. R., Kirchhof, P., & Fabritz, L. (2020). Reduced left atrial cardiomyocyte PITX2 and elevated circulating BMP10 predict atrial fibrillation after ablation. JCI INSIGHT, 5(16), [e139179]. https://doi.org/10.1172/jci.insight.139179

Vancouver

Reyat JS, Chua W, Cardoso VR, Witten A, Kastner PM, Kabir SN et al. Reduced left atrial cardiomyocyte PITX2 and elevated circulating BMP10 predict atrial fibrillation after ablation. JCI INSIGHT. 2020 Aug 20;5(16). e139179. https://doi.org/10.1172/jci.insight.139179

Bibtex

@article{c40d0e5da4db4582b740ffdb04475be0,
title = "Reduced left atrial cardiomyocyte PITX2 and elevated circulating BMP10 predict atrial fibrillation after ablation",
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.",
keywords = "Aged, Atrial Appendage/cytology, Atrial Fibrillation/etiology, Biomarkers/blood, Bone Morphogenetic Proteins/blood, Catheter Ablation, Female, Homeodomain Proteins/genetics, Humans, Male, Middle Aged, Myocytes, Cardiac/metabolism, Thoracoscopy, Transcription Factors/genetics",
author = "Reyat, {Jasmeet S} and Winnie Chua and Cardoso, {Victor R} and Anika Witten and Kastner, {Peter M} and Kabir, {S Nashitha} and Sinner, {Moritz F} and Robin Wesselink and Holmes, {Andrew P} and Davor Pavlovic and Monika Stoll and Stefan K{\"a}{\"a}b and Gkoutos, {Georgios V} and {de Groot}, {Joris R} and Paulus Kirchhof and Larissa Fabritz",
year = "2020",
month = aug,
day = "20",
doi = "10.1172/jci.insight.139179",
language = "English",
volume = "5",
journal = "JCI INSIGHT",
issn = "2379-3708",
publisher = "The American Society for Clinical Investigation",
number = "16",

}

RIS

TY - JOUR

T1 - Reduced left atrial cardiomyocyte PITX2 and elevated circulating BMP10 predict atrial fibrillation after ablation

AU - Reyat, Jasmeet S

AU - Chua, Winnie

AU - Cardoso, Victor R

AU - Witten, Anika

AU - Kastner, Peter M

AU - Kabir, S Nashitha

AU - Sinner, Moritz F

AU - Wesselink, Robin

AU - Holmes, Andrew P

AU - Pavlovic, Davor

AU - Stoll, Monika

AU - Kääb, Stefan

AU - Gkoutos, Georgios V

AU - de Groot, Joris R

AU - Kirchhof, Paulus

AU - Fabritz, Larissa

PY - 2020/8/20

Y1 - 2020/8/20

N2 - 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.

AB - 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.

KW - Aged

KW - Atrial Appendage/cytology

KW - Atrial Fibrillation/etiology

KW - Biomarkers/blood

KW - Bone Morphogenetic Proteins/blood

KW - Catheter Ablation

KW - Female

KW - Homeodomain Proteins/genetics

KW - Humans

KW - Male

KW - Middle Aged

KW - Myocytes, Cardiac/metabolism

KW - Thoracoscopy

KW - Transcription Factors/genetics

U2 - 10.1172/jci.insight.139179

DO - 10.1172/jci.insight.139179

M3 - SCORING: Journal article

C2 - 32814717

VL - 5

JO - JCI INSIGHT

JF - JCI INSIGHT

SN - 2379-3708

IS - 16

M1 - e139179

ER -