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

Jasmeet S. Reyat, Winnie Chua, Victor R. Cardoso, Anika Witten, Peter M. Kastner, S. Nashitha Kabir, Moritz F. Sinner, Robin Wesselink, Andrew P. Holmes, Davor Pavlovic, Monika Stoll, Stefan Kaeaeb, Georgios Gkoutos, Joris R. de Groot, Paulus Kirchhof*, Larissa Fabritz

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Web of Science)

Abstract

BACKGROUND. Genomic 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.

METHODS. mRNA 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.

RESULTS. Reduced concentrations of cardiomyocyte PITX2, but not whole LAA tissue PITX2, were associated with AF recurrence after thoracoscopic AF ablation (16% decreased recurrence per 2(-(Delta Delta Ct)) 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.

CONCLUSIONS. Reduced 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.

Original languageEnglish
Article number139179
Number of pages16
JournalJCI INSIGHT
Volume5
Issue number16
DOIs
Publication statusPublished - 20 Aug 2020

Keywords

  • LEFT-RIGHT ASYMMETRY
  • RADIOFREQUENCY ABLATION
  • NATRIURETIC PEPTIDE
  • SHORT-TERM
  • RECURRENCE
  • RISK
  • VARIANTS
  • 4Q25
  • AMIODARONE
  • EXPRESSION

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