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

## TL;DR

Low levels of PITX2 in heart cells and high levels of BMP10 in blood predict whether atrial fibrillation will return after treatment.

## Contribution

Identifies PITX2 in cardiomyocytes and BMP10 as novel biomarkers for predicting AF recurrence after ablation.

## Key findings

- Reduced cardiomyocyte PITX2 is linked to lower AF recurrence after ablation.
- Elevated BMP10 outperforms other biomarkers in predicting AF recurrence.
- BMP10 is confirmed as a key gene repressed by PITX2 in the heart.

## Abstract

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.

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.

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–(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.

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.

ClinicalTrials.gov NCT01091389, NL50069.018.14, Dutch National Registry of Clinical Research Projects EK494-16.

British Heart Foundation, European Union (H2020), Leducq Foundation.

Building on genomic and experimental findings, low PITX2 in left atrial cardiomyocytes and high BMP10 in plasma predict recurrent atrial fibrillation in patients after ablation.