Clin Res Cardiol (2021). 10.1007/s00392-021-01933-9

Increased atrial TASK-1 mRNA expression is associated with elevated p-wave terminal force in patients with preserved ejection fraction
P. Hegner1, S. Lebek1, M. Tafelmeier1, D. Camboni2, S. Schopka2, C. Schmid2, L. S. Maier1, M. Arzt1, S. Wagner1
1Klinik und Poliklinik für Innere Med. II, Kardiologie, Universitätsklinikum Regensburg, Regensburg; 2Herz-, Thorax- und herznahe Gefäßchirurgie, Universitätsklinikum Regensburg, Regensburg;

Background/Objective: Recently, the atrial-selectively expressed potassium channel TASK-1 (TWIK-related acid sensitive potassium channel 1) has been shown to be upregulated in chronic atrial fibrillation (AF), and was identified as a potential antiarrhythmic target, especially in patients with preserved ejection fraction. However, the mechanisms for TASK-1 upregulation are insufficiently understood and clinical markers for increased TASK-1 expression are missing. Interestingly, magnitude of p-wave terminal force in ecg lead V1(PTFV1), is associated with electrical and functional atrial remodeling, which are precursors of AF development.

 

Purpose: We tested the hypothesis that in patients with preserved ejection fraction (LVEF≥45) in sinus rhythm, an abnormal PTFV1 may indicate atrial TASK-1 upregulation.

 

Methods: We enrolled 54 patients undergoing coronary artery bypass grafting and analyzed right atrial appendage biopsies for expression of KCNK3 (TASK-1) mRNA (real-time qPCR). All samples were measured as triplicates and the averages were used for the comparative threshold cycle (Ct) relative quantification analysis method and expressed as percent of β-actin. Echocardiography was performed to assess left ventricular ejection fraction (LVEF). PTFV1 was assessed as the product of negative p-wave amplitude and duration in lead V1 and defined as abnormal if ≥4000 ms*μV. Student’s t-test was performed to compare normally distributed continuous variables, additionally simple linear regression was performed. Multivariate regression analyses were performed to account for potential confounders.

 

Results: Interestingly, in patients with an abnormal PTFV1 atrial expression of TASK-1 mRNA was significantly increased (Fig. 1A, mean±SEM 60.7±4.47 to 87.6±8.94, p=0.01) and magnitude of PTFV1 correlated significantly with TASK-1 mRNA expression (Fig. 1B, 95% CI of slope 4.52 to 29.6, R2=0.13, p<0.01). Importantly, TASK-1 mRNA was significantly correlated with PTFV1 independent of age, gender, body mass index, LVEF, kidney function and diabetes in a multivariate linear regression model (R2=0.3, p=0.02).

 

Conclusion: An increased TASK-1 mRNA gene expression was positively correlated with p-wave terminal force, providing a possible explanation for an increased risk of AF in these patients



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