Clin Res Cardiol (2021). 10.1007/s00392-021-01933-9 |
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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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https://dgk.org/kongress_programme/ht2021/BS659.htm |