The Effect of Dapagliflozin Treatment on Epicardial Adipose Tissue Volume and P-Wave Indices: An Ad-hoc Analysis of The Previous Randomized Clinical Trial

Aim: Epicardial adipose tissue (EAT) may be associated with arrhythmogenesis. P-wave indices such as P-wave dispersion and P-wave variation indicated a slowed conduction velocity within the atria. This study investigated the effect of dapagliflozin on EAT volume and P-wave indices. Methods: In the present ad hoc analysis, 35 patients with type 2 diabetes mellitus and coronary artery disease were classified into dapagliflozin group (n = 18) and conventional treatment group (n = 17). At baseline, EAT volume, HbA1c and plasma level of tumor necrotic factor-α (TNF-α) levels, echocardiography, and 12-lead electrocardiogram (ECG) were performed. EAT volume was measured using computed tomography. Using 12-lead ECG, P-wave indices were measured. Results: At baseline, EAT volumes in the dapagliflozin and conventional treatment groups were 113 ± 20 and 110 ± 27 cm(3), respectively. Not only HbA1c and plasma level of TNF-α but also echocardiography findings including left atrial dimension and P-wave indices were comparable between the two groups. After 6 months, plasma level of TNF-α as well as EAT volume significantly decreased in the dapagliflozin group only. P-wave dispersion and P-wave variation significantly decreased in the dapagliflozin group only (−9.2 ± 8.7 vs. 5.9 ± 19.9 ms, p = 0.01; −3.5 ± 3.5 vs. 1.7 ± 5.9 ms, p = 0.01). The change in P-wave dispersion correlated with changes in EAT volume and plasma level of TNF-α. In multivariate analysis, the change in EAT volume was an independent determinant of the change in P-wave dispersion. Conclusion: Dapagliflozin reduced plasma level of TNF-α, EAT volume, and P-wave indices, such as P-wave dispersion. The changes in P-wave indices were especially associated with changes in EAT volume. The number and date of registration: UMIN000035660, 24/Jan/2019