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

Takao Sato, Yoshifusa Aizawa, Sho Yuasa, Satoshi Fujita, Yoshio Ikeda, Masaaki Okabe, Takao Sato, Yoshifusa Aizawa, Sho Yuasa, Satoshi Fujita, Yoshio Ikeda, Masaaki Okabe

Abstract

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 cm3, 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.

Keywords: Atrial fibrillation; Epicardial adipose tissue; P-wave indices; SGLT-2 inhibitor.

Conflict of interest statement

All authors declare no competing interests.

Figures

Fig. 1.
Fig. 1.
Flowchart for the present study Forty patients were enrolled. At baseline, computed tomography (CT), blood examination, ultrasound cardiography, and electrocardiogram (ECG) were performed. However, ECG examination for five patients was not retrospectively performed at follow-up. Therefore, the final study population consisted of 35 patients.
Fig. 2.
Fig. 2.
Measurement of epicardial adipose tissue (EAT) volumes with multislice computed tomography See text for details. (a) Axial images. A region of interest was manually placed along the visceral pericardium. (b) EAT was extracted on an axial image (green).
Fig. 3.
Fig. 3.
A representative P-wave dispersion measurement (a) At baseline, measurement of leads II and V2 demonstrated maximum and minimum P-wave durations of 135 and 70 ms, respectively, and P-wave dispersion of 65 ms. (b) At 6-month follow-up, measurement of leads V6 and aVL demonstrated maximum and minimum P-wave durations of 125 and 70 ms, respectively, and P-wave dispersion of 55 ms.
Fig. 4.
Fig. 4.
Correlation between changes in P-wave dispersion or P-wave variation and changes in EAT volume or inflammatory marker (TNF-α) (a, b): Figures (a) and (b) show the correlation between the change in P-wave dispersion and changes in epicardial adipose tissue volume and plasma level of TNF-α. See text for details. (c, d): Figures (c) and (d) show the correlation between the change in P-wave variation and changes in epicardial adipose tissue volume and plasma level of TNF-α. See text for details.

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