Impact of Dapagliflozin on the Left Ventricular Diastolic Function in Diabetic Patients with Heart Failure Complicating Cardiovascular Risk Factors

Fumitaka Soga, Hidekazu Tanaka, Kazuhiro Tatsumi, Yasuhide Mochizuki, Hiroyuki Sano, Hiromi Toki, Kensuke Matsumoto, Junya Shite, Hideyuki Takaoka, Tomofumi Doi, Ken-Ichi Hirata, Fumitaka Soga, Hidekazu Tanaka, Kazuhiro Tatsumi, Yasuhide Mochizuki, Hiroyuki Sano, Hiromi Toki, Kensuke Matsumoto, Junya Shite, Hideyuki Takaoka, Tomofumi Doi, Ken-Ichi Hirata

Abstract

Objective Our aim was to investigate the impact of the sodium glucose cotransporter type 2 (SGLT2) inhibitor on the left ventricular (LV) diastolic function in type 2 diabetes mellitus (T2DM) patients with chronic heart failure (HF) complicating cardiovascular risk factors. Methods We analyzed data from our previous prospective multicenter study, in which we investigated the effect of dapagliflozin on the LV diastolic function of T2DM patients with stable HF at five institutions in Japan. Patients who had been taking at least 1 antidiabetic drug other than SGLT2 inhibitors started treatment with dapagliflozin. Echocardiography was performed at baseline and six months after the administration of dapagliflozin. Cardiovascular risk factors other than T2DM were age, gender, hypertension, dyslipidemia, history of cardiovascular events and overweight. Results The LV diastolic function, defined as the ratio of the mitral inflow E to the mitral e' annular velocities (E/e'), significantly decreased from 9.3 to 8.5 by six months after the administration of dapagliflozin (p=0.020) as previously reported. A multivariate logistic regression analysis showed that dyslipidemia was the only independent determinant of improvement in the E/e' after the administration of dapagliflozin among cardiovascular risk factors. Furthermore, the relative change in the E/e' from baseline to six months after the administration of dapagliflozin for HF patients with preserved ejection fraction (HFpEF) and dyslipidemia was significantly larger than that for HFpEF patients without dyslipidemia (-15.2% vs. 29.6%, p=0.014), but no such finding was observed in non-HFpEF patients. Conclusion SGLT2 inhibitors may exert a more beneficial effect on the LV diastolic function for T2DM patients with stable HF, especially those with complicating dyslipidemia, than existing treatments.

Keywords: SGLT2 inhibitor; diabetes mellitus; diastolic function; dyslipidemia; echocardiography.

Conflict of interest statement

The authors state that they have no Conflict of Interest (COI).

Figures

Figure 1.
Figure 1.
Bar graphs of the relative changes in the E/e’ from baseline to six months after the administration of dapagliflozin, showing that these changes in the E/e’ in patients with dyslipidemia tended to be larger than in patients without dyslipidemia, although without statistically significant difference.
Figure 2.
Figure 2.
Bar graphs of the relative changes in the E/e’ from baseline to six months after the administration of dapagliflozin, showing that the relative changes in the E/e’ in HFpEF patients with dyslipidemia were significantly larger than those in HFpEF patients without dyslipidemia, although such finding was not observed in non-HFpEF patients. HFpEF: heart failure with preserved ejection fraction
Figure 3.
Figure 3.
A linear regression analysis comparing the relative changes in the lipid profiles from baseline to six months after the administration of dapagliflozin and those in the E/e’, showing a significant correlation between changes in the HDL-C levels and those in the E/e’. HDL-C: high-density lipoprotein cholesterol

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