Impact of dapagliflozin on left ventricular diastolic function of patients with type 2 diabetic mellitus with chronic heart failure

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

Background: The objective of this study was to investigate the impact of sodium glucose cotransporter type 2 (SGLT2) inhibitors on left ventricular (LV) diastolic function of type 2 diabetes mellitus (T2DM) patients with heart failure (HF).

Methods: This trial was a prospective multicenter study of 58 T2DM patients with stable HF at five institutions in Japan. Patients who had been taking at least one antidiabetic drugs other than SGLT2 inhibitors started the administration of 5 mg/day of dapagliflozin. The physical examinations, blood tests, and echocardiography were performed at baseline and 6 months after administration of dapagliflozin. The primary endpoint was defined as a change in mitral inflow E and mitral e' annular velocities (E/e') between baseline and 6 months after the administration of dapagliflozin. The secondary end points consisted of a change in brain natriuretic peptide (BNP), LV mass index (LVMI) and left atrial volume index (LAVI).

Results: E/e' significantly decreased from 9.3 to 8.5 cm/s (p = 0.020) 6 months after administration of dapagliflozin. LAVI and LVMI significantly decreased from 31 to 26 mL/m2 (p = 0.001), and from 75.0 to 67.0 g/m2 (p < 0.001), respectively, 6 months after administration of dapagliflozin. No significant change was observed in BNP (from 27.9 to 28.9 pg/mL; p = 0.132) 6 months after administration of dapagliflozin, except for a significant decrease from 168.8 to 114.3 pg/mL (p = 0.012) in patients with BNP ≥ 100 pg/mL.

Conclusion: This prospective multicenter trial showed the beneficial effect of SGLT2 inhibitors on LV diastolic functional parameters for T2DM patients with HF. Our findings may thus offer a new insight into the management of T2DM patients. Trial registration UMIN000019789, Registered 28 September 2014, Date of registration: 11/14/2015, Date of enrolment of the first participant to the trial: 6/15/2016, Date of enrolment of the last participant to the trial: 12/9/2017.

Keywords: Heart failure; Left ventricular diastolic function; Sodium glucose cotransporter type 2 inhibitors; Type 2 diabetes mellitus.

Figures

Fig. 1
Fig. 1
Result for primary end point, showing a significant decrease in E/e′ 6 months after administration of dapagliflozin
Fig. 2
Fig. 2
Results for secondary end points show a significant decrease in LAVI and LVMI significant decreased 6 months after administration of dapagliflozin. No significant change was observed in BNP 6 months after administration of dapagliflozin
Fig. 3
Fig. 3
BNP decreased significantly in T2DM patients with BNP ≥ 100 pg/mL, but not in those with BNP 

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