Effect of Empagliflozin on Left Ventricular Volumes in Patients with Type 2 Diabetes, or Prediabetes, and Heart Failure with Reduced Ejection Fraction (SUGAR-DM-HF)

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of heart failure hospitalization and cardiovascular death in patients with heart failure and reduced ejection fraction (HFrEF). However, their effects on cardiac structure and function in HFrEF are uncertain. Methods: We designed a multicenter randomized, double-blind, placebo-controlled trial to investigate the cardiac effects of empagliflozin in patients in NYHA functional class II to IV with a left ventricular (LV) ejection fraction ≤40% and type 2 diabetes or prediabetes. Patients were randomized 1:1 to empagliflozin 10 milligrams once daily or placebo, stratified by age (<65 and ≥65 years) and glycemic status (diabetes or prediabetes). The co-primary outcomes were change from baseline to 36 weeks in LV end-systolic volume indexed to body surface area (LVESVi) and LV global longitudinal strain (LV GLS) measured using cardiovascular magnetic resonance (CMR). Secondary efficacy outcomes included other CMR measures (LVEDVi, LVEF), diuretic intensification, symptoms (Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS)), 6-minute walk distance (6MWD), B-lines on lung ultrasound and biomarkers (including NT-proBNP). Results: From April 2018 to August 2019, 105 patients were randomized: 77 (73.3%) male, mean age 68.7 [SD 11.1] years, 82 (78.1%) diabetes and 23 (21.9%) prediabetes, mean LVEF 32.5% [9.8%], and 81 (77.1%) NYHA II and 24 (22.9%) NYHA III. Patients received standard treatment for HFrEF. Compared with placebo, empagliflozin reduced LVESVi by 6.0 (-10.8 to -1.2) ml/m 2 (p=0.015). There was no difference in LV GLS. Empagliflozin reduced LVEDVi by 8.2 (-13.7 to -2.6) ml/m 2 (p=0.0042) and reduced NT-proBNP by 28 (2 to 47) %, p=0.038. There were no between-group differences in other CMR measures, KCCQ-TSS, 6MWD or B-lines. Conclusions: The SGLT2 inhibitor empagliflozin reduced LV volumes in patients with HFrEF and type 2 diabetes or prediabetes. Favorable reverse LV remodeling may be a mechanism by which SGLT2 inhibitors reduce HF hospitalization and mortality in HFrEF. Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique Identifier: NCT03485092.

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Positive effect of dapagliflozin on left ventricular longitudinal function for type 2 diabetic mellitus patients with chronic heart failure

European Heart Journal ◽

10.1093/ehjci/ehaa946.1009 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

H Tanaka ◽

F Soga ◽

K Tatsumi ◽

Y Mochizuki ◽

H Sano ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Diastolic Function ◽

Myocardial Function ◽

Sglt2 Inhibitor ◽

Left Ventricular ◽

Sglt2 Inhibitors ◽

Prospective Multicenter Study ◽

Lv Diastolic Function

Abstract Background Type 2 diabetes mellitus (T2DM) has come to be considered an independent predictor of mortality, and also a contributor to the development of heart failure (HF) with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). Left ventricular (LV) longitudinal myocardial dysfunction as assessed in terms of lower global longitudinal strain (GLS), has been identified even in T2DM patients with preserved LV ejection fraction (LVEF), and should be considered the first marker of a preclinical form of DM-related cardiac dysfunction, leading to HFpEF. Sodium glucose cotransporter type 2 (SGLT2) inhibitors represent a new class of anti-hyperglycemic agents for T2DM, but the effect of SGLT2 inhibitors on LV longitudinal myocardial function in T2DM patients with HF remains uncertain. To examine this effect, as well as the association of LV longitudinal myocardial function with LV diastolic function after administration of SGLT2 inhibitor in T2DM patients with stable HF, we analyzed data from our previous prospective multicenter study, in which we investigated the effect of SGLT2 inhibitor on LV diastolic functional parameters of T2DM patients with stable HF at five institutions in Japan. Methods Our previous 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. Echocardiography was performed at baseline and 6 months after administration of dapagliflozin. LV diastolic function was defined as the ratio of mitral inflow E to mitral e' annular velocities (E/e'). LV longitudinal myocardial function was assessed as GLS based on the current guidelines. Results E/e' significantly decreased from 9.3 to 8.5 cm/s 6 months after administration of dapagliflozin (p=0.020) as previously described, while GLS showed significant improvement from 15.5±3.5% to 16.9±4.1% (p<0.01) 6 months after administration of dapagliflozin. Furthermore, improvement of GLS in HFpEF patients was more significant from 17.0±1.9% to 18.7±2.0% (p<0.001), compared to that in HFrEF patients from 11.3±3.8% to 11.8±4.6% (p=0.13). It was noteworthy that multiple regression analysis showed that the change in GLS after administration of dapagliflozin was the only independent determinant parameter for the change in E/e' after administration of dapagliflozin. Conclusion Dapagliflozin was found to be associated with improvement of LV longitudinal myocardial function, which led to further improvement of LV diastolic function of T2DM patients with stable HF. GLS-guided management may thus lead to improved management of T2DM patients with stable HF. Representative case Funding Acknowledgement Type of funding source: None

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Dapagliflozin and the Incidence of Type 2 Diabetes in Patients With Heart Failure and Reduced Ejection Fraction: An Exploratory Analysis From DAPA-HF

10.2337/figshare.13235543 ◽

2020 ◽

Author(s):

Silvio E Inzucchi ◽

Kieran F Docherty ◽

Lars Køber ◽

Mikhail N Kosiborod ◽

Felipe A Martinez ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Ejection Fraction ◽

Sglt2 Inhibitor ◽

Adverse Outcomes ◽

Exploratory Analysis ◽

Diabetes Incidence ◽

Reduced Ejection Fraction ◽

Patients With Heart Failure

Objective The SGLT2 inhibitor dapagliflozin reduced the risk of cardiovascular mortality and worsening heart failure in the <a>Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure </a>trial (DAPA-HF). This report explores the effect of dapagliflozin on incident type 2 diabetes in the non-diabetic cohort enrolled in the trial. Research Design/Methods The subgroup of 2605 patients with heart failure and reduced ejection fraction (HFrEF), no prior history of diabetes, and a HbA1c of <6.5% at baseline was randomized to dapagliflozin 10 mg daily or placebo. In this exploratory analysis, surveillance for new onset diabetes was accomplished through periodic HbA1c testing as part of the study protocol and comparison between the treatment groups assessed through a Cox proportional hazards model. Results At baseline, the mean HbA1c was 5.8%. At 8 months, there were minimal changes, with a placebo-adjusted change in the dapagliflozin group of -0.04%. Over a median follow-up of 18 months, diabetes developed in 93/1307 patients (7.1%) in the placebo group and 64/1298 (4.9%) in the dapagliflozin group. Dapagliflozin led to a 32% reduction in diabetes incidence (HR 0.68, 95% CI, 0.50-0.94; p=0.019.) More than 95% of the participants who developed type 2 diabetes had prediabetes at baseline (HbA1c 5.7-6.4%.) Participants who developed diabetes in DAPA-HF had a higher subsequent mortality than those who did not. Conclusions In this exploratory analysis among patients with HFrEF, treatment with dapagliflozin reduced the incidence of new diabetes. This potential benefit needs confirmation in trials of longer duration and in people without heart failure.

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Dapagliflozin and the Incidence of Type 2 Diabetes in Patients With Heart Failure and Reduced Ejection Fraction: An Exploratory Analysis From DAPA-HF

10.2337/figshare.13235543.v1 ◽

2020 ◽

Author(s):

Silvio E Inzucchi ◽

Kieran F Docherty ◽

Lars Køber ◽

Mikhail N Kosiborod ◽

Felipe A Martinez ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Ejection Fraction ◽

Sglt2 Inhibitor ◽

Adverse Outcomes ◽

Exploratory Analysis ◽

Diabetes Incidence ◽

Reduced Ejection Fraction ◽

Patients With Heart Failure

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Effects of SGLT2 inhibitors on cardiovascular outcomes in patients with stage 3/4 CKD: A meta-analysis

PLoS ONE ◽

10.1371/journal.pone.0261986 ◽

2022 ◽

Vol 17 (1) ◽

pp. e0261986

Author(s):

Ning Li ◽

Guowei Zhou ◽

Yawei Zheng ◽

Dan Lv ◽

Xiangjun Zhu ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Ejection Fraction ◽

Cardiovascular Outcomes ◽

Sglt2 Inhibitors ◽

Atherosclerotic Cardiovascular Disease ◽

Reduced Ejection Fraction ◽

Stage 4

Introduction After stage 3 CKD, the risk of adverse cardiovascular events increased significantly. Therefore, we performed a meta-analysis to investigate the cardiovascular protective effect of SGLT2 inhibitors in patients with stage 3/4 CKD with different baseline kidney function or underlying diseases. Method To identify eligible trials, we systematically searched the Embase, PubMed, Web of Science, and Cochrane library databases from inception to April 15, 2021. The primary cardiovascular outcome was defined as a combination of cardiovascular mortality and hospitalization due to heart failure. Baseline kidney functions (stage 3a CKD: eGFR45-59mL/min per 1.73m2, stage 3b CKD: eGFR30-44mL/min per 1.73m2, stage 4 CKD: eGFR<30mL/min per 1.73m2) and underlying diseases (Type 2 diabetes, heart failure (Preserved ejection fraction or reduced ejection fraction), atherosclerotic cardiovascular disease) were used to stratify efficacy and safety outcomes. The results were subjected to a sensitivity analysis to ensure that they were reliable. Results In the present study, a total of eleven trials were included that involved a total of 27,823 patients with stage 3/4 CKD. The treatment and control groups contained 14,451 and 13,372 patients, respectively. In individuals with stage 3/4 CKD, SGLT2 inhibitors reduced the risk of primary cardiovascular outcomes by 26% (HR 0.74, [95% CI 0.69–0.80], I2 = 0.00%), by 30% in patients with stage 3a CKD (HR 0.70, [95% CI 0.59–0.84], I2 = 18.70%), by 23% in patients with stage 3b CKD (HR 0.77, [95% CI 0.66–0.90], I2 = 2.12%), and by 29% in patients with stage 4 CKD (HR 0.71, [95% CI 0.53–0.96], I2 = 0.00%). The risk of primary outcomes was reduced by 29% (HR 0.71, [95% CI 0.63–0.80], I2 = 0.00%) in patients with type 2 diabetes, by 28% (HR 0.72, [95% CI 0.56–0.93], I2 = 37.23%) in patients with heart failure with preserved ejection fraction, by 21% (HR 0.79, [95% CI 0.70–0.89], I2 = 0.00%) in patients with heart failure with reduced ejection fraction, and by 25% (HR 0.75, [95% CI 0.64–0.88], I2 = 0.00%) in patients with atherosclerotic cardiovascular disease. Conclusions For stage 3/4 CKD, SGLT2 inhibitors significantly decreased the risk of primary cardiovascular outcomes, and these benefits were consistent throughout the spectrum of different kidney functions, even in stage 4 CKD. There was no evidence of increased adverse outcomes across different baseline clinical complications, such as type 2 diabetes, heart failure, or atherosclerotic cardiovascular disease.

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Type 2 diabetes and heart failure: Characteristics and prognosis in preserved, mid-range and reduced ventricular function

Diabetes and Vascular Disease Research ◽

10.1177/1479164118794619 ◽

2018 ◽

Vol 15 (6) ◽

pp. 494-503 ◽

Cited By ~ 16

Author(s):

Isabelle Johansson ◽

Ulf Dahlström ◽

Magnus Edner ◽

Per Näsman ◽

Lars Rydén ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Left Ventricular Ejection Fraction ◽

Ejection Fraction ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Preserved Ejection Fraction ◽

Ventricular Ejection Fraction ◽

Reduced Ejection Fraction

Objective: To study the characteristics and prognostic implications of type 2 diabetes in different heart failure entities from a nationwide perspective. Methods: This observational study comprised 30,696 heart failure patients prospectively included in the Swedish Heart Failure Registry (SwedeHF) 2003–2011 from specialist care, with mortality information available until December 2014. Patients were categorized into three heart failure entities by their left ventricular ejection fraction (heart failure with preserved ejection fraction: ⩾50%, heart failure with mid-range ejection fraction: 40%–49% and heart failure with reduced ejection fraction: <40%). All-cause mortality stratified by type 2 diabetes and heart failure entity was studied by Cox regression. Results: Among the patients, 22% had heart failure with preserved ejection fraction, 21% had heart failure with mid-range ejection fraction and 57% had heart failure with reduced ejection fraction. The proportion of type 2 diabetes was similar, ≈25% in each heart failure entity. Patients with type 2 diabetes and heart failure with preserved ejection fraction were older, more often female and burdened with hypertension and renal impairment compared with heart failure with mid-range ejection fraction and heart failure with reduced ejection fraction patients among whom ischaemic heart disease was more common. Type 2 diabetes remained an independent mortality predictor across all heart failure entities after multivariable adjustment, somewhat stronger in heart failure with left ventricular ejection fraction below 50% (hazard ratio, 95% confidence interval; heart failure with preserved ejection fraction: 1.32 [1.22–1.43], heart failure with mid-range ejection fraction: 1.51 [1.39–1.65], heart failure with reduced ejection fraction: 1.46 [1.39–1.54]; p-value for interaction, p = 0.0049). Conclusion: Type 2 diabetes is an independent mortality predictor across all heart failure entities increasing mortality risk by 30%–50%. In type 2 diabetes, the heart failure with mid-range ejection fraction entity resembles heart failure with reduced ejection fraction in clinical characteristics, risk factor pattern and prognosis.

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Effect of canagliflozin on N-terminal pro-brain natriuretic peptide in patients with type 2 diabetes and chronic heart failure according to baseline use of glucose-lowering agents

Cardiovascular Diabetology ◽

10.1186/s12933-021-01369-5 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Atsushi Tanaka ◽

Shigeru Toyoda ◽

Takumi Imai ◽

Kazuki Shiina ◽

Hirofumi Tomiyama ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Ejection Fraction ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Left Ventricular ◽

Sglt2 Inhibitors ◽

Left Ventricular Ejection ◽

Glucose Lowering

Abstract Background Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of a deterioration in heart failure (HF) and mortality in patients with a broad range of cardiovascular risks. Recent guidelines recommend considering the use of SGLT2 inhibitors in patients with type 2 diabetes (T2D) and HF, irrespective of their glycemic control status and background use of other glucose-lowering agents including metformin. However, only a small number of studies have investigated whether the effects of SGLT2 inhibitor in these patients differ by the concomitant use of other glucose-lowering agents. Methods This was a post-hoc analysis of the CANDLE trial (UMIN000017669), an investigator-initiated, multicenter, open-label, randomized, controlled trial. The primary aim of the analysis was to assess the effect of 24 weeks of treatment with canagliflozin, relative to glimepiride, on N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration in patients with T2D and clinically stable chronic HF. In the present analysis, the effect of canagliflozin on NT-proBNP concentration was assessed in the patients according to their baseline use of other glucose-lowering agents. Results Almost all patients in the CANDLE trial presented as clinically stable (New York Heart Association class I to II), with about 70% of participants having HF with a preserved ejection fraction phenotype (defined as a left ventricular ejection fraction ≥ 50%) at baseline. Of the 233 patients randomized to either canagliflozin (100 mg daily) or glimepiride (starting dose 0.5 mg daily), 85 (36.5%) had not been taking any glucose-lowering agents at baseline (naïve). Of the 148 patients who had been taking at least one glucose-lowering agent at baseline (non-naïve), 44 (29.7%) and 127 (85.8%) had received metformin or a dipeptidyl dipeptidase-4 (DPP-4) inhibitor, respectively. The group ratio (canagliflozin vs. glimepiride) of proportional changes in the geometric means of NT-proBNP concentration was 0.95 (95% confidence interval [CI] 0.76 to 1.18, p = 0.618) for the naïve subgroup, 0.92 (95% CI 0.79 to1.07, p = 0.288) for the non-naïve subgroup, 0.90 (95% CI 0.68 to 1.20, p = 0.473) for the metformin-user subgroup, and 0.91 (95% CI 0.77 to 1.08, p = 0.271) for the DPP-4 inhibitor-user subgroup. No heterogeneity in the effect of canagliflozin, relative to glimepiride, on NT-proBNP concentration was observed in the non-naïve subgroups compared to that in the naïve subgroup. Conclusion The impact of canagliflozin treatment on NT-proBNP concentration appears to be independent of the background use of diabetes therapy in the patient population examined. Trial registration University Medical Information Network Clinical Trial Registry, number 000017669. Registered on May 25, 2015

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Effects of SGLT2 inhibitor dapagliflozin in patients with heart failure with reduced ejection fraction

Russian Journal of Cardiology ◽

10.15829/1560-4071-2020-4049 ◽

2020 ◽

Vol 25 (8) ◽

pp. 4049

Author(s):

N. R. Khasanov

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Drug Class ◽

Sglt2 Inhibitor ◽

Cardiovascular Death ◽

Sglt2 Inhibitors ◽

Reduced Ejection Fraction ◽

Patients With Heart Failure ◽

Recommended Therapy

SGLT2 inhibitors have been shown to reduce the risk of cardiovascular events and the development and decompensation of heart failure (HF) in patients with type 2 diabetes (T2D). The improved prognosis in HF may be related not only to the hypoglycemic effect of this drug class. The DAPA-HF study, which included patients with HF with reduced ejection fraction, demonstrated the benefit of dapagliflozin in reducing the risk of cardiovascular death and worsening HF, as well as improving HF symptoms compared to placebo, regardless of the presence of T2D and the recommended therapy for HF.

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Impact of canagliflozin in natriuretic peptides in patients with type 2 diabetes after hospitalization for acute heart failure

European Heart Journal ◽

10.1093/eurheartj/ehab724.0902 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

E Martin Dorado ◽

R Gonzalez Manzanares ◽

J.C Castillo Dominguez ◽

J Lopez Aguilera ◽

J Perea ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Ejection Fraction ◽

Acute Decompensated Heart Failure ◽

Signs And Symptoms ◽

Sglt2 Inhibitors ◽

Control Group ◽

Dipeptidyl Peptidase 4 ◽

Reduced Ejection Fraction

Abstract Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated to reduce the risk of hospitalization for heart failure (HF) in patients with type 2 diabetes mellitus (T2D). We aimed to assess the changes in N-terminal pro-B-type natriuretic peptide (NT-ProBNP) concentrations in a cohort of patients hospitalized for HF according to whether or not they received canagliflozin at discharge. Methods This cohort study included all patients with T2D admitted for HF from January 2017 to December 2019 in a single center. We excluded patients whose treatment with SGLT2 inhibitors were contraindicated (eGFR ≤45 ml/min/1.73 m2) and those who had other SGLT2 inhibitors than canagliflozin in their treatment at discharged. All patients had received a primary diagnosis of acute decompensated heart failure, including signs and symptoms of fluid overload and a concentration of NT-ProBNP of 1400 pg/mL at least. NT-ProBNP concentrations were collected at 3 months, 6 months, and 1 year after hospitalization with laboratory records if available. The aim of this study is to compare mean NT-ProBNP levels at hospital discharge and 3, 6 and 12 moths of follow-up in patients treated with and without canagliflozin. Results We included a total of 102 patients, 45 patients (44.1%) were prescribed canagliflozin and the remaining 57 (55.9%) were not prescribed any SGLT2 inhibitors (control group). There were no significant differences in clinical and comorbidities in both groups, except for age; slightly younger in the canagliflozin group (69,2±10,3 vs 73,2±11,1; p=0,04). Treatment at discharge was also similar, patients in the control group received more dipeptidyl peptidase-4 (DPP-4) inhibitors (21.1% vs 6.7%; p=0.04). Low rate of patients received sacubitril-valsartan (15,6%) in the canagliflozin group and 14% in the control group. More than a half of patients in both groups have HF with reduced ejection fraction. Mean levels of peptides were similar in both groups at hospital admission and discharge. During the first period of 3 months, we observed a decreased of NT-ProBNP concentration in both groups, but significantly inferior in canagliflozin group (p<0,001). At 6 and 12 months, NT-ProBNP levels were practically maintained in patients treated with canagliflozin, whereas levels in patients in the control group were increased. Difference in both groups at a 12 month-period was significantly superior (p=0,004), with a median reduction of concentration levels at discharge of 64.3% in the canagliflozin group and 15,8% in control group. There were no differences in patients with HF from those with reduced ejection fraction and preserved. Conclusions Canagliflozin therapy at discharge was associated with a significant reduction in NT-ProBNP concentration in patients with diabetes after hospitalization for HF. FUNDunding Acknowledgement Type of funding sources: None. NT-ProBNP according to canagliflozin

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Letter by Singh et al Regarding Article, “Effect of Empagliflozin on Left Ventricular Volumes in Patients With Type 2 Diabetes, or Prediabetes, and Heart Failure With Reduced Ejection Fraction (SUGAR-DM-HF)”

Circulation ◽

10.1161/circulationaha.120.053057 ◽

2021 ◽

Vol 144 (3) ◽

Author(s):

Jagdeep S. Singh ◽

Allan D. Struthers ◽

Chim C. Lang

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Ejection Fraction ◽

Left Ventricular ◽

Left Ventricular Volumes ◽

Ventricular Volumes ◽

Reduced Ejection Fraction

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Positive effect of dapagliflozin on left ventricular longitudinal function for type 2 diabetic mellitus patients with chronic heart failure

Cardiovascular Diabetology ◽

10.1186/s12933-019-0985-z ◽

2020 ◽

Vol 19 (1) ◽

Cited By ~ 7

Author(s):

Hidekazu Tanaka ◽

Fumitaka Soga ◽

Kazuhiro Tatsumi ◽

Yasuhide Mochizuki ◽

Hiroyuki Sano ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Diastolic Function ◽

Longitudinal Strain ◽

Myocardial Function ◽

Global Longitudinal Strain ◽

Sglt2 Inhibitor ◽

Left Ventricular ◽

Lv Diastolic Function

Abstract Background The effect of sodium glucose cotransporter type 2 (SGLT2) inhibitor on left ventricular (LV) longitudinal myocardial function in type 2 diabetes mellitus (T2DM) patients with heart failure (HF) has remained unclear. Methods We analyzed data from our previous prospective multicenter study, in which we investigated the effect of the SGLT2 inhibitor dapagliflozin on LV diastolic functional parameters of T2DM patients with stable HF at five institutions in Japan. Echocardiography was performed at baseline and 6 months after administration of dapagliflozin. LV diastolic function was defined as the ratio of mitral inflow E to mitral e′ annular velocities (E/e′). LV longitudinal myocardial function was assessed as global longitudinal strain (GLS), which in turn was determined as the averaged peak longitudinal strain from standard LV apical views. Results E/e′ significantly decreased from 9.3 to 8.5 cm/s 6 months after administration of dapagliflozin (p = 0.020) as previously described, while GLS showed significant improvement from 15.5 ± 3.5% to 16.9 ± 4.1% (p < 0.01) 6 months after administration of dapagliflozin. Furthermore, improvement of GLS in HF with preserved ejection fraction patients was more significant from 17.0 ± 1.9% to 18.7 ± 2.0% (p < 0.001), compared to that in HF with mid-range ejection fraction and HF with reduced ejection fraction patients from 14.4 ± 2.4% to 15.5 ± 1.8% (p = 0.06) and from 8.1 ± 1.5% to 7.8 ± 2.1% (p = 0.44), respectively. It was noteworthy that multiple regression analysis showed that the change in GLS after administration of dapagliflozin was the only independent determinant parameters for the change in E/e′ after administration of dapagliflozin. Conclusion Dapagliflozin was found to be associated with improvement of LV longitudinal myocardial function, which led to further improvement of LV diastolic function of T2DM patients with stable HF. GLS-guided management may thus lead to improved management of T2DM patients with stable HF.

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