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

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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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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impact of dapagliflozin on left ventricular diastolic function in diabetic patients with heart failure complicating cardiovascular risk factors

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa356.021 ◽

2021 ◽

Vol 22 (Supplement_1) ◽

Author(s):

F Soga ◽

H Tanaka ◽

K Tatsumi ◽

Y Mochizuki ◽

H Sano ◽

...

Keyword(s):

Risk Factors ◽

Heart Failure ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Diastolic Function ◽

Sglt2 Inhibitor ◽

Density Lipoprotein ◽

Left Ventricular ◽

Lv Diastolic Function

Abstract Funding Acknowledgements Type of funding sources: None. Background Type 2 diabetes mellitus (T2DM) is a well-known risk factor for heart failure (HF), even in patients without a structural heart disease or a symptom of HF. Diabetes-related cardiomyopathy is presented as an left ventricular (LV) diastolic dysfunction, which, like cardiovascular disease, is a contributor of the development of HF in both patients with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). Furthermore, comorbid factors other than T2DM also have been identified as high risk factors for of progression to HF. Dapagliflozin is a sodium glucose cotransporter type 2 (SGLT2) inhibitor, and represents a new class of anti-hyperglycemic agents for T2DM. A result from a recent large clinical trial showed that dapagliflozin reduced risk of worsening HF or death from cardiovascular causes for patients with HFrEF compared to those who received a placebo, regardless of the presence or absence of T2DM. However, the effect of SGLT2 inhibitors on LV diastolic function in T2DM patients with HF who had cardiovascular risk factors other than T2DM remains uncertain. Purpose Our purpose was to investigate the impact of dapagliflozin on LV diastolic function in T2DM patients with stable HF complicating cardiovascular risk factors. Methods We analyzed data from our previous prospective multicenter study, which investigate the effect of dapagliflozin on LV diastolic function of 53 T2DM patients with stable HF at five institutions in Japan. Patients who had been taking at least one antidiabetic drugs other than SGLT2 inhibitor started the administration of dapagliflozin. Cardiovascular risk factors other than T2DM was determined as age, gender, hypertension, dyslipidemia, history of cardiovascular events and overweight. 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. Multivariate logistic regression analysis showed that dyslipidemia was the only independent determinant of an improvement of E/e’ among cardiovascular risk factors. Furthermore, relative changes in E/e’ from baseline to 6 months after administration of dapagliflozin seen in HFpEF patients with dyslipidemia were significantly larger than those in HFpEF patients without dyslipidemia (-15.2% vs. 29.6%, p = 0.014), but such a difference was not observed in non-HFpEF patients. In addition, relative changes in high-density lipoprotein cholesterol (HDL-C) from baseline to 6 months after administration of dapagliflozin had significant correlation with those in E/e’ (r=-0.300, p = 0.038). However, such correlations were not observed in low-density lipoprotein cholesterol (LDL-C) and triglyceride (r = 0.05, p = 0.72 and r = 0.05, p = 0.73). Conclusion: Dapagliflozin was more beneficial effect on LV diastolic function for T2DM patients with stable HF, especially those with complicating dyslipidemia. Our findings may thus offer a new insight into the management of T2DM patients with HF. Abstract Figure.

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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.120.052186 ◽

2020 ◽

Author(s):

Matthew M. Y. Lee ◽

Katriona J. M. Brooksbank ◽

Kirsty Wetherall ◽

Kenneth Mangion ◽

Giles Roditi ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Ejection Fraction ◽

Global Longitudinal Strain ◽

Sglt2 Inhibitor ◽

Left Ventricular ◽

Sglt2 Inhibitors ◽

Reduced Ejection Fraction ◽

B Lines

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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P1508 Left ventricular diastolic function plays a different role on mortality depending on the severity of systolic dysfunction in acute heart failure patients with reduced ejection fraction

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez319.932 ◽

2020 ◽

Vol 21 (Supplement_1) ◽

Author(s):

K Nakamura ◽

A Yamada ◽

S Jinno ◽

M Kato ◽

A Takahashi ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Diastolic Function ◽

Acute Heart Failure ◽

Cardiac Death ◽

Systolic Dysfunction ◽

Left Ventricular ◽

Group Iii ◽

Group I ◽

Lv Diastolic Function

Abstract Background It remains to be clarified whether clinical significance of left ventricular (LV) diastolic function differs depending on the severity of LV systolic dysfunction in patients with acute heart failure (AHF). The aim of this study was to examine the prognostic role of LV diastolic function in AHF patients with various systolic dysfunction.Methods: We studied consecutive hospitalized AHF patients with LV ejection fraction (LVEF) <50%. The exclusion criteria were as follows: atrial fibrillation, severe mitral regurgitation, and inadequate echo image quality. They underwent echocardiography on admission. The eligible patients (n = 289, 165 males, 76 ± 10 years) were divided into 4 groups based on LVEF and left atrial pressure (LAP) grade estimated as in the ESC guidelines: Group I (LVEF 40-49% (mildly reduced LVEF)/normal LAP, n = 28), II (mildly reduced EF/increased LAP, n = 38), III (LVEF <40% (severely reduced LVEF)/normal LAP, n = 110), and IV (severely reduced LVEF/increased LAP, n = 113). Cardiac death was examined up to 60 months.Results: In total, 58 patients (20%) died because of cardiac events during the follow-up (mean 20 ± 19 months). In patients with mildly reduced LVEF, Group I showed significantly less cardiac death ratio than II (n = 1 vs 10, Group I vs II, p = 0.03). On the other hand, in patients with severely reduced LVEF, there was no significant difference in cardiac death ratio between Group III and IV (n = 23 vs 24, Group III vs IV, p = 0.80). That is, LAP grade was a prognostic marker when the patients had mild LV systolic dysfunction, whereas it did not contribute to the prediction of cardiac mortality when patients showed severely reduced LV systolic function. Group I showed significantly better prognosis than those with severe LV systolic dysfunction regardless of LAP grade (Group III, IV) (Group I vs III, p = 0.04; Group I vs IV, p = 0.04).Conclusions: LV diastolic function may have a different clinical significance depending on the severity of LV systolic dysfunction in AHF patients.

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New antidiabetic therapy and HFpEF: light at the end of tunnel?

Heart Failure Reviews ◽

10.1007/s10741-021-10106-9 ◽

2021 ◽

Author(s):

Marijana Tadic ◽

Carla Sala ◽

Sahrai Saeed ◽

Guido Grassi ◽

Giuseppe Mancia ◽

...

Keyword(s):

Ejection Fraction ◽

Diastolic Function ◽

Negative Impact ◽

Left Ventricular ◽

Sglt2 Inhibitors ◽

Antidiabetic Therapy ◽

Positive Message ◽

Increased Risk ◽

The Impact ◽

Lv Diastolic Function

AbstractNew antidiabetic therapy that includes sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor (GLP-1R) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors showed significant benefit on cardiovascular outcomes in patients with and without type 2 diabetes mellitus, and this was particularly confirmed for SGLT2 inhibitors in subjects with heart failure (HF) with reduced ejection fraction (HFrEF). Their role on patients with HF with preserved ejection fraction (HFpEF) is still not elucidated, but encouraging results coming from the clinical studies indicate their beneficial role. The role of GLP-1R agonists and particularly DPP-4 inhibitors is less clear and debatable. Findings from the meta-analyses are sending positive message about the use of GLP-1R agonists in HFrEF therapy and revealed the improvement of left ventricular (LV) diastolic function in HFpEF. Nevertheless, the relevant medical societies still consider their effect as neutral or insufficiently investigated in HF patients. The impact of DPP-4 inhibitors in HF is the most controversial due to conflicting data that range from negative impact and increased risk of hospitalization due to HF, throughout neutral effect, to beneficial influence on LV diastolic dysfunction. However, this is a very heterogeneous group of medications and some professional societies made clear discrepancy between saxagliptin that might increase risk of HF hospitalization and those DPP-4 inhibitors that have no effect on hospitalization. The aim of this review is to summarize current clinical evidence about the effect of new antidiabetic medications on LV diastolic function and their potential benefits in HFpEF patients.

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Association of glycemic variability with left ventricular diastolic function in type 2 diabetes mellitus

Cardiovascular Diabetology ◽

10.1186/s12933-019-0971-5 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 8

Author(s):

Shun Yokota ◽

Hidekazu Tanaka ◽

Yasuhide Mochizuki ◽

Fumitaka Soga ◽

Kentaro Yamashita ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Ejection Fraction ◽

Diastolic Function ◽

Glycemic Variability ◽

Left Ventricular ◽

Lv Diastolic Dysfunction ◽

Lv Diastolic Function

Abstract Background Type 2 diabetes mellitus (T2DM) is a major cause of heart failure (HF) with preserved ejection fraction (HFpEF), usually presenting as left ventricular (LV) diastolic dysfunction. Thus, LV diastolic function should be considered a crucial marker of a preclinical form of DM-related cardiac dysfunction. However, the impact of glycemic variability (GV) on LV diastolic function in such patients remains unclear. Methods We studied 100 asymptomatic T2DM patients with preserved LV ejection fraction (LVEF) without coronary artery disease (age: 60 ± 14 years, female: 45%). GV was evaluated as standard deviation of blood glucose level using continuous glucose monitoring system for at least 72 consecutive hours. LV diastolic function was defined as mitral inflow E and mitral e’ annular velocities (E/e’), and > 14 was determined as abnormal. Results E/e’ in patients with high GV (≥ 35.9 mg/dL) was significantly higher than that in patients with low GV (11.3 ± 3.9 vs. 9.8 ± 2.8, p = 0.03) despite similar age, gender-distribution, and hemoglobin A1c (HbA1c). Multivariate logistic regression analysis showed that GV ≥ 35.9 mg/dL (odds ratio: 3.67; 95% confidence interval: 1.02–13.22; p < 0.05) was an independently associated factor, as was age, of E/e’ > 14. In sequential logistic models for the associations of LV diastolic dysfunction, one model based on clinical variables including age, gender and hypertension was not improved by addition of HbA1c (p = 0.67) but was improved by addition of high GV (p = 0.04). Conclusion Since HFpEF is a syndrome caused by diverse agents, reducing GV may represent a potential new therapeutic strategy for the prevention of the development of HFpEF in T2DM patients.

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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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Abstract 16307: Tofogliflozin Improves Pulmonary Hypertension With Heart Failure With Preserved Ejection Fraction Mice

Circulation ◽

10.1161/circ.142.suppl_3.16307 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Yusuke Joki ◽

Hakuoh Konishi ◽

Kiyoshi Takasu ◽

Tohru Minamino

Keyword(s):

Heart Failure ◽

Pulmonary Hypertension ◽

Ejection Fraction ◽

Beneficial Effect ◽

Right Ventricular ◽

Sglt2 Inhibitor ◽

Systolic Pressure ◽

Left Ventricular ◽

Sglt2 Inhibitors ◽

Urine Glucose

Introduction: Pulmonary hypertension (PH) is a syndrome of increased pulmonary artery pressure and often leads to death. Left heart diseases(LHD) are frequently complicated by PH (PH-LHD), classified group2. In particular, PH with heart failure with preserved LV ejection fraction (HFpEF) is higher prevalence metabolic syndrome and poor prognosis than LHD without PH. Tofogliflozin (TOFO) is SGLT2 inhibitor as a therapeutic agent for diabetes. Recent study revealed SGLT2 inhibitors have a beneficial effect on heart failure. However it has not been clarified that SGLT2 inhibitors affect PH-LHD. This study examined whether TOFO improved for PH-LHD. Hypothesis: We hypothesis TOFO has a protective effect for PH with HFpEF. Methods: We used two HFpEF mice models, induced by transverse aortic constriction (TAC) surgery and high fat diet (HFD). TAC model: C57BL/6J mice were subjected to TAC. Sham and TAC mice were treated with TOFO 3mg/kg in water by day or only water. After 4weeks, each mouse was measured physical data, Body weight (BW), Left ventricular weight (LV), Right ventricular weight (RV), right ventricular systolic pressure (RVSP), UCG, collected blood and urine glucose. HFD model: AKR/J mice fed a HFD for 20weeks. Regular diet and HFD mice were treated with TOHO 3mg/kg in water by day or only water. 20weeks later each mouse measured above data. Results and Conclusions: Mice treated with TOFO had significantly higher urine glucose concentrations. TAC induced left ventricular hypertrophy, increased HW/BW ratio and RVSP. However TAC+TOFO mice were reduced hypertrophy and LV/BW ratio than TAC group. Moreover TAC+TOFO mice were improved RV/LV ratio and RVSP (Figure). AKR/J+HFD groups substantially higher BW and occurred PH than RFD groups. In contrast with HFD, TOFO treated group ameliorated BW, RW/LW ratio, moreover normal RVSP. These results showed Tofogliflozin had a beneficial effect for PH with HFpEF.

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The dawn of the four-drug era? SGLT2 inhibition in heart failure with reduced ejection fraction

Therapeutic Advances in Cardiovascular Disease ◽

10.1177/17539447211002678 ◽

2021 ◽

Vol 15 ◽

pp. 175394472110026

Author(s):

Michael V. Genuardi ◽

Paul J. Mather

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Controlled Trial ◽

Sglt2 Inhibitor ◽

The United States ◽

Sglt2 Inhibitors ◽

Current Guideline ◽

Converting Enzyme Inhibitors ◽

Reduced Ejection Fraction

Sodium-glucose cotransporter type 2 (SGLT2) inhibitors are a relatively new class of antihyperglycemic drug with salutary effects on glucose control, body weight, and blood pressure. Emerging evidence now indicates that these drugs may have a beneficial effect on outcomes in heart failure with reduced ejection fraction (HFrEF). Post-approval cardiovascular outcomes data for three of these agents (canagliflozin, empagliflozin, and dapagliflozin) showed an unexpected improvement in cardiovascular endpoints, including heart failure hospitalization and mortality, among patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease or risk factors. These studies were followed by a placebo controlled trial of dapagliflozin in patients with HFrEF both with and without T2DM, showing a reduction in all-cause mortality comparable to current guideline-directed HFrEF medical therapies such as angiotensin-converting enzyme inhibitors and beta-blockers. In this review, we discuss the current landscape of evidence, safety and adverse effects, and proposed mechanisms of action for use of these agents for patients with HFrEF. The United States (US) and European guidelines are reviewed, as are the current US federally approved indications for each SGLT2 inhibitor. Use of these agents in clinical practice may be limited by an uncertain insurance environment, especially in patients without T2DM. Finally, we discuss practical considerations for the cardiovascular clinician, including within-class differences of the SGLT2 inhibitors currently available on the US market (217/300).

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