scholarly journals SGLT2 Inhibitors and Their Mode of Action in Heart Failure—Has the Mystery Been Unravelled?

2021 ◽  
Author(s):  
Steffen Pabel ◽  
Nazha Hamdani ◽  
Mark Luedde ◽  
Samuel Sossalla
Keyword(s):  
Heart Failure ◽  
Clinical Evidence ◽  
Ion Homeostasis ◽  
Cardiac Contractility ◽  
Sglt2 Inhibitors ◽  
New Drugs ◽  
Metabolic Effects ◽  
Patients With Heart Failure ◽  
Underlying Mechanisms ◽  
And Oxidative Stress

Abstract Purpose of review SGLT2 inhibitors (SGLT2i) are new drugs for patients with heart failure (HF) irrespective of diabetes. However, the mechanisms of SGLT2i in HF remain elusive. This article discusses the current clinical evidence for using SGLT2i in different types of heart failure and provides an overview about the possible underlying mechanisms. Recent findings Clinical and basic data strongly support and extend the use of SGLT2i in HF. Improvement of conventional secondary risk factors is unlikely to explain the prognostic benefits of these drugs in HF. However, different multidirectional mechanisms of SGLT2i could improve HF status including volume regulation, cardiorenal mechanisms, metabolic effects, improved cardiac remodelling, direct effects on cardiac contractility and ion-homeostasis, reduction of inflammation and oxidative stress as well as an impact on autophagy and adipokines. Summary Further translational studies are needed to determine the mechanisms of SGLT2i in HF. However, basic and clinical evidence encourage the use of SGLT2i in HFrEF and possibly HFpEF.

scholarly journals Treatment of Patients with Heart failure and Type 2 Diabetes: a review of the literature

2019 ◽  
Vol 13 (4) ◽  
pp. 205-224
Author(s):  
Elisa Fabbri ◽  
Maurizio Nizzoli
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Sglt2 Inhibitors ◽  
New Drugs ◽  
Review Of The Literature ◽  
Glucose Lowering ◽  
Promising Tool ◽  
Patients With Heart Failure ◽  
Underlying Mechanisms

Heart failure (HF) and type 2 diabetes (T2D) often coexist and having both the diseases compared to having one alone is associated with greater challenges in their management/treatment and worse outcomes. The present review of the literature is aimed at providing a comprehensive synopsis of the main evidences about the treatment of the two coexisting conditions. In particular, the recent introduction of new glucose-lowering drugs has been deeply changing the therapeutic approach to T2D. Big randomized controlled trails (RCTs) developed to test the cardiovascular safety of these new drugs consistently highlighted a reduction of the risk of hospitalization for HF in patients with T2D treated with sodium-glucose co-transporter 2 (SGLT2) inhibitors, suggesting a potential and revolutionary class effect probably related to their diuretic effect. Moreover, a renal protective effect of this drug class has also been emerging and the beneficial effect of SGLT2 inhibitors on the risk of HF hospitalization seems to be even greater in patients with worse renal function. In conclusion, although the underlying mechanisms are not fully understood, SGLT2 inhibitors appear to be a promising tool to treat HF and T2D. Ongoing RCTs specifically enrolling patients with HF treated with SGLT2 inhibitors will provide more insights and further information.

scholarly journals Effects of SGLT2 Inhibitors on Ion Homeostasis and Oxidative Stress associated Mechanisms in Heart Failure

2021 ◽  
Vol 143 ◽  
pp. 112169
Author(s):  
Gloria M. Gager ◽  
Dirk von Lewinski ◽  
Harald Sourij ◽  
Bernd Jilma ◽  
Ceren Eyileten ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ion Homeostasis ◽  
Sglt2 Inhibitors ◽  
And Oxidative Stress

scholarly journals Sodium-Glucose Cotransporter 2 Inhibitors and Heart Failure: A Bedside-to-Bench Journey

2021 ◽  
Vol 8 ◽  
Author(s):  
Donato Cappetta ◽  
Antonella De Angelis ◽  
Gabriella Bellocchio ◽  
Marialucia Telesca ◽  
Eleonora Cianflone ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ion Homeostasis ◽  
Sglt2 Inhibitors ◽  
Diabetic Patients ◽  
Cellular Targets ◽  
Multifactorial Diseases ◽  
Positive Effects ◽  
Sodium Glucose Cotransporter ◽  
Underlying Mechanisms ◽  
The Moment

Type 2 diabetes mellitus (T2DM) and heart failure (HF) are multifactorial diseases sharing common risk factors, such as obesity, hyperinsulinemia, and inflammation, with underlying mechanisms including endothelial dysfunction, inflammation, oxidative stress, and metabolic alterations. Cardiovascular benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors observed in diabetic and non-diabetic patients are also related to their cardiac-specific, SGLT-independent mechanisms, in addition to the metabolic and hemodynamic effects. In search of the possible underlying mechanisms, a research campaign has been launched proposing varied mechanisms of action that include intracellular ion homeostasis, autophagy, cell death, and inflammatory processes. Moreover, the research focus was widened toward cellular targets other than cardiomyocytes. At the moment, intracellular sodium level reduction is the most explored mechanism of direct cardiac effects of SGLT2 inhibitors that mediate the benefits in heart failure in addition to glucose excretion and diuresis. The restoration of cardiac Na+ levels with consequent positive effects on Ca2+ handling can directly translate into improved contractility and relaxation of cardiomyocytes and have antiarrhythmic effects. In this review, we summarize clinical trials, studies on human cells, and animal models, that provide a vast array of data in support of repurposing this class of antidiabetic drugs.

scholarly journals Revisiting the clinical evidence of heart rate target in patients with heart failure treated with beta-blockers

2021 ◽  
Vol 25 (11) ◽  
pp. 762-773
Author(s):  
Xue Geng ◽  
◽  
Jidong Zhang ◽  
Yanan Zhang ◽  
Haijuan Hu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Clinical Evidence ◽  
Beta Blockers ◽  
Patients With Heart Failure

SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials

The Lancet ◽  
2020 ◽  
Vol 396 (10254) ◽  
pp. 819-829 ◽  
Author(s):  
Faiez Zannad ◽  
João Pedro Ferreira ◽  
Stuart J Pocock ◽  
Stefan D Anker ◽  
Javed Butler ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Meta Analysis ◽  
Sglt2 Inhibitors ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure

scholarly journals Two-year follow-up of patients with heart failure with reduced ejection fraction receiving cardiac contractility modulation

2020 ◽  
Vol 25 (7) ◽  
pp. 3853
Author(s):  
M. A. Vander ◽  
E. A. Lyasnikova ◽  
L. A. Belyakova ◽  
M. A. Trukshina ◽  
V. L. Galenco ◽  
...  
Keyword(s):  
Heart Failure ◽  
Independent Predictor ◽  
Nyha Class ◽  
Cardiac Contractility ◽  
Composite Endpoint ◽  
Class Ii ◽  
Cardiac Contractility Modulation ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure

Aim. To assess the 2-year prognosis of patients with heart failure with reduced ejection fraction (HFrEF) receiving cardiac contractility modulation (CCM).Material and methods. This single-center observational study included 55 patients (46 men, mean age 53±11 years) with NYHA class II-III HFrEF receiving optimal medical therapy, with sinus rhythm, QRS <130 ms or QRS<150 ms with nonspecific intraventricular conduction delay. NYHA class II and III were established in 76% and 24% of patients, respectively. All patients were implanted with CCM devices between October 2016 and September 2017. Follow-up visits were carried out every 3 months during the 1st year and every 6 months during the 2nd year of observation. The primary composite endpoint was mortality and heart transplantation. Secondary composite endpoints included death, heart transplantation, paroxysmal ventricular tachycardia/ ventricular fibrillation, hospitalizations due decompensated HFResults. The one-year and two-year survival rate was 95% and 80%, respectively. Primary endpoint was observed in 20% of patients. NYHA class III and higher levels of N-terminal pro-brain natriuretic peptide (NTproBNP) were associated with unfavorable prognosis (p=0,014 and p=0,026, respectively). NTproBNP was an independent predictor of survival (p=0,018). CCM contributed to a significant decrease in hospitalizations due to decompensated HF (p<0,0001). The secondary endpoint was observed in 18 (33%) of patients during the 1st year. The predictor for the secondary composite endpoint was NTproBNP (p=0,047).Conclusion. CCM is associated with a significant decrease in hospitalization rate due to decompensated HF. The 2-year survival rate of patients with NYHA class II-III HF receiving CCM was 80%. The NTproBNP level was an independent predictor of survival in patients receiving CMM for 2 years. Further longer-term studies of the CCM efficacy are required.

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