scholarly journals Heart Failure Challenge in T2DM

2021 ◽  
Vol 23 (Supplement_D) ◽  
Author(s):  
Osama Elmaraghi
Keyword(s):  
Heart Failure ◽  
Sglt2 Inhibitor ◽  
Clinical Syndrome ◽  
Reduced Ejection Fraction ◽  
New Class ◽  
Glucose Reabsorption ◽  
Urinary Glucose ◽  
Patients With Heart Failure ◽  
Outcome Trial ◽  
Glucose Excretion

Abstract Introduction Heart failure is a clinical syndrome caused by a structural and/or functional cardiac abnormality, resulting in a reduced cardiac output and/or elevated intracardiac pressures at rest or during stress.1 There are 463 million patient with diabetes mellitus all over the world .2 People with diabetes have a 2- to 5-fold higher risk of developing HF3, On the other hand more than 30% of patients with heart failure also have diabetes. Patients with heart failure and diabetes have a worse prognosis than those without diabetes4. UKPDs, Accord and advance trials showed that Intensive glycaemic control has not been shown to significantly impact the risk of HF.5,6 SGLT2 inhibitor is a new class of drugs to treat diabetes by inhibiting SGT2 decreases glucose reabsorption and increases urinary glucose excretion, improving glucose control in the diabetic patient.7 At 2015 EMPA-REG OUTCOME trial showed that Empagliflozin in addition to reduction of HBa1c, reduced the 3MAC by 14%, CV death by 38% and HHF by 35%. Is these cardiovascular benefit were a chance? 8 Then DECLARE-TMI58, CNVAS and VIRTIS trials showed that Dapagliflizon, Canagliflozin and ertuglifozin respectively in addition to reduction of HBa1c, reduce HHFso it is a class effect. 9,10,11 Because in these trials starting treatment at the preclinical stage may prevent HF progression and improve outcomes. Objective We have 3 questions to be answered: There are 4 trials to answer these Questions DAPA HF, DELIVER, EMPEROR-Reduced and EMPEROR –Preserved. DAPA-HF and EMPEROR –Reduced include patients with HF with reduced ejection fraction, diabetic and non-diabetic the result of both was reduce the risk of worsening HF or death from cardiovascular causes regardless of the presence or absence of DM. 10,11 Conclusion The results of these trials FDA Approves Dapagliflozin for low EF-Heart Failure in diabetic and Non-diabetic. FDA had granted Fast Track status for empagliflozin. Waiting the result of other trials.12

scholarly journals Increase in SGLT1-mediated transport explains renal glucose reabsorption during genetic and pharmacological SGLT2 inhibition in euglycemia

2014 ◽  
Vol 306 (2) ◽  
pp. F188-F193 ◽  
Author(s):  
Timo Rieg ◽  
Takahiro Masuda ◽  
Maria Gerasimova ◽  
Eric Mayoux ◽  
Kenneth Platt ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Plasma Concentrations ◽  
Sglt2 Inhibitor ◽  
Double Knockout ◽  
Glucose Reabsorption ◽  
Urinary Glucose ◽  
Sglt2 Inhibition ◽  
Renal Glucose Reabsorption ◽  
Glucose Excretion ◽  
Free Plasma

In the kidney, the sodium-glucose cotransporters SGLT2 and SGLT1 are thought to account for >90 and ∼3% of fractional glucose reabsorption (FGR), respectively. However, euglycemic humans treated with an SGLT2 inhibitor maintain an FGR of 40–50%, mimicking values in Sglt2 knockout mice. Here, we show that oral gavage with a selective SGLT2 inhibitor (SGLT2-I) dose dependently increased urinary glucose excretion (UGE) in wild-type (WT) mice. The dose-response curve was shifted leftward and the maximum response doubled in Sglt1 knockout (Sglt1−/−) mice. Treatment in diet with the SGLT2-I for 3 wk maintained 1.5- to 2-fold higher urine glucose/creatinine ratios in Sglt1−/− vs. WT mice, associated with a temporarily greater reduction in blood glucose in Sglt1−/− vs. WT after 24 h (−33 vs. −11%). Subsequent inulin clearance studies under anesthesia revealed free plasma concentrations of the SGLT2-I (corresponding to early proximal concentration) close to the reported IC50 for SGLT2 in mice, which were associated with FGR of 64 ± 2% in WT and 17 ± 2% in Sglt1−/−. Additional intraperitoneal application of the SGLT2-I (maximum effective dose in metabolic cages) increased free plasma concentrations ∼10-fold and reduced FGR to 44 ± 3% in WT and to −1 ± 3% in Sglt1−/−. The absence of renal glucose reabsorption was confirmed in male and female Sglt1/Sglt2 double knockout mice. In conclusion, SGLT2 and SGLT1 account for renal glucose reabsorption in euglycemia, with 97 and 3% being reabsorbed by SGLT2 and SGLT1, respectively. When SGLT2 is fully inhibited by SGLT2-I, the increase in SGLT1-mediated glucose reabsorption explains why only 50–60% of filtered glucose is excreted.

scholarly journals Towards quadruple therapy for heart failure with reduced ejection fraction: DAPA-HF secondary analysis data

2020 ◽  
Vol 25 (5) ◽  
pp. 3870
Author(s):  
Zh. D. Kobalava ◽  
V. V. Medovchshikov ◽  
N. B. Yeshniyazov
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Sglt2 Inhibitor ◽  
Secondary Analysis ◽  
Analysis Data ◽  
Adverse Outcomes ◽  
Reduced Ejection Fraction ◽  
Sodium Glucose Cotransporter ◽  
Patients With Heart Failure ◽  
First Time

Patients with heart failure with reduced ejection fraction (HFrEF), despite optimal evidence-based treatment, have a high residual risk of adverse outcomes. The favorable results of studies on cardiovascular safety and the effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D), including outcomes associated with heart failure, were the reason for studying the effectiveness in patients with HFrEF regardless of the T2D status. For the first time in the DAPA-HF study, the SGLT2 inhibitor dapagliflozin in patients with HFrEF showed a positive effect on hard endpoints. Data of the secondary analysis confirmed the effectiveness of dapagliflozin regardless of the T2D status, therapy, age, and quality of life. The results of DAPA-HF have become a serious statement for changing the standards of the guideline-recommended therapy of HFrEF.

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

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

<b>Objective </b> <p>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.</p> <p><b> </b></p> <p><b>Research Design/Methods</b></p> <p>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.</p> <p><b> </b></p> <p><b>Results</b></p> <p>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.</p> <p><b>Conclusions</b></p> <p>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.</p>

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

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

<b>Objective </b> <p>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.</p> <p><b> </b></p> <p><b>Research Design/Methods</b></p> <p>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.</p> <p><b> </b></p> <p><b>Results</b></p> <p>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.</p> <p><b>Conclusions</b></p> <p>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.</p>

scholarly journals PATOMEKANISME PENYAKIT GAGAL JANTUNG KONGESTIF

el–Hayah ◽  
2014 ◽  
Vol 4 (2) ◽  
pp. 81 ◽  
Author(s):  
Lailia Nur Rachma
Keyword(s):  
Heart Failure ◽  
Clinical Manifestations ◽  
The United States ◽  
Clinical Syndrome ◽  
The Body ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
Male Patients ◽  
Failure Prognosis ◽  
The Cost

<em>Heart failure is a clinical syndrome characterized by abnormalities in the structure or function of the heart, resulting in inability of heart to pump blood to meet the metabolic needs of the body tissue. Heart failure is characterized by clinical manifestations such as circulation congestion, tightness, fatigue, and weakness. Heart failure is a major problem in industrial and developing Country. Currently, the incidence and prevalence of heart failure tends to increase, it is also accompanied by an increase in mortality of heart failure cases. In the United States, 1 million patients hospitalized due to heart failure cases, which contribute to 50,000 deaths each year. While the number of visits to the hospital due to heart failure estimated at 6.5 million. Heart failure prognosis is generally poor despite the patients accepted adequate therapy. From the data obtained, only about 35% of male patients and 50% female patients who survived after the onset of acute heart failure. Generaly, the data obtained high mortality are occurs in patients with grade IV (presence of symptoms at rest) is about 30-70%, grade III (presence of symptoms with mild activity) 10-20%, class II (presence of symptoms when the activity being 5-10 %). Higher mortality was found in older patients, men, patients with reduced ejection fraction, and in patients with coronary disease. Once someone is suffering from heart failure, then he shall bear the very high cost. In America, the cost of issued for heart failure therapy between 15-40 trillion US$. In this review, we will discuss about pathomechanism of heart failure. So it is expected to be a reference to the diagnosis of patients with heart failure, which is expected to be recognized early on that could ultimately improve the quality of heart failure patient life, and reduce the number of mortality due to heart failure</em>

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

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.

scholarly journals Risk Stratification of Sudden Cardiac Death in Patients with Heart Failure: An update

2018 ◽  
Vol 7 (11) ◽  
pp. 436 ◽  
Author(s):  
Daniele Masarone ◽  
Giuseppe Limongelli ◽  
Ernesto Ammendola ◽  
Marina Verrengia ◽  
Rita Gravino ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sudden Cardiac Death ◽  
Risk Stratification ◽  
Cardiac Death ◽  
Clinical Syndrome ◽  
Pump Failure ◽  
Reduced Ejection Fraction ◽  
Clinical Challenge ◽  
Patients With Heart Failure ◽  
Symptoms And Signs

Heart failure (HF) is a complex clinical syndrome in which structural/functional myocardial abnormalities result in symptoms and signs of hypoperfusion and/or pulmonary or systemic congestion at rest or during exercise. More than 80% of deaths in patients with HF recognize a cardiovascular cause, with most being either sudden cardiac death (SCD) or death caused by progressive pump failure. Risk stratification of SCD in patients with HF and preserved (HFpEF) or reduced ejection fraction (HFrEF) represents a clinical challenge. This review will give an update of current strategies for SCD risk stratification in both HFrEF and HFpEF.

Abstract 16353: Effects of Dapagliflozin on Physical and Social Activity Limitations in Patients With Heart Failure and Reduced Ejection Fraction: An Analysis of DAPA-HF

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Kieran Docherty ◽  
Mikhail N Kosiborod ◽  
Silvio E Inzucchi ◽  
Lars Kober ◽  
Anna Maria Langkilde ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Kansas City ◽  
Social Activity ◽  
Sglt2 Inhibitor ◽  
Sexual Relationships ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
Individual Domain ◽  
Physical Limitations

Background: Patients with heart failure and reduced ejection fraction (HFrEF) suffer limitations in physical and social activities. We examined whether the SGLT2 inhibitor dapagliflozin improved the degree of physical and social activity limitation measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ) in DAPA-HF. Hypothesis: Dapagliflozin, compared with placebo, would reduce the limitations of physical and social activity experienced by patients with HFrEF. Methods: We examined the effect of dapagliflozin on the physical and social limitation domains of the KCCQ at 8 months (prespecified analysis time point). Mean change from baseline was calculated using a linear regression model adjusted for baseline values with no imputation for missing data. Scores range from 0-100, with higher scores indicating better health status. Findings: At baseline, 4443 (94%) patients had available KCCQ data. Mean baseline physical limitations and social limitations scores were 66.0±24.0 and 65.5±27.4, respectively. Of the 10 individual domains that constitute these scores, the greatest limitations reported by patients at baseline were in doing gardening or housework or carrying groceries, hurrying/jogging and sexual relationships. Dapagliflozin improved physical and social limitations scores at 8 months (placebo-corrected mean difference +1.88 [95%CI 0.66,3.10] and +1.60 [0.18,3.01], respectively). Each individual domain reflecting physical and social limitations improved with dapagliflozin with the exception of sexual relationships (Table); the greatest improvements were seen in doing gardening or housework or carrying groceries (+2.48 [0.63,4.33]), hobbies and recreational activities (+2.46 [0.75-4.17]), and walking 100yd on level ground (+2.29 [0.62,3.96]). Interpretation: In DAPA-HF, dapagliflozin, compared with placebo, improved physical and social limitations as measured by the KCCQ in patients with HFrEF.

scholarly journals Sodium–Glucose Co-transporter 2 Inhibitors in Heart Failure: Recent Data and Implications for Practice

2020 ◽  
Vol 6 ◽  
Author(s):  
Giuseppe Rosano ◽  
David Quek ◽  
Felipe Martínez
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Ejection Fraction ◽  
Large Scale ◽  
Chronic Phase ◽  
Cardiovascular Death ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
Sglt2 Inhibition ◽  
Outcome Trial

Heart failure is a shared chronic phase of many cardiac diseases and its prevalence is on the rise globally. Previous large-scale cardiovascular outcomes trials of sodium–glucose co-transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D) have suggested that these agents may help to prevent primary and secondary hospitalisation due to heart failure and cardiovascular death in these patients. Data from the Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure (DAPA-HF) and Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction (EMPEROR-Reduced) have demonstrated the positive clinical impact of SGLT2 inhibition in patients with heart failure with reduced ejection fraction both with and without T2D. These data have led to the approval of dapagliflozin for the treatment of patients with heart failure with reduced ejection fraction, irrespective of T2D status. This article reviews the latest data reported from the DAPA-HF and EMPEROR-Reduced trials and their clinical implications for the treatment of patients with heart failure.

The Role of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Heart Failure, Regardless of Diabetes Status: Focus on Cardiovascular Disease

2021 ◽  
pp. 106002802098511
Author(s):  
Filipe Ferrari ◽  
Vítor M. Martins ◽  
Rafael S. Scheffel ◽  
Anderson D. da Silveira ◽  
Marcelo Trotte Motta ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Data Extraction ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Reduced Ejection Fraction ◽  
Sodium Glucose Cotransporter ◽  
Diabetes Status ◽  
Neprilysin Inhibitor ◽  
Patients With Heart Failure

Objective: To provide clinical guidance and an overview of the available data on the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with heart failure with reduced ejection fraction (HFrEF), regardless of the presence of type 2 diabetes mellitus (T2DM). Data Sources: We searched the MEDLINE database via PubMed (from January 2015 to November 2020) for the following key terms: SGLT2 inhibitors, sodium-glucose co-transporter-2 inhibitors, SGLT2i, heart failure, and heart failure with reduced ejection fraction. Study Selection and Data Extraction: To be included in the review, the articles needed to assess the effects of SGLT2 inhibitors in the heart failure (HF) scenario. Data Synthesis: There is consistent evidence that SGLT2 inhibitors reduce the risk of major adverse cardiovascular (CV) events and hospitalization in patients with HFrEF, even in the absence of T2DM. On May 5, 2020, the U.S. Food and Drug Administration approved dapagliflozin for adults with HFrEF, regardless of the presence of T2DM, even in those patients on standard therapy, including an angiotensin receptor/neprilysin inhibitor. Relevance to Patient Care and Clinical Practice: The SGLT2 inhibitors are well tolerated, and their once-daily dosing without the need for adjustments is convenient. These drugs can be considered a major breakthrough in pharmacotherapy for HF, providing physicians with a new treatment approach to reduce major clinical outcomes. Conclusions: SGLT2 inhibitor therapy reduces CV death and hospitalizations in HFrEF patients regardless of T2DM. The decision to prescribe this class of drugs should not be determined by glycemic status.

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