CaMKII and GLUT1 in heart failure and the role of gliflozins

Publication date: Available online 14 February 2020Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): M. Trum, S. Wagner, L.S. Maier, J. MustrophAbstractEmpagliflozin, a selective sodium-glucose co-transporter 2 (SGLT2) inhibitor, has been shown to reduce mortality and hospitalization for heart failure in diabetic patients in the EMPA-REG-OUTCOME trial (Zinman et al., 2015). Surprisingly, dapagliflozin, another SGLT2 inhibitor, exerted comparable effects on clinical endpoints even in the absence of diabetes mellitus (DAPA-HF trial) McMurray et al. (2019). There is a myriad of suggested underlying mechanisms ranging from improved glycemic control and hemodynamic effects to altered myocardial metabolism, inflammation, neurohumoral activation and intracellular ion homeostasis.Here, we review the effects of gliflozins on cardiac electro-mechanical coupling with an emphasis on novel CaMKII-mediated pathways and on cardiac glucose and ketone metabolism in the failing heart. We focus on empagliflozin as it is the gliflozin with the most abundant experimental evidence for direct effects on the heart. Where useful, we aim to compare empagliflozin to other gliflozins. To facilitate understanding of empagliflozin-induced alterations, we first give a short summary of the pathophysiological role of CaMKII in heart failure, as well as cardiac changes of glucose and ketone body metabolism in the failing heart.
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research

Related Links:

Risk factors such as diabetes mellitus (DM) have been associated with increased risk of mortality in patients with heart failure (HF). Obesity in diabetic patients worsens outcomes. However, there appears to be an obesity paradox in which stable HF patients with higher body mass index (BMI) have better survival. We sought to evaluate the association of DM and BMI with mortality in patients with end stage HF on palliative inotropic therapy.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: (567) Source Type: research
AbstractAimsNon ‐cardiac comorbidities are highly prevalent in patients with heart failure (HF). Our objective was to define the association between non‐cardiac comorbidity burden and clinical outcomes, costs of care, and length of stay within a large randomized trial of acute HF patients.Methods and resultsPatients with complete medical history for the following comorbidities were included: diabetes mellitus, chronic obstructive pulmonary disease, chronic liver disease, history of cancer within the last 5  years, chronic renal disease (baseline serum creatinine>3.0  mg/mL), current smoking, alcohol ab...
Source: European Journal of Heart Failure - Category: Cardiology Authors: Tags: Research Article Source Type: research
Left ventricular ejection fraction (LVEF) trajectories and functional recovery with current heart failure (HF) management is increasingly recognized. Type 2 diabetes mellitus (T2D) leads to a worse prognosis i...
Source: Cardiovascular Diabetology - Category: Cardiology Authors: Tags: Original investigation Source Type: research
RARITAN, N.J., March 20, 2020 – The Janssen Pharmaceutical Companies of Johnson &Johnson announced today that it will unveil late-breaking data from its leading cardiovascular and metabolism portfolio during the virtual American College of Cardiology’s 69th Annual Scientific Session together with the World Congress of Cardiology (ACC.20/WCC) on March 28-30, 2020. Notably, four late-breaking abstracts for XARELTO® (rivaroxaban) will be presented, including data from the Phase 3 VOYAGER PAD study in patients with symptomatic peripheral artery disease (PAD) after lower-extremity revascularization.Click to ...
Source: Johnson and Johnson - Category: Pharmaceuticals Source Type: news
Recent clinical trials have demonstrated significant reductions in heart failure hospitalization and cardiovascular death with sodium-glucose cotransport protein 2 inhibitors in patients with or without type 2 diabetes mellitus.1-3 The mechanism of cardiovascular benefit with sodium-glucose transport coprotein 2 inhibitors was investigated in the EMPA-HEART CardioLink-6 trial, a double-blind, placebo-controlled clinical trial that randomized patients with type 2 diabetes and stable coronary artery disease to empagliflozin 10  mg once daily (n = 49) or placebo (n = 48).
Source: Journal of the American Society of Echocardiography - Category: Cardiology Authors: Tags: Letters to the Editor Source Type: research
Abstract Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. Vitamin D deficiency has been identified as a potential risk factor for a number of diseases unrelated to the classical skeletal pathophysiology, such as cancer and CVD, but the effects of vitamin D supplementation are less clear. Purpose of this narrative review is to discuss the evidence suggesting an association between vitamin D status and CVD as well as the results of supplementation studies. Vitamin D deficiency has been associated with CVD risk factors such as hypertension, dyslipidemia and diabetes mellitus as well...
Source: Current Vascular Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Curr Vasc Pharmacol Source Type: research
Abstract Type 2 diabetes mellitus (T2DM) is a rapidly evolving global health issue associated with a markedly increased risk of cardiovascular (CV) morbidity and mortality. The hyperglycaemic milieu contributes to the development of CV complications via several pathological pathways, leading to increased arterial stiffness (AS), that can be considered as a predictor of CV events in patients with diabetes. The measurement of AS is increasingly used for the clinical assessment of patients. Several methodologies were used in large population studies to assess AS; the most commonly used is the pulse wave velocity (PWV...
Source: Current Vascular Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Curr Vasc Pharmacol Source Type: research
Authors: Guthrie R Abstract Review of:Rosenstock J, Perkovic V, Johansen, OE, et al. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial. JAMA. 2019;321:69-79.McGuire DK, Alexander JH, Johansen OE, et al. Linagliptin effects on heart failure and related outcomes in individuals with type 2 diabetes mellitus at high cardiovascular and renal risk in CARMELINA. Circulation. 2019;139:351-361.These two papers describe the findings from the CARMELINA trial (Cardiovascular and Renal Microvascular Outco...
Source: Postgraduate Medicine - Category: Internal Medicine Tags: Postgrad Med Source Type: research
Abstract More than 70% of adults treated for primary hypertension will eventually require at least two antihypertensive agents, either initially as combination therapy or as add-on therapy if monotherapy and lifestyle modifications do not achieve adequate blood pressure control. Four main classes of medications are used in combination therapy for the treatment of hypertension: thiazide diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs). ACEIs and ARBs should not be used simultaneously. In black patients, at least one agent should be a thi...
Source: American Family Physician - Category: Primary Care Authors: Tags: Am Fam Physician Source Type: research
Conclusion: BMI has a nonlinear relationship with 1-year unplanned readmission in patients with myocardial infarction. The 1-year unplanned readmission rate of overweight patients (BMI > 29.3 kg/m2) has increased significantly. Obesity paradox does not exist in terms of readmission of Chinese patients with myocardial infarction after PCI. PMID: 32148951 [PubMed]
Source: Cardiology Research and Practice - Category: Cardiology Authors: Tags: Cardiol Res Pract Source Type: research
More News: Brain | Cardiology | Dapagliflozin | Diabetes | Diabetes Mellitus | Empagliflozin | Endocrinology | Forxiga | Heart | Heart Failure | Jardiance | Molecular Biology | Neurology | SGLT2 Inhibitors | Sodium