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充血性心力衰竭

科研文章

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Mechanical circulatory support devices for acute right ventricular failure How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction Titration of Medical Therapy for Heart Failure With Reduced Ejection Fraction Sex- and Race-Related Differences in Characteristics and Outcomes of Hospitalizations for Heart Failure With Preserved Ejection Fraction Association of Left Ventricular Systolic Function With Incident Heart Failure in Late Life From ACE Inhibitors/ARBs to ARNIs in Coronary Artery Disease and Heart Failure (Part 2/5) A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation Aliskiren, Enalapril, or Aliskiren and Enalapril in Heart Failure Lifestyle Modifications for Preventing and Treating Heart Failure

Clinical Trial2020 Aug 8.

JOURNAL:Cardiovasc Drugs Ther. Article Link

Metformin Lowers Body Weight But Fails to Increase Insulin Sensitivity in Chronic Heart Failure Patients without Diabetes: a Randomized, Double-Blind, Placebo-Controlled Study

AH Larsen, H Wiggers, Niels Jessen et al. Keywords: HF; hyperinsulinemic euglycemic clamp; Insulin sensitivity; metformin

ABSTRACT

PURPOSE - The glucose-lowering drug metformin has recently been shown to reduce myocardial oxygen consumption and increase myocardial efficiency in chronic heart failure (HF) patients without diabetes. However, it remains to be established whether these beneficial myocardial effects are associated with metformin-induced alterations in whole-body insulin sensitivity and substrate metabolism.


METHODS - Eighteen HF patients with reduced ejection fraction and without diabetes (median age, 65 (interquartile range 55–68); ejection fraction 39 ± 6%; HbA1c 5.5 to 6.4%) were randomized to receive metformin (n= 10) or placebo (n= 8) for 3 months. We studied the effects of metformin on whole-body insulin sensitivity using a two-step hyperinsulinemic euglycemic clamp incorporating isotope-labeled tracers of glucose, palmitate, and urea. Substrate metabolism and skeletal muscle mitochondrial respiratory capacity were determined by indirect calorimetry and high-resolution respirometry, and body composition was assessed by bioelectrical impedance analysis. The primary outcome measure was change in insulin sensitivity.


RESULTS - Compared with placebo, metformin treatment lowered mean glycated hemoglobin levels (absolute mean difference, − 0.2%; 95% CI − 0.3 to 0.0;p= 0.03), reduced body weight (− 2.8 kg; 95% CI − 5.0 to − 0.6;p= 0.02), and increased fasting glucagon levels (3.2 pmol L−1; 95% CI 0.4 to 6.0;p= 0.03). No changes were observed in whole-body insulin sensitivity, endogenous glucose production, and peripheral glucose disposal or oxidation with metformin. Equally, resting energy expenditure, lipid and urea turnover, and skeletal muscle mitochondrial respiratory capacity remained unaltered.


CONCLUSION - Increased myocardial efficiency during metformin treatment is not mediated through improvements in insulin action in HF patients without diabetes.


CLINICAL TRIAL REGISTRATION - URL: https://clinicaltrials.gov. Unique identifier: NCT02810132. Date of registration: June 22, 2016.