Jørgen Frøkiær

A randomised, double-blind, placebo-controlled trial of metformin on myocardial efficiency in insulin-resistant chronic heart failure patients without diabetes

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A randomised, double-blind, placebo-controlled trial of metformin on myocardial efficiency in insulin-resistant chronic heart failure patients without diabetes. / Larsen, Anders Hostrup; Jessen, Niels; Nørrelund, Helene; Tolbod, Lars Poulsen; Harms, Hendrik Johannes; Feddersen, Søren; Nielsen, Flemming; Brøsen, Kim; Hansson, Nils Henrik; Frøkiaer, Jørgen; Poulsen, Steen Hvitfeldt; Sörensen, Jens; Wiggers, Henrik.

In: European Journal of Heart Failure, Vol. 22, No. 9, 09.2020, p. 1628-1637.

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Larsen, Anders Hostrup ; Jessen, Niels ; Nørrelund, Helene ; Tolbod, Lars Poulsen ; Harms, Hendrik Johannes ; Feddersen, Søren ; Nielsen, Flemming ; Brøsen, Kim ; Hansson, Nils Henrik ; Frøkiaer, Jørgen ; Poulsen, Steen Hvitfeldt ; Sörensen, Jens ; Wiggers, Henrik. / A randomised, double-blind, placebo-controlled trial of metformin on myocardial efficiency in insulin-resistant chronic heart failure patients without diabetes. In: European Journal of Heart Failure. 2020 ; Vol. 22, No. 9. pp. 1628-1637.

Bibtex

@article{9f8dd9e3e8894a26981f22aa50d2f2e9,
title = "A randomised, double-blind, placebo-controlled trial of metformin on myocardial efficiency in insulin-resistant chronic heart failure patients without diabetes",
abstract = "AIMS: The present study tested the hypothesis that metformin treatment may increase myocardial efficiency (stroke work/myocardial oxygen consumption) in insulin-resistant patients with heart failure and reduced ejection fraction (HFrEF) without diabetes.METHODS AND RESULTS: Thirty-six HFrEF patients (ejection fraction 37 ± 8%; median age 66 years) were randomised to metformin (n = 19) or placebo (n = 17) for 3 months in addition to standard heart failure therapy. The primary endpoint was change in myocardial efficiency expressed as the work metabolic index (WMI), assessed by 11 C-acetate positron emission tomography and transthoracic echocardiography. Compared with placebo, metformin treatment (1450 ± 550 mg/day) increased WMI [absolute mean difference, 1.0 mmHg·mL·m-2 ·106 ; 95% confidence interval (CI) 0.1 to 1.8; P = 0.03], equivalent to a 20% relative efficiency increase. Patients with above-median plasma metformin levels displayed greater WMI increase (25% vs. -4%; P = 0.02). Metformin reduced myocardial oxygen consumption (-1.6 mL O2 ·100 g-1 ·min-1 ; P = 0.014). Cardiac stroke work was preserved (-2 J; 95% CI -11 to 7; P = 0.69). Metformin reduced body weight (-2.2 kg; 95% CI -3.6 to -0.8; P = 0.003) and glycated haemoglobin levels (-0.2%; 95% CI -0.3 to 0.0; P = 0.02). Changes in resting and exercise ejection fraction, global longitudinal strain, and exercise capacity did not differ between groups.CONCLUSION: Metformin treatment in non-diabetic HFrEF patients improved myocardial efficiency by reducing myocardial oxygen consumption. Measurement of circulating metformin levels differentiated responders from non-responders. These energy-sparing effects of metformin encourage further large-scale investigations in heart failure patients without diabetes.",
author = "Larsen, {Anders Hostrup} and Niels Jessen and Helene N{\o}rrelund and Tolbod, {Lars Poulsen} and Harms, {Hendrik Johannes} and S{\o}ren Feddersen and Flemming Nielsen and Kim Br{\o}sen and Hansson, {Nils Henrik} and J{\o}rgen Fr{\o}kiaer and Poulsen, {Steen Hvitfeldt} and Jens S{\"o}rensen and Henrik Wiggers",
note = "{\textcopyright} 2019 European Society of Cardiology.",
year = "2020",
month = sep,
doi = "10.1002/ejhf.1656",
language = "English",
volume = "22",
pages = "1628--1637",
journal = "European Journal of Heart Failure",
issn = "1388-9842",
publisher = "JohnWiley & Sons Ltd.",
number = "9",

}

RIS

TY - JOUR

T1 - A randomised, double-blind, placebo-controlled trial of metformin on myocardial efficiency in insulin-resistant chronic heart failure patients without diabetes

AU - Larsen, Anders Hostrup

AU - Jessen, Niels

AU - Nørrelund, Helene

AU - Tolbod, Lars Poulsen

AU - Harms, Hendrik Johannes

AU - Feddersen, Søren

AU - Nielsen, Flemming

AU - Brøsen, Kim

AU - Hansson, Nils Henrik

AU - Frøkiaer, Jørgen

AU - Poulsen, Steen Hvitfeldt

AU - Sörensen, Jens

AU - Wiggers, Henrik

N1 - © 2019 European Society of Cardiology.

PY - 2020/9

Y1 - 2020/9

N2 - AIMS: The present study tested the hypothesis that metformin treatment may increase myocardial efficiency (stroke work/myocardial oxygen consumption) in insulin-resistant patients with heart failure and reduced ejection fraction (HFrEF) without diabetes.METHODS AND RESULTS: Thirty-six HFrEF patients (ejection fraction 37 ± 8%; median age 66 years) were randomised to metformin (n = 19) or placebo (n = 17) for 3 months in addition to standard heart failure therapy. The primary endpoint was change in myocardial efficiency expressed as the work metabolic index (WMI), assessed by 11 C-acetate positron emission tomography and transthoracic echocardiography. Compared with placebo, metformin treatment (1450 ± 550 mg/day) increased WMI [absolute mean difference, 1.0 mmHg·mL·m-2 ·106 ; 95% confidence interval (CI) 0.1 to 1.8; P = 0.03], equivalent to a 20% relative efficiency increase. Patients with above-median plasma metformin levels displayed greater WMI increase (25% vs. -4%; P = 0.02). Metformin reduced myocardial oxygen consumption (-1.6 mL O2 ·100 g-1 ·min-1 ; P = 0.014). Cardiac stroke work was preserved (-2 J; 95% CI -11 to 7; P = 0.69). Metformin reduced body weight (-2.2 kg; 95% CI -3.6 to -0.8; P = 0.003) and glycated haemoglobin levels (-0.2%; 95% CI -0.3 to 0.0; P = 0.02). Changes in resting and exercise ejection fraction, global longitudinal strain, and exercise capacity did not differ between groups.CONCLUSION: Metformin treatment in non-diabetic HFrEF patients improved myocardial efficiency by reducing myocardial oxygen consumption. Measurement of circulating metformin levels differentiated responders from non-responders. These energy-sparing effects of metformin encourage further large-scale investigations in heart failure patients without diabetes.

AB - AIMS: The present study tested the hypothesis that metformin treatment may increase myocardial efficiency (stroke work/myocardial oxygen consumption) in insulin-resistant patients with heart failure and reduced ejection fraction (HFrEF) without diabetes.METHODS AND RESULTS: Thirty-six HFrEF patients (ejection fraction 37 ± 8%; median age 66 years) were randomised to metformin (n = 19) or placebo (n = 17) for 3 months in addition to standard heart failure therapy. The primary endpoint was change in myocardial efficiency expressed as the work metabolic index (WMI), assessed by 11 C-acetate positron emission tomography and transthoracic echocardiography. Compared with placebo, metformin treatment (1450 ± 550 mg/day) increased WMI [absolute mean difference, 1.0 mmHg·mL·m-2 ·106 ; 95% confidence interval (CI) 0.1 to 1.8; P = 0.03], equivalent to a 20% relative efficiency increase. Patients with above-median plasma metformin levels displayed greater WMI increase (25% vs. -4%; P = 0.02). Metformin reduced myocardial oxygen consumption (-1.6 mL O2 ·100 g-1 ·min-1 ; P = 0.014). Cardiac stroke work was preserved (-2 J; 95% CI -11 to 7; P = 0.69). Metformin reduced body weight (-2.2 kg; 95% CI -3.6 to -0.8; P = 0.003) and glycated haemoglobin levels (-0.2%; 95% CI -0.3 to 0.0; P = 0.02). Changes in resting and exercise ejection fraction, global longitudinal strain, and exercise capacity did not differ between groups.CONCLUSION: Metformin treatment in non-diabetic HFrEF patients improved myocardial efficiency by reducing myocardial oxygen consumption. Measurement of circulating metformin levels differentiated responders from non-responders. These energy-sparing effects of metformin encourage further large-scale investigations in heart failure patients without diabetes.

U2 - 10.1002/ejhf.1656

DO - 10.1002/ejhf.1656

M3 - Journal article

C2 - 31863557

VL - 22

SP - 1628

EP - 1637

JO - European Journal of Heart Failure

JF - European Journal of Heart Failure

SN - 1388-9842

IS - 9

ER -