Rationale and design of a multicentre, randomized, placebo-controlled trial of mirabegron, a Beta3-adrenergic receptor agonist on left ventricular mass and diastolic function in patients with structural heart disease Beta3-left ventricular hypertrophy (Beta3-LVH)

Anne Catherine Pouleur, Stefan Anker, Dulce Brito, Oana Brosteanu, Dirk Hasenclever, Barbara Casadei, Frank Edelmann, Gerasimos Filippatos, Damien Gruson, Ignatios Ikonomidis, Renaud Lhommel, Masliza Mahmod, Stefan Neubauer, Alexandre Persu, Bernhard L. Gerber, Stefan Piechnik, Burkert Pieske, Elisabeth Pieske-Kraigher, Fausto Pinto, Piotr PonikowskiMichele Senni, Jean Noël Trochu, Nancy Van Overstraeten, Rolf Wachter, Jean Luc Balligand

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Aims: Progressive left ventricular (LV) remodelling with cardiac myocyte hypertrophy, myocardial fibrosis, and endothelial dysfunction plays a key role in the onset and progression of heart failure with preserved ejection fraction. The Beta3-LVH trial will test the hypothesis that the β3 adrenergic receptor agonist mirabegron will improve LV hypertrophy and diastolic function in patients with hypertensive structural heart disease at high risk for developing heart failure with preserved ejection fraction. Methods and results: Beta3-LVH is a randomized, placebo-controlled, double-blind, two-armed, multicentre, European, parallel group study. A total of 296 patients will be randomly assigned to receive either mirabegron 50 mg daily or placebo over 12 months. The main inclusion criterion is the presence of LV hypertrophy, that is, increased LV mass index (LVMi) or increased wall thickening by echocardiography. The co-primary endpoints are a change in LVMi by cardiac magnetic resonance imaging and a change in LV diastolic function (assessed by the E/e′ ratio). Secondary endpoints include mirabegron's effects on cardiac fibrosis, left atrial volume index, maximal exercise capacity, and laboratory markers. Two substudies will evaluate mirabegron's effect on endothelial function by pulse amplitude tonometry and brown fat activity by positron emission tomography using 17F-fluorodeoxyglucose. Morbidity and mortality as well as safety aspects will also be assessed. Conclusions: Beta3-LVH is the first large-scale clinical trial to evaluate the effects of mirabegron on LVMi and diastolic function in patients with LVH. Beta3-LVH will provide important information about the clinical course of this condition and may have significant impact on treatment strategies and future trials in these patients.

Original languageEnglish
Pages (from-to)830-841
Number of pages12
JournalESC heart failure
Volume5
Issue number5
DOIs
Publication statusPublished - 1 Oct 2018
Externally publishedYes

Fingerprint

Adrenergic Agonists
Left Ventricular Hypertrophy
Heart Diseases
Randomized Controlled Trials
Placebos
Fibrosis
Heart Failure
Ventricular Remodeling
Brown Adipose Tissue
Manometry
Cardiomegaly
Left Ventricular Function
Cardiac Myocytes
Positron-Emission Tomography
Echocardiography
Pulse
mirabegron
Biomarkers
Magnetic Resonance Imaging
Clinical Trials

Keywords

  • Heart failure with preserved ejection fraction
  • Hypertensive structural heart disease
  • Mirabegron
  • β adrenergic receptor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Rationale and design of a multicentre, randomized, placebo-controlled trial of mirabegron, a Beta3-adrenergic receptor agonist on left ventricular mass and diastolic function in patients with structural heart disease Beta3-left ventricular hypertrophy (Beta3-LVH). / Pouleur, Anne Catherine; Anker, Stefan; Brito, Dulce; Brosteanu, Oana; Hasenclever, Dirk; Casadei, Barbara; Edelmann, Frank; Filippatos, Gerasimos; Gruson, Damien; Ikonomidis, Ignatios; Lhommel, Renaud; Mahmod, Masliza; Neubauer, Stefan; Persu, Alexandre; Gerber, Bernhard L.; Piechnik, Stefan; Pieske, Burkert; Pieske-Kraigher, Elisabeth; Pinto, Fausto; Ponikowski, Piotr; Senni, Michele; Trochu, Jean Noël; Van Overstraeten, Nancy; Wachter, Rolf; Balligand, Jean Luc.

In: ESC heart failure, Vol. 5, No. 5, 01.10.2018, p. 830-841.

Research output: Contribution to journalArticle

Pouleur, AC, Anker, S, Brito, D, Brosteanu, O, Hasenclever, D, Casadei, B, Edelmann, F, Filippatos, G, Gruson, D, Ikonomidis, I, Lhommel, R, Mahmod, M, Neubauer, S, Persu, A, Gerber, BL, Piechnik, S, Pieske, B, Pieske-Kraigher, E, Pinto, F, Ponikowski, P, Senni, M, Trochu, JN, Van Overstraeten, N, Wachter, R & Balligand, JL 2018, 'Rationale and design of a multicentre, randomized, placebo-controlled trial of mirabegron, a Beta3-adrenergic receptor agonist on left ventricular mass and diastolic function in patients with structural heart disease Beta3-left ventricular hypertrophy (Beta3-LVH)', ESC heart failure, vol. 5, no. 5, pp. 830-841. https://doi.org/10.1002/ehf2.12306
Pouleur, Anne Catherine ; Anker, Stefan ; Brito, Dulce ; Brosteanu, Oana ; Hasenclever, Dirk ; Casadei, Barbara ; Edelmann, Frank ; Filippatos, Gerasimos ; Gruson, Damien ; Ikonomidis, Ignatios ; Lhommel, Renaud ; Mahmod, Masliza ; Neubauer, Stefan ; Persu, Alexandre ; Gerber, Bernhard L. ; Piechnik, Stefan ; Pieske, Burkert ; Pieske-Kraigher, Elisabeth ; Pinto, Fausto ; Ponikowski, Piotr ; Senni, Michele ; Trochu, Jean Noël ; Van Overstraeten, Nancy ; Wachter, Rolf ; Balligand, Jean Luc. / Rationale and design of a multicentre, randomized, placebo-controlled trial of mirabegron, a Beta3-adrenergic receptor agonist on left ventricular mass and diastolic function in patients with structural heart disease Beta3-left ventricular hypertrophy (Beta3-LVH). In: ESC heart failure. 2018 ; Vol. 5, No. 5. pp. 830-841.
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abstract = "Aims: Progressive left ventricular (LV) remodelling with cardiac myocyte hypertrophy, myocardial fibrosis, and endothelial dysfunction plays a key role in the onset and progression of heart failure with preserved ejection fraction. The Beta3-LVH trial will test the hypothesis that the β3 adrenergic receptor agonist mirabegron will improve LV hypertrophy and diastolic function in patients with hypertensive structural heart disease at high risk for developing heart failure with preserved ejection fraction. Methods and results: Beta3-LVH is a randomized, placebo-controlled, double-blind, two-armed, multicentre, European, parallel group study. A total of 296 patients will be randomly assigned to receive either mirabegron 50 mg daily or placebo over 12 months. The main inclusion criterion is the presence of LV hypertrophy, that is, increased LV mass index (LVMi) or increased wall thickening by echocardiography. The co-primary endpoints are a change in LVMi by cardiac magnetic resonance imaging and a change in LV diastolic function (assessed by the E/e′ ratio). Secondary endpoints include mirabegron's effects on cardiac fibrosis, left atrial volume index, maximal exercise capacity, and laboratory markers. Two substudies will evaluate mirabegron's effect on endothelial function by pulse amplitude tonometry and brown fat activity by positron emission tomography using 17F-fluorodeoxyglucose. Morbidity and mortality as well as safety aspects will also be assessed. Conclusions: Beta3-LVH is the first large-scale clinical trial to evaluate the effects of mirabegron on LVMi and diastolic function in patients with LVH. Beta3-LVH will provide important information about the clinical course of this condition and may have significant impact on treatment strategies and future trials in these patients.",
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T1 - Rationale and design of a multicentre, randomized, placebo-controlled trial of mirabegron, a Beta3-adrenergic receptor agonist on left ventricular mass and diastolic function in patients with structural heart disease Beta3-left ventricular hypertrophy (Beta3-LVH)

AU - Pouleur, Anne Catherine

AU - Anker, Stefan

AU - Brito, Dulce

AU - Brosteanu, Oana

AU - Hasenclever, Dirk

AU - Casadei, Barbara

AU - Edelmann, Frank

AU - Filippatos, Gerasimos

AU - Gruson, Damien

AU - Ikonomidis, Ignatios

AU - Lhommel, Renaud

AU - Mahmod, Masliza

AU - Neubauer, Stefan

AU - Persu, Alexandre

AU - Gerber, Bernhard L.

AU - Piechnik, Stefan

AU - Pieske, Burkert

AU - Pieske-Kraigher, Elisabeth

AU - Pinto, Fausto

AU - Ponikowski, Piotr

AU - Senni, Michele

AU - Trochu, Jean Noël

AU - Van Overstraeten, Nancy

AU - Wachter, Rolf

AU - Balligand, Jean Luc

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Aims: Progressive left ventricular (LV) remodelling with cardiac myocyte hypertrophy, myocardial fibrosis, and endothelial dysfunction plays a key role in the onset and progression of heart failure with preserved ejection fraction. The Beta3-LVH trial will test the hypothesis that the β3 adrenergic receptor agonist mirabegron will improve LV hypertrophy and diastolic function in patients with hypertensive structural heart disease at high risk for developing heart failure with preserved ejection fraction. Methods and results: Beta3-LVH is a randomized, placebo-controlled, double-blind, two-armed, multicentre, European, parallel group study. A total of 296 patients will be randomly assigned to receive either mirabegron 50 mg daily or placebo over 12 months. The main inclusion criterion is the presence of LV hypertrophy, that is, increased LV mass index (LVMi) or increased wall thickening by echocardiography. The co-primary endpoints are a change in LVMi by cardiac magnetic resonance imaging and a change in LV diastolic function (assessed by the E/e′ ratio). Secondary endpoints include mirabegron's effects on cardiac fibrosis, left atrial volume index, maximal exercise capacity, and laboratory markers. Two substudies will evaluate mirabegron's effect on endothelial function by pulse amplitude tonometry and brown fat activity by positron emission tomography using 17F-fluorodeoxyglucose. Morbidity and mortality as well as safety aspects will also be assessed. Conclusions: Beta3-LVH is the first large-scale clinical trial to evaluate the effects of mirabegron on LVMi and diastolic function in patients with LVH. Beta3-LVH will provide important information about the clinical course of this condition and may have significant impact on treatment strategies and future trials in these patients.

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KW - Heart failure with preserved ejection fraction

KW - Hypertensive structural heart disease

KW - Mirabegron

KW - β adrenergic receptor

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