The first-in-man randomized trial of a beta3 adrenoceptor agonist in chronic heart failure: the BEAT-HF trial

European Journal of Heart Failure

Volumn 19, Issue 4, 2017, Pages 566-575

  Bundgaard, Henning ^a   Axelsson, Anna ^a   Hartvig Thomsen, Jakob ^a   Sørgaard, Mathias ^a   Kofoed, Klaus F ^a   Hasselbalch, Rasmus ^a   Fry, Natasha A S ^b   Valeur, Nana ^a   Boesgaard, Søren ^a   Gustafsson, Finn ^a   Køber, Lars ^a   Iversen, Kasper ^a   Rasmussen, Helge H ^c  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b UNIVERSITY OF SYDNEY   (Australia)

^c ROYAL NORTH SHORE HOSPITAL   (Australia)

Author keywords

Adrenergic receptors; Cardiac contractility; Heart failure; Membrane sodium potassium pump; Neurohormonal activation; Oxidant stress

Indexed keywords

MIRABEGRON; PLACEBO; ACETANILIDE DERIVATIVE; BETA 3 ADRENERGIC RECEPTOR STIMULATING AGENT; THIAZOLE DERIVATIVE;

ADULT; ARTICLE; COMPUTER ASSISTED TOMOGRAPHY; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG HYPERSENSITIVITY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ECHOCARDIOGRAPHY; ENDOCARDITIS; FEMALE; FEVER; HEART FAILURE; HEART LEFT VENTRICLE EJECTION FRACTION; HUMAN; INFECTION; MAJOR CLINICAL STUDY; MALE; NEW YORK HEART ASSOCIATION CLASS; RANDOMIZED CONTROLLED TRIAL; SUDDEN CARDIAC DEATH; THORAX PAIN; URINARY TRACT INFECTION; AGED; DIAGNOSTIC IMAGING; HEART STROKE VOLUME; MIDDLE AGED; PATHOPHYSIOLOGY; X-RAY COMPUTED TOMOGRAPHY;

ACETANILIDES; ADRENERGIC BETA-3 RECEPTOR AGONISTS; ADULT; AGED; DOUBLE-BLIND METHOD; FEMALE; HEART FAILURE; HUMANS; MALE; MIDDLE AGED; STROKE VOLUME; THIAZOLES; TOMOGRAPHY, X-RAY COMPUTED;

EID: 85007203552     PISSN: 13889842     EISSN: 18790844     Source Type: Journal    
DOI: 10.1002/ejhf.714     Document Type: Article

References (33)

1. Tarone G, Balligand JL, Bauersachs J, Clerk A, De WL, Heymans S, Hilfiker-Kleiner D, Hirsch E, Iaccarino G, Knoll R, Leite-Moreira AF, Lourenco AP, Mayr M, Thum T, Tocchetti CG. Targeting myocardial remodelling to develop novel therapies for heart failure: a position paper from the Working Group on Myocardial Function of the European Society of Cardiology. Eur J Heart Fail 2014;16:494–508.
2. Moniotte S, Kobzik L, Feron O, Trochu JN, Gauthier C, Balligand JL. Upregulation of beta(3)-adrenoceptors and altered contractile response to inotropic amines in human failing myocardium. Circulation 2001;103:1649–1655.
3. Liggett SB, Freedman NJ, Schwinn DA, Lefkowitz RJ. Structural basis for receptor subtype-specific regulation revealed by a chimeric beta 3/beta 2-adrenergic receptor. Proc Natl Acad Sci USA 1993;90:3665–3669.
4. Rozec B, Gauthier C. beta3-adrenoceptors in the cardiovascular system: putative roles in human pathologies. Pharmacol Ther 2006;111:652–673.
5. Gauthier C, Leblais V, Kobzik L, Trochu JN, Khandoudi N, Bril A, Balligand JL, Le Marec H. The negative inotropic effect of beta3-adrenoceptor stimulation is mediated by activation of a nitric oxide synthase pathway in human ventricle. J Clin Invest 1998;102:1377–1384.
6. Altan VM, Arioglu E, Guner S, Ozcelikay AT. The influence of diabetes on cardiac beta-adrenoceptor subtypes. Heart Fail Rev 2007;12:58–65.
7. Morimoto A, Hasegawa H, Cheng HJ, Little WC, Cheng CP. Endogenous α3-adrenoceptor activation contributes to left ventricular and cardiomyocyte dysfunction in heart failure. Am J Physiol Heart Circ Physiol 2004;286:H2425–H2433.
8. 2+ current by beta3-adrenergic stimulation in failing rat heart. J Pharmacol Exp Ther 2005;315:1203–1211.
9. Bundgaard H, Liu CC, Garcia A, Hamilton EJ, Huang Y, Chia KK, Hunyor SN, Figtree GA, Rasmussen HH. beta(3) adrenergic stimulation of the cardiac Na + −K+ pump by reversal of an inhibitory oxidative modification. Circulation 2010;122:2699–2708.
10. Pieske B, Maier LS, Piacentino V, III, Weisser J, Hasenfuss G, Houser S. Rate dependence of [Na+]i and contractility in nonfailing and failing human myocardium. Circulation 2002;106:447–453.
11. Bay J, Kohlhaas M, Maack C. Intracellular Na(+) and cardiac metabolism. J Mol Cell Cardiol 2013;61:20–27.
12. Liu CC, Fry NA, Hamilton EJ, Chia KK, Garcia A, Karimi GK, Figtree GA, Clarke RJ, Bundgaard H, Rasmussen HH. Redox-dependent regulation of the Na(+)–K(+) pump: new twists to an old target for treatment of heart failure. J Mol Cell Cardiol 2013;61:94–101.
13. Tyagi P, Tyagi V, Chancellor M. Mirabegron: a safety review. Expert Opin Drug Saf 2011;10:287–294.
14. Kristensen TS, Kofoed KF, Moller DV, Ersboll M, Kuhl T, von der Recke P, Kober L, Nielsen MB, Kelbaek H. Quantitative assessment of left ventricular systolic wall thickening using multidetector computed tomography. Eur J Radiol 2009;72:92–97.
15. Gheorghiade M, Greene SJ, Butler J, Filippatos G, Lam CS, Maggioni AP, Ponikowski P, Shah SJ, Solomon SD, Kraigher-Krainer E, Samano ET, Muller K, Roessig L, Pieske B. Effect of vericiguat, a soluble guanylate cyclase stimulator, on natriuretic peptide levels in patients with worsening chronic heart failure and reduced ejection fraction: the SOCRATES-REDUCED randomized trial. JAMA 2015;314:2251–2262.
16. Heymes C, Bendall JK, Ratajczak P, Cave AC, Samuel JL, Hasenfuss G, Shah AM. Increased myocardial NADPH oxidase activity in human heart failure. J Am Coll Cardiol 2003;41:2164–2171.
17. Maack C, Kartes T, Kilter H, Schafers HJ, Nickenig G, Bohm M, Laufs U. Oxygen free radical release in human failing myocardium is associated with increased activity of rac1-GTPase and represents a target for statin treatment. Circulation 2003;108:1567–1574.
18. Chia KK, Liu CC, Hamilton EJ, Garcia A, Fry NA, Hannam W, Figtree GA, Rasmussen HH. Stimulation of the cardiac myocyte Na + −K+ pump due to reversal of its constitutive oxidative inhibition. Am J Physiol Cell Physiol 2015;309:C239–C250.
19. Maurer MS, Sackner-Bernstein JD, El-Khoury RL, Yushak M, King DL, Burkhoff D. Mechanisms underlying improvements in ejection fraction with carvedilol in heart failure. Circ Heart Fail 2009;2:189–196.
20. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Jr., Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2013;128:e240–e327.
21. Francis GS, Bartos JA, Adatya S. Inotropes. J Am Coll Cardiol 2014;63:2069–2078.
22. White CN, Liu CC, Garcia A, Hamilton EJ, Chia KK, Figtree GA, Rasmussen HH. Activation of cAMP-dependent signaling induces oxidative modification of the cardiac Na + −K+ pump and inhibits its activity. J Biol Chem 2010;285:13712–13720.
23. Balligand JL. Cardiac salvage by tweaking with beta-3-adrenergic receptors. Cardiovasc Res 2016;111:128–133.
24. Cohn JN, Pfeffer MA, Rouleau J, Sharpe N, Swedberg K, Straub M, Wiltse C, Wright TJ. Adverse mortality effect of central sympathetic inhibition with sustained-release moxonidine in patients with heart failure (MOXCON). Eur J Heart Fail 2003;5:659–667.
25. Swedberg K, Bristow MR, Cohn JN, Dargie H, Straub M, Wiltse C, Wright TJ. Effects of sustained-release moxonidine, an imidazoline agonist, on plasma norepinephrine in patients with chronic heart failure. Circulation 2002;105:1797–1803.
26. Floras JS. The ‘unsympathetic’ nervous system of heart failure. Circulation 2002;105:1753–1755.
27. Hoffmann C, Leitz MR, Oberdorf-Maass S, Lohse MJ, Klotz KN. Comparative pharmacology of human beta-adrenergic receptor subtypes—characterization of stably transfected receptors in CHO cells. Naunyn Schmiedebergs Arch Pharmacol 2004;369:151–159.
28. Ekundayo OJ, Markland A, Lefante C, Sui X, Goode PS, Allman RM, Ali M, Wahle C, Thornton PL, Ahmed A. Association of diuretic use and overactive bladder syndrome in older adults: a propensity score analysis. Arch Gerontol Geriatr 2009;49:64–68.
29. Rasmussen HH, Figtree GA, Krum H, Bundgaard H. The use of beta3-adrenergic receptor agonists in the treatment of heart failure. Curr Opin Investig Drugs 2009;10:955–962.
30. Burgoyne JR, Mongue-Din H, Eaton P, Shah AM. Redox signaling in cardiac physiology and pathology. Circ Res 2012;111:1091–1106.
31. Erdmann E, Semigran MJ, Nieminen MS, Gheorghiade M, Agrawal R, Mitrovic V, Mebazaa A. Cinaciguat, a soluble guanylate cyclase activator, unloads the heart but also causes hypotension in acute decompensated heart failure. Eur Heart J 2013;34:57–67.
32. William M, Vein J, Hamilton E, Garcia A, Bundgaard H, Clarke R, Rasmussen H. The nitric oxide donor sodium nitroprusside stimulates the Na + −K+ pump in isolated rabbit cardiac myocytes. J Physiol 2005;565:815–825.
33. Cole GD, Dhutia NM, Shun-Shin MJ, Willson K, Harrison J, Raphael CE, Zolgharni M, Mayet J, Francis DP. Defining the real-world reproducibility of visual grading of left ventricular function and visual estimation of left ventricular ejection fraction: impact of image quality, experience and accreditation. Int J Cardiovasc Imaging 2015;31:1303–1314.