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Serelaxin a novel treatment for acute heart failure

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References

  • Fonarow GC, Abraham WT, Albert NM, et al. Influence of a performance-improvement initiative on quality of care for patients hospitalized with heart failure: results of the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF). Arch Intern Med 2007;167(14):1493-502
  • Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics–2014 update: a report from the American Heart Association. Circulation 2014;129(3):e28-e292
  • Stevenson LW. Are hemodynamic goals viable in tailoring heart failure therapy? Hemodynamic goals are relevant. Circulation 2006;113(7):1020-7. discussion 33
  • Cotter G, Metra M, Milo-Cotter O, et al. Fluid overload in acute heart failure–re-distribution and other mechanisms beyond fluid accumulation. Eur J Heart Fail 2008;10(2):165-9
  • Gheorghiade M, Follath F, Ponikowski P, et al. Assessing and grading congestion in acute heart failure: a scientific statement from the acute heart failure committee of the heart failure association of the European Society of Cardiology and endorsed by the European Society of Intensive Care Medicine. Eur J Heart Fail 2010;12(5):423-33
  • Teerlink JR, Cotter G, Davison BA, et al. Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial. Lancet 2013;381(9860):29-39
  • Metra M, Cotter G, Davison BA, et al. Effect of serelaxin on cardiac, renal, and hepatic biomarkers in the Relaxin in Acute Heart Failure (RELAX-AHF) development program: correlation with outcomes. J Am Coll Cardiol 2013;61(2):196-206
  • Stewart DR, Celniker AC, Taylor CAJr, et al. Relaxin in the peri-implantation period. J Clin Endocrinol Metab 1990;70(6):1771-3
  • Dschietzig T, Richter C, Bartsch C, et al. The pregnancy hormone relaxin is a player in human heart failure. FASEB J 2001;15(12):2187-95
  • Gavino ES, Furst DE. Recombinant relaxin: a review of pharmacology and potential therapeutic use. BioDrugs 2001;15(9):609-14
  • Available from: www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM390444.pdf
  • Kobalava Z, Villevalde S, Kotovskaya Y, et al. Pharmacokinetics of serelaxin in patients with hepatic impairment: A single-dose, open-label, parallel-group study. Br J Clin Pharmacol 2014. [Epub ahead of print]
  • International 4700 en venta. Available from: www.marketbook.gt/list/list.aspx?OHID=4393905&Manu=INTERNATIONAL&ETID=1&Mdltxt=4700&MdlX=Contains&notfound=1&LP=TRK
  • Kumagai J, Hsu SY, Matsumi H, et al. INSL3/Leydig insulin-like peptide activates the LGR8 receptor important in testis descent. J Biol Chem 2002;277(35):31283-6
  • Bathgate RA, Halls ML, van der Westhuizen ET, et al. Relaxin family peptides and their receptors. Physiol Rev 2013;93(1):405-80
  • Novak J, Parry LJ, Matthews JE, et al. Evidence for local relaxin ligand-receptor expression and function in arteries. FASEB J 2006;20(13):2352-62
  • Haynes WG, Webb DJ. Endothelin as a regulator of cardiovascular function in health and disease. J Hypertens 1998;16(8):1081-98
  • Schneider MP, Boesen EI, Pollock DM. Contrasting actions of endothelin ET(A) and ET(B) receptors in cardiovascular disease. Annu Rev Pharmacol Toxicol 2007;47:731-59
  • Chow BS, Chew EG, Zhao C, et al. Relaxin signals through a RXFP1-pERK-nNOS-NO-cGMP-dependent pathway to up-regulate matrix metalloproteinases: the additional involvement of iNOS. PLoS One 2012;7(8):e42714
  • Sasser JM, Molnar M, Baylis C. Relaxin ameliorates hypertension and increases nitric oxide metabolite excretion in angiotensin II but not N(omega)-nitro-L-arginine methyl ester hypertensive rats. Hypertension 2011;58(2):197-204
  • Masini E, Nistri S, Vannacci A, et al. Relaxin inhibits the activation of human neutrophils: involvement of the nitric oxide pathway. Endocrinology 2004;145(3):1106-12
  • Fisher C, MacLean M, Morecroft I, et al. Is the pregnancy hormone relaxin also a vasodilator peptide secreted by the heart? Circulation 2002;106(3):292-5
  • Dschietzig T, Bartsch C, Richter C, et al. Relaxin, a pregnancy hormone, is a functional endothelin-1 antagonist: attenuation of endothelin-1-mediated vasoconstriction by stimulation of endothelin type-B receptor expression via ERK-1/2 and nuclear factor-kappaB. Circ Res 2003;92(1):32-40
  • Conrad KP, Shroff SG. Effects of relaxin on arterial dilation, remodeling, and mechanical properties. Curr Hypertens Rep 2011;13(6):409-20
  • Jelinic M, Leo CH, Post Uiterweer ED, et al. Localization of relaxin receptors in arteries and veins, and region-specific increases in compliance and bradykinin-mediated relaxation after in vivo serelaxin treatment. FASEB J 2014;28(1):275-87
  • Conrad KP. Maternal vasodilation in pregnancy: the emerging role of relaxin. Am J Physiol Regul Integr Comp Physiol 2011;301(2):R267-75
  • Teichman SL, Unemori E, Teerlink JR, et al. Relaxin: review of biology and potential role in treating heart failure. Curr Heart Fail Rep 2010;7(2):75-82
  • Smith MC, Danielson LA, Conrad KP, et al. Influence of recombinant human relaxin on renal hemodynamics in healthy volunteers. J Am Soc Nephrol 2006;17(11):3192-7
  • Samuel CS, Unemori EN, Mookerjee I, et al. Relaxin modulates cardiac fibroblast proliferation, differentiation, and collagen production and reverses cardiac fibrosis in vivo. Endocrinology 2004;145(9):4125-33
  • Heeg MH, Koziolek MJ, Vasko R, et al. The antifibrotic effects of relaxin in human renal fibroblasts are mediated in part by inhibition of the Smad2 pathway. Kidney Int 2005;68(1):96-109
  • Mookerjee I, Hewitson TD, Halls ML, et al. Relaxin inhibits renal myofibroblast differentiation via RXFP1, the nitric oxide pathway, and Smad2. FASEB J 2009;23(4):1219-29
  • Dschietzig T, Teichman S, Unemori E, et al. Intravenous recombinant human relaxin in compensated heart failure: a safety, tolerability, and pharmacodynamic trial. J Card Fail 2009;15(3):182-90
  • Teerlink JR, Metra M, Felker GM, et al. Relaxin for the treatment of patients with acute heart failure (Pre-RELAX-AHF): a multicentre, randomised, placebo-controlled, parallel-group, dose-finding phase IIb study. Lancet 2009;373(9673):1429-39
  • Ponikowski P, Mitrovic V, Ruda M, et al. A randomized, double-blind, placebo-controlled, multicentre study to assess haemodynamic effects of serelaxin in patients with acute heart failure. Eur Heart J 2014;35(7):431-41
  • Voors AA, Dahlke M, Meyer S, et al. Renal hemodynamic effects of serelaxin in patients with chronic heart failure: a randomized, placebo-controlled study. Circ Heart Fail 2014;7(6):994-1002
  • Anderson S, Brenner BM. The role of intraglomerular pressure in the initiation and progression of renal disease. J Hypertens Suppl 1986;4(5):S236-8
  • Metra M, Ponikowski P, Cotter G, et al. Effects of serelaxin in subgroups of patients with acute heart failure: results from RELAX-AHF. Eur Heart J 2013;34(40):3128-36
  • Filippatos G, Teerlink JR, Farmakis D, et al. Serelaxin in acute heart failure patients with preserved left ventricular ejection fraction: results from the RELAX-AHF trial. Eur Heart J 2013; Epub ahead of print
  • Mehra S, Walker J, Patterson K, et al. Autoantibodies in systemic sclerosis. Autoimmun Rev 2013;12(3):340-54
  • Safety of repeat doses of IV serelaxin in subjects with chronic heart failure (RELAX-REPEAT). Available from: https://clinicaltrials.gov/ct2/show/NCT01982292
  • Yancy CW, Jessup M, Bozkurt B, et al. 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. J Am Coll Cardiol 2013;62(16):e147-239
  • McMurray JJ, Adamopoulos S, Anker SD, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2012;14(8):803-69
  • Valente MA, Voors AA, Damman K, et al. Diuretic response in acute heart failure: clinical characteristics and prognostic significance. Eur Heart J 2014; Epub ahead of print
  • Leto L, Aspromonte N, Feola M. Efficacy and safety of loop diuretic therapy in acute decompensated heart failure: a clinical review. Heart Fail Rev 2014;19(2):237-46
  • Metra M, Cotter G, Gheorghiade M, et al. The role of the kidney in heart failure. Eur Heart J 2012;33(17):2135-42
  • Wakai A, McCabe A, Kidney R, et al. Nitrates for acute heart failure syndromes. Cochrane Database Syst Rev 2013;8:CD005151
  • Metra M, Bettari L, Carubelli V, et al. Use of inotropic agents in patients with advanced heart failure: lessons from recent trials and hopes for new agents. Drugs 2011;71(5):515-25
  • O’Connor CM, Starling RC, Hernandez AF, et al. Effect of nesiritide in patients with acute decompensated heart failure. N Engl J Med 2011;365(1):32-43
  • McMurray JJ, Teerlink JR, Cotter G, et al. Effects of tezosentan on symptoms and clinical outcomes in patients with acute heart failure: the VERITAS randomized controlled trials. JAMA 2007;298(17):2009-19
  • Gheorghiade M, Konstam MA, Burnett JC, et al. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials. JAMA 2007;297(12):1332-43
  • Massie BM, O’Connor CM, Metra M, et al. Rolofylline, an adenosine A1-receptor antagonist, in acute heart failure. N Engl J Med 2010;363(15):1419-28
  • Pang PS, Konstam MA, Krasa HB, et al. Effects of tolvaptan on dyspnoea relief from the EVEREST trials. Eur Heart J 2009;30(18):2233-40
  • Metra M, Bugatti S, Bettari L, et al. Can we improve the treatment of congestion in heart failure? Expert Opin Pharmacother 2011;12(9):1369-79
  • Rehman SU, Mueller T, Januzzi JLJr. Characteristics of the novel interleukin family biomarker ST2 in patients with acute heart failure. J Am Coll Cardiol 2008;52(18):1458-65
  • Rogowski O, Shnizer S, Wolff R, et al. Increased serum levels of oxidative stress are associated with hospital readmissions due to acute heart failure. Cardiology 2011;118(1):33-7
  • Kalogeropoulos AP, Tang WH, Hsu A, et al. High sensitivity C-reactive protein in acute heart failure: Insights from the ASCEND-HF trial. J Card Fail 2014. [Epub ahead of print]
  • Shantsila E, Wrigley BJ, Blann AD, et al. A contemporary view on endothelial function in heart failure. Eur J Heart Fail 2012;14(8):873-81
  • Fischer D, Rossa S, Landmesser U, et al. Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death. Eur Heart J 2005;26(1):65-9
  • Katz SD, Hryniewicz K, Hriljac I, et al. Vascular endothelial dysfunction and mortality risk in patients with chronic heart failure. Circulation 2005;111(3):310-14
  • Meyer B, Mortl D, Strecker K, et al. Flow-mediated vasodilation predicts outcome in patients with chronic heart failure: comparison with B-type natriuretic peptide. J Am Coll Cardiol 2005;46(6):1011-18
  • Baccari MC, Bani D. Relaxin and nitric oxide signalling. Current protein & peptide science 2008;9(6):638-45
  • Kociol RD, Pang PS, Gheorghiade M, et al. Troponin elevation in heart failure prevalence, mechanisms, and clinical implications. J Am Coll Cardiol 2010;56(14):1071-8
  • Ronco C, Cicoira M, McCullough PA. Cardiorenal syndrome type 1: pathophysiological crosstalk leading to combined heart and kidney dysfunction in the setting of acutely decompensated heart failure. J Am Coll Cardiol 2012;60(12):1031-42
  • Nikolaou M, Parissis J, Yilmaz MB, et al. Liver function abnormalities, clinical profile, and outcome in acute decompensated heart failure. Eur Heart J 2013;34(10):742-9

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