Potential new drug treatments for congestive heart failure

References

• Bui AL, Horwich TB, Fonarow GC. Epidemiology and risk profile of heart failure. Nat Rev Cardiol. 2011;8(1):30–41.
   PubMed Web of Science ®Google Scholar
• Go AS, Mozzaffarian D, Roger RL, et al. Heart disease and stroke statistics – 2014 update: a report from the American Heart Association. Circulation. 2014;129:e28–292.
   PubMed Web of Science ®Google Scholar
• Heidenreich PA, Albert NM, Allen LA, et al. Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ Heart Fail. 2013;6(3):606–619.
   PubMed Web of Science ®Google Scholar
• McMurray JJV, Packer M, Desai A, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993–1004.
   PubMed Web of Science ®Google Scholar
• Tarone G, Balligand JL, Bauersachs J, et al. Targeting myocardial remodeling 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.
   PubMed Web of Science ®Google Scholar
• Givertz MM, Teerlink JR, Albert NM, et al. Acute decompensated heart failure: update on new and emerging evidence and directions for future research. J Card. 2013;19:371–389.
   Google Scholar
• McMurray JJ, Adamopoulos S, Anker SD, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012. Euro J of Heart Fail. 2012;14:803–869.
   PubMed Web of Science ®Google Scholar
• Mentz RJ, Felker GM, Ahmad T, et al. Learning from recent trials and shaping the future of acute heart failure trials. Am Heart J. 2012;166:629–635.
   Web of Science ®Google Scholar
• Colucci WS, Elkayam U, Horton DP, et al. Intervenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure. N Eng J Med. 2000;343:246–253.
   PubMed Web of Science ®Google Scholar
• O’Connor CM, Starling RC, Hernandez AF, et al. Effect of nesiritide in patients with acute decompensated heart failure. N Eng J Med. 2011;365:32–43.
   PubMed Web of Science ®Google Scholar
• Follath F, Cleland JG, Just H, et al. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomized double-blind trial. Lancet. 2002;360:196–202.
   PubMed Web of Science ®Google Scholar
• Mebazaa A, Nieminen MS, Packer M, et al. Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial. JAMA. 2007;297:1883–1891.
   PubMed Web of Science ®Google Scholar
• Packer M, Colucci W, Fisher L, et al. Effect of levosimendan on the short-term clinical course of patients with acutely decompensated heart failure. J Am Coll Card: Heart Fail. 2012;1:103–111.
   Web of Science ®Google Scholar
• Packer M, Colucci W, Fisher L, et al. REVIVE Heart Failure Study Group. JACC Heart Fail. 2013;1(2):103–111.
   PubMed Web of Science ®Google Scholar
• Di Somma S, Magrini L. Drug therapy for acute heart failure. Rev Esp Cardiol. 2015;68:706–713.
   PubMed Web of Science ®Google Scholar
• Hsu SY, Nakabayashi K, Nishi S, et al. Activation of orphan receptors s by the hormone relaxin. Science. 2002;295(5555):671–674.
   PubMed Web of Science ®Google Scholar
• McGuane JT, Debrah JE, Sautina L, et al. Relaxin induces rapid dilation of rodent small renal and human subcutaneous arteries via PI3 kinase and nitric oxide. Endocrinology. 2011;152(7):2686–2696.
   Web of Science ®Google Scholar
• Leo CH, Jelinic M, Parkington HC, et al. Acute intravenous injection of serelaxin (recombinant human relaxin-2) causes rapid and sustained bradykinin-mediated vasorelaxation. J Am Heart Assoc. 2014;3(1):e000493.
   Google Scholar
• Neverova N, Teerlink JR. Serelaxin: a potential new drug for the treatment for the treatment of acute heart failure. Expert Opin Investig Drugs. 2014;23(7):1017–1026.
   PubMed Web of Science ®Google Scholar
• Dschietzig T, Teichman S, Unemori E, et al. Intravenous recombinant human relaxin in compensated heart failure: a safety, tolerability, and pharmacodynamics trial. J Card Fail. 2009;15(3):182–190.
   PubMed Web of Science ®Google Scholar
• Teerlink JR, Metra M, Felker GM, et al. Relaxin for the treatment of patients with acute heart failure (Pre-RELAX-AHF): a multicenter, randomized, placebo-controlled, parallel-group, dose-finding phase IIb study. Lancet. 2009;373(967):1429–1439.
   PubMed Web of Science ®Google Scholar
• Teerlink JR, Cotter G, Davison BA, et al. Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomized, placebo-controlled trial. Lancet. 2013;381(9860):29–39.
   PubMed Web of Science ®Google Scholar
• Metra M, Cotter G, Davison BA, et al., RELAX-AHF Investigators. 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.
   PubMed Web of Science ®Google Scholar
• Munagala VK, Burnett JC Jr, Redfield MM. The natriuretic peptides in cardiovascular medicine. Curr Probl Cardiol. 2004;29(12):707–769.
   PubMed Web of Science ®Google Scholar
• Burger AJ. A review of the renal and neurohormonal effects of B-type natriuretic peptide. Congest Heart Fail. 2005;11(1):30–38.
   PubMedGoogle Scholar
• De Zeeuw D, Janseen WM, De Jong PE. Atrial natriuretic factor: its pathophysiological significance in humans. Kidney Int. 1992;41:1115–1133.
   PubMed Web of Science ®Google Scholar
• van der Zander K, Houben AJ, Hofstra L, et al. Hemodynamic and renal effects of low-dose brain natriuretic peptide infusion in humans: a randomized, placebo-controlled crossover study. Am J Physiol Heart Circ Physiol. 2003;285:H1206–H1212.
   Google Scholar
• Jensen KT, Carsten J, Pedersen EB. Effect of BNP on renal hemodynamics, tubular function and vasoactive hormones in humans. Am J Physiol-Renal Physiol. 1998;274:F63–F72.
   Google Scholar
• Lumsden NG, Khambata RS, Hobbs AJ. C-type natriuretic peptide (CNP): cardiovascular roles and potential as a therapeutic target. Curr Pharm Des. 2010;16:4080–4088.
   PubMed Web of Science ®Google Scholar
• Elsner D, Muders F, Müntze A, et al. Efficacy of prolonged infusion of urodilatin [ANP-(95-126)] in patients with congestive heart failure. Am Heart J. 1995;129:766–773.
   PubMed Web of Science ®Google Scholar
• Kentsch M, Ludwig D, Drummer C, et al. Haemodynamic and renal effects of urodilatin bolus injections in patients with congestive heart failure. Eur J Clin Invest. 1992;22:662–669.
   PubMed Web of Science ®Google Scholar
• Mitrovic V, Hernandez AF, Meyer M, et al. Role of guanylate cyclase modulators in decompensated heart failure. Heart Fail Rev. 2009;14:309–319.
   PubMed Web of Science ®Google Scholar
• Kentsch M, Ludwig D, Drummer C, et al. Haemodynamic and renal effects of urodilantin in healthy volunteers. Eur J Clin Invest. 1992;22:319–325.
   PubMed Web of Science ®Google Scholar
• Vesely DL. Urodilantin: a better natriuretic peptide? Curr Heart Fail Rep. 2007;4:147–152.
   PubMedGoogle Scholar
• Mitrovic V, Luss H, Nitsche K, et al. Effects of the renal natriuretic peptide urodilatin (ularitide) in patients with decompensated chronic heart failure: a double-blind, placebo-controlled, ascending-dose trial. Am Heart J. 2005;150:1239.e1–1238.e1.
   PubMed Web of Science ®Google Scholar
• Mitrovic V, Seferovic PM, Simeunovic D, et al. Haemodynamic and clinical effects of ularitide in decompensated heart failure. Eur Heart J. 2006;27:2823–2832.
   PubMed Web of Science ®Google Scholar
• Flather MD, Yusuf S, Kober L, et al., ACE-Inhibitor Myocardial Infarction Collaborative Group. Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systemic overview of data from individual patients. Lancet. 2000;355:1575–1581.
   PubMed Web of Science ®Google Scholar
• Lee VC, Rhew DC, Dylan M, et al. Meta-analysis: angiotensin-receptor blockers in chronic heart failure and high-risk acute myocardial infarction. Ann Intern Med. 2004;141:693–704.
   PubMed Web of Science ®Google Scholar
• Swedberg K, Kjekshus J. Effects of enalapril on mortality in severe congestive heart failure – the CONSENSUS Trial Study Group. N Eng J Med. 1987;316:1429–1435.
   PubMed Web of Science ®Google Scholar
• Effect of enalapril on survival in patients with reduced left ventricular ejection fraction and congestive heart failure – The SOLVD Investigators. N Eng J Med. 1991;325:293–302.
   PubMed Web of Science ®Google Scholar
• Pitt B, Poole-Wilson PA, Segal R, et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomized trial—the Losartan Heart Failure Survival Study ELITE II. Lancet. 2000 May 6;355:1582–1587.
   PubMed Web of Science ®Google Scholar
• Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure – the Valsartan Heart Failure Trial Investigators. N Eng J Med. 2001;345:1667–1675.
   PubMed Web of Science ®Google Scholar
• Violin JD, Dewire SM, Barnes WG, et al. G protein-coupled receptor kinase and beta-arrestin-mediated desensitization of the angiotensin II type 1A receptor elucidated by diacylglycerol dynamics. J Biol Chem. 2006;281:36411–36419.
   PubMed Web of Science ®Google Scholar
• Felker GM, Butler J, Collins SP, et al. Heart failure therapeutics on the basis of a biased ligand of the angiotensin-2 type 1 receptor. Rationale and design of the BLAST-AHF study (Biased Ligand of the Angiotensin Receptor Study in Acute Heart Failure). J Am Coll Cardiol HF. 2015;3:193–201.
   Google Scholar
• Violin JD, Dewire SM, Yamashita D, et al. Selectively engaging beta-arrestins at the angiotensin II type 1 receptor reduces blood pressure and increase cardiac performance. J Pharmacol Exp Ther. 2010;335:572–579.
   PubMed Web of Science ®Google Scholar
• Boerrigter G, Lark MW, Whalen EJ. Cardiorenal actions of TRV20027, a novel β-arrestin-biased ligand at the angiotensin II type I receptor, in healthy and heart failure canines: a novel therapeutic strategy for acute heart failure. Circ Heart Fail. 2011;4:770–778.
   PubMed Web of Science ®Google Scholar
• Soergel DG, Subach RA, Cowan CL, et al. First clinical experience with TVR027: pharmacokinetics and pharmacodynamics in healthy volunteers. J Clin Pharmacol. 2013;53:892–899.
   PubMed Web of Science ®Google Scholar
• Konstam MA, Gheorghiade M, Burnett JC Jr, et al. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA. 2007;297:1319–1331.
   PubMed Web of Science ®Google Scholar
• Gheorghiade M, Bohm M, Greene SJ, et al. Effect of aliskiren on postdischarge mortality and heart failure readmissions among patients hospitalized for heart failure: the ASTRONAUT randomized trial. JAMA. 2013;309:1125–1135.
   PubMed Web of Science ®Google Scholar
• Von Lueder TG, Sangaralingham SJ, Wang BH, et al. Renin-angiotensin blockade combined with natriuretic peptide system augmentation: novel therapeutic concepts to combat heart failure. Circ Heart Fail. 2013;6:594–605.
   PubMed Web of Science ®Google Scholar
• Mills J, Vardeny O. The role of neprilysin inhibitors in cardiovascular disease. Curr Heart Fail Rep. 2015;12:389–394.
   PubMedGoogle Scholar
• Basvishi C, Messerlie FH, Kadosh B, et al. Role of neprilysin inhibitor combinations in hypertension: insights from hypertension and heart failure trials. Eur Heart J. 2015;36(30):1967–1973.
   PubMed Web of Science ®Google Scholar
• Ando S, Rahman MA, Butler GC, et al. Comparison of candoxatril and atrial natriuretic factor in healthy men. Effects on hemodynamics, sympathetic activity, heart frate variability, and endothelin. Hypertension. 1995;26:1160–1166.
   PubMed Web of Science ®Google Scholar
• Swedberg K, Komajda M, Bohm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT: a randomized placebo-controlled study. Lancet. 2010;376:875–885.
   PubMed Web of Science ®Google Scholar
• Packer M, Carver JR, Rodeheffer RJ, et al. Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. N Engl J Med. 1991;325(21):1468–1475.
   PubMed Web of Science ®Google Scholar
• Malik FI, Morgan BP. Cardiac myosin activation part 1: from concept to clinic. J Mol Cell Cardiol. 2011;51:454–461.
   PubMed Web of Science ®Google Scholar
• Malik FI, Hartman JJ, Elias KA, et al. Cardiac myosin activation: a potential therapeutic approach for systolic heart failure. Science. 2011;331(6023):1439–1443.
   PubMed Web of Science ®Google Scholar
• Shen YT, Malik FI, Zhao X, et al. Improvement of cardiac function by a cardiac myosin activator in conscious dogs with systolic heart failure. Circ Heart Fail. 2010;3(4):522–527.
   PubMed Web of Science ®Google Scholar
• deGoma EM, Vagelos RH, Fowler MB, et al. Emerging therapies for the management of decompensated heart failure: from bench to bedside. J Am Coll Cardiol. 2006;48(12):2397–2409.
   PubMed Web of Science ®Google Scholar
• Teerlink JR, Clarke CP, Saikali KG, et al. Dose-dependent augmentation of cardiac systolic function with the selective cardiac myosin activator, omecamtiv mecarbil: a first-in-man study. Lancet. 2011;378:667–675.
   PubMed Web of Science ®Google Scholar
• Cleland JG, Teerlink JR, Senior R, et al. The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial. Lancet. 2011;378:676–683.
   PubMed Web of Science ®Google Scholar
• Greenberg BH, Chou W, Saikali KG, et al. Safety and tolerability of omecamtiv mecarbil during exercise in patients with ischemic cardiomyopathy and angina. J Am Coll Cardiol HF. 2015;3:22–29.
   Google Scholar
• Whelan RS, Kaplinskiy V, Kitsis RN. Cell death in the pathogenesis of heart disease: mechanisms and significance. Annu Rev Physiol. 2010;72:19–44.
   PubMed Web of Science ®Google Scholar
• Tsai EJ, Kass DA. Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics. Pharmacol Ther. 2009;122(3):216–238.
   PubMed Web of Science ®Google Scholar
• Gheorghiade M, Marti CN, Sabbah HN, et al. Soluble guanylate cyclase: a potential therapeutic target for heart failure. Heart Fail Rev. 2013;18(2):123–134.
   PubMed Web of Science ®Google Scholar
• Martin F, Baskaran P, Ma X, et al. Structure of cinaciquat (BAY 58-2667) bound to nostoc H-NOX domain reveals insights into heme-mimetic activation of the soluble guanylyl cyclase. J Biol Chem. 2010;285(29):22651–22657.
   PubMed Web of Science ®Google Scholar
• Gheorghiade M, Greene SJ, Filippatos G, et al., COMPOSE Investigators. Cinaciguat, a soluble guanylate cyclase activator: results from the randomized, controlled, phase IIb COMPOSE programme in acute heart failure syndromes. Eur J Heart Fail. 2012;14(9):1056–1066.
   PubMed Web of Science ®Google Scholar
• Makowski CT, Rissmiller RW, Bullington WM, et al. Riociguat: a novel new drug for treatment of pulmonary hypertension. Pharmacotherapy. 2015;35:502–519.
   PubMed Web of Science ®Google Scholar
• Bonderman D, Ghio S, Felix SB, et al. Riociguat for patients with pulmonary hypertension caused by systolic left ventricular dysfunction. Circulation. 2013;128:502–511.
   PubMed Web of Science ®Google Scholar
• Taichman DB, Ornelas J, Chung L, et al. Pharmacologic therapy for pulmonary arterial hypertension in adults CHEST guideline and expert panel report. Chest. 2014;146:449–475.
   PubMed Web of Science ®Google Scholar
• Pieske B, Butler J, Filippatos G, et al. Rationale and design of the SOluble guanylate Cyclase stimulatoR in heArT failurE Studies (SOCRATES). Eur J Heart Fail. 2014;16:1026–1038.
   PubMed Web of Science ®Google Scholar
• Gheorghiade M, Greene SJ, Butler J, et al. 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.
   PubMed Web of Science ®Google Scholar
• McMurray JJ. CONSENSUS to EMPHASIS: the overwhelming evidence which makes blockade of the renin-angiotensin-aldosterone system the cornerstone of therapy for systolic heart failure. Eur J Heart Fail. 2011;13:929–936.
   PubMed Web of Science ®Google Scholar
• Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348:1309–1321.
   PubMed Web of Science ®Google Scholar
• Pitt B, Zannad F, Remme W, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341:709–717.
   PubMed Web of Science ®Google Scholar
• Zannad F, McMurray JJ, Krum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364:11–21.
   PubMed Web of Science ®Google Scholar
• Albert NM, Yancy CW, Liang L, et al. Use of aldosterone antagonists in heart failure. JAMA. 2009;302:1658–1665.
   PubMed Web of Science ®Google Scholar
• Maggioni A, Dahlstrom U, Filippatos G, et al. EURObservation Research Programme: the Heart Failure Pilot Survey (ESC-HF Pilot). Eur J Heart Failure. 2010;12:1076–1084.
   PubMed Web of Science ®Google Scholar
• Kolkhof P, Borden SA. Molecular pharmacology of the mineralocorticoid receptor: prospects for novel therapeutics. Mol Col Endocrinol. 2012;350:310–317.
   PubMed Web of Science ®Google Scholar
• Kolkhof P, Nowack C, Eitner F. Nonsteroidal antagonists of the mineralocorticoid receptor. Curr Opin Nephrol Hypertens. 2015;24:417–424.
   PubMed Web of Science ®Google Scholar
• Delbeck M, Kretschmer A, Kast R, et al. Cardiorenal protection by BAY 94-8862, a novel non-steroidal mineralocorticoid receptor antagonist in a preclinical model of hypertension and diastolic heart failure. Eur Heart J. 2012;33:772–773.
   Web of Science ®Google Scholar
• Kolkhlf P, Kretschmer A, Baerfacker L, et al. Improved survival and nephroprotection in hypertensive rats by BAY 94-8862, a novel non-steroidal mineralocorticoid receptor antagonist. Eur Heart J. 2012;33:978–979.
   Web of Science ®Google Scholar
• Pitt B, Filippatos G, Gheorghiade M, et al. Rationale and design of ARTS: a randomized, double-blind study of BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease. Eur J Heart Fail. 2012;14:668–675.
   PubMed Web of Science ®Google Scholar
• Pitt B, Kober L, Ponikoowski P, et al. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial. Eur Heart J. 2013;34(31):2463.
   Web of Science ®Google Scholar
• Pitt B, Anker SD, Bohm M, et al. Rationale and design of MinerAlocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF): a randomized study of finerenone vs eplerenone in patients who have worsening chronic heart failure with diabetes and/or chronic kidney disease. Eur J Heart Fail. 2015;17:224–232.
   PubMed Web of Science ®Google Scholar
• Slamon DJ, Leyland-Jone B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–792.
   PubMed Web of Science ®Google Scholar
• Ozcelik C, Erdmann B, Pilz B, et al. Conditional mutation of the ErbB2 (HER2) receptor in cardiomyocytes leads to dilated cardiomyopathy. Proc Natl Acad Sci USA. 2002;99:8880–8885.
   PubMed Web of Science ®Google Scholar
• Garcia-Rivello H, Taranda J, Said M, et al. Dilated cardiomyopathy in Erb-b4-deficient ventricular muscle. Am J Physiol Heart Circ Physiol. 2005;289:H1153–H1160.
   PubMed Web of Science ®Google Scholar
• De Keulenaer GW, Doggen K, Lemmens K. The vulnerability of the heart as a pleuricellular paracrine organ: lessons from unexpected triggers of heart failure in targeted ErbB anticancer therapy. Circ Res. 2010;106:35–46.
   PubMed Web of Science ®Google Scholar
• Pentassuglia L, Sawyer DB, De Zeeuw D, et al. The role of neuregulin-1beta/ErbB signaling in the heart. Exp Cell Res. 2009;315:627–637.
   PubMed Web of Science ®Google Scholar
• Odiete O, Hill MF, Sawyer DB. Neuregulin in cardiovascular development and disease. Circ Res. 2012;111:1376–1385.
   PubMed Web of Science ®Google Scholar
• Bersell K, Arab S, Haring B, et al. Neuregulin1/ErbB4 signaling induces cardiomyocyte proliferation and repair of heart injury. Cell. 2009;136:257–270.
   Web of Science ®Google Scholar
• Liu X, Gu X, Li Z, et al. Neuregulin-1/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy. J Am Coll Cardiol. 2006;48:1438–1447.
   PubMed Web of Science ®Google Scholar
• Gao R, Zhang J, Cheng L, et al. A phase II, randomized, double-blind, multicenter, based on standard therapy, placebo-controlled study of the efficacy and safety of recombinant human neuregulin-1 in patients with chronic heart failure. J Am Coll Cardiol. 2010;55:1907–1914.
   PubMed Web of Science ®Google Scholar
• Abbour A, Hayward CS, Keogh AM, et al. Parenteral administration of recombinant human neuregulin-1 to patients with stable chronic heart failure produces favourable acute and chronic haemodynamic responses. Eur J Heart Fail. 2011;13:83–92.
   PubMed Web of Science ®Google Scholar