{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:39:28Z","timestamp":1773661168716,"version":"3.50.1"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2013,7,9]],"date-time":"2013-07-09T00:00:00Z","timestamp":1373328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr Heart Fail Rep"],"published-print":{"date-parts":[[2013,9]]},"DOI":"10.1007\/s11897-013-0148-6","type":"journal-article","created":{"date-parts":[[2013,7,8]],"date-time":"2013-07-08T06:25:45Z","timestamp":1373264745000},"page":"198-203","source":"Crossref","is-referenced-by-count":7,"title":["Relaxin for Treatment of Acute Heart Failure: Making the Case for Treating Targeted Patient Profiles"],"prefix":"10.1007","volume":"10","author":[{"given":"Jaime A.","family":"Hernandez-Montfort","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonali","family":"Arora","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mara T.","family":"Slawsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,7,9]]},"reference":[{"key":"148_CR1","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1001\/archinte.167.14.1493","volume":"167","author":"GC Fonarow","year":"2007","unstructured":"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;167:1493\u2013502.","journal-title":"Arch Intern Med"},{"key":"148_CR2","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1161\/CIRCULATIONAHA.107.696906","volume":"116","author":"SD Solomon","year":"2007","unstructured":"Solomon SD, Dobson J, Pocock S, et al. Influence of nonfatal hospitalization for heart failure on subsequent mortality in patients with chronic heart failure. Circulation. 2007;116:1482\u20137.","journal-title":"Circulation"},{"key":"148_CR3","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.jacc.2008.10.041","volume":"53","author":"M Gheorghiade","year":"2009","unstructured":"Gheorghiade M, Pang PS. Acute heart failure syndromes. J Am Coll Cardiol. 2009;53:557\u201373.","journal-title":"J Am Coll Cardiol"},{"key":"148_CR4","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1093\/eurheartj\/ehs104","volume":"33","author":"JJ McMurray","year":"2012","unstructured":"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 Heart J. 2012;33:1787\u2013847.","journal-title":"Eur Heart J"},{"key":"148_CR5","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1093\/eurjhf\/hfr182","volume":"14","author":"S Laribi","year":"2012","unstructured":"Laribi S, Aouba A, Nikolaou M, et al. Trends in death attributed to heart failure over the past two decades in Europe. Eur J Heart Fail. 2012;14:234\u20139.","journal-title":"Eur J Heart Fail"},{"key":"148_CR6","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.ejheart.2008.01.007","volume":"10","author":"G Cotter","year":"2008","unstructured":"Cotter G, Metra M, Milo-Cotter O, Dittrich HC, Gheorghiade M. Fluid overload in acute heart failure\u2014re-distribution and other mechanisms beyond fluid accumulation. Eur J Heart Fail. 2008;10:165\u20139.","journal-title":"Eur J Heart Fail"},{"key":"148_CR7","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1093\/eurjhf\/hfq045","volume":"12","author":"M Gheorghiade","year":"2010","unstructured":"Gheorghiade M, Follath F, Ponikowski P, et al. Assessing and treating 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;12:423\u201333.","journal-title":"Eur J Heart Fail"},{"key":"148_CR8","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1093\/eurheartj\/ehs205","volume":"33","author":"M Metra","year":"2012","unstructured":"Metra M, Cotter G, Gheorghiade M, Dei Cas L, Voors AA. The role of the kidney in heart failure. Eur Heart J. 2012;33:2135\u201342.","journal-title":"Eur Heart J"},{"key":"148_CR9","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1161\/CIRCULATIONAHA.111.062430","volume":"126","author":"D Gupta","year":"2012","unstructured":"Gupta D, Georgiopoulou VV, Kalogeropoulos AP, et al. Dietary sodium intake in heart failure. Circulation. 2012;126:479\u201385.","journal-title":"Circulation"},{"key":"148_CR10","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1056\/NEJMoa1005419","volume":"364","author":"MG Felker","year":"2011","unstructured":"Felker MG, Lee KL, Bull DA, et al. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011;364:797\u2013805.","journal-title":"N Engl J Med"},{"key":"148_CR11","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1056\/NEJMoa1100171","volume":"365","author":"CM O\u2019Connor","year":"2011","unstructured":"O\u2019Connor CM, Starling RC, Hernandez AF, et al. Effect of nesiritide in patients with acute decompensated heart failure. N Engl J Med. 2011;365:32\u201343.","journal-title":"N Engl J Med"},{"key":"148_CR12","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1001\/jama.287.12.1541","volume":"287","author":"SM Cuffe","year":"2002","unstructured":"Cuffe SM, Califf RM, Adams KF, et al. Short-term intravenous milrinone for acute exacerbation of chronic heart failure. J Am Med Assoc. 2002;287:1541\u20137.","journal-title":"J Am Med Assoc"},{"key":"148_CR13","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.ejheart.2005.12.003","volume":"8","author":"JGF Cleland","year":"2006","unstructured":"Cleland JGF, Freemantle N, Coletta AP, Clark AL. Clinical trials update from the American Heart Association: REPAIR-AMI, ASTAMI, JELIS, MEGA, REVIVE-II, SURVIVE, and PROACTIVE. Eur J Heart Fail. 2006;8:105\u201310.","journal-title":"Eur J Heart Fail"},{"key":"148_CR14","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1159\/000318048","volume":"116","author":"G Cotter","year":"2010","unstructured":"Cotter G, Voors AA, Davison BD. Acute heart failure clinical drug development: From planning to proof of activity to phase III. Cardiology. 2010;116:292\u2013301.","journal-title":"Cardiology"},{"key":"148_CR15","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jacc.2005.03.051","volume":"46","author":"WT Abraham","year":"2005","unstructured":"Abraham WT, Kirkwood AF, Fonarow GC, et al. In-hospital mortality in patients with acute decompensated heart failure requiring intravenous vasoactive medications. An analysis from the Acute Decompensated Heart Failure National Registry (ADHERE). J Am Coll Cardiol. 2005;46:57\u201364.","journal-title":"J Am Coll Cardiol"},{"key":"148_CR16","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1001\/jama.2011.515","volume":"305","author":"M Gheorghiade","year":"2011","unstructured":"Gheorghiade M, Braunwald E. A proposed model for initial assessment and management of acute heart failure syndromes. JAMA. 2011;305:1702\u20133.","journal-title":"JAMA"},{"key":"148_CR17","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.ahj.2011.10.009","volume":"163","author":"M Gheorghiade","year":"2012","unstructured":"\u2022\u2022 Gheorghiade M, Pang P, O\u2019Connor CM, et al. Clinical development of pharmacologic agents for acute heart failure syndromes: A proposal for a mechanistic translational phase. Am Heart J. 2012;163:149\u201355. This article proposes insertion of a translational phase trial during clinical development of a pharmacologic agent to test the mechanistic hypothesis in a small, clinically \u201chomogeneous\u201d group of patients before proceeding to a phase II trial.","journal-title":"Am Heart J"},{"key":"148_CR18","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1016\/j.jacc.2011.11.082","volume":"60","author":"CN Marti","year":"2012","unstructured":"\u2022 Marti CN, Gheorghiade M, Kalogeropoulos AP, et al. Endothelial dysfunction, arterial stiffness and heart failure. J Am Coll Cardiol. 2012;60:1455\u201369. This article focuses on the importance of endothelial function and vascular stiffness as targets for investigation of therapies in acute heart failure.","journal-title":"J Am Coll Cardiol"},{"key":"148_CR19","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/S0140-6736(97)08417-1","volume":"351","author":"G Cotter","year":"1998","unstructured":"Cotter G, Metzkor E, Kaluski E, Faigenberg Z, et al. Randomized trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary edema. Lancet. 1998;351:389\u201393.","journal-title":"Lancet"},{"key":"148_CR20","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s10741-008-9129-3","volume":"14","author":"SL Teichman","year":"2009","unstructured":"Teichman SL, Unemori E, Dschietzig T, et al. Relaxin, a pleiotropic vasodilator for the treatment of heart failure. Heart Fail Rev. 2009;14:321\u20139.","journal-title":"Heart Fail Rev"},{"key":"148_CR21","doi-asserted-by":"crossref","first-page":"R267","DOI":"10.1152\/ajpregu.00156.2011","volume":"301","author":"KP Conrad","year":"2011","unstructured":"Conrad KP. Maternal vasodilation in pregnancy: The emerging role of relaxin. Am J Physiol Regul Integr Comp Physiol. 2011;301:R267\u201375.","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"148_CR22","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s11897-010-0010-z","volume":"7","author":"SL Teichman","year":"2010","unstructured":"\u2022 Teichman SL, Unemori E, Teerlink JR. Relaxin: Review of biology and potential in treating heart failure. Curr Heart Fail Rep. 2010;7:75\u201382. This article provides an overview of relaxin biology and physiologic effects of relaxin in preclinical and clinical studies.","journal-title":"Curr Heart Fail Rep"},{"key":"148_CR23","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.cardfail.2009.01.008","volume":"15","author":"T Dschietzig","year":"2009","unstructured":"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;15:182\u201390.","journal-title":"J Card Fail"},{"key":"148_CR24","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1016\/S0140-6736(09)60622-X","volume":"373","author":"JR Teerlink","year":"2009","unstructured":"Teerlink JR, Metra M, Felker MG, et al. Relaxin for the treatment of patients with acute heart failure (pre-RELAX-AHF): A multicentre, randomized, placebo-controlled, parallel-group, dose-finding phase IIb study. Lancet. 2009;373:1429\u201339.","journal-title":"Lancet"},{"key":"148_CR25","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0140-6736(12)61855-8","volume":"381","author":"JR Teerlink","year":"2013","unstructured":"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;381:29\u201339.","journal-title":"Lancet"},{"key":"148_CR26","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.jacc.2011.09.062","volume":"59","author":"S Schwartzenberg","year":"2012","unstructured":"\u2022 Schwartzenberg S, Redfield MM, From AM, et al. Effects of vasodilation in heart failure with preserved or reduced ejection fraction implications of distinct pathophysiologies on response to therapy. J Am Coll Cardiol. 2012;59:442\u201351. This study, which examined the effects of nitroprusside in distinct heart failure profiles, emphasizes the importance of developing targeted heart failure therapies.","journal-title":"J Am Coll Cardiol"},{"key":"148_CR27","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/S0735-1097(13)60197-7","volume":"61","author":"M Metra","year":"2013","unstructured":"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. J Am Coll Cardiol. 2013;61:196\u2013206.","journal-title":"J Am Coll Cardiol"},{"key":"148_CR28","doi-asserted-by":"crossref","unstructured":"Effects of tezosentan on symptoms and clinical outcomes in patients with acute heart failure: the VERITAS randomized controlled trials. JAMA 2007;298:2009\u20132019.","DOI":"10.1001\/jama.298.17.2009"},{"key":"148_CR29","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.jacc.2011.03.057","volume":"58","author":"CM O\u2019Connor","year":"2011","unstructured":"O\u2019Connor CM, Fiuzat M, Swedberg K, et al. Influence of global region on outcomes in heart failure beta-blocker trials. J Am Coll Cardiol. 2011;58:915\u201322.","journal-title":"J Am Coll Cardiol"},{"key":"148_CR30","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ahj.2006.02.038","volume":"155","author":"G Cotter","year":"2008","unstructured":"Cotter G, Felker GM, Adams KF, et al. The pathophysiology of acute heart failure-is it all about fluid accumulation? Am Heart J. 2008;155:9\u201318.","journal-title":"Am Heart J"},{"key":"148_CR31","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.ejheart.2007.12.007","volume":"10","author":"PC Colombo","year":"2008","unstructured":"Colombo PC, Onat D, Sabbah HN. Acute heart failure as \u201cacute endothelitis\u201d-interaction of fluid overload and endothelial dysfunction. Eur J Heart Fail. 2008;10:170\u20135.","journal-title":"Eur J Heart Fail"},{"key":"148_CR32","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1159\/000318048","volume":"116","author":"G Cotter","year":"2010","unstructured":"\u2022 Cotter G, Voors AA, Davison BD. Acute heart failure clinical drug development: from planning to proof of activity to phase III. Cardiology. 2010;116:292\u2013301. This article compared multiple clinical AHF trials and demonstrated a high degree of heterogeneity in patient characteristics and outcome measures.","journal-title":"Cardiology"},{"key":"148_CR33","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ahj.2011.11.023","volume":"164","author":"SP Collins","year":"2012","unstructured":"\u2022 Collins SP, Lindsell CJ, Pang PS, et al. Bayesian adaptive trial design in acute heart failure syndromes: moving beyond the mega trial. Am Heart J. 2012;164:138\u201345. This article proposes an AHF clinical trial design that is based on patient phenotypes.","journal-title":"Am Heart J"}],"container-title":["Current Heart Failure Reports"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11897-013-0148-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s11897-013-0148-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11897-013-0148-6","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,7,17]],"date-time":"2019-07-17T12:56:10Z","timestamp":1563368170000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s11897-013-0148-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,7,9]]},"references-count":33,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,9]]}},"alternative-id":["148"],"URL":"https:\/\/doi.org\/10.1007\/s11897-013-0148-6","relation":{},"ISSN":["1546-9530","1546-9549"],"issn-type":[{"value":"1546-9530","type":"print"},{"value":"1546-9549","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7,9]]}}}