title: New strategies for heart failure with preserved ejection fraction: the importance of targeted therapies for heart failure phenotypes.
abstract: The management of heart failure with reduced ejection fraction (HF-REF) has improved significantly over the last two decades. In contrast, little or no progress has been made in identifying evidence-based, effective treatments for heart failure with preserved ejection fraction (HF-PEF). Despite the high prevalence, mortality, and cost of HF-PEF, large phase III international clinical trials investigating interventions to improve outcomes in HF-PEF have yielded disappointing results. Therefore, treatment of HF-PEF remains largely empiric, and almost no acknowledged standards exist. There is no single explanation for the negative results of past HF-PEF trials. Potential contributors include an incomplete understanding of HF-PEF pathophysiology, the heterogeneity of the patient population, inadequate diagnostic criteria, recruitment of patients without true heart failure or at early stages of the syndrome, poor matching of therapeutic mechanisms and primary pathophysiological processes, suboptimal study designs, or inadequate statistical power. Many novel agents are in various stages of research and development for potential use in patients with HF-PEF. To maximize the likelihood of identifying effective therapeutics for HF-PEF, lessons learned from the past decade of research should be applied to the design, conduct, and interpretation of future trials. This paper represents a synthesis of a workshop held in Bergamo, Italy, and it examines new and emerging therapies in the context of specific, targeted HF-PEF phenotypes where positive clinical benefit may be detected in clinical trials. Specific considerations related to patient and endpoint selection for future clinical trials design are also discussed.
authors.affiliation: Cardiovascular Department, Hospital Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Senni
authors.affiliation: Institute for Cardiovascular Research, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Paulus
authors.affiliation: Cardiovascular Department, Hospital Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Gavazzi
authors.affiliation: Wales Heart Research Institute, Cardiff University, Cardiff, UK.
authors.forename: Alan G
authors.initials: AG
authors.lastname: Fraser
authors.affiliation: Division of Cardiovascular Sciences Centre for Applied Medical Research and Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, University of Navarra, Pamplona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Díez
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.affiliation: Institute for Surgical Research, Department of Cardiology, and Center for Cardiological Innovation, University of Oslo, Oslo, Norway.
authors.forename: Otto A
authors.initials: OA
authors.lastname: Smiseth
authors.affiliation: Heart Failure Unit, Department of Biomedical Sciences for Health, IRCCS Policlinico San Donato, University of Milano, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Guazzi
authors.affiliation: National University Health System, Singapore, Singapore.
authors.forename: Carolyn S P
authors.initials: CS
authors.lastname: Lam
authors.affiliation: ANMCO Research Center, Florence, Italy.
authors.forename: Aldo P
authors.initials: AP
authors.lastname: Maggioni
authors.affiliation: Department of Cardiology and Pneumology, Charité-University Medicine Berlin, Campus Benjamin Franklin, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Tschöpe
authors.affiliation: Cardiology, Department of Experimental and Applied Medicine, University of Brescia, Brescia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA Section of Cardiology, Ann Arbor Veterans Affairs Medical Center, Ann Arbor, MI, USA.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Hummel
authors.affiliation: Department of Cardiology and Pneumology, University of Göttingen, Göttingen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Edelmann
authors.affiliation: Division of Cardiology, University of Perugia School of Medicine, Perugia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ambrosio
authors.affiliation: Monash University, Melbourne, Australia University of Warwick, Conventry, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Stewart Coats
authors.affiliation: Athens University Hospital Attikon, Athens, Greece.
authors.forename: Gerasimos S
authors.initials: GS
authors.lastname: Filippatos
authors.affiliation: Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Mihai
authors.initials: M
authors.lastname: Gheorghiade
authors.affiliation: Department of Innovative Clinical Trials, University Medical Centre Gottingen, Gottingen, Germany Applied Cachexia Research, Department of Cardiology, Charite, Campus CVK, Berlin, Germany.
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.affiliation: Framingham Heart Study, Framingham, MA, USA Division of Cardiology, Boston University School of Medicine, Boston, MA, USA Center for Population Studies, National Heart, Lung, and Blood Institute, Bethesda, MD, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pfeffer
authors.affiliation: Department of Clinical Research, Campbell University College of Pharmacy and Health Sciences, North Carolina, USA.
authors.forename: Wendy Gattis
authors.initials: WG
authors.lastname: Stough
authors.affiliation: Department of Cardiology, Medical University Graz, Ludwig-Boltzmann-Institute for Heart Failure Research, Auenbruggerplatz 15, 8010 Graz, Austria burkert.pieske@medunigraz.at.
authors.forename: Burkert M
authors.initials: BM
authors.lastname: Pieske
mesh_terms: D000613:Aminobutyrates / Q000627:therapeutic use; D000740:Anemia / Q000517:prevention & control; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D001713:Biphenyl Compounds; D002316:Cardiotonic Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003925:Diabetic Angiopathies / Q000517:prevention & control; D004232:Diuretics / Q000627:therapeutic use; D004338:Drug Combinations; D005081:Exercise Therapy / Q000379:methods; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy*; D006706:Homeostasis; D006801:Humans; D006976:Hypertension, Pulmonary / Q000517:prevention & control; D000090463:Iron Deficiencies; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D058990:Molecular Targeted Therapy / Q000379:methods; D009765:Obesity / Q000517:prevention & control; D064887:Observational Studies as Topic; D018579:Patient Selection; D010641:Phenotype; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use; D026941:Sodium Channel Blockers / Q000627:therapeutic use; D013318:Stroke Volume / Q000502:physiology; D013777:Tetrazoles / Q000627:therapeutic use; D000068756:Valsartan; D059289:Vascular Stiffness / Q000502:physiology
chemical_list: D000613:Aminobutyrates; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D002316:Cardiotonic Agents; D004232:Diuretics; D004338:Drug Combinations; D000451:Mineralocorticoid Receptor Antagonists; D058986:Phosphodiesterase 5 Inhibitors; D026941:Sodium Channel Blockers; D013777:Tetrazoles; D000068756:Valsartan; C549068:sacubitril and valsartan sodium hydrate drug combination
keywords: Clinical trial; Diabetes mellitus; Exercise tolerance; Heart failure, Diastolic; Phenotype; Preserved ejection fraction
references.citation: J Card Fail. 2011 Jul;17(7):547-55
references.pmid: 21703526
references.citation: Circulation. 2006 Nov 14;114(20):2138-47
references.pmid: 17088459
references.citation: J Mol Cell Cardiol. 1993 May;25(5):563-75
references.pmid: 8377216
references.citation: Curr Diab Rep. 2009 Feb;9(1):79-86
references.pmid: 19192429
references.citation: Circulation. 2003 Feb 11;107(5):656-8
references.pmid: 12578861
references.citation: J Muscle Res Cell Motil. 2006;27(5-7):435-44
references.pmid: 16897574
references.citation: Echocardiography. 2012 Oct;29(9):1045-53
references.pmid: 22672221
references.citation: Circ Heart Fail. 2012 Nov;5(6):710-9
references.pmid: 23076838
references.citation: Am J Kidney Dis. 2013 Jun;61(6):975-83
references.pmid: 23474006
references.citation: Circulation. 2006 Aug 1;114(5):397-403
references.pmid: 16864724
references.citation: Circulation. 2011 Dec 6;124(23):2491-501
references.pmid: 22064591
references.citation: Am Heart J. 2011 Dec;162(6):966-972.e10
references.pmid: 22137068
references.citation: J Am Coll Cardiol. 2007 Jan 2;49(1):88-96
references.pmid: 17207727
references.citation: J Mol Cell Cardiol. 2002 Aug;34(8):951-69
references.pmid: 12234765
references.citation: N Engl J Med. 2014 Apr 10;370(15):1383-92
references.pmid: 24716680
references.citation: Circulation. 2002 Dec 3;106(23):2967-72
references.pmid: 12460880
references.citation: Circulation. 2005 Oct 11;112(15):2254-62
references.pmid: 16203909
references.citation: Clin Sci (Lond). 2003 Nov;105(5):591-9
references.pmid: 12831396
references.citation: Am J Cardiol. 2005 Dec 1;96(11):1543-8
references.pmid: 16310437
references.citation: Circ Res. 2012 Mar 16;110(6):841-50
references.pmid: 22343711
references.citation: Eur J Heart Fail. 2011 Jan;13(1):76-82
references.pmid: 20861128
references.citation: J Mol Cell Cardiol. 2005 Mar;38(3):475-83
references.pmid: 15733907
references.citation: Circulation. 2011 Jul 12;124(2):164-74
references.pmid: 21709061
references.citation: Am J Cardiol. 1993 Jan 21;71(3):12A-16A
references.pmid: 8421998
references.citation: J Am Coll Cardiol. 2006 Jan 3;47(1):76-84
references.pmid: 16386668
references.citation: J Am Coll Cardiol. 2011 Jul 26;58(5):474-80
references.pmid: 21777743
references.citation: Hypertension. 1996 Mar;27(3 Pt 2):481-90
references.pmid: 8613190
references.citation: Circulation. 2011 May 10;123(18):2006-13; discussion 2014
references.pmid: 21555723
references.citation: Hypertension. 2012 May;59(5):1069-78
references.pmid: 22493070
references.citation: Curr Opin Cardiol. 2008 Jul;23(4):340-9
references.pmid: 18520718
references.citation: Circulation. 2006 Apr 25;113(16):1966-73
references.pmid: 16618817
references.citation: JAMA. 2013 Mar 27;309(12):1268-77
references.pmid: 23478662
references.citation: J Am Coll Cardiol. 2009 Mar 31;53(13):1119-26
references.pmid: 19324256
references.citation: Circulation. 2004 Sep 28;110(13):1799-805
references.pmid: 15364801
references.citation: Heart. 2003 Oct;89(10):1152-6
references.pmid: 12975404
references.citation: Lancet. 2012 Oct 20;380(9851):1387-95
references.pmid: 22932717
references.citation: J Am Coll Cardiol. 2010 Feb 9;55(6):526-37
references.pmid: 20152557
references.citation: Circ J. 2005 Apr;69(4):432-8
references.pmid: 15791038
references.citation: Circ Heart Fail. 2011 Jan;4(1):53-8
references.pmid: 20952583
references.citation: Eur Heart J. 2012 Jul;33(14):1750-7
references.pmid: 21821849
references.citation: Diabetologia. 2010 Jul;53(7):1331-40
references.pmid: 20386878
references.citation: Int J Cardiol. 2013 Feb 20;163(2):206-11
references.pmid: 22130225
references.citation: J Am Coll Cardiol. 2009 Jun 30;54(1):36-46
references.pmid: 19555838
references.citation: Am J Cardiol. 2010 Jul 15;106(2):284-6
references.pmid: 20599017
references.citation: J Am Coll Cardiol. 2007 Jan 16;49(2):198-207
references.pmid: 17222731
references.citation: Circulation. 2008 May 13;117(19):2544-65
references.pmid: 18391114
references.citation: Circ Cardiovasc Imaging. 2011 Sep;4(5):482-9
references.pmid: 21788358
references.citation: Circ Res. 2009 Jan 2;104(1):12-4
references.pmid: 19118283
references.citation: Lancet. 2010 Apr 10;375(9722):1255-66
references.pmid: 20236700
references.citation: Int J Cardiol. 2012 Dec 15;162(1):6-13
references.pmid: 22664368
references.citation: Br Heart J. 1991 Dec;66(6):443-7
references.pmid: 1772710
references.citation: Eur J Heart Fail. 2000 Dec;2(4):393-8
references.pmid: 11113716
references.citation: J Am Coll Cardiol. 2007 Mar 6;49(9):972-81
references.pmid: 17336721
references.citation: J Am Coll Cardiol. 2001 Jun 1;37(7):1943-9
references.pmid: 11401136
references.citation: Int J Cardiol. 2012 Jul 26;158(3):337-43
references.pmid: 21794933
references.citation: Circulation. 2005 Feb 15;111(6):774-81
references.pmid: 15699264
references.citation: Eur J Heart Fail. 2013 Oct;15(10):1095-101
references.pmid: 23650131
references.citation: Circulation. 2009 Jun 23;119(24):3085-92
references.pmid: 19506113
references.citation: Hypertension. 2012 Jul;60(1):64-70
references.pmid: 22665121
references.citation: Eur Heart J. 2008 Jun;29(11):1377-85
references.pmid: 18413309
references.citation: Eur Heart J. 2012 Jul;33(14):1716-7
references.pmid: 22730487
references.citation: Eur Heart J. 2012 Jan;33(2):176-82
references.pmid: 21900289
references.citation: JACC Heart Fail. 2013 Apr;1(2):115-22
references.pmid: 24621836
references.citation: Am J Physiol Heart Circ Physiol. 2007 Jan;292(1):H175-9
references.pmid: 16905598
references.citation: Circulation. 2004 Nov 9;110(19):3081-7
references.pmid: 15520317
references.citation: J Cardiopulm Rehabil. 2006 Mar-Apr;26(2):86-9
references.pmid: 16569976
references.citation: J Am Coll Cardiol. 2010 Jun 29;56(1):24-30
references.pmid: 20620713
references.citation: Circ Res. 2002 Jun 14;90(11):1181-8
references.pmid: 12065321
references.citation: J Hum Hypertens. 1999 Oct;13(10):711-6
references.pmid: 10516743
references.citation: Am J Kidney Dis. 1996 Oct;28(4):535-40
references.pmid: 8840943
references.citation: Circ Heart Fail. 2012 Sep 1;5(5):653-9
references.pmid: 22991405
references.citation: Eur J Heart Fail. 2013 Jan;15(1):85-93
references.pmid: 23018991
references.citation: Eur Heart J. 2013 Aug;34(31):2453-63
references.pmid: 23713082
references.citation: Eur Heart J. 2009 Oct;30(20):2493-537
references.pmid: 19713419
references.citation: Circulation. 2011 Dec 20;124(25):2882-91
references.pmid: 22144574
references.citation: J Am Coll Cardiol. 2002 Jun 5;39(11):1780-6
references.pmid: 12039491
references.citation: Circulation. 1991 Jun;83(6):1849-65
references.pmid: 1828192
references.citation: J Cardiovasc Pharmacol Ther. 2011 Jun;16(2):168-72
references.pmid: 20924097
references.citation: Int J Cardiol. 2011 Mar 3;147(2):278-82
references.pmid: 19896733
references.citation: Eur Heart J. 2006 Oct;27(19):2338-45
references.pmid: 16963472
references.citation: Hypertension. 2006 May;47(5):901-11
references.pmid: 16585423
references.citation: Eur Heart J. 2011 Mar;32(6):670-9
references.pmid: 21138935
references.citation: Circulation. 2000 May 2;101(17):2118-21
references.pmid: 10790356
references.citation: Diabetes. 2012 Apr;61(4):944-53
references.pmid: 22344560
references.citation: Eur Heart J. 2013 Sep;34(36):2839-49
references.pmid: 22833515
references.citation: Eur J Heart Fail. 2010 Aug;12(8):874-82
references.pmid: 20538867
references.citation: J Am Coll Cardiol. 2007 Aug 21;50(8):768-77
references.pmid: 17707182
references.citation: Semin Dial. 2012 Jan-Feb;25(1):35-41
references.pmid: 22273530
references.citation: Pharmacol Rep. 2009 Jan-Feb;61(1):139-45
references.pmid: 19307702
references.citation: Am J Physiol Heart Circ Physiol. 2011 Dec;301(6):H2372-82
references.pmid: 21926338
references.citation: Circulation. 1989 Apr;79(4):845-53
references.pmid: 2924415
references.citation: Circulation. 2011 May 10;123(18):1996-2004; discussion 2005
references.pmid: 21555722
references.citation: Int J Cardiol. 2014 May 1;173(2):163-9
references.pmid: 24630337
references.citation: Diabetologia. 2011 Apr;54(4):722-30
references.pmid: 21085926
references.citation: Herz. 2000 May;25(3):299-306
references.pmid: 10904856
references.citation: Circulation. 2012 Aug 14;126(7):830-9
references.pmid: 22806632
references.citation: Circulation. 2012 Aug 21;126(8):975-90
references.pmid: 22908015
references.citation: J Am Coll Cardiol. 2010 Jan 26;55(4):300-5
references.pmid: 20117433
references.citation: Circulation. 2006 Apr 25;113(16):1922-5
references.pmid: 16636184
references.citation: J Am Coll Cardiol. 2001 Oct;38(4):955-62
references.pmid: 11583864
references.citation: Eur J Heart Fail. 2011 Jun;13(6):656-63
references.pmid: 21613429
references.citation: Circulation. 2004 Jan 27;109(3):433-8
references.pmid: 14744958
references.citation: Circulation. 2004 Aug 3;110(5):558-65
references.pmid: 15277317
references.citation: Circ Heart Fail. 2012 Nov;5(6):720-6
references.pmid: 22936826
references.citation: Eur J Heart Fail. 2009 Jan;11(1):39-47
references.pmid: 19147455
references.citation: Clin Sci (Lond). 2007 Sep;113(6):267-78
references.pmid: 17683282
references.citation: Am J Respir Crit Care Med. 2005 Jul 1;172(1):105-13
references.pmid: 15817798
references.citation: Circulation. 2002 Mar 26;105(12):1503-8
references.pmid: 11914262
references.citation: Heart. 2013 Feb;99(4):259-66
references.pmid: 23221388
references.citation: Circulation. 1996 Mar 1;93(5):1026-32
references.pmid: 8598066
references.citation: Am J Med. 2009 Nov;122(11):1029-36
references.pmid: 19854331
references.citation: Eur Heart J. 2013 Feb;34(7):529-39
references.pmid: 23041499
references.citation: J Am Coll Cardiol. 2011 Oct 18;58(17):1780-91
references.pmid: 21996391
references.citation: J Card Fail. 2011 Aug;17(8):634-42
references.pmid: 21807324
references.citation: Chest. 2014 Nov;146(5):1274-1285
references.pmid: 24991733
references.citation: Eur Heart J. 2008 Feb;29(3):339-47
references.pmid: 18156618
references.citation: J Am Coll Cardiol. 2012 Mar 6;59(10):910-2
references.pmid: 22381426
references.citation: J Clin Pharmacol. 2010 Apr;50(4):401-14
references.pmid: 19934029
references.citation: J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239
references.pmid: 23747642
references.citation: J Hypertens. 2011 Jul;29(7):1439-47
references.pmid: 21610514
references.citation: Kidney Int. 2001 Oct;60(4):1525-31
references.pmid: 11576368
references.citation: Circ Heart Fail. 2011 Sep;4(5):538-40
references.pmid: 21934089
references.citation: Circ Heart Fail. 2010 Jan;3(1):29-34
references.pmid: 19917649
references.citation: Cardiovasc Drugs Ther. 1994 Oct;8(5):741-7
references.pmid: 7873471
references.citation: Circ Res. 1990 Oct;67(4):787-94
references.pmid: 2145089
references.citation: J Am Coll Cardiol. 1989 Jun;13(7):1637-52
references.pmid: 2656824
references.citation: J Card Fail. 2005 Apr;11(3):191-5
references.pmid: 15812746
references.citation: Clin Cardiol. 2011 Jul;34(7):426-32
references.pmid: 21538388
references.citation: Int J Cardiol. 2013 Oct 12;168(5):4652-7
references.pmid: 23968714
references.citation: Heart. 2007 Jan;93(1):59-64
references.pmid: 16952975
references.citation: N Engl J Med. 2008 Dec 4;359(23):2456-67
references.pmid: 19001508
references.citation: Circulation. 2004 Sep 7;110(10):1263-8
references.pmid: 15313958
references.citation: Circ Heart Fail. 2013 Nov;6(6):1165-71
references.pmid: 23985432
references.citation: Diabetologia. 2008 Oct;51(10):1930-2
references.pmid: 18663426
references.citation: Am J Physiol Regul Integr Comp Physiol. 2002 Jan;282(1):R166-72
references.pmid: 11742835
references.citation: N Engl J Med. 2001 Dec 6;345(23):1689-97
references.pmid: 11759649
references.citation: Clin Exp Hypertens. 2005 May;27(4):355-67
references.pmid: 15921072
references.citation: Lancet. 2003 Sep 6;362(9386):777-81
references.pmid: 13678871
references.citation: JAMA. 2012 Nov 28;308(20):2108-17
references.pmid: 23188027
references.citation: J Am Coll Cardiol. 2000 Jan;35(1):201-8
references.pmid: 10636281
references.citation: Diabetologia. 2002 Nov;45(11):1515-22
references.pmid: 12436334
references.citation: Circulation. 2001 Jun 5;103(22):2668-73
references.pmid: 11390335
references.citation: Circulation. 2005 Dec 13;112(24):3738-44
references.pmid: 16330684
references.citation: Circ Heart Fail. 2011 May;4(3):324-31
references.pmid: 21350053
references.citation: J Mol Cell Cardiol. 1994 Jul;26(7):809-20
references.pmid: 7966349
references.citation: Arteriosclerosis. 1986 Mar-Apr;6(2):166-9
references.pmid: 3954670
references.citation: Hypertension. 2001 Nov;38(5):1222-6
references.pmid: 11711527
references.citation: J Am Coll Cardiol. 2003 Jun 4;41(11):1933-9
references.pmid: 12798560
references.citation: J Am Coll Cardiol. 1992 Jul;20(1):3-16
references.pmid: 1318886
references.citation: J Mol Cell Cardiol. 2008 Jul;45(1):32-43
references.pmid: 18439620
references.citation: Hypertension. 2012 Nov;60(5):1200-6
references.pmid: 23033371
references.citation: Diabet Med. 2005 Dec;22(12):1720-5
references.pmid: 16401318
references.citation: Am J Cardiol. 2004 Apr 1;93(7):870-5
references.pmid: 15050491
references.citation: Circ Heart Fail. 2013 Mar;6(2):254-63
references.pmid: 23258574
references.citation: Circ Heart Fail. 2010 Mar;3(2):294-305
references.pmid: 20107192
references.citation: Cardiovasc Ther. 2011 Aug;29(4):e6-21
references.pmid: 20370792
references.citation: J Am Coll Cardiol. 2006 Dec 19;48(12):2485-9
references.pmid: 17174186
references.citation: Circ Heart Fail. 2010 Sep;3(5):588-95
references.pmid: 20543134
references.citation: J Am Coll Cardiol. 2013 Oct 8;62(15):1330-8
references.pmid: 23916925
references.citation: Circulation. 1998 Nov 24;98(21):2282-9
references.pmid: 9826315
references.citation: JAMA. 2013 Feb 27;309(8):781-91
references.pmid: 23443441
references.citation: J Am Coll Cardiol. 2012 Oct 30;60(18):1787-9
references.pmid: 23040569
references.citation: Am Heart J. 2006 Feb;151(2):457-62
references.pmid: 16442914
references.citation: Eur J Heart Fail. 2009 Feb;11(2):198-204
references.pmid: 19168519
references.citation: Eur Heart J. 2007 Oct;28(20):2539-50
references.pmid: 17428822
references.citation: J Hum Hypertens. 2005 Feb;19(2):133-8
references.pmid: 15361890
references.citation: Circ Res. 2009 Jan 2;104(1):87-94
references.pmid: 19023132
references.citation: Am J Cardiol. 2012 Feb 1;109(3):383-9
references.pmid: 22112740
references.citation: J Am Coll Cardiol. 2014 Feb 11;63(5):447-56
references.pmid: 24184245
references.citation: J Am Coll Cardiol. 2013 Jul 23;62(4):263-71
references.pmid: 23684677
references.citation: J Clin Hypertens (Greenwich). 2002 Jan-Feb;4(1):41-6
references.pmid: 11821636
references.citation: Echocardiography. 2005 Aug;22(7):561-70
references.pmid: 16060892
references.citation: JAMA. 2013 Nov 20;310(19):2050-60
references.pmid: 24240932
references.citation: Eur Heart J. 2012 Jul;33(14):1787-847
references.pmid: 22611136
references.citation: Eur Heart J. 2005 Nov;26(21):2232-7
references.pmid: 15987710