title: WHO's in second?: A practical review of World Health Organization group 2 pulmonary hypertension.
abstract: World Health Organization (WHO) group 2 pulmonary hypertension (PH) due to left-side heart disease (ie, heart failure or left-sided valvular heart disease) is the most common form of PH in western countries. Distinguishing patients with WHO group 2 PH, particularly the subset of patients with PH due to heart failure with preserved ejection fraction (HFpEF), from those with WHO group 1 pulmonary arterial hypertension (PAH) is challenging. Separating the two conditions is of vital importance because treatment strategies differ completely. Furthermore, therapies that are indicated for WHO group 1 PAH may be harmful in patients with WHO group 2 PH. We review the somewhat confusing PH nomenclature and the WHO classification system and rationale behind it. We then focus on left-side heart disorders that cause PH. An aging population and advances in the medical management of common cardiovascular disorders have caused the prevalence of heart failure to rise significantly, with more than one-half of patients having HFpEF. We review contemporary studies that focus on clinical and echocardiographic findings that help to distinguish HFpEF from PAH in the patient with PH. We discuss the typical, and sometimes atypical, hemodynamic profiles that characterize these two groups, review challenges in the interpretation of data obtained by right-sided heart catheterization, and highlight special maneuvers that may be required for accurate diagnosis. Finally, we review the largely disappointing studies on the use of PAH-specific therapies in patients with WHO group 2 PH, including the use of prostacyclins, endothelin receptor antagonists, and the more promising phosphodiesterase-5 inhibitors.
authors.affiliation: University of Iowa Carver College of Medicine, Iowa City, IA. Electronic address: sif-hansdottir@uiowa.edu.
authors.forename: Sif
authors.initials: S
authors.lastname: Hansdottir
authors.affiliation: University of Iowa Carver College of Medicine, Iowa City, IA.
authors.forename: Dayna J
authors.initials: DJ
authors.lastname: Groskreutz
authors.affiliation: University of Iowa Carver College of Medicine, Iowa City, IA.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Gehlbach
mesh_terms: D000367:Age Factors; D000959:Antihypertensive Agents / Q000627:therapeutic use; D003937:Diagnosis, Differential; D004452:Echocardiography; D006333:Heart Failure / Q000150:complications / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000145:classification* / Q000175:diagnosis* / Q000188:drug therapy* / Q000209:etiology; D012307:Risk Factors; D009626:Terminology as Topic; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000503:physiopathology; D014944:World Health Organization
chemical_list: D000959:Antihypertensive Agents
references.citation: Circulation. 2011 Dec 6;124(23):2491-501
references.pmid: 22064591
references.citation: J Am Coll Cardiol. 1992 Jan;19(1):48-54
references.pmid: 1729345
references.citation: Chest. 2012 Aug;142(2):448-456
references.pmid: 22281797
references.citation: J Am Coll Cardiol. 2010 Apr 20;55(16):1701-10
references.pmid: 20394874
references.citation: Chest. 2007 Feb;131(2):395-401
references.pmid: 17296639
references.citation: J Am Soc Echocardiogr. 1999 Aug;12(8):655-62
references.pmid: 10441222
references.citation: Chest. 2011 Nov;140(5):1267-1273
references.pmid: 21622547
references.citation: J Am Coll Cardiol. 1991 Apr;17(5):1065-72
references.pmid: 2007704
references.citation: J Heart Lung Transplant. 2010 Feb;29(2):201-8
references.pmid: 20113910
references.citation: Clin Chest Med. 2007 Mar;28(1):233-41, x
references.pmid: 17338938
references.citation: Circulation. 2011 Jul 12;124(2):164-74
references.pmid: 21709061
references.citation: J Am Coll Cardiol. 2009 Mar 31;53(13):1119-26
references.pmid: 19324256
references.citation: Am Heart J. 1997 Jul;134(1):44-54
references.pmid: 9266782
references.citation: Am J Cardiol. 1982 Nov;50(5):1044-50
references.pmid: 7137030
references.citation: J Am Coll Cardiol. 2010 Mar 16;55(11):1080-90
references.pmid: 20096533
references.citation: Eur J Heart Fail. 2005 Oct;7(6):1011-6
references.pmid: 16227139
references.citation: J Am Coll Cardiol. 2010 Sep 7;56(11):855-63
references.pmid: 20813283
references.citation: Am J Cardiol. 2002 Jul 15;90(2):188-9
references.pmid: 12106858
references.citation: Am J Pathol. 1936 Sep;12(5):573-598.15
references.pmid: 19970288
references.citation: J Am Soc Echocardiogr. 2008 Jun;21(6):715-9
references.pmid: 18325734
references.citation: J Am Coll Cardiol. 2007 Nov 27;50(22):2136-44
references.pmid: 18036451
references.citation: Am J Cardiol. 2010 Jul 15;106(2):284-6
references.pmid: 20599017
references.citation: Chest. 1993 Jun;103(6):1877-83
references.pmid: 8404117
references.citation: J Am Coll Cardiol. 2012 Jan 31;59(5):442-51
references.pmid: 22281246
references.citation: Chest. 2005 May;127(5):1637-46
references.pmid: 15888840
references.citation: J Am Coll Cardiol. 2002 Apr 3;39(7):1214-9
references.pmid: 11923049
references.citation: J Am Coll Cardiol. 2001 Jan;37(1):183-8
references.pmid: 11153735
references.citation: Heart. 2006 Jan;92(1):85-9
references.pmid: 16365357
references.citation: Circ Heart Fail. 2011 Sep;4(5):541-5
references.pmid: 21934090
references.citation: Jpn Circ J. 1979 Oct;43(10):945-54
references.pmid: 513267
references.citation: Thorax. 2004 Jun;59(6):536-7
references.pmid: 15170042
references.citation: J Am Coll Cardiol. 2008 Sep 23;52(13):e1-142
references.pmid: 18848134
references.citation: J Card Fail. 2008 Oct;14(8):695-702
references.pmid: 18926442
references.citation: Am J Cardiol. 2011 Apr 1;107(7):1046-51
references.pmid: 21296325
references.citation: Eur Respir J. 2009 Oct;34(4):888-94
references.pmid: 19324955
references.citation: Q J Med. 1991 Jul;80(291):589-95
references.pmid: 1946939
references.citation: Radiographics. 2012 Jul-Aug;32(4):1085-7
references.pmid: 22786995
references.citation: J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S85-S96
references.pmid: 19555862
references.citation: Eur Heart J. 2009 Oct;30(20):2493-537
references.pmid: 19713419
references.citation: J Thorac Cardiovasc Surg. 2011 Jun;141(6):1424-30
references.pmid: 21596173
references.citation: Chest. 2009 Jul;136(1):31-36
references.pmid: 19188551
references.citation: N Engl J Med. 1965 Sep 2;273:509-14
references.pmid: 14324511
references.citation: J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S43-S54
references.pmid: 19555858
references.citation: J Thorac Cardiovasc Surg. 2011 Oct;142(4):800-8
references.pmid: 21320709
references.citation: J Pathol. 1973 Dec;111(4):239-45
references.pmid: 4359794
references.citation: Circ Cardiovasc Imaging. 2012 Nov;5(6):765-75
references.pmid: 22914595
references.citation: J Heart Lung Transplant. 2010 Feb;29(2):195-200
references.pmid: 19782604
references.citation: J Thorac Cardiovasc Surg. 1997 Oct;114(4):627-34
references.pmid: 9338649
references.citation: J Heart Valve Dis. 2004 Nov;13(6):942-7; discussion 947-8
references.pmid: 15597587
references.citation: J Card Fail. 2005 Feb;11(1):12-20
references.pmid: 15704058
references.citation: Circulation. 1959 Mar;19(3):386-94
references.pmid: 13629800
references.citation: J Am Coll Cardiol. 1989 Aug;14(2):319-22
references.pmid: 2754121
references.citation: Circulation. 2008 Oct 7;118(15):e523-661
references.pmid: 18820172
references.citation: J Am Coll Cardiol. 2009 Aug 11;54(7):595-600
references.pmid: 19660688
references.citation: Chest. 1975 Jul;68(1):28-31
references.pmid: 1149525
references.citation: J Am Coll Cardiol. 1997 Nov 15;30(6):1527-33
references.pmid: 9362412
references.citation: Am J Physiol Heart Circ Physiol. 2006 Apr;290(4):H1528-33
references.pmid: 16284226
references.citation: Circulation. 2007 Oct 2;116(14):1555-62
references.pmid: 17785618
references.citation: J Am Coll Cardiol. 2009 Apr 28;53(17):1573-619
references.pmid: 19389575
references.citation: J Am Coll Cardiol. 2010 Sep 7;56(11):864-6
references.pmid: 20813284
references.citation: J Am Coll Cardiol. 2010 Sep 7;56(11):845-54
references.pmid: 20813282
references.citation: J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S10-S19
references.pmid: 19555853
references.citation: Eur J Heart Fail. 2008 Feb;10(2):149-56
references.pmid: 18279770
references.citation: N Engl J Med. 1955 Jun 9;252(23):979-83
references.pmid: 14370465
references.citation: Circulation. 2012 Aug 21;126(8):975-90
references.pmid: 22908015
references.citation: Circulation. 2009 Jan 27;119(3):e21-181
references.pmid: 19075105
references.citation: Circulation. 1995 Nov 1;92(9 Suppl):II137-42
references.pmid: 7586397
references.citation: J Am Coll Cardiol. 2005 Nov 15;46(10):1883-90
references.pmid: 16286176
references.citation: Eur J Cardiothorac Surg. 2007 Apr;31(4):698-702
references.pmid: 17289396
references.citation: Congest Heart Fail. 2006 Nov-Dec;12(6):347-8
references.pmid: 17170591
references.citation: JAMA. 2009 Jan 21;301(3):286-94
references.pmid: 19155455
references.citation: J Card Fail. 2010 Jun;16(6):e1-194
references.pmid: 20610207
references.citation: Ann Intern Med. 1987 Aug;107(2):216-23
references.pmid: 3605900
references.citation: J Appl Physiol (1985). 1995 Mar;78(3):890-900
references.pmid: 7775334
references.citation: Eur Respir J. 2009 Dec;34(6):1219-63
references.pmid: 19749199
references.citation: Circ Heart Fail. 2009 Mar;2(2):105-12
references.pmid: 19808325
references.citation: J Heart Lung Transplant. 2010 Nov;29(11):1253-8
references.pmid: 20620083
references.citation: Clin Chest Med. 2001 Sep;22(3):385-91, vii
references.pmid: 11590835
references.citation: Eur Respir J. 2013 Oct;42(4):1083-91
references.pmid: 23258775
references.citation: Am Heart J. 2012 Apr;163(4):589-94
references.pmid: 22520524
references.citation: Am J Cardiol. 1972 Dec;30(8):820-6
references.pmid: 4634279
references.citation: J Appl Physiol (1985). 1991 Aug;71(2):573-82
references.pmid: 1718936
references.citation: Eur Heart J. 2003 Feb;24(4):320-8
references.pmid: 12581679
references.citation: J Heart Lung Transplant. 2012 Sep;31(9):913-33
references.pmid: 22884380
references.citation: Circulation. 2002 Aug 13;106(7):E24-30
references.pmid: 12176966
references.citation: Am J Cardiol. 2001 Jan 1;87(1):86-94
references.pmid: 11137840
references.citation: Circulation. 1995 Aug 1;92(3):622-31
references.pmid: 7634477
references.citation: J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S55-S66
references.pmid: 19555859
references.citation: Am J Cardiol. 2007 Apr 15;99(8):1146-50
references.pmid: 17437745
references.citation: Circ Heart Fail. 2011 May;4(3):257-65
references.pmid: 21411741
references.citation: Circ Heart Fail. 2010 Sep;3(5):588-95
references.pmid: 20543134
references.citation: Circ Heart Fail. 2011 Sep;4(5):644-50
references.pmid: 21606213
references.citation: Chest. 2009 Jul;136(1):37-43
references.pmid: 19255293
references.citation: Cardiology. 2008;109(4):273-80
references.pmid: 17873492
references.citation: Chest. 2007 Jan;131(1):94-100
references.pmid: 17218561
references.citation: Eur J Prev Cardiol. 2012 Oct;19(5):960-71
references.pmid: 23126000
references.citation: J Am Coll Cardiol. 2002 Aug 21;40(4):789-95
references.pmid: 12204512
references.citation: Heart. 2012 Dec;98(24):1805-11
references.pmid: 22760869
references.citation: Cardiol J. 2012;19(2):153-8
references.pmid: 22461048
references.citation: Circulation. 2000 Oct 3;102(14):1718-23
references.pmid: 11015353
references.citation: Chest. 2002 Feb;121(2):513-8
references.pmid: 11834666
references.citation: J Am Soc Echocardiogr. 2007 Jun;20(6):738-43
references.pmid: 17543745
references.citation: Ann Thorac Surg. 2007 May;83(5):1697-705
references.pmid: 17462383