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J Am Coll Cardiol, 2009; 54:43-54, doi:10.1016/j.jacc.2009.04.012
© 2009 by the American College of Cardiology Foundation
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STATE-OF-THE-ART PAPER

Updated Clinical Classification of Pulmonary Hypertension

Gérald Simonneau, MD*,*, Ivan M. Robbins, MD{dagger}, Maurice Beghetti, MD{ddagger}, Richard N. Channick, MD§, Marion Delcroix, MD, PhD||, Christopher P. Denton, MD, PhD, C. Gregory Elliott, MD#, Sean P. Gaine, MD, PhD**, Mark T. Gladwin, MD{dagger}{dagger}, Zhi-Cheng Jing, MD{ddagger}{ddagger}, Michael J. Krowka, MD§§, David Langleben, MD||||, Norifumi Nakanishi, MD, PhD¶¶ and Rogério Souza, MD##

* Centre National de Référence des Maladies Vasculaires Pulmonaires, Université Paris-Sud Hôpital Antoine Béclère, Clamart, France
{dagger} Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
{ddagger} Pediatric Cardiology Unit, Hôpital des Enfants, University Hospital of Geneva, Geneva, Switzerland
§ Division of Pulmonary and Critical Care Medicine, UCSD Medical Center, La Jolla, California
|| Center for Pulmonary Vascular Disease, Department of Pneumology, Gasthuisberg University Hospital, Leuven, Belgium
Centre for Rheumatology, Royal Free Hospital, London, United Kingdom
# Department of Medicine, Intermountain Medical Center, University of Utah, Salt Lake City, Utah
** Department of Respiratory Medicine, Mater Misericordiae University Hospital, University College Dublin, Dublin, Ireland
{dagger}{dagger} Pulmonary, Allergy, and Critical Care Medicine, Hemostasis and Vascular Biology Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
{ddagger}{ddagger} Department of Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China
§§ Department of Pulmonary and Critical Care Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
|||| Center for Pulmonary Vascular Disease, Sir Mortimer B. Davis Jewish General Hospital, Montréal, Québec, Canada
¶¶ Division of Cardiology and Pulmonary Circulation, Department of Internal Medicine National Cardiovascular Center, Osaka, Japan
## Pulmonary Department, Heart Institute, University of São Paulo Medical School, São Paulo, Brazil

Manuscript received February 6, 2009; accepted April 15, 2009.

* Reprint requests and correspondence: Dr. Gérald Simonneau, Centre National de Référence des Maladies Vasculaires Pulmonaires, Service de Pneumologie, Hôpital Antoine Béclère, Assistance Publique, Hôpitaux de Paris, Université Paris-Sud (XI), 157, rue de la Porte de Trivaux, 92140 Clamart, France (Email: gerald.simonneau{at}abc.aphp.fr).

The aim of a clinical classification of pulmonary hypertension (PH) is to group together different manifestations of disease sharing similarities in pathophysiologic mechanisms, clinical presentation, and therapeutic approaches. In 2003, during the 3rd World Symposium on Pulmonary Hypertension, the clinical classification of PH initially adopted in 1998 during the 2nd World Symposium was slightly modified. During the 4th World Symposium held in 2008, it was decided to maintain the general architecture and philosophy of the previous clinical classifications. The modifications adopted during this meeting principally concern Group 1, pulmonary arterial hypertension (PAH). This subgroup includes patients with PAH with a family history or patients with idiopathic PAH with germline mutations (e.g., bone morphogenetic protein receptor-2, activin receptor-like kinase type 1, and endoglin). In the new classification, schistosomiasis and chronic hemolytic anemia appear as separate entities in the subgroup of PAH associated with identified diseases. Finally, it was decided to place pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis in a separate group, distinct from but very close to Group 1 (now called Group 1'). Thus, Group 1 of PAH is now more homogeneous.

Key Words: pulmonary hypertension • clinical classification • pulmonary arterial hypertension

Abbreviations and Acronyms
  BMPR2 = bone morphogenetic protein receptor type 2
  CHD = congenital heart disease
  CTEPH = chronic thromboembolic pulmonary hypertension
  ESRD = end-stage renal disease
  HIV = human immunodeficiency virus
  IPAH = idiopathic pulmonary arterial hypertension
  OR = odds ratio
  PAH = pulmonary arterial hypertension
  PAP = pulmonary arterial pressure
  PCH = pulmonary capillary hemangiomatosis
  PH = pulmonary hypertension
  POPH = portopulmonary hypertension
  PPH = primary pulmonary hypertension
  PVOD = pulmonary veno-occlusive disease
  PVR = pulmonary vascular resistance
  SCD = sickle cell disease
  TRV = tricuspid regurgitation jet velocity


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J. Hoffmann, J. Yin, M. Kukucka, N. Yin, I. Saarikko, A. Sterner-Kock, H. Fujii, H. Leong-Poi, H. Kuppe, R. T. Schermuly, et al.
Mast cells promote lung vascular remodelling in pulmonary hypertension
Eur. Respir. J., June 1, 2011; 37(6): 1400 - 1410.
[Abstract] [Full Text] [PDF]

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 Ther Adv Respir DisHome page
T. Gessler, W. Seeger, and T. Schmehl
The potential for inhaled treprostinil in the treatment of pulmonary arterial hypertension
Therapeutic Advances in Respiratory Disease, June 1, 2011; 5(3): 195 - 206.
[Abstract] [PDF]

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 ChestHome page
S. Valmary, P. Dorfmuller, D. Montani, M. Humbert, P. Brousset, and B. Degano
Human {gamma}-Herpesviruses Epstein-Barr Virus and Human Herpesvirus-8 Are Not Detected in the Lungs of Patients With Severe Pulmonary Arterial Hypertension
Chest, June 1, 2011; 139(6): 1310 - 1316.
[Abstract] [Full Text] [PDF]

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 FASEB J.Home page
V. P. Krymskaya, J. Snow, G. Cesarone, I. Khavin, D. A. Goncharov, P. N. Lim, S. C. Veasey, K. Ihida-Stansbury, P. L. Jones, and E. A. Goncharova
mTOR is required for pulmonary arterial vascular smooth muscle cell proliferation under chronic hypoxia
FASEB J, June 1, 2011; 25(6): 1922 - 1933.
[Abstract] [Full Text] [PDF]

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 Circ Heart FailHome page
B. A. Borlaug
Discerning Pulmonary Venous From Pulmonary Arterial Hypertension Without the Help of a Catheter
Circ Heart Fail, May 1, 2011; 4(3): 235 - 237.
[Full Text] [PDF]

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 Circ Heart FailHome page
N. S. Hill, I. Preston, and K. Roberts
Defining the Phenotypes for Pulmonary Hypertension Associated With Diastolic Heart Failure
Circ Heart Fail, May 1, 2011; 4(3): 238 - 240.
[Full Text] [PDF]

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 Circ Heart FailHome page
T. Thenappan, S. J. Shah, M. Gomberg-Maitland, B. Collander, A. Vallakati, P. Shroff, and S. Rich
Clinical Characteristics of Pulmonary Hypertension in Patients With Heart Failure and Preserved Ejection Fraction
Circ Heart Fail, May 1, 2011; 4(3): 257 - 265.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
M. M. Dulohery and F. Maldonado
An Uncommon Cause of Pulmonary Hypertension
Am. J. Respir. Crit. Care Med., April 15, 2011; 183(8): 1112 - 1112.
[Full Text] [PDF]

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 ThoraxHome page
E. Soon, C. M. Treacy, M. R. Toshner, R. MacKenzie-Ross, V. Manglam, M. Busbridge, M. Sinclair-McGarvie, J. Arnold, K. K. Sheares, N. W. Morrell, et al.
Unexplained iron deficiency in idiopathic and heritable pulmonary arterial hypertension
Thorax, April 1, 2011; 66(4): 326 - 332.
[Abstract] [Full Text] [PDF]

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 BloodHome page
M. Yoder and S. Rounds
Bad blood, bad endothelium: ill fate?
Blood, March 31, 2011; 117(13): 3479 - 3480.
[Full Text] [PDF]

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 CirculationHome page
D. Farmakis and A. Aessopos
Pulmonary Hypertension Associated With Hemoglobinopathies: Prevalent But Overlooked
Circulation, March 22, 2011; 123(11): 1227 - 1232.
[Full Text] [PDF]

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 Eur Respir JHome page
R. J. Barst, S. I. Ertel, M. Beghetti, and D. D. Ivy
Pulmonary arterial hypertension: a comparison between children and adults
Eur. Respir. J., March 1, 2011; 37(3): 665 - 677.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
M. Gomberg-Maitland, C. Dufton, R. J. Oudiz, and R. L. Benza
Compelling Evidence of Long-Term Outcomes in Pulmonary Arterial Hypertension?: A Clinical Perspective
J. Am. Coll. Cardiol., March 1, 2011; 57(9): 1053 - 1061.
[Abstract] [Full Text] [PDF]

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 ChestHome page
M. Gomberg-Maitland
Naming and Understanding Rare Diseases: International Classification of Diseases Coding and the Epidemiologic Designations of Idiopathic Pulmonary Arterial Hypertension
Chest, March 1, 2011; 139(3): 482 - 483.
[Full Text] [PDF]

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 The Journal of RheumatologyHome page
G. SUBRAMANIAN and S. MEHTA
Treatment of Pulmonary Arterial Hypertension: Great Expectations!
J Rheumatol, March 1, 2011; 38(3): 403 - 405.
[Full Text] [PDF]

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 ChestHome page
J. Link, C. Glazer, F. Torres, and K. Chin
International Classification of Diseases Coding Changes Lead to Profound Declines in Reported Idiopathic Pulmonary Arterial Hypertension Mortality and Hospitalizations: Implications for Database Studies
Chest, March 1, 2011; 139(3): 497 - 504.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
S.-J. Lee, A. Smith, L. Guo, T.-P. Alastalo, M. Li, H. Sawada, X. Liu, Z.-H. Chen, E. Ifedigbo, Y. Jin, et al.
Autophagic Protein LC3B Confers Resistance against Hypoxia-induced Pulmonary Hypertension
Am. J. Respir. Crit. Care Med., March 1, 2011; 183(5): 649 - 658.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
B. S. Zuckerbraun, P. George, and M. T. Gladwin
Nitrite in pulmonary arterial hypertension: therapeutic avenues in the setting of dysregulated arginine/nitric oxide synthase signalling
Cardiovasc Res, February 15, 2011; 89(3): 542 - 552.
[Abstract] [Full Text] [PDF]

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 Mayo Clin Proc.Home page
C. D. Burger, A. J. Foreman, D. P. Miller, R. E. Safford, M. D. McGoon, and D. B. Badesch
Comparison of Body Habitus in Patients With Pulmonary Arterial Hypertension Enrolled in the Registry to Evaluate Early and Long-term PAH Disease Management With Normative Values From the National Health and Nutrition Examination Survey
Mayo Clin. Proc., February 1, 2011; 86(2): 105 - 112.
[Abstract] [Full Text] [PDF]

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 Arch. Dis. Child. Fetal Neonatal Ed.Home page
R. Dhillon
The management of neonatal pulmonary hypertension
Arch. Dis. Child. Fetal Neonatal Ed., January 30, 2011; (2011) adc.2009.180091v1.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
J. S. Arkles, A. R. Opotowsky, J. Ojeda, F. Rogers, T. Liu, V. Prassana, L. Marzec, H. I. Palevsky, V. A. Ferrari, and P. R. Forfia
Shape of the Right Ventricular Doppler Envelope Predicts Hemodynamics and Right Heart Function in Pulmonary Hypertension
Am. J. Respir. Crit. Care Med., January 15, 2011; 183(2): 268 - 276.
[Abstract] [Full Text] [PDF]

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 HeartHome page
R. Naeije
In defence of exercise stress tests for the diagnosis of pulmonary hypertension
Heart, January 15, 2011; 97(2): 94 - 95.
[Full Text] [PDF]

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 ChestHome page
A. E. Frost, D. B. Badesch, R. J. Barst, R. L. Benza, C. G. Elliott, H. W. Farber, A. Krichman, T. G. Liou, G. E. Raskob, P. Wason, et al.
The Changing Picture of Patients With Pulmonary Arterial Hypertension in the United States: How REVEAL Differs From Historic and Non-US Contemporary Registries
Chest, January 1, 2011; 139(1): 128 - 137.
[Abstract] [Full Text] [PDF]

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 ChestHome page
A. R. Tonelli, K. K. Mubarak, N. Li, R. Carrie, and H. Alnuaimat
Effect of Balloon Inflation Volume on Pulmonary Artery Occlusion Pressure in Patients With and Without Pulmonary Hypertension
Chest, January 1, 2011; 139(1): 115 - 121.
[Abstract] [Full Text] [PDF]

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 ChestHome page
R. Cartin-Ceba, K. Swanson, V. Iyer, R. H. Wiesner, and M. J. Krowka
Safety and Efficacy of Ambrisentan for the Treatment of Portopulmonary Hypertension
Chest, January 1, 2011; 139(1): 109 - 114.
[Abstract] [Full Text] [PDF]

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 BMJ Case ReportsHome page
J. Olin, S. Abman, R. Grady, D. Ivy, M. Lovell, D. Partrick, and V. Balasubramaniam
A 7-year-old with pulmonary hypertension.
BMJ Case Reports, January 1, 2011; 2011: bcr0220113843 - bcr0220113843.
[Abstract] [Full Text] [PDF]

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 Oxford Textbook of Heart FailureHome page
T. J. Corte and S. J. Wort
31 Pulmonary hypertension
Oxford Textbook of Heart Failure, January 1, 2011; 1(1): med-9780199577729-chapter - med-9780199577729-chapter.
[Abstract] [Full Text]

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 Eur Respir RevHome page
C. Jardim, S. Hoette, and R. Souza
Contemporary issues in pulmonary hypertension
Eur. Respir. Rev., December 1, 2010; 19(118): 266 - 271.
[Full Text] [PDF]

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 Eur Respir RevHome page
J.-L. Vachiery and G. Simonneau
Management of severe pulmonary arterial hypertension
Eur. Respir. Rev., December 1, 2010; 19(118): 279 - 287.
[Abstract] [Full Text] [PDF]


 
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