Pulmonary hypertension classification: Difference between revisions

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Revision as of 16:34, 26 February 2018

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Richard Channick, M.D.; Assistant Editor(s)-in-Chief: Ralph Matar; Lisa Prior, Ann Slater, R.N.; Rim Halaby, M.D. [2]

Overview

Pulmonary hypertension (PH) has been previously classified as primary (currently known as idiopathic pulmonary arterial hypertension or IPAH) and secondary in 1973. In 1988, a clinical classification of PH into 5 groups has been developed during the 2nd World Symposium on PH in Evian, France. The clinical classification has been updated regularly as the understanding of PH expanded; nevertheless, the main scheme of classification into the 5 main groups remained intact. The classification of PH has been last modified in 2013 during the 5th World Symposium on Pulmonary Hypertension in Nice, France. The main 5 groups of PH include pulmonary arterial hypertension (Group 1), pulmonary hypertension due to left heart disease (Group 2), pulmonary hypertension due to chronic lung disease and/or hypoxia (Group 3), chronic thromboembolic pulmonary hypertension (Group 4), and pulmonary hypertension due to unclear multifactorial mechanisms (Group 5).

Classification

Clinical Classification

PH was first classified into primary and secondary in 1973 during the World Health Organization (WHO) meeting on PH in Geneva, Switzerland.^[1]

The 2-group classification of PH was replaced by a clinical 5-group classification in the 2nd World Symposium on Pulmonary Hypertension in 1998 in Evian, France.^[2] Since then, the clinical classification of PH was updated in the following meetings:
- The 3d World Symposium on Pulmonary Hypertension (2003) in Venice, Italy^[3]
- The 4th World Symposium on Pulmonary Hypertension (2008) in Dana Point, California, USA^[4]
- The 5th World Symposium on Pulmonary Hypertension (2013) in Nice, France^[5]

The updated clinical classification has been adopted by the Guidelines Committee of the European Society of Cardiology (ESC), European Respiratory Society (ERS), and International Society of Heart and Lung Transplantation (ISHLT).
It is currently used by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the labeling of new drugs approved for the treatment of PH.

Shown below is a table summarizing the updated clinical classification of PH.^[5]

Abbreviations: BMPR, bone morphogenic protein receptor type II; CAV1, caveolin-1; ENG, endoglin; HIV, human immunodeficiency virus.

Group 1. Pulmonary arterial hypertension (PAH)
1.1. Idiopathic PAH
1.2. Heritable PAH 1.2.1 BMPR2 1.2.2 ALK-1, ENG, SMAD9, CAV1, KCNK3 1.2.3 Unknown
1.3 Drug and toxin induced Definite (an epidemic or large multicenter epidemiological studies demonstrating an association between a drug and PAH) Aminorex Fenfluramine Dexfenfluramine Toxic rapeseed oil Benfluorex SSRIs Likely (a single case-control study demonstrating an association or a multiple-case series) Amphetamines L-Tryptophan Methamphetamines Dasatinib Possible (drugs with similar mechanisms of action as those in the definite or likely category but which have not yet been studied) Cocaine Phenylpropanolamine St. John's wort Chemotherapeutic agents Interferon α and β Amphetamine-like drugs Unlikely (one in which a drug has been studied in epidemiological studies and an association with PAH has not been demonstrated) Oral contraceptives Estrogen Cigarette smoking
1.4 Associated with: 1.4.1 Connective tissue disease 1.4.2 HIV infection 1.4.3 Portal hypertension 1.4.4 Congenital heart diseases 1.4.5 Schistosomiasis
1’ Pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis (PCH)
1’’ Persistent pulmonary hypertension of the newborn (PPHN)
Group 2. Pulmonary hypertension due to left heart disease
2.1 Left ventricular systolic dysfunction
2.2 Left ventricular diastolic dysfunction
2.3 Valvular disease
2.4 Congenital/acquired left heart inflow/outflow tract obstruction and congenital cardiomyopathies
Group 3. Pulmonary hypertension due to lung diseases and/or hypoxia
3.1 Chronic obstructive pulmonary disease
3.2 Interstitial lung disease
3.3 Other pulmonary diseases with mixed restrictive and obstructive pattern
3.4 Sleep-disordered breathing
3.5 Alveolar hypoventilation disorders
3.6 Chronic exposure to high altitude
3.7 Developmental lung diseases
Group 4. Chronic thromboembolic pulmonary hypertension (CTEPH)
Group 5. Pulmonary hypertension with unclear multifactorial mechanisms
5.1 Hematologic disorders: chronic hemolytic anemia, myeloproliferative disorders, splenectomy
5.2 Systemic disorders: sarcoidosis, pulmonary histiocytosis, lymphangioleiomyomatosis
5.3 Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders
5.4 Others: tumor obstruction, fibrosing mediastinitis, chronic renal failure, segmental PH

WHO Functional Classification

The WHO functional classification is used for the assessment of the severity of PH in order to tailor the choice of therapy. Shown below is a table summarizing the different functional classes.^[6]

Class	Description
I	No limitation of usual physical activity No increased dyspnea, fatigue, chest pain, or presyncope upon ordinary physical activity
II	Mild limitation of physical activity No discomfort at rest Increased dyspnea, fatigue, chest pain, or presyncope upon normal physical activity
III	Marked limitation of physical activity No discomfort at rest Increased dyspnea, fatigue, chest pain, or presyncope upon less than ordinary activity
IV	Inability to perform any physical activity at rest with/without signs of right ventricular failure Dyspnea and/or fatigue may be present at rest Increased dyspnea, fatigue, chest pain, or presyncope by almost any physical activity

Classification Based on Hemodynamical Findings

Abbreviations: PAP: Pulmonary artery pressure; PWP: pulmonary wedge pressure

Type of pulmonary hypertension	Possible clinical class	Mean PAP	PWP
Pre-capillary	Class I Class III Class IV Class V	≥ 25 mmHg	≤ 15 mmHg
Post-capillary	Class II	≥ 25 mmHg	> 15 mmHg

Classification Based on Histopathological Findings

PH is a pathological condition present in different disease states that share similar clinical manifestation and some common histopathological features. Shown below is a table that summarizes the classification of PH based on histopathology findings.^[7]

Class	Histopathological findings^[7]
Pulmonary arteriopathy	Constrictive lesions in pulmonary arteries Medial hypertrophy Intimal thickening Adventitial thickening Complex lesions in pulmonary arteries Plexiform lesions Dilatation lesions Arteritis
Pulmonary arteriopathy with venous-venular changes	Changes similar to pulmonary arteriopathy PLUS Changes in venules and veins
Pulmonary occlusive venopathy (with or without arteriopathy)	Changes in venules and veins Diffuse fibrotic occlusion Intimal thickening Medial thickening Adventitial thickening Changes in the capillaries Dilatation Congestion Changes in the interstitium Edema Fibrosis Hemosiderosis
Pulmonary microvasculopathy (with or without arteriopathy and/on venopathy)	Changes in the capillaries Localized capillary proliferation Changes in the interstitium Edema Fibrosis Hemosiderosis
Unclassified	Non specific changes

References

↑ Hatano S, Strasser T. Primary Pulmonary Hypertension. Report on a WHO Meeting. October 15–17, 1973, Geneva: World Health Organization, 1975.
↑ Rich S, Rubin LJ, Abenhail L, et al. Executive summary from the World Symposium on Primary Pulmonary Hypertension 1998, Evian, France, September 6-10, 1998. Geneva: The World Health Organization.
↑ Simonneau G, Galiè N, Rubin LJ, Langleben D, Seeger W, Domenighetti G; et al. (2004). "Clinical classification of pulmonary hypertension". J Am Coll Cardiol. 43 (12 Suppl S): 5S–12S. doi:10.1016/j.jacc.2004.02.037. PMID 15194173.
↑ Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP; et al. (2009). "Updated clinical classification of pulmonary hypertension". J Am Coll Cardiol. 54 (1 Suppl): S43–54. doi:10.1016/j.jacc.2009.04.012. PMID 19555858.
↑ ^5.0 ^5.1 Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A; et al. (2013). "Updated clinical classification of pulmonary hypertension". J Am Coll Cardiol. 62 (25 Suppl): D34–41. doi:10.1016/j.jacc.2013.10.029. PMID 24355639.
↑ Rich S, Rubin LJ, Abenhail L, et al. Executive summary from the World Symposium on Primary Pulmonary Hypertension 1998, Evian, France, September 6-10, 1998. Geneva: The World Health Organization.
↑ ^7.0 ^7.1 Pietra GG, Capron F, Stewart S, Leone O, Humbert M, Robbins IM; et al. (2004). "Pathologic assessment of vasculopathies in pulmonary hypertension". J Am Coll Cardiol. 43 (12 Suppl S): 25S–32S. doi:10.1016/j.jacc.2004.02.033. PMID 15194175.

Template:WikiDoc Sources

[WHO1973-1] Hatano S, Strasser T. Primary Pulmonary Hypertension. Report on a WHO Meeting. October 15–17, 1973, Geneva: World Health Organization, 1975.

[2] Rich S, Rubin LJ, Abenhail L, et al. Executive summary from the World Symposium on Primary Pulmonary Hypertension 1998, Evian, France, September 6-10, 1998. Geneva: The World Health Organization.

[pmid15194173-3] Simonneau G, Galiè N, Rubin LJ, Langleben D, Seeger W, Domenighetti G; et al. (2004). "Clinical classification of pulmonary hypertension". J Am Coll Cardiol. 43 (12 Suppl S): 5S–12S. doi:10.1016/j.jacc.2004.02.037. PMID 15194173.

[pmid19555858-4] Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP; et al. (2009). "Updated clinical classification of pulmonary hypertension". J Am Coll Cardiol. 54 (1 Suppl): S43–54. doi:10.1016/j.jacc.2009.04.012. PMID 19555858.

[pmid24355639-5] 5.0 ^5.1 Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A; et al. (2013). "Updated clinical classification of pulmonary hypertension". J Am Coll Cardiol. 62 (25 Suppl): D34–41. doi:10.1016/j.jacc.2013.10.029. PMID 24355639.

[6] Rich S, Rubin LJ, Abenhail L, et al. Executive summary from the World Symposium on Primary Pulmonary Hypertension 1998, Evian, France, September 6-10, 1998. Geneva: The World Health Organization.

[pmid15194175-7] 7.0 ^7.1 Pietra GG, Capron F, Stewart S, Leone O, Humbert M, Robbins IM; et al. (2004). "Pathologic assessment of vasculopathies in pulmonary hypertension". J Am Coll Cardiol. 43 (12 Suppl S): 25S–32S. doi:10.1016/j.jacc.2004.02.033. PMID 15194175.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

@@ Line 5: / Line 5: @@
 ==Overview==
-Pulmonary hypertension (PH) has been previously classified as primary (currently known as idiopathic pulmonary arterial hypertension or IPAH) and secondary in 1973.<ref name=WHO1973>Hatano S, Strasser T. Primary Pulmonary Hypertension. Report on a WHO Meeting. October 15–17, 1973, Geneva: World Health Organization, 1975.</ref>  In 1988, a clinical classification of PH into 5 groups has been developed during the 2nd World Symposium on Pulmonary Hypertension in Evian, France.<ref>Rich S, Rubin LJ, Abenhail L, et al. Executive summary from the World Symposium on Primary Pulmonary Hypertension 1998, Evian, France, September 6-10, 1998. Geneva: The World Health Organization.</ref> The clinical classification has been updated regularly as the understanding of PH expanded; nevertheless, the main scheme of classification into the 5 main groups remained intact.  The classification of PH has been last modified in 2013 during the 5th World Symposium on Pulmonary Hypertension in Nice, France.<ref name="pmid24355639">{{cite journal| author=Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A et al.| title=Updated clinical classification of pulmonary hypertension. | journal=J Am Coll Cardiol | year= 2013 | volume= 62 | issue= 25 Suppl | pages= D34-41 | pmid=24355639 | doi=10.1016/j.jacc.2013.10.029 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24355639  }} </ref> The main 5 groups of PH include pulmonary arterial hypertension (Group 1), pulmonary hypertension due to left heart disease (Group 2), pulmonary hypertension due to chronic lung disease and/or [[hypoxia]] (Group 3), chronic [[VTE|thromboembolic]] pulmonary hypertension (Group 4), and pulmonary hypertension due to unclear multifactorial mechanisms (Group 5).<ref name="pmid24355639">{{cite journal| author=Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A et al.| title=Updated clinical classification of pulmonary hypertension. | journal=J Am Coll Cardiol | year= 2013 | volume= 62 | issue= 25 Suppl | pages= D34-41 | pmid=24355639 | doi=10.1016/j.jacc.2013.10.029 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24355639  }} </ref>
+Pulmonary hypertension (PH) has been previously classified as primary (currently known as idiopathic pulmonary arterial hypertension or IPAH) and secondary in 1973.  In 1988, a clinical classification of PH into 5 groups has been developed during the 2nd World Symposium on PH in Evian, France. The clinical classification has been updated regularly as the understanding of PH expanded; nevertheless, the main scheme of classification into the 5 main groups remained intact.  The classification of PH has been last modified in 2013 during the 5th World Symposium on Pulmonary Hypertension in Nice, France. The main 5 groups of PH include pulmonary arterial hypertension (Group 1), pulmonary hypertension due to left heart disease (Group 2), pulmonary hypertension due to chronic lung disease and/or [[hypoxia]] (Group 3), chronic [[VTE|thromboembolic]] pulmonary hypertension (Group 4), and pulmonary hypertension due to unclear multifactorial mechanisms (Group 5).
 ==Classification==
 ===Clinical Classification===
-PH was first classified into primary and secondary in 1973 during the [[World Health Organization]] (WHO) meeting on PH in Geneva, Switzerland.<ref name=WHO1973>Hatano S, Strasser T. Primary Pulmonary Hypertension. Report on a WHO Meeting. October 15–17, 1973, Geneva: World Health Organization, 1975.</ref>
+* PH was first classified into primary and secondary in 1973 during the [[World Health Organization]] (WHO) meeting on PH in Geneva, Switzerland.<ref name="WHO1973">Hatano S, Strasser T. Primary Pulmonary Hypertension. Report on a WHO Meeting. October 15–17, 1973, Geneva: World Health Organization, 1975.</ref>
-The 2-group classification of PH was replaced by a clinical 5-group classification in the 2nd World Symposium on Pulmonary Hypertension in 1998 in Evian, France.<ref>Rich S, Rubin LJ, Abenhail L, et al. Executive summary from the World Symposium on Primary Pulmonary Hypertension 1998, Evian, France, September 6-10, 1998. Geneva: The World Health Organization.</ref> Since then, the clinical classification of PH was updated in the following meetings:
+* The 2-group classification of PH was replaced by a clinical 5-group classification in the 2nd World Symposium on Pulmonary Hypertension in 1998 in Evian, France.<ref>Rich S, Rubin LJ, Abenhail L, et al. Executive summary from the World Symposium on Primary Pulmonary Hypertension 1998, Evian, France, September 6-10, 1998. Geneva: The World Health Organization.</ref> Since then, the clinical classification of PH was updated in the following meetings:
-* The 3d World Symposium on Pulmonary Hypertension (2003) in Venice, Italy<ref name="pmid15194173">{{cite journal| author=Simonneau G, Galiè N, Rubin LJ, Langleben D, Seeger W, Domenighetti G et al.| title=Clinical classification of pulmonary hypertension. | journal=J Am Coll Cardiol | year= 2004 | volume= 43 | issue= 12 Suppl S | pages= 5S-12S | pmid=15194173 | doi=10.1016/j.jacc.2004.02.037 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15194173  }} </ref>
+** ''The 3d World Symposium on Pulmonary Hypertension (2003) in Venice, Italy<ref name="pmid15194173">{{cite journal| author=Simonneau G, Galiè N, Rubin LJ, Langleben D, Seeger W, Domenighetti G et al.| title=Clinical classification of pulmonary hypertension. | journal=J Am Coll Cardiol | year= 2004 | volume= 43 | issue= 12 Suppl S | pages= 5S-12S | pmid=15194173 | doi=10.1016/j.jacc.2004.02.037 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15194173  }} </ref>''
-* The 4th World Symposium on Pulmonary Hypertension (2008) in Dana Point, California, USA<ref name="pmid19555858">{{cite journal| author=Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP et al.| title=Updated clinical classification of pulmonary hypertension. | journal=J Am Coll Cardiol | year= 2009 | volume= 54 | issue= 1 Suppl | pages= S43-54 | pmid=19555858 | doi=10.1016/j.jacc.2009.04.012 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19555858  }} </ref>
+** ''The 4th World Symposium on Pulmonary Hypertension (2008) in Dana Point, California, USA<ref name="pmid19555858">{{cite journal| author=Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP et al.| title=Updated clinical classification of pulmonary hypertension. | journal=J Am Coll Cardiol | year= 2009 | volume= 54 | issue= 1 Suppl | pages= S43-54 | pmid=19555858 | doi=10.1016/j.jacc.2009.04.012 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19555858  }} </ref>''
-* The 5th World Symposium on Pulmonary Hypertension (2013) in Nice, France<ref name="pmid24355639">{{cite journal| author=Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A et al.| title=Updated clinical classification of pulmonary hypertension. | journal=J Am Coll Cardiol | year= 2013 | volume= 62 | issue= 25 Suppl | pages= D34-41 | pmid=24355639 | doi=10.1016/j.jacc.2013.10.029 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24355639  }} </ref>
+** ''The 5th World Symposium on Pulmonary Hypertension (2013) in Nice, France<ref name="pmid24355639">{{cite journal| author=Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A et al.| title=Updated clinical classification of pulmonary hypertension. | journal=J Am Coll Cardiol | year= 2013 | volume= 62 | issue= 25 Suppl | pages= D34-41 | pmid=24355639 | doi=10.1016/j.jacc.2013.10.029 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24355639  }} </ref>''
-The updated clinical classification has been adopted by the Guidelines Committee of the European Society of Cardiology (ESC), European Respiratory Society (ERS), and International Society of Heart and Lung Transplantation (ISHLT).  It is currently used by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the labeling of new drugs approved for the treatment of PH.
+* The updated clinical classification has been adopted by the Guidelines Committee of the European Society of Cardiology (ESC), European Respiratory Society (ERS), and International Society of Heart and Lung Transplantation (ISHLT).
+* It is currently used by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the labeling of new drugs approved for the treatment of PH.
 Shown below is a table summarizing the updated clinical classification of PH.<ref name="pmid24355639">{{cite journal| author=Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A et al.| title=Updated clinical classification of pulmonary hypertension. | journal=J Am Coll Cardiol | year= 2013 | volume= 62 | issue= 25 Suppl | pages= D34-41 | pmid=24355639 | doi=10.1016/j.jacc.2013.10.029 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24355639  }} </ref>
@@ Line 24: / Line 24: @@
 {| style="cellpadding=0; cellspacing= 0; width: 600px;"
 |-
-| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=left |'''Group 1. Pulmonary arterial hypertension (PAH)'''
+| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="left" |'''Group 1. Pulmonary arterial hypertension (PAH)'''
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left colspan=2 |'''1.1. Idiopathic PAH'''
+| colspan="2" style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |'''1.1. Idiopathic PAH'''
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left colspan=2 |'''1.2. Heritable PAH''' <br>
+| colspan="2" style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |'''1.2. Heritable PAH''' <br>
 .2.1 [[BMPR2]] <br>
 .2.2 [[ALK-1]], [[Endoglin|ENG]], [[SMAD9]], [[CAV1]], [[KCNK3]] <br>
 .2.3 Unknown
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left colspan=2 |'''1.3 Drug and toxin induced''' <br>
+| colspan="2" style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |'''1.3 Drug and toxin induced''' <br>
 ''Definite'' (an epidemic or large multicenter epidemiological studies demonstrating an association between a drug and PAH) <br>
 *[[Aminorex]] <br>
@@ Line 58: / Line 58: @@
 *[[Cigarette smoking]]
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left colspan=2 |'''1.4 Associated with:''' <br>
+| colspan="2" style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |'''1.4 Associated with:''' <br>
 .4.1 [[Connective tissue disease]] <br>
 .4.2 [[HIV infection]] <br>
@@ Line 65: / Line 65: @@
 .4.5 [[Schistosomiasis]] <br>
 |-
-| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=left |'''1’ Pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis (PCH)'''
+| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="left" |'''1’ Pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis (PCH)'''
 |-
-| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=left |'''1’’ Persistent pulmonary hypertension of the newborn (PPHN)'''
+| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="left" |'''1’’ Persistent pulmonary hypertension of the newborn (PPHN)'''
 |-
-| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=left |'''Group 2. Pulmonary hypertension due to left heart disease'''
+| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="left" |'''Group 2. Pulmonary hypertension due to left heart disease'''
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left colspan=2 |2.1 [[Left ventricular systolic dysfunction]]
+| colspan="2" style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |2.1 [[Left ventricular systolic dysfunction]]
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left colspan=2 |2.2 [[diastolic dysfunction|Left ventricular diastolic dysfunction]]
+| colspan="2" style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |2.2 [[diastolic dysfunction|Left ventricular diastolic dysfunction]]
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left colspan=2 |2.3 [[Valvular disease]]
+| colspan="2" style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |2.3 [[Valvular disease]]
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left colspan=2 |2.4 [[Congenital heart disease|Congenital]]/acquired left heart inflow/outflow tract obstruction and congenital [[cardiomyopathies]]
+| colspan="2" style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |2.4 [[Congenital heart disease|Congenital]]/acquired left heart inflow/outflow tract obstruction and congenital [[cardiomyopathies]]
 |-
-| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=left |'''Group 3. Pulmonary hypertension due to lung diseases and/or hypoxia'''
+| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="left" |'''Group 3. Pulmonary hypertension due to lung diseases and/or hypoxia'''
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left colspan=2 |3.1 [[Chronic obstructive pulmonary disease]]
+| colspan="2" style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |3.1 [[Chronic obstructive pulmonary disease]]
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left colspan=2 |3.2 [[Interstitial lung disease]]
+| colspan="2" style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |3.2 [[Interstitial lung disease]]
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left colspan=2 |3.3 Other pulmonary diseases with mixed restrictive and obstructive pattern
+| colspan="2" style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |3.3 Other pulmonary diseases with mixed restrictive and obstructive pattern
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left colspan=2 |3.4 Sleep-disordered breathing
+| colspan="2" style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |3.4 Sleep-disordered breathing
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left colspan=2 |3.5 Alveolar [[hypoventilation]] disorders
+| colspan="2" style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |3.5 Alveolar [[hypoventilation]] disorders
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left colspan=2 |3.6 Chronic exposure to high altitude
+| colspan="2" style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |3.6 Chronic exposure to high altitude
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left colspan=2 |3.7 Developmental lung diseases
+| colspan="2" style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |3.7 Developmental lung diseases
 |-
-| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=left |'''Group 4. Chronic thromboembolic pulmonary hypertension (CTEPH)'''
+| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="left" |'''Group 4. Chronic thromboembolic pulmonary hypertension (CTEPH)'''
 |-
-| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=left |'''Group 5. Pulmonary hypertension with unclear multifactorial mechanisms'''
+| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="left" |'''Group 5. Pulmonary hypertension with unclear multifactorial mechanisms'''
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left colspan=2 |5.1 Hematologic disorders: chronic [[hemolytic anemia]], [[myeloproliferative disorder]]s, [[splenectomy]]
+| colspan="2" style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |5.1 Hematologic disorders: chronic [[hemolytic anemia]], [[myeloproliferative disorder]]s, [[splenectomy]]
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left colspan=2 |5.2 Systemic disorders: [[sarcoidosis]], [[Langerhans cell histiocytosis|pulmonary histiocytosis]], [[lymphangioleiomyomatosis]]
+| colspan="2" style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |5.2 Systemic disorders: [[sarcoidosis]], [[Langerhans cell histiocytosis|pulmonary histiocytosis]], [[lymphangioleiomyomatosis]]
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left colspan=2 |5.3 Metabolic disorders: [[glycogen storage disease]], [[Gaucher disease]], [[thyroid]] disorders
+| colspan="2" style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |5.3 Metabolic disorders: [[glycogen storage disease]], [[Gaucher disease]], [[thyroid]] disorders
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left colspan=2 |5.4 Others: [[tumor]] obstruction, fibrosing [[mediastinitis]], [[chronic renal failure]], segmental PH
+| colspan="2" style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |5.4 Others: [[tumor]] obstruction, fibrosing [[mediastinitis]], [[chronic renal failure]], segmental PH
 |}
@@ Line 113: / Line 113: @@
 {| style="cellpadding=0; cellspacing= 0; width: 600px;"
 |-
-| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=left |'''Class''' || style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=left |'''Description'''
+| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="left" |'''Class''' || style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="left" |'''Description'''
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 30%" align=left | '''I''' || style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left |No limitation of usual physical activity <br>No increased dyspnea, fatigue, chest pain, or presyncope upon ordinary physical activity
+| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 30%" align="left" | '''I''' || style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |No limitation of usual physical activity <br>No increased dyspnea, fatigue, chest pain, or presyncope upon ordinary physical activity
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 30%" align=left|'''II''' || style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left|Mild limitation of physical activity <br> No discomfort at rest <br> Increased dyspnea, fatigue, chest pain, or presyncope upon normal physical activity
+| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 30%" align="left" |'''II''' || style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |Mild limitation of physical activity <br> No discomfort at rest <br> Increased dyspnea, fatigue, chest pain, or presyncope upon normal physical activity
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 30%" align=left|'''III''' || style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left|Marked limitation of physical activity <br> No discomfort at rest <br> Increased dyspnea, fatigue, chest pain, or presyncope upon less than ordinary activity
+| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 30%" align="left" |'''III''' || style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |Marked limitation of physical activity <br> No discomfort at rest <br> Increased dyspnea, fatigue, chest pain, or presyncope upon less than ordinary activity
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 30%" align=left |'''IV''' || style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left |Inability to perform any physical activity at rest with/without signs of right ventricular failure <br> Dyspnea and/or fatigue may be present at rest <br>  Increased dyspnea, fatigue, chest pain, or presyncope by almost any physical activity
+| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 30%" align="left" |'''IV''' || style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align="left" |Inability to perform any physical activity at rest with/without signs of right ventricular failure <br> Dyspnea and/or fatigue may be present at rest <br>  Increased dyspnea, fatigue, chest pain, or presyncope by almost any physical activity
 |}
@@ Line 130: / Line 130: @@
 {| style="cellpadding=0; cellspacing= 0; width: 600px;"
 |-
-| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=left |'''Type of pulmonary hypertension''' || style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=left |'''Possible clinical class''' || style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=left |'''Mean PAP''' || style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=left |'''PWP'''
+| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="left" |'''Type of pulmonary hypertension''' || style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="left" |'''Possible clinical class''' || style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="left" |'''Mean PAP''' || style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="left" |'''PWP'''
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align=left|'''Pre-capillary''' || style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align=left|Class I <br> Class III <br> Class IV <br> Class V || style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align=left|≥ 25 mmHg || style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align=left|≤ 15 mmHg
+| style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align="left" |'''Pre-capillary''' || style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align="left" |Class I <br> Class III <br> Class IV <br> Class V || style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align="left" |≥ 25 mmHg || style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align="left" |≤ 15 mmHg
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align=left|'''Post-capillary''' ||  style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align=left|Class II ||style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align=left|≥ 25 mmHg || style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align=left|> 15 mmHg
+| style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align="left" |'''Post-capillary''' || style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align="left" |Class II || style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align="left" |≥ 25 mmHg || style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align="left" |> 15 mmHg
 |}
@@ Line 141: / Line 141: @@
 {| style="cellpadding=0; cellspacing= 0; width: 600px;"
 |-
-| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=left |'''Class''' || style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align=left |'''Histopathological findings'''<ref name="pmid15194175">{{cite journal| author=Pietra GG, Capron F, Stewart S, Leone O, Humbert M, Robbins IM et al.| title=Pathologic assessment of vasculopathies in pulmonary hypertension. | journal=J Am Coll Cardiol | year= 2004 | volume= 43 | issue= 12 Suppl S | pages= 25S-32S | pmid=15194175 | doi=10.1016/j.jacc.2004.02.033 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15194175  }} </ref>
+| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="left" |'''Class''' || style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="left" |'''Histopathological findings'''<ref name="pmid15194175">{{cite journal| author=Pietra GG, Capron F, Stewart S, Leone O, Humbert M, Robbins IM et al.| title=Pathologic assessment of vasculopathies in pulmonary hypertension. | journal=J Am Coll Cardiol | year= 2004 | volume= 43 | issue= 12 Suppl S | pages= 25S-32S | pmid=15194175 | doi=10.1016/j.jacc.2004.02.033 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15194175  }} </ref>
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align=left|'''Pulmonary arteriopathy''' || style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align=left|''Constrictive lesions in pulmonary arteries'' <br>
+| style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align="left" |'''Pulmonary arteriopathy''' || style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align="left" |''Constrictive lesions in pulmonary arteries'' <br>
 * Medial hypertrophy <br>
 * Intimal thickening <br>
@@ Line 152: / Line 152: @@
 * [[Arteritis]] <br>
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align=left|'''Pulmonary arteriopathy with venous-venular changes''' || style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align=left| ''Changes similar to pulmonary arteriopathy'' <br> PLUS<br> ''Changes in venules and veins''
+| style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align="left" |'''Pulmonary arteriopathy with venous-venular changes''' || style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align="left" | ''Changes similar to pulmonary arteriopathy'' <br> PLUS<br> ''Changes in venules and veins''
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width:50%" align=left|'''Pulmonary occlusive venopathy''' <br> (with or without arteriopathy) || style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align=left|''Changes in venules and veins'' <br>
+| style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width:50%" align="left" |'''Pulmonary occlusive venopathy''' <br> (with or without arteriopathy) || style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align="left" |''Changes in venules and veins'' <br>
 * Diffuse fibrotic occlusion<br>
 * Intimal thickening <br>
@@ Line 167: / Line 167: @@
 * [[Hemosiderosis]]
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align=left|'''Pulmonary microvasculopathy''' <br> (with or without arteriopathy and/on venopathy)|| style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align=left|''Changes in the capillaries'' <br>
+| style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align="left" |'''Pulmonary microvasculopathy''' <br> (with or without arteriopathy and/on venopathy)|| style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align="left" |''Changes in the capillaries'' <br>
 * Localized capillary proliferation <br>
 ''Changes in the interstitium'' <br>
@@ Line 174: / Line 174: @@
 * [[Hemosiderosis]]
 |-
-| style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align=left|'''Unclassified''' || style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align=left| ''Non specific changes''
+| style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align="left" |'''Unclassified''' || style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align="left" | ''Non specific changes''
 |}