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Pulmonary hypertension, primary, 6(PPH6)

MedGen UID:: 1052365
•Concept ID:: CN377269
•: Disease or Syndrome

Synonym:	PPH6

Gene (location): Gene(s) directly associated with this condition or phenotype.	CAPNS1 (19q13.12)

Monarch Initiative:	MONDO:0958334
OMIM®:	620777

Definition

Primary pulmonary hypertension-6 (PPH6) is characterized by markedly elevated pulmonary arterial hypertension, associated with reduced oxygen saturation and diffuse ground-glass opacities on chest x-ray. Lung biopsy shows thickening of the alveolar septae and abnormally proliferating capillaries (Postma et al., 2023). For a general phenotypic description and a discussion of genetic heterogeneity of primary pulmonary hypertension, see PPH1 (178600). [from OMIM]

Professional guidelines

PubMed

Portopulmonary Hypertension: Management and Liver Transplantation Evaluation.

DuBrock HM
Chest 2023 Jul;164(1):206-214. Epub 2023 Jan 14 doi: 10.1016/j.chest.2023.01.009. PMID: 36649754

Drug-Drug Interactions in the Management of Patients With Pulmonary Arterial Hypertension.

Wu S, Hoang HB, Yang JZ, Papamatheakis DG, Poch DS, Alotaibi M, Lombardi S, Rodriguez C, Kim NH, Fernandes TM
Chest 2022 Dec;162(6):1360-1372. Epub 2022 Jul 14 doi: 10.1016/j.chest.2022.06.042. PMID: 35841932 Free PMC Article

Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol.

Attard G, Murphy L, Clarke NW, Cross W, Jones RJ, Parker CC, Gillessen S, Cook A, Brawley C, Amos CL, Atako N, Pugh C, Buckner M, Chowdhury S, Malik Z, Russell JM, Gilson C, Rush H, Bowen J, Lydon A, Pedley I, O'Sullivan JM, Birtle A, Gale J, Srihari N, Thomas C, Tanguay J, Wagstaff J, Das P, Gray E, Alzoueb M, Parikh O, Robinson A, Syndikus I, Wylie J, Zarkar A, Thalmann G, de Bono JS, Dearnaley DP, Mason MD, Gilbert D, Langley RE, Millman R, Matheson D, Sydes MR, Brown LC, Parmar MKB, James ND; Systemic Therapy in Advancing or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators
Lancet 2022 Jan 29;399(10323):447-460. Epub 2021 Dec 23 doi: 10.1016/S0140-6736(21)02437-5. PMID: 34953525 Free PMC Article

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Recent clinical studies

Etiology

Portopulmonary Hypertension: Management and Liver Transplantation Evaluation.

DuBrock HM
Chest 2023 Jul;164(1):206-214. Epub 2023 Jan 14 doi: 10.1016/j.chest.2023.01.009. PMID: 36649754

Risk stratification and response to therapy in patients with pulmonary arterial hypertension and comorbidities: A COMPERA analysis.

Rosenkranz S, Pausch C, Coghlan JG, Huscher D, Pittrow D, Grünig E, Staehler G, Vizza CD, Gall H, Distler O, Delcroix M, Ghofrani HA, Ewert R, Kabitz HJ, Skowasch D, Behr J, Milger K, Halank M, Wilkens H, Seyfarth HJ, Held M, Scelsi L, Neurohr C, Vonk-Noordegraaf A, Ulrich S, Klose H, Claussen M, Eisenmann S, Schmidt KH, Remppis BA, Skride A, Jureviciene E, Gumbiene L, Miliauskas S, Löffler-Ragg J, Lange TJ, Olsson KM, Hoeper MM, Opitz C
J Heart Lung Transplant 2023 Jan;42(1):102-114. Epub 2022 Oct 13 doi: 10.1016/j.healun.2022.10.003. PMID: 36333206

Sotatercept for the treatment of pulmonary arterial hypertension: PULSAR open-label extension.

Humbert M, McLaughlin V, Gibbs JSR, Gomberg-Maitland M, Hoeper MM, Preston IR, Souza R, Waxman AB, Ghofrani HA, Escribano Subias P, Feldman J, Meyer G, Montani D, Olsson KM, Manimaran S, de Oliveira Pena J, Badesch DB
Eur Respir J 2023 Jan;61(1) Epub 2023 Jan 6 doi: 10.1183/13993003.01347-2022. PMID: 36041750 Free PMC Article

Mendelian randomisation and experimental medicine approaches to interleukin-6 as a drug target in pulmonary arterial hypertension.

Toshner M, Church C, Harbaum L, Rhodes C, Villar Moreschi SS, Liley J, Jones R, Arora A, Batai K, Desai AA, Coghlan JG, Gibbs JSR, Gor D, Gräf S, Harlow L, Hernandez-Sanchez J, Howard LS, Humbert M, Karnes J, Kiely DG, Kittles R, Knightbridge E, Lam B, Lutz KA, Nichols WC, Pauciulo MW, Pepke-Zaba J, Suntharalingam J, Soubrier F, Trembath RC, Schwantes-An TL, Wort SJ, Wilkins MR, Gaine S, Morrell NW, Corris PA; Uniphy Clinical Trials Network
Eur Respir J 2022 Mar;59(3) Epub 2022 Mar 10 doi: 10.1183/13993003.02463-2020. PMID: 34588193 Free PMC Article

Idiopathic pulmonary arterial hypertension phenotypes determined by cluster analysis from the COMPERA registry.

Hoeper MM, Pausch C, Grünig E, Klose H, Staehler G, Huscher D, Pittrow D, Olsson KM, Vizza CD, Gall H, Benjamin N, Distler O, Opitz C, Gibbs JSR, Delcroix M, Ghofrani HA, Rosenkranz S, Ewert R, Kaemmerer H, Lange TJ, Kabitz HJ, Skowasch D, Skride A, Jureviciene E, Paleviciute E, Miliauskas S, Claussen M, Behr J, Milger K, Halank M, Wilkens H, Wirtz H, Pfeuffer-Jovic E, Harbaum L, Scholtz W, Dumitrescu D, Bruch L, Coghlan G, Neurohr C, Tsangaris I, Gorenflo M, Scelsi L, Vonk-Noordegraaf A, Ulrich S, Held M
J Heart Lung Transplant 2020 Dec;39(12):1435-1444. Epub 2020 Sep 30 doi: 10.1016/j.healun.2020.09.011. PMID: 33082079

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Diagnosis

Systemic Lupus Erythematosus and Pulmonary Hypertension.

Parperis K, Velidakis N, Khattab E, Gkougkoudi E, Kadoglou NPE
Int J Mol Sci 2023 Mar 7;24(6) doi: 10.3390/ijms24065085. PMID: 36982160 Free PMC Article

Portopulmonary Hypertension: Management and Liver Transplantation Evaluation.

DuBrock HM
Chest 2023 Jul;164(1):206-214. Epub 2023 Jan 14 doi: 10.1016/j.chest.2023.01.009. PMID: 36649754

The physiological basis of pulmonary arterial hypertension.

Naeije R, Richter MJ, Rubin LJ
Eur Respir J 2022 Jun;59(6) Epub 2022 Jun 16 doi: 10.1183/13993003.02334-2021. PMID: 34737219 Free PMC Article

Idiopathic pulmonary arterial hypertension phenotypes determined by cluster analysis from the COMPERA registry.

Survival in patients with primary pulmonary hypertension. Results from a national prospective registry.

D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Kernis JT
Ann Intern Med 1991 Sep 1;115(5):343-9. doi: 10.7326/0003-4819-115-5-343. PMID: 1863023

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Therapy

New Drugs and Therapies in Pulmonary Arterial Hypertension.

Shah AJ, Beckmann T, Vorla M, Kalra DK
Int J Mol Sci 2023 Mar 19;24(6) doi: 10.3390/ijms24065850. PMID: 36982922 Free PMC Article

Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension.

Hoeper MM, Badesch DB, Ghofrani HA, Gibbs JSR, Gomberg-Maitland M, McLaughlin VV, Preston IR, Souza R, Waxman AB, Grünig E, Kopeć G, Meyer G, Olsson KM, Rosenkranz S, Xu Y, Miller B, Fowler M, Butler J, Koglin J, de Oliveira Pena J, Humbert M; STELLAR Trial Investigators
N Engl J Med 2023 Apr 20;388(16):1478-1490. Epub 2023 Mar 6 doi: 10.1056/NEJMoa2213558. PMID: 36877098

Sotatercept for the treatment of pulmonary arterial hypertension: PULSAR open-label extension.

Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease.

Waxman A, Restrepo-Jaramillo R, Thenappan T, Ravichandran A, Engel P, Bajwa A, Allen R, Feldman J, Argula R, Smith P, Rollins K, Deng C, Peterson L, Bell H, Tapson V, Nathan SD
N Engl J Med 2021 Jan 28;384(4):325-334. Epub 2021 Jan 13 doi: 10.1056/NEJMoa2008470. PMID: 33440084

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Prognosis

Systemic Lupus Erythematosus and Pulmonary Hypertension.

Parperis K, Velidakis N, Khattab E, Gkougkoudi E, Kadoglou NPE
Int J Mol Sci 2023 Mar 7;24(6) doi: 10.3390/ijms24065085. PMID: 36982160 Free PMC Article

Portopulmonary Hypertension: Management and Liver Transplantation Evaluation.

DuBrock HM
Chest 2023 Jul;164(1):206-214. Epub 2023 Jan 14 doi: 10.1016/j.chest.2023.01.009. PMID: 36649754

Idiopathic pulmonary arterial hypertension phenotypes determined by cluster analysis from the COMPERA registry.

Moderate pulmonary embolism treated with thrombolysis (from the "MOPETT" Trial).

Sharifi M, Bay C, Skrocki L, Rahimi F, Mehdipour M; “MOPETT” Investigators
Am J Cardiol 2013 Jan 15;111(2):273-7. Epub 2012 Oct 24 doi: 10.1016/j.amjcard.2012.09.027. PMID: 23102885

Survival in patients with primary pulmonary hypertension. Results from a national prospective registry.

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Clinical prediction guides

Risk stratification and response to therapy in patients with pulmonary arterial hypertension and comorbidities: A COMPERA analysis.

Phenotyping of idiopathic pulmonary arterial hypertension: a registry analysis.

Hoeper MM, Dwivedi K, Pausch C, Lewis RA, Olsson KM, Huscher D, Pittrow D, Grünig E, Staehler G, Vizza CD, Gall H, Distler O, Opitz C, Gibbs JSR, Delcroix M, Park DH, Ghofrani HA, Ewert R, Kaemmerer H, Kabitz HJ, Skowasch D, Behr J, Milger K, Lange TJ, Wilkens H, Seyfarth HJ, Held M, Dumitrescu D, Tsangaris I, Vonk-Noordegraaf A, Ulrich S, Klose H, Claussen M, Eisenmann S, Schmidt KH, Swift AJ, Thompson AAR, Elliot CA, Rosenkranz S, Condliffe R, Kiely DG, Halank M
Lancet Respir Med 2022 Oct;10(10):937-948. Epub 2022 Jun 28 doi: 10.1016/S2213-2600(22)00097-2. PMID: 35777416 Free PMC Article

COMPERA 2.0: a refined four-stratum risk assessment model for pulmonary arterial hypertension.

Hoeper MM, Pausch C, Olsson KM, Huscher D, Pittrow D, Grünig E, Staehler G, Vizza CD, Gall H, Distler O, Opitz C, Gibbs JSR, Delcroix M, Ghofrani HA, Park DH, Ewert R, Kaemmerer H, Kabitz HJ, Skowasch D, Behr J, Milger K, Halank M, Wilkens H, Seyfarth HJ, Held M, Dumitrescu D, Tsangaris I, Vonk-Noordegraaf A, Ulrich S, Klose H, Claussen M, Lange TJ, Rosenkranz S
Eur Respir J 2022 Jul;60(1) Epub 2022 Jul 7 doi: 10.1183/13993003.02311-2021. PMID: 34737226 Free PMC Article

Mendelian randomisation and experimental medicine approaches to interleukin-6 as a drug target in pulmonary arterial hypertension.

Idiopathic pulmonary arterial hypertension phenotypes determined by cluster analysis from the COMPERA registry.

See all (1380)

Recent systematic reviews

Exercise-based rehabilitation programmes for pulmonary hypertension.

Morris NR, Kermeen FD, Jones AW, Lee JY, Holland AE
Cochrane Database Syst Rev 2023 Mar 22;3(3):CD011285. doi: 10.1002/14651858.CD011285.pub3. PMID: 36947725 Free PMC Article

Multiparameters associated to successful weaning from VA ECMO in adult patients with cardiogenic shock or cardiac arrest: Systematic review and meta-analysis.

Burgos LM, Seoane L, Diez M, Baro Vila RC, Furmento JF, Vrancic M, Aissaoui N
Ann Card Anaesth 2023 Jan-Mar;26(1):4-11. doi: 10.4103/aca.aca_79_22. PMID: 36722581 Free PMC Article

Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019.

Global Burden of Disease 2019 Cancer Collaboration, Kocarnik JM, Compton K, Dean FE, Fu W, Gaw BL, Harvey JD, Henrikson HJ, Lu D, Pennini A, Xu R, Ababneh E, Abbasi-Kangevari M, Abbastabar H, Abd-Elsalam SM, Abdoli A, Abedi A, Abidi H, Abolhassani H, Adedeji IA, Adnani QES, Advani SM, Afzal MS, Aghaali M, Ahinkorah BO, Ahmad S, Ahmad T, Ahmadi A, Ahmadi S, Ahmed Rashid T, Ahmed Salih Y, Akalu GT, Aklilu A, Akram T, Akunna CJ, Al Hamad H, Alahdab F, Al-Aly Z, Ali S, Alimohamadi Y, Alipour V, Aljunid SM, Alkhayyat M, Almasi-Hashiani A, Almasri NA, Al-Maweri SAA, Almustanyir S, Alonso N, Alvis-Guzman N, Amu H, Anbesu EW, Ancuceanu R, Ansari F, Ansari-Moghaddam A, Antwi MH, Anvari D, Anyasodor AE, Aqeel M, Arabloo J, Arab-Zozani M, Aremu O, Ariffin H, Aripov T, Arshad M, Artaman A, Arulappan J, Asemi Z, Asghari Jafarabadi M, Ashraf T, Atorkey P, Aujayeb A, Ausloos M, Awedew AF, Ayala Quintanilla BP, Ayenew T, Azab MA, Azadnajafabad S, Azari Jafari A, Azarian G, Azzam AY, Badiye AD, Bahadory S, Baig AA, Baker JL, Balakrishnan S, Banach M, Bärnighausen TW, Barone-Adesi F, Barra F, Barrow A, Behzadifar M, Belgaumi UI, Bezabhe WMM, Bezabih YM, Bhagat DS, Bhagavathula AS, Bhardwaj N, Bhardwaj P, Bhaskar S, Bhattacharyya K, Bhojaraja VS, Bibi S, Bijani A, Biondi A, Bisignano C, Bjørge T, Bleyer A, Blyuss O, Bolarinwa OA, Bolla SR, Braithwaite D, Brar A, Brenner H, Bustamante-Teixeira MT, Butt NS, Butt ZA, Caetano Dos Santos FL, Cao Y, Carreras G, Catalá-López F, Cembranel F, Cerin E, Cernigliaro A, Chakinala RC, Chattu SK, Chattu VK, Chaturvedi P, Chimed-Ochir O, Cho DY, Christopher DJ, Chu DT, Chung MT, Conde J, Cortés S, Cortesi PA, Costa VM, Cunha AR, Dadras O, Dagnew AB, Dahlawi SMA, Dai X, Dandona L, Dandona R, Darwesh AM, das Neves J, De la Hoz FP, Demis AB, Denova-Gutiérrez E, Dhamnetiya D, Dhimal ML, Dhimal M, Dianatinasab M, Diaz D, Djalalinia S, Do HP, Doaei S, Dorostkar F, Dos Santos Figueiredo FW, Driscoll TR, Ebrahimi H, Eftekharzadeh S, El Tantawi M, El-Abid H, Elbarazi I, Elhabashy HR, Elhadi M, El-Jaafary SI, Eshrati B, Eskandarieh S, Esmaeilzadeh F, Etemadi A, Ezzikouri S, Faisaluddin M, Faraon EJA, Fares J, Farzadfar F, Feroze AH, Ferrero S, Ferro Desideri L, Filip I, Fischer F, Fisher JL, Foroutan M, Fukumoto T, Gaal PA, Gad MM, Gadanya MA, Gallus S, Gaspar Fonseca M, Getachew Obsa A, Ghafourifard M, Ghashghaee A, Ghith N, Gholamalizadeh M, Gilani SA, Ginindza TG, Gizaw ATT, Glasbey JC, Golechha M, Goleij P, Gomez RS, Gopalani SV, Gorini G, Goudarzi H, Grosso G, Gubari MIM, Guerra MR, Guha A, Gunasekera DS, Gupta B, Gupta VB, Gupta VK, Gutiérrez RA, Hafezi-Nejad N, Haider MR, Haj-Mirzaian A, Halwani R, Hamadeh RR, Hameed S, Hamidi S, Hanif A, Haque S, Harlianto NI, Haro JM, Hasaballah AI, Hassanipour S, Hay RJ, Hay SI, Hayat K, Heidari G, Heidari M, Herrera-Serna BY, Herteliu C, Hezam K, Holla R, Hossain MM, Hossain MBH, Hosseini MS, Hosseini M, Hosseinzadeh M, Hostiuc M, Hostiuc S, Househ M, Hsairi M, Huang J, Hugo FN, 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Male S, Malik AA, Mansournia MA, Martini S, Masoumi SZ, Mathur P, McKee M, Mehrotra R, Mendoza W, Menezes RG, Mengesha EW, Mesregah MK, Mestrovic T, Miao Jonasson J, Miazgowski B, Miazgowski T, Michalek IM, Miller TR, Mirzaei H, Mirzaei HR, Misra S, Mithra P, Moghadaszadeh M, Mohammad KA, Mohammad Y, Mohammadi M, Mohammadi SM, Mohammadian-Hafshejani A, Mohammed S, Moka N, Mokdad AH, Molokhia M, Monasta L, Moni MA, Moosavi MA, Moradi Y, Moraga P, Morgado-da-Costa J, Morrison SD, Mosapour A, Mubarik S, Mwanri L, Nagarajan AJ, Nagaraju SP, Nagata C, Naimzada MD, Nangia V, Naqvi AA, Narasimha Swamy S, Ndejjo R, Nduaguba SO, Negoi I, Negru SM, Neupane Kandel S, Nguyen CT, Nguyen HLT, Niazi RK, Nnaji CA, Noor NM, Nuñez-Samudio V, Nzoputam CI, Oancea B, Ochir C, Odukoya OO, Ogbo FA, Olagunju AT, Olakunde BO, Omar E, Omar Bali A, Omonisi AEE, Ong S, Onwujekwe OE, Orru H, Ortega-Altamirano DV, Otstavnov N, Otstavnov SS, Owolabi MO, P A M, Padubidri JR, Pakshir K, Pana A, Panagiotakos D, Panda-Jonas S, Pardhan S, Park EC, Park EK, Pashazadeh Kan F, Patel HK, Patel JR, Pati S, Pattanshetty SM, Paudel U, Pereira DM, Pereira RB, Perianayagam A, Pillay JD, Pirouzpanah S, Pishgar F, Podder I, Postma MJ, Pourjafar H, Prashant A, Preotescu L, Rabiee M, Rabiee N, Radfar A, Radhakrishnan RA, Radhakrishnan V, Rafiee A, Rahim F, Rahimzadeh S, Rahman M, Rahman MA, Rahmani AM, Rajai N, Rajesh A, Rakovac I, Ram P, Ramezanzadeh K, Ranabhat K, Ranasinghe P, Rao CR, Rao SJ, Rawassizadeh R, Razeghinia MS, Renzaho AMN, Rezaei N, Rezaei N, Rezapour A, Roberts TJ, Rodriguez JAB, Rohloff P, Romoli M, Ronfani L, Roshandel G, Rwegerera GM, S M, Sabour S, Saddik B, Saeed U, Sahebkar A, Sahoo H, Salehi S, Salem MR, Salimzadeh H, Samaei M, Samy AM, Sanabria J, Sankararaman S, Santric-Milicevic MM, Sardiwalla Y, Sarveazad A, Sathian B, Sawhney M, Saylan M, Schneider IJC, Sekerija M, Seylani A, Shafaat O, Shaghaghi Z, Shaikh MA, Shamsoddin E, Shannawaz M, Sharma R, Sheikh A, Sheikhbahaei S, Shetty A, Shetty JK, Shetty PH, Shibuya K, Shirkoohi R, Shivakumar KM, Shivarov V, Siabani S, Siddappa Malleshappa SK, Silva DAS, Singh JA, Sintayehu Y, Skryabin VY, Skryabina AA, Soeberg MJ, Sofi-Mahmudi A, Sotoudeh H, Steiropoulos P, Straif K, Subedi R, Sufiyan MB, Sultan I, Sultana S, Sur D, Szerencsés V, Szócska M, Tabarés-Seisdedos R, Tabuchi T, Tadbiri H, Taherkhani A, Takahashi K, Talaat IM, Tan KK, Tat VY, Tedla BAA, Tefera YG, Tehrani-Banihashemi A, Temsah MH, Tesfay FH, Tessema GA, Thapar R, Thavamani A, Thoguluva Chandrasekar V, Thomas N, Tohidinik HR, Touvier M, Tovani-Palone MR, Traini E, Tran BX, Tran KB, Tran MTN, Tripathy JP, Tusa BS, Ullah I, Ullah S, Umapathi KK, Unnikrishnan B, Upadhyay E, Vacante M, Vaezi M, Valadan Tahbaz S, Velazquez DZ, Veroux M, Violante FS, Vlassov V, Vo B, Volovici V, Vu GT, Waheed Y, Wamai RG, Ward P, Wen YF, Westerman R, Winkler AS, Yadav L, Yahyazadeh Jabbari SH, Yang L, Yaya S, Yazie TSY, Yeshaw Y, Yonemoto N, Younis MZ, Yousefi Z, Yu C, Yuce D, 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Pulmonary hypertension, primary, 6(PPH6)

Definition

Professional guidelines

PubMed

Recent clinical studies

Etiology

Diagnosis

Therapy

Prognosis

Clinical prediction guides

Recent systematic reviews

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Table of contents

Clinical resources

Practice guidelines

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