Skip to main content
SpringerLink
Log in

Prognostication in PAH–CHD

  • Chapter
  • First Online:
Pulmonary Hypertension in Adult Congenital Heart Disease

Part of the book series: Congenital Heart Disease in Adolescents and Adults ((CHDAA))

  • 806 Accesses

Abstract

Patients with pulmonary arterial hypertension associated with congenital heart disease (PAH–CHD), particularly those with Eisenmenger syndrome (ES), are significantly impaired in their exercise capacity and have a relatively high mortality compared to other groups of CHD patients. Optimal clinical management of these patients requires reliable morbidity and mortality risk stratification algorithms. Due to the heterogeneity of CHD lesions, multi-organ dysfunction and wide spectrum of comorbidities, mortality risk stratification in PAH–CHD remains challenging. Multiple parameters have been associated with mortality and include type of underlying congenital lesion, exercise performance, arterial oxygen saturation, markers of myocardial injury, natriuretic peptides, renal dysfunction, hyponatraemia and hypoalbuminaemia. Most of the studies report, however, relative rather than absolute mortality risk and often focus on particular subgroups of PAH–CHD patients, especially ES. A recent, large multicentre study provides multivariable absolute mortality risk estimates in ES patients based on five simple parameters (age, presence of pre-tricuspid shunt, arterial oxygen saturation at rest, 6-min walk test distance and the presence of pericardial effusion) and may aid clinical management. Further studies are needed, particularly in other PAH–CHD subgroups, to establish new prognostication models and also to externally validate currently available statistical algorithms. Moreover, prospective randomized studies should investigate the impact of advanced PAH therapies and iron supplementation on mortality.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ACHD:

Adult congenital heart disease

ASD:

Atrial septal defect

AVSD:

Atrioventricular septal defect

CHD:

Congenital heart disease

ES:

Eisenmenger syndrome

PAH:

Pulmonary arterial hypertension

RV:

Right ventricle

SMR:

Standardized mortality ratio

VSD:

Ventricular septal defect

References

  1. Steele PM, Fuster V, Cohen M, Ritter DG, McGoon DC (1987) Isolated atrial septal defect with pulmonary vascular obstructive disease—long-term follow-up and prediction of outcome after surgical correction. Circulation 76(5):1037–1042. Epub 1987/11/01

    Article  CAS  PubMed  Google Scholar 

  2. Kidd L, Driscoll DJ, Gersony WM, Hayes CJ, Keane JF, O'Fallon WM et al (1993) Second natural history study of congenital heart defects. Results of treatment of patients with ventricular septal defects. Circulation 87(2 Suppl):I38–I51. Epub 1993/02/01

    CAS  PubMed  Google Scholar 

  3. Engelfriet PM, Duffels MG, Moller T, Boersma E, Tijssen JG, Thaulow E et al (2007) Pulmonary arterial hypertension in adults born with a heart septal defect: the Euro Heart Survey on adult congenital heart disease. Heart 93(6):682–687. Epub 2006/12/14

    Article  PubMed  Google Scholar 

  4. Diller GP, Dimopoulos K, Broberg CS, Kaya MG, Naghotra US, Uebing A et al (2006) Presentation, survival prospects, and predictors of death in Eisenmenger syndrome: a combined retrospective and case-control study. Eur Heart J 27(14):1737–1742. Epub 2006/06/24

    Article  PubMed  Google Scholar 

  5. Diller GP, Kempny A, Alonso-Gonzalez R, Swan L, Uebing A, Li W et al (2015) Survival prospects and circumstances of death in contemporary adult congenital heart disease patients under follow-up at a large tertiary centre. Circulation 132(22):2118–2125. Epub 2015/09/16

    Article  PubMed  Google Scholar 

  6. Manes A, Palazzini M, Leci E, Bacchi Reggiani ML, Branzi A, Galiè N (2014) Current era survival of patients with pulmonary arterial hypertension associated with congenital heart disease: a comparison between clinical subgroups. Eur Heart J 35(11):716–724

    Article  PubMed  Google Scholar 

  7. Cowie MR, Sarkar S, Koehler J, Whellan DJ, Crossley GH, Tang WH et al (2013) Development and validation of an integrated diagnostic algorithm derived from parameters monitored in implantable devices for identifying patients at risk for heart failure hospitalization in an ambulatory setting. Eur Heart J 34(31):2472–2480. Epub 2013/03/21

    Article  PubMed  PubMed Central  Google Scholar 

  8. Fonarow GC, Adams KF Jr, Abraham WT, Yancy CW, Boscardin WJ (2005) Risk stratification for in-hospital mortality in acutely decompensated heart failure: classification and regression tree analysis. JAMA 293(5):572–580. Epub 2005/02/03

    Article  CAS  PubMed  Google Scholar 

  9. Lee DS, Austin PC, Rouleau JL, Liu PP, Naimark D, Tu JV (2003) Predicting mortality among patients hospitalized for heart failure: derivation and validation of a clinical model. JAMA 290(19):2581–2587. Epub 2003/11/20

    Article  CAS  PubMed  Google Scholar 

  10. Levy WC, Mozaffarian D, Linker DT, Sutradhar SC, Anker SD, Cropp AB et al (2006) The Seattle Heart Failure Model: prediction of survival in heart failure. Circulation 113(11):1424–1433. Epub 2006/03/15

    Article  PubMed  Google Scholar 

  11. Wu C, Camacho FT, Wechsler AS, Lahey S, Culliford AT, Jordan D et al (2012) Risk score for predicting long-term mortality after coronary artery bypass graft surgery. Circulation 125(20):2423–2430. Epub 2012/05/02

    Article  PubMed  PubMed Central  Google Scholar 

  12. O’Boyle F, Mediratta N, Fabri B, Pullan M, Chalmers J, McShane J et al (2012) Long-term survival after coronary artery bypass surgery stratified by EuroSCORE. Eur J Cardiothorac Surg 42(1):101–106. discussion 6–7. Epub 2012/01/06

    Article  PubMed  Google Scholar 

  13. Fonarow GC, Albert NM, Curtis AB, Gheorghiade M, Heywood JT, Liu Y et al (2011) Associations between outpatient heart failure process-of-care measures and mortality. Circulation 123(15):1601–1610. Epub 2011/04/06

    Article  PubMed  Google Scholar 

  14. Mylotte D, Pilote L, Ionescu-Ittu R, Abrahamowicz M, Khairy P, Therrien J et al (2014) Specialized adult congenital heart disease care: the impact of policy on mortality. Circulation 129(18):1804–1812

    Article  PubMed  Google Scholar 

  15. Benza RL, Gomberg-Maitland M, Miller DP, Frost A, Frantz RP, Foreman AJ et al (2012) The REVEAL Registry risk score calculator in patients newly diagnosed with pulmonary arterial hypertension. Chest 141(2):354–362. Epub 2011/06/18

    Article  PubMed  Google Scholar 

  16. Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V et al (2010) Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation 122(2):156–163. Epub 2010/06/30

    Article  PubMed  Google Scholar 

  17. Lee WT, Ling Y, Sheares KK, Pepke-Zaba J, Peacock AJ, Johnson MK (2012) Predicting survival in pulmonary arterial hypertension in the UK. Eur Respir J 40(3):604–611. Epub 2012/05/05

    Article  PubMed  Google Scholar 

  18. Thenappan T, Shah SJ, Rich S, Tian L, Archer SL, Gomberg-Maitland M (2010) Survival in pulmonary arterial hypertension: a reappraisal of the NIH risk stratification equation. Eur Respir J 35(5):1079–1087. Epub 2009/12/25

    Article  CAS  PubMed  Google Scholar 

  19. Partin C (2003) The evolution of Eisenmenger's eponymic enshrinement. Am J Cardiol 92(10):1187–1191. Epub 2003/12/12

    Article  PubMed  Google Scholar 

  20. Wood P (1958) The Eisenmenger syndrome or pulmonary hypertension with reversed central shunt. Br Med J 2(5099):755–762. Epub 1958/09/27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hopkins WE, Waggoner AD (2002) Severe pulmonary hypertension without right ventricular failure: the unique hearts of patients with Eisenmenger syndrome. Am J Cardiol 89(1):34–38. Epub 2002/01/10

    Article  PubMed  Google Scholar 

  22. Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA et al (2009) Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J 30(20):2493–2537. Epub 2009/08/29

    Article  PubMed  Google Scholar 

  23. Dimopoulos K, Inuzuka R, Goletto S, Giannakoulas G, Swan L, Wort SJ et al (2010) Improved survival among patients with Eisenmenger syndrome receiving advanced therapy for pulmonary arterial hypertension. Circulation 121(1):20–25. Epub 2009/12/23

    Article  PubMed  Google Scholar 

  24. Webb G, Gatzoulis MA (2006) Atrial septal defects in the adult: recent progress and overview. Circulation 114(15):1645–1653

    Article  PubMed  Google Scholar 

  25. Kempny A, Sørensen Hjortshøj C, Hong G, Li W, Opotowsky A, Landzberg M, et al. (2016) Predictors of death in adult patients with Eisenmenger syndrome. In: 10th National Heart and Lung Institute Annual Postgraduate Research Day, Imperial College, London

    Google Scholar 

  26. Moceri P, Kempny A, Liodakis E, Alonso Gonzales R, Germanakis I, Diller G-P et al (2015) Physiological differences between various types of Eisenmenger syndrome and relation to outcome. Int J Cardiol 179:455–460

    Article  PubMed  Google Scholar 

  27. Diller GP, Lammers AE, Haworth SG, Dimopoulos K, Derrick G, Bonhoeffer P et al (2010) A modelling study of atrial septostomy for pulmonary arterial hypertension, and its effect on the state of tissue oxygenation and systemic blood flow. Cardiol Young 20(1):25–32. Epub 2010/02/11

    Article  PubMed  Google Scholar 

  28. Diller G-P, Kempny A, Inuzuka R, Radke R, Wort SJ, Baumgartner H et al (2014) Survival prospects of treatment naïve patients with Eisenmenger: a systematic review of the literature and report of own experience. Heart 100(17):1366–1372

    Article  PubMed  Google Scholar 

  29. Raphael C, Briscoe C, Davies J, Ian Whinnett Z, Manisty C, Sutton R et al (2007) Limitations of the New York Heart Association functional classification system and self-reported walking distances in chronic heart failure. Heart 93(4):476–482. Epub 2006/09/29

    Article  PubMed  Google Scholar 

  30. Spoladore R, Fragasso G, Montanaro C, D'Amato R, Palloshi A, Salerno A et al (2010) NYHA Class II subgrouping: correlation with left ventricular dysfunction questionnaire (LVD-36) and ejection fraction. Minerva Cardioangiol 58(4):441–448. Epub 2010/10/13

    CAS  PubMed  Google Scholar 

  31. Diller GP, Dimopoulos K, Okonko D, Li W, Babu-Narayan SV, Broberg CS et al (2005) Exercise intolerance in adult congenital heart disease: comparative severity, correlates, and prognostic implication. Circulation 112(6):828–835. Epub 2005/08/03

    Article  PubMed  Google Scholar 

  32. Kempny A, Dimopoulos K, Alonso-Gonzalez R, Alvarez-Barredo M, Tutarel O, Uebing A et al (2013) Six-minute walk test distance and resting oxygen saturations but not functional class predict outcome in adult patients with Eisenmenger syndrome. Int J Cardiol 168(5):4784–4789. Epub 2013/08/22

    Article  PubMed  Google Scholar 

  33. Dimopoulos K, Giannakoulas G, Wort SJ, Gatzoulis MA (2008) Pulmonary arterial hypertension in adults with congenital heart disease: distinct differences from other causes of pulmonary arterial hypertension and management implications. Curr Opin Cardiol 23(6):545–554. Epub 2008/10/03

    Article  PubMed  Google Scholar 

  34. Irisawa H, Takeuchi K, Inui N, Miyakawa S, Morishima Y, Mizushima T et al (2014) Incremental shuttle walk test as a valuable assessment of exercise performance in patients with pulmonary arterial hypertension. Circ J 78(1):215–221

    Article  PubMed  Google Scholar 

  35. Galiè N, Beghetti M, Gatzoulis MA, Granton J, Berger RMF, Lauer A et al (2006) Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study. Circulation 114(1):48–54

    Article  PubMed  Google Scholar 

  36. Hoeper MM, Schwarze M, Ehlerding S, Adler-Schuermeyer A, Spiekerkoetter E, Niedermeyer J et al (2000) Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. N Engl J Med 342(25):1866–1870

    Article  CAS  PubMed  Google Scholar 

  37. ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories (2002) ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 166(1):111–117

    Article  Google Scholar 

  38. Dimopoulos K, Giannakoulas G, Bendayan I, Liodakis E, Petraco R, Diller GP et al (2013) Cardiothoracic ratio from postero-anterior chest radiographs: a simple, reproducible and independent marker of disease severity and outcome in adults with congenital heart disease. Int J Cardiol 166(2):453–457. Epub 2011/12/06

    Article  PubMed  Google Scholar 

  39. Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A et al (2016) 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J 37(1):67–119. Epub 2015/09/01

    Article  PubMed  Google Scholar 

  40. Grapsa J, Pereira Nunes MC, Tan TC, Cabrita IZ, Coulter T, Smith BC, et al. (2015) Echocardiographic and hemodynamic predictors of survival in precapillary pulmonary hypertension: seven-year follow-up. Circ Cardiovasc Imaging 8(6). Epub 2015/06/13

    Google Scholar 

  41. Moceri P, Dimopoulos K, Liodakis E, Germanakis I, Kempny A, Diller GP et al (2012) Echocardiographic predictors of outcome in eisenmenger syndrome. Circulation 126(12):1461–1468. Epub 2012/08/18

    Article  PubMed  Google Scholar 

  42. van Veldhuisen DJ, Anker SD, Ponikowski P, Macdougall IC (2011) Anemia and iron deficiency in heart failure: mechanisms and therapeutic approaches. Nat Rev Cardiol 8(9):485–493. Epub 2011/06/02

    Article  PubMed  Google Scholar 

  43. Van De Bruaene A, Delcroix M, Pasquet A, De Backer J, De Pauw M, Naeije R et al (2011) Iron deficiency is associated with adverse outcome in Eisenmenger patients. Eur Heart J 32(22):2790–2799. Epub 2011/05/25

    Article  Google Scholar 

  44. Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H et al (2009) Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 361(25):2436–2448. Epub 2009/11/19

    Article  CAS  PubMed  Google Scholar 

  45. Ponikowski P, van Veldhuisen DJ, Comin-Colet J, Ertl G, Komajda M, Mareev V et al (2015) Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiencydagger. Eur Heart J 36(11):657–668. Epub 2014/09/02

    Article  CAS  PubMed  Google Scholar 

  46. Viethen T, Gerhardt F, Dumitrescu D, Knoop-Busch S, ten Freyhaus H, Rudolph TK et al (2014) Ferric carboxymaltose improves exercise capacity and quality of life in patients with pulmonary arterial hypertension and iron deficiency: a pilot study. Int J Cardiol 175(2):233–239. Epub 2014/06/02

    Article  PubMed  Google Scholar 

  47. Tay EL, Peset A, Papaphylactou M, Inuzuka R, Alonso-Gonzalez R, Giannakoulas G et al (2011) Replacement therapy for iron deficiency improves exercise capacity and quality of life in patients with cyanotic congenital heart disease and/or the Eisenmenger syndrome. Int J Cardiol 151(3):307–312. Epub 2010/06/29

    Article  PubMed  Google Scholar 

  48. Dimopoulos K, Diller GP, Koltsida E, Pijuan-Domenech A, Papadopoulou SA, Babu-Narayan SV et al (2008) Prevalence, predictors, and prognostic value of renal dysfunction in adults with congenital heart disease. Circulation 117(18):2320–2328. Epub 2008/04/30

    Article  PubMed  Google Scholar 

  49. Dimopoulos K, Diller GP, Petraco R, Koltsida E, Giannakoulas G, Tay EL et al (2010) Hyponatraemia: a strong predictor of mortality in adults with congenital heart disease. Eur Heart J 31(5):595–601. Epub 2009/11/26

    Article  CAS  PubMed  Google Scholar 

  50. Schuuring MJ, van Riel AC, Vis JC, Duffels MG, van Straalen JP, Boekholdt SM et al (2013) High-sensitivity troponin T is associated with poor outcome in adults with pulmonary arterial hypertension due to congenital heart disease. Congenit Heart Dis 8(6):520–526. Epub 2012/12/18

    Article  PubMed  Google Scholar 

  51. Torbicki A, Kurzyna M, Kuca P, Fijalkowska A, Sikora J, Florczyk M et al (2003) Detectable serum cardiac troponin T as a marker of poor prognosis among patients with chronic precapillary pulmonary hypertension. Circulation 108(7):844–848. Epub 2003/08/06

    Article  CAS  PubMed  Google Scholar 

  52. Scognamiglio G, Kempny A, Price LC, Alonso-Gonzalez R, Marino P, Swan L et al (2014) C-reactive protein in adults with pulmonary arterial hypertension associated with congenital heart disease and its prognostic value. Heart 100(17):1335–1341

    Article  CAS  PubMed  Google Scholar 

  53. Quarck R, Nawrot T, Meyns B, Delcroix M (2009) C-reactive protein: a new predictor of adverse outcome in pulmonary arterial hypertension. J Am Coll Cardiol 53(14):1211–1218. Epub 2009/04/04

    Article  CAS  PubMed  Google Scholar 

  54. Verma S, Wang CH, Li SH, Dumont AS, Fedak PW, Badiwala MV et al (2002) A self-fulfilling prophecy: C-reactive protein attenuates nitric oxide production and inhibits angiogenesis. Circulation 106(8):913–919. Epub 2002/08/21

    Article  CAS  PubMed  Google Scholar 

  55. Arquès S, Ambrosi P, Gélisse R, Luccioni R, Habib G (2003) Hypoalbuminemia in elderly patients with acute diastolic heart failure. J Am Coll Cardiol 42(4):712–716

    Article  PubMed  Google Scholar 

  56. Cowger J, Sundareswaran K, Rogers JG, Park SJ, Pagani FD, Bhat G et al (2013) Predicting survival in patients receiving continuous flow left ventricular assist devices: the HeartMate II risk score. J Am Coll Cardiol 61(3):313–321

    Article  CAS  PubMed  Google Scholar 

  57. Uthamalingam S, Kandala J, Daley M, Patvardhan E, Capodilupo R, Moore SA et al (2010) Serum albumin and mortality in acutely decompensated heart failure. Am Heart J 160(6):1149–1155

    Article  CAS  PubMed  Google Scholar 

  58. Kempny A, Diller GP, Alonso-Gonzalez R, Uebing A, Rafiq I, Li W et al (2015) Hypoalbuminemia predicts outcome in adult patients with congenital heart disease. Heart 101(9):699–705. Epub 2015/03/05

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Hesse B, Parving HH, Lund-Jacobsen H, Noer I (1976) Transcapillary escape rate of albumin and right atrial pressure in chronic congestive heart failure before and after treatment. Circ Res 39(3):358–362

    Article  CAS  PubMed  Google Scholar 

  60. Diller GP, van Eijl S, Okonko DO, Howard LS, Ali O, Thum T et al (2008) Circulating endothelial progenitor cells in patients with Eisenmenger syndrome and idiopathic pulmonary arterial hypertension. Circulation 117(23):3020–3030. Epub 2008/06/04

    Article  CAS  PubMed  Google Scholar 

  61. Yusen RD et al (2015) The Registry of the International Society for Heart and Lung Transplantation: Thirtysecond Official Adult Lung and Heart-Lung Transplantation Report-2015; Focus Theme: Early Graft Failure. J Heart Lung Transplant 34(10):1264–1277

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Adult Congenital Heart Centre and National Centre for Pulmonary Hypertension, Royal Brompton Hospital, Imperial College, London, UK

    Aleksander Kempny M.D.

Authors
  1. Aleksander Kempny M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aleksander Kempny M.D. .

Editor information

Editors and Affiliations

  1. Adult Congenital Heart Centre and Centre for Pulmonary Hypertension, Royal Brompton Hospital and Imperial College, London, United Kingdom

    Konstantinos Dimopoulos

  2. University Hospital, Münster, Germany

    Gerhard-Paul Diller

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Kempny, A. (2017). Prognostication in PAH–CHD. In: Dimopoulos, K., Diller, GP. (eds) Pulmonary Hypertension in Adult Congenital Heart Disease. Congenital Heart Disease in Adolescents and Adults. Springer, Cham. https://doi.org/10.1007/978-3-319-46028-4_21

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-46028-4_21

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-46026-0

  • Online ISBN: 978-3-319-46028-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation