Skip to main content
SpringerLink
Log in

Hemodynamic Evaluation of Children with Persistent or Recurrent Pulmonary Arterial Hypertension Following Complete Repair of Congenital Heart Disease

  • Original Article
  • Published:
Pediatric Cardiology Aims and scope Submit manuscript

Abstract

Persistent or recurrent pulmonary arterial hypertension (PAH) following complete surgical repair of congenital heart disease (CHD) represents one of the largest group of PAH associated with CHD (PAH-CHD) in recent registry studies and seems to have a particularly poor prognosis. However, little is known about this fourth clinical subclass of PAH-CHD, especially in children. The purpose of this study was to assess specific characteristics of invasive hemodynamics of this disease in children, including acute vasodilator testing (AVT) and pulmonary endothelial function (PEF) and to compare to patients with idiopathic PAH (IPAH), who usually present with a similar fatal clinical course. Thirty-two children with PAH were included in the study, twelve of these patients had PAH-CHD subclass 4 (mean age 8.0 ± 3.4 years) and twenty children had IPAH (mean age 8.6 ± 4.4 years). Cardiac catheterization was performed in all children, including AVT and PEF. PEF was assessed by changes in pulmonary blood flow in response to acetylcholine (Ach) using Doppler flow measurements. Pulmonary flow reserve (PFR) was calculated as the ratio of pulmonary blood flow velocity in response to Ach relative to baseline values. At baseline, the ratio of mean PA pressure to mean systemic arterial pressure (mPAP/mSAP) was comparably high in both groups (0.78 ± 0.32 vs. 0.80 ± 0.22), while the indexed pulmonary vascular resistance (PVRI) was significantly lower in the PAH-CHD group (12.6 ± 6.8 WUxm2) compared to IPAH patients (19.9 ± 10.6 WUxm2) (p = 0.04). Cardiac index was significantly higher in the PAH-CHD group (4.19 ± 1.09 l/min/m2 vs. 3.23 ± 0.76) (p = 0.017). However, AVT revealed a significantly larger maximum response (percentage of fall of PVR/SVR ratio during AVT) in the IPAH group (37 ± 22%) compared to the PAH-CHD group (13 ± 23%) (p = 0.017). PEF showed no significant difference between both patient groups (PFR 1.69 ± 0.71 vs. 1.73 ± 0.68) (p = 0.76). Our study demonstrates significant pulmonary vascular disease in children with persistent or recurrent PAH following complete surgical repair of CHD similar to IPAH patients. Although baseline measures appeared to be more favorable, pulmonary vasoreactivity was markedly impaired in PAH-CHD subclass 4, which may contribute to its negative impact on the long-term outcome of this patient group.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Berger RM, Beghetti M, Humpl T, Raskob GE, Ivy DD, Jing ZC, Bonnet D, Schulze-Neick I, Barst RJ (2012) Clinical features of paediatric pulmonary hypertension: a registry study. Lancet 379(9815):537–546. doi:10.1016/S0140-6736(11)61621-8

    Article  PubMed  PubMed Central  Google Scholar 

  2. Manes A, Palazzini M, Leci E, Bacchi Reggiani ML, Branzi A, Galie 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. doi:10.1093/eurheartj/eht072

    Article  PubMed  Google Scholar 

  3. Ghofrani HA, Galie N, Grimminger F, Grunig E, Humbert M, Jing ZC, Keogh AM, Langleben D, Kilama MO, Fritsch A, Neuser D, Rubin LJ (2013) Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med 369(4):330–340. doi:10.1056/NEJMoa1209655

    Article  CAS  PubMed  Google Scholar 

  4. Pulido T, Adzerikho I, Channick RN, Delcroix M, Galie N, Ghofrani HA, Jansa P, Jing ZC, Le Brun FO, Mehta S, Mittelholzer CM, Perchenet L, Sastry BK, Sitbon O, Souza R, Torbicki A, Zeng X, Rubin LJ, Simonneau G (2013) Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med 369(9):809–818. doi:10.1056/NEJMoa1213917

    Article  CAS  PubMed  Google Scholar 

  5. Sitbon O, Channick R, Chin KM, Frey A, Gaine S, Galie N, Ghofrani HA, Hoeper MM, Lang IM, Preiss R, Rubin LJ, Di Scala L, Tapson V, Adzerikho I, Liu J, Moiseeva O, Zeng X, Simonneau G, McLaughlin VV, Investigators G (2015) Selexipag for the treatment of pulmonary arterial hypertension. N Engl J Med 373(26):2522–2533. doi:10.1056/NEJMoa1503184

    Article  CAS  PubMed  Google Scholar 

  6. Rosenkranz S, Ghofrani HA, Beghetti M, Ivy D, Frey R, Fritsch A, Weimann G, Saleh S, Apitz C (2015) Riociguat for pulmonary arterial hypertension associated with congenital heart disease. Heart 101(22):1792–1799. doi:10.1136/heartjnl-2015-307832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Latus H, Delhaas T, Schranz D, Apitz C (2015) Treatment of pulmonary arterial hypertension in children. Nat Rev Cardiol 12(4):244–254. doi:10.1038/nrcardio.2015.6

    Article  CAS  PubMed  Google Scholar 

  8. Apitz C, Hansmann G, Schranz D (2016) Hemodynamic assessment and acute pulmonary vasoreactivity testing in the evaluation of children with pulmonary vascular disease. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK. Heart 102(Suppl 2):ii23–ii29. doi:10.1136/heartjnl-2014-307340

    Article  CAS  PubMed  Google Scholar 

  9. Zimmermann R, Kreuder J, Michel-Behnke I, Voelkel NF, Schranz D (2006) Pulmonary flow reserve in children with idiopathic pulmonary arterial hypertension: implications for diagnosis and therapy. Eur J Med Res 11(5):208–213

    CAS  PubMed  Google Scholar 

  10. Apitz C, Zimmermann R, Kreuder J, Jux C, Latus H, Pons-Kuhnemann J, Kock I, Bride P, Kreymborg KG, Michel-Behnke I, Schranz D (2012) Assessment of pulmonary endothelial function during invasive testing in children and adolescents with idiopathic pulmonary arterial hypertension. J Am Coll Cardiol 60(2):157–164. doi:10.1016/j.jacc.2012.04.010

    Article  PubMed  Google Scholar 

  11. Latus H, Werz A, Kock I, Rupp S, Kerst G, Kreuder J, Schranz D, Apitz C (2014) Systemic arterial endothelial function in children and young adults with idiopathic pulmonary arterial hypertension: is there a relation to pulmonary endothelium-dependent relaxation? Pediatr Cardiol 35(5):844–850. doi:10.1007/s00246-014-0864-z

    Article  PubMed  Google Scholar 

  12. Haworth SG, Hislop AA (2009) Treatment and survival in children with pulmonary arterial hypertension: the UK Pulmonary Hypertension Service for Children 2001–2006. Heart 95(4):312–317. doi:10.1136/hrt.2008.150086

    Article  CAS  PubMed  Google Scholar 

  13. Douwes JM, Humpl T, Bonnet D, Beghetti M, Ivy DD, Berger RM, Investigators T (2016) Acute vasodilator response in pediatric pulmonary arterial hypertension: current clinical practice from the TOPP REGISTRY. J Am Coll Cardiol 67(11):1312–1323. doi:10.1016/j.jacc.2016.01.015

    Article  PubMed  Google Scholar 

  14. van Loon RL, Roofthooft MT, Hillege HL, ten Harkel AD, van Osch-Gevers M, Delhaas T, Kapusta L, Strengers JL, Rammeloo L, Clur SA, Mulder BJ, Berger RM (2011) Pediatric pulmonary hypertension in the Netherlands: epidemiology and characterization during the period 1991 to 2005. Circulation 124(16):1755–1764. doi:10.1161/CIRCULATIONAHA.110.969584

    Article  PubMed  Google Scholar 

  15. Douwes JM, van Loon RL, Hoendermis ES, Vonk-Noordegraaf A, Roofthooft MT, Talsma MD, Hillege HL, Berger RM (2011) Acute pulmonary vasodilator response in paediatric and adult pulmonary arterial hypertension: occurrence and prognostic value when comparing three response criteria. Eur Heart J 32(24):3137–3146. doi:10.1093/eurheartj/ehr282

    Article  PubMed  Google Scholar 

  16. Hall SM, Haworth SG (1992) Onset and evolution of pulmonary vascular disease in young children: abnormal postnatal remodelling studied in lung biopsies. J Pathol 166(2):183–193. doi:10.1002/path.1711660216

    Article  CAS  PubMed  Google Scholar 

  17. Haworth SG (1984) Pulmonary vascular disease in different types of congenital heart disease. Implications for interpretation of lung biopsy findings in early childhood. Br Heart J 52(5):557–571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hallidie-Smith KA, Hollman A, Cleland WP, Bentall HH, Goodwin JF (1969) Effects of surgical closure of ventricular septal defects upon pulmonary vascular disease. Br Heart J 31(2):246–260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hallidie-Smith KA, Wilson RS, Hart A, Zeidifard E (1977) Functional status of patients with large ventricular septal defect and pulmonary vascular disease 6 to 16 years after surgical closure of their defect in childhood. Br Heart J 39(10):1093–1101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Heath D, Edwards JE (1958) The pathology of hypertensive pulmonary vascular disease; a description of six grades of structural changes in the pulmonary arteries with special reference to congenital cardiac septal defects. Circulation 18(4 Part 1):533–547

    Article  CAS  PubMed  Google Scholar 

  21. Rabinovitch M, Keane JF, Norwood WI, Castaneda AR, Reid L (1984) Vascular structure in lung tissue obtained at biopsy correlated with pulmonary hemodynamic findings after repair of congenital heart defects. Circulation 69(4):655–667

    Article  CAS  PubMed  Google Scholar 

  22. Wessel DL, Adatia I, Giglia TM, Thompson JE, Kulik TJ (1993) Use of inhaled nitric oxide and acetylcholine in the evaluation of pulmonary hypertension and endothelial function after cardiopulmonary bypass. Circulation 88(5 Pt 1):2128–2138

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pediatric Heart Center, Justus-Liebig-University Giessen, Feulgenstr. 10-12, 35392, Giessen, Germany

    Heiner Latus, Inken Wagner, Stefan Ostermayer, Gunter Kerst, Joachim Kreuder, Dietmar Schranz & Christian Apitz

  2. Division of Pediatric Cardiology, University Children’s Hospital Ulm, Eythstr. 24, 89075, Ulm, Germany

    Christian Apitz

Authors
  1. Heiner Latus
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Inken Wagner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stefan Ostermayer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gunter Kerst
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Joachim Kreuder
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dietmar Schranz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Christian Apitz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Heiner Latus or Christian Apitz.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Latus, H., Wagner, I., Ostermayer, S. et al. Hemodynamic Evaluation of Children with Persistent or Recurrent Pulmonary Arterial Hypertension Following Complete Repair of Congenital Heart Disease. Pediatr Cardiol 38, 1342–1349 (2017). https://doi.org/10.1007/s00246-017-1667-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00246-017-1667-9

Keywords

Search

Navigation