Pediatric Cardiology

, Volume 38, Issue 7, pp 1342–1349 | Cite as

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

  • Heiner Latus
  • Inken Wagner
  • Stefan Ostermayer
  • Gunter Kerst
  • Joachim Kreuder
  • Dietmar Schranz
  • Christian Apitz
Original Article

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.

Keywords

Idiopathic pulmonary arterial hypertension Pulmonary arterial hypertension associated with congenital heart disease Endothelial dysfunction Pulmonary flow reserve 

Notes

Compliance with Ethical Standards

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.

References

  1. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 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 CrossRefPubMedGoogle Scholar
  3. 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 CrossRefPubMedGoogle Scholar
  4. 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 CrossRefPubMedGoogle Scholar
  5. 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 CrossRefPubMedGoogle Scholar
  6. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 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 CrossRefPubMedGoogle Scholar
  8. 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 CrossRefPubMedGoogle Scholar
  9. 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):208–213PubMedGoogle Scholar
  10. 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 CrossRefPubMedGoogle Scholar
  11. 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 CrossRefPubMedGoogle Scholar
  12. 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 CrossRefPubMedGoogle Scholar
  13. 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 CrossRefPubMedGoogle Scholar
  14. 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 CrossRefPubMedGoogle Scholar
  15. 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 CrossRefPubMedGoogle Scholar
  16. 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 CrossRefPubMedGoogle Scholar
  17. 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):557–571CrossRefPubMedPubMedCentralGoogle Scholar
  18. 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):246–260CrossRefPubMedPubMedCentralGoogle Scholar
  19. 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):1093–1101CrossRefPubMedPubMedCentralGoogle Scholar
  20. 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):533–547CrossRefPubMedGoogle Scholar
  21. 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):655–667CrossRefPubMedGoogle Scholar
  22. 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):2128–2138CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Heiner Latus
    • 1
  • Inken Wagner
    • 1
  • Stefan Ostermayer
    • 1
  • Gunter Kerst
    • 1
  • Joachim Kreuder
    • 1
  • Dietmar Schranz
    • 1
  • Christian Apitz
    • 1
    • 2
  1. 1.Pediatric Heart CenterJustus-Liebig-University GiessenGiessenGermany
  2. 2.Division of Pediatric CardiologyUniversity Children’s Hospital UlmUlmGermany

Personalised recommendations