Skip to main content
SpringerLink
Log in

Initial experience with bosentan (Tracleer®) as treatment for pulmonary arterial hypertension (PAH) due to congenital heart disease in infants and young children

Erste Erfahrungen mit Bosentan (Tracleer®) zur Behandlung der pulmonal-arteriellen Hypertension von Säuglingen und Kleinkindern mit angeborenem Herzfehler

  • ORIGINAL PAPER
  • Published:
Zeitschrift für Kardiologie Aims and scope Submit manuscript

Zusammenfassung

Hintergrund

Bosentan, ein dualer Endothelin-Rezeptor-Antagonist, ist bei der Behandlung der idiopatischen (primären) Form der pulmonalarteriellen Hypertonie (PAH) als effektive Therapieform eingesetzt worden. Wir haben Bosentan im Rahmen eines Heilversuches bei Säuglingen und Kleinkindern eingesetzt, welche bereits präoperativ einen erhöhten Lungengefäßwiderstand und damit eine Kontraindikation zur operativen Korrektur entwickelt hatten, oder bei schwerer persistierender postoperative pulmonal-arterieller Hypertension Zeichen der Rechtsherz-Insuffizienz mit Minderung der körperlichen Belastbarkeit zeigten.

Patienten und Methodik

Sieben Kinder mit PAH und angeborenem Herzfehlern (mittleres Alter 3,8 Jahre, Bereich 1,5 bis 6,4 Jahre) erhielten 3 mg/kg/d Bosentan (Tracleer®) oral. Klinische, echokardiographische und hämodynamische Daten sowie übliche Laborparameter wurden vor und unter Behandlung gemessen. Leberzell-Enzyme wurden routinemäßig monatlich bestimmt.

Ergebnisse

Die mittlere Behandlungsdauer mit Bosentan war 8,6±5 Monate. Während dieser Zeit ereigneten sich keine signifikanten Nebenwirkungen. Der klinische Zustand blieb stabil oder verbesserte sich bei allen Patienten: die NYHA-Klasse erholte sich von 2,6±0,6 auf 1,7±0,6 (p<0,05). Der rechtsventrikuläre systolische Druck (RVSP) fiel von 96±11 mmHg auf 71±26 mmHg ab (p<0,05).

Schlussfolgerung

Die Behandlung mit Bosentan wurde bei Säuglingen und Kleinkindern mit PAH bei angeborenen Herzfehlern gut vertragen ohne wesentliche Nebenwirkungen und bewirkte eine Stabilisierung des klinischen Zustandes. Eine deutliche Verminderung des rechtsventrikulären Druckes konnte gezeigt werden. Das Dosis-Regime erscheint somit adäquat und sicher für die Behandlung von Patienten in diesem Alter und scheint in einer Senkung des pathologisch erhöhten Lungengefäßwiderstandes zu resultieren.

Summary

Introduction

Bosentan, a dual endothelin-receptor antagonist, has been shown to be an effective treatment option in patients with the idiopathic form of pulmonary arterial hypertension (PAH). We used bosentan as compassionate treatment in infants and young children with congenital heart disease (CHD) who had a) PAH preoperatively representing a contraindication to corrective surgery or b) persisting PAH after corrective surgery causing right heart failure and reduced exercise tolerance.

Methods

Seven children with PAH due to CHD (median age 3.8 years; range 1.5 to 6.4 years) received 3 mg/kg/d bosentan (Tracleer®) orally. Clinical, echocardiographic and hemodynamic parameters were measured and laboratory tests performed before treatment and during steady state while on treatment. Routine liver function parameters were monitored monthly.

Results

Mean bosentan treatment time was 8.6±5 months. During bosentan therapy there were no significant adverse events. The clinical status remained stable or improved in all patients: NYHA class decreased from 2.6±0.6 to 1.7±0.6 (p<0.05). This was associated with a mean reduction of the right ventricular systolic pressure (RVSP) from 96±11 mmHg to 71±26 mmHg (p<0.05).

Conclusions

Treatment with bosentan in infants and young children with PAH due to congenital heart disease was tolerated without significant side effects and resulted in stabilization of clinical status. A significant reduction in right ventricular systolic pressure (RVSP) could be demonstrated. These results suggest that the dose regimen used is appropriate and safe for the treatment of infants and children with PAH, resulting in a reduction of pathologically increased pulmonary vascular resistance.

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

References

  1. Barst RJ, Ivy D, Dingemanse J, Widlitz A, Schmitt K, Doran A, Bingaman D, Nguyen N, Gaitonde M, van Giersbergen PL (2003) Pharmacokinetics, safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension. Clin Pharmacol Ther 73(4):372–382

    Article  PubMed  Google Scholar 

  2. Chen SJ, Chen YF, Meng QC, Durand J, Dicarlo VS, Oparil S (1995) Endothelin-receptor antagonist bosentan prevents and reverses hypoxic pulmonary hypertension in rats. J Appl Physiol 79(6):2122–2131

    PubMed  Google Scholar 

  3. Fattinger K, Funk C, Pantze M, Weber C, Reichen J, Stieger B, Meier PJ (2001) The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: a potential mechanism for hepatic adverse reactions. Clin Pharmacol Ther 69(4):223–231

    Article  PubMed  Google Scholar 

  4. Ghofrani HA, Rose F, Schermuly RT, Olschewski H, Wiedemann R, Kreckel A, Weissmann N, Ghofrani S, Enke B, Seeger W, Grimminger F (2003) Oral sildenafil as long-term adjunct therapy to inhaled iloprost in severe pulmonary arterial hypertension. J Am Coll Cardiol 42(1):158–164

    Article  PubMed  Google Scholar 

  5. Krum H, Charlon V, Widmann T, Packer M (1999) Long-term, open-label experience with an endothelin receptor antagonist, bosentan, in patients with severe chronic heart failure. Circulation 100(Suppl I):646

    Google Scholar 

  6. Luscher TF, Barton M (2000) Endothelins and endothelin receptor antagonists: therapeutic considerations for a novel class of cardiovascular drugs. Circulation 102(19):2434–2440

    PubMed  Google Scholar 

  7. Mebazaa A, Karpati P, Renaud E, Algotsson L (2004) Acute right ventricular failure–from pathophysiology to new treatments. Intensive Care Med 30(2):185–196

    Article  PubMed  Google Scholar 

  8. Olschewski H, Seeger W, Ghofrani HA, Schmehl T, Winkler J, Wilkens H, Hoper MM, Behr J, Kleber FX (2000) Inhaled iloprost to treat severe pulmonary hypertension. An uncontrolled trial. German PPH Study Group. Pneumologie 54(6):222–224

    Article  PubMed  Google Scholar 

  9. Peacock A, Naeije R, Galie N, Reeves JT (2004) End points in pulmonary arterial hypertension: the way forward. Eur Respir J 23(6):947–953

    PubMed  Google Scholar 

  10. Rosenzweig EB, Kerstein D, Barst RJ (1999) Long-term prostacyclin for pulmonary hypertension with associated congenital heart defects. Circulation 99(14):1858–1865

    PubMed  Google Scholar 

  11. Ross RD, Bollinger RO, Pinsky WW (1992) Grading the severity of congestive heart failure in infants. Pediatr Cardiol 13(2):72–75

    Article  PubMed  Google Scholar 

  12. Rubin LJ, Badesch DB, Barst RJ, Galie N, Black CM, Keogh A, Pulido T, Frost A, Roux S, Leconte I, Landzberg M, Simonneau G (2002) Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 346(12):896–903

    Article  PubMed  Google Scholar 

  13. Sitbon O, Badesch DB, Channick RN, Frost A, Robbins IM, Simonneau G, Tapson VF, Rubin LJ (2003) Effects of the dual endothelin receptor antagonist bosentan in patients with pulmonary arterial hypertension: a 1-year follow-up study. Chest 124(1):247–254

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinik für Angeborene Herzfehler/Kinderkardiologie, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    N. Gilbert, Y.-C. Luther, O. Miera, N. Nagdyman, P. Ewert, F. Berger, P. E. Lange & I. Schulze-Neick

Authors
  1. N. Gilbert
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y.-C. Luther
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O. Miera
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. Nagdyman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Ewert
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F. Berger
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P. E. Lange
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. I. Schulze-Neick
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I. Schulze-Neick.

Additional information

Die Arbeit wurde teilweise unterstützt durch das Kompetenznetz Angeborene Herzfehler, gefördert vom deutschen Bundesministerium für Bildung und Forschung (Förderkennzeichen: 01G10210).

This work was supported, in part, by the Kompetenznetz Angeborene Herzfehler (Competence Network for Congenital Heart Defects), and funded by the Federal Ministry of Education and Research (BMBF), FKZ 01G10210.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gilbert, N., Luther, YC., Miera, O. et al. Initial experience with bosentan (Tracleer®) as treatment for pulmonary arterial hypertension (PAH) due to congenital heart disease in infants and young children. ZS Kardiologie 94, 570–574 (2005). https://doi.org/10.1007/s00392-005-0266-6

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-005-0266-6

Schlüsselwörter

Key words

Search

Navigation