Hostname: page-component-cd9895bd7-jkksz Total loading time: 0 Render date: 2024-12-18T20:42:48.489Z Has data issue: false hasContentIssue false
  • English
  • Français

Treatment initiation in paediatric pulmonary hypertension: insights from a multinational registry

Published online by Cambridge University Press:  20 December 2016

Tilman Humpl ,
Rolf M. F. Berger ,
Eric D. Austin ,
Margrit S. Fasnacht Boillat ,
Damien Bonnet ,
Dunbar D. Ivy ,
Malgorzata Zuk ,
Maurice Beghetti  and
Ingram Schulze-Neick
Tilman Humpl*
Affiliation:
Department of Critical Care Medicine, Division of Cardiology, Hospital for Sick Children, Toronto, Canada
Rolf M. F. Berger
Affiliation:
Department of Pediatrics, University Medical Center Groningen, Groningen, The Netherlands
Eric D. Austin
Affiliation:
Division of Pulmonary Medicine, Vanderbilt Children’s Hospital, Nashville, United States of America
Margrit S. Fasnacht Boillat
Affiliation:
Klinik für Kinder- und Jugendmedizin, Kantonsspital Winterthur, Winterthur, Switzerland
Damien Bonnet
Affiliation:
Paediatric Cardiology, Université Paris Descartes, Necker Enfants Malades, Paris, France
Dunbar D. Ivy
Affiliation:
Department of Pediatrics, Section of Cardiology, University of Colorado, Aurora, United States of America
Malgorzata Zuk
Affiliation:
Department of Cardiology, Children’s Memorial Health Institute, Warsaw, Poland
Maurice Beghetti
Affiliation:
Children’s University Hospital, Geneva, Switzerland
Ingram Schulze-Neick
Affiliation:
Great Ormond Street Hospital for Sick Children, London, United Kingdom
*
Correspondence to Dr T. Humpl, Department of Critical Care Medicine, Division of Cardiology, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8. Tel: +1 416 813 4918; E-mail: [email protected].
Get access Rights & Permissions [Opens in a new window]

Abstract

Different treatment options for pulmonary hypertension have emerged in recent years, and evidence-based management strategies have improved quality of life and survival in adults. In children with pulmonary vascular disease, therapeutic algorithms are not so clearly defined; this study determined current treatment initiation in children with pulmonary hypertension in participating centres of a registry.

Through the multinational Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension registry, patient demographics, diagnosis, and treatment as judged and executed by the local physician were collected. Inclusion criteria were >3 months and <18 years of age and diagnostic cardiac catheterisation consistent with pulmonary hypertension (mean pulmonary arterial pressure ⩾25 mmHg, pulmonary vascular resistance index ⩾3 Wood units×m2, and mean pulmonary capillary wedge pressure ⩽12 mmHg).

At diagnostic catheterisation, 217/244 patients (88.9%) were treatment naïve for pulmonary hypertension-targeted therapy. Targeted therapy was initiated after catheterisation in 170 (78.3%) treatment-naïve patients. A total of 19 patients received supportive therapy, 28 patients were not started on therapy, and 26 patients (10.7%) were on targeted treatment before catheterisation. Among treatment-naïve subjects, treatment was initiated with one targeted drug (n=112, 51.6%), dual therapy (n=39, 18%) or triple-therapy (n=5, 2.3%), and calcium channel blockers with one targeted medication in one patient (0.5%). Phosphodiesterase inhibitors type 5 were used frequently; some patients with pulmonary hypertension related to lung disease received targeted therapy.

There is a diverse therapeutic approach for children with pulmonary hypertension with a need of better-defined treatment algorithms based on paediatric consensus for different aetiologies including the best possible diagnostic workup.

Keywords

Pulmonary hypertensionchildrentreatment
Type
Original Articles
Information
Cardiology in the Young , Volume 27 , Issue 6 , August 2017 , pp. 1123 - 1132
Check for updates
Copyright
© Cambridge University Press 2016 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

TOPP registry investigators (not listed in the author’s list) by country alphabetical order: R. Weintraub, Department of Cardiology, Royal Children’s Hospital, Melbourne, Australia. R. Geiger, Pediatric Cardiology, Innsbruck Medical University, Innsbruck, Austria. S. Mattos, Maternal-Fetal Cardiac Unit, Royal Portuguese Hospital, Recife, Brazil. Z. C. Jing and Z. Y. Han, Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. L. Sondergaard and T. Jensen, Rigshospitalet, Heart Center, University of Copenhagen, Copenhagen, Denmark. M. Levy, Paediatric Cardiology, Université Paris Descartes, Necker Enfants Malades, Paris, France. S. Mebus, German Heart Centre, Munich, Germany. C. Apitz, Universitätsklinikum Giessen, Giessen, Germany. A. Szatmari and L. Ablonczy, Pediatric Cardiac Center, Hungarian Institute of Cardiology, Budapest, Hungary. O. Milanesi and V. Favero, Dipartimento di Pediatria, Universita di Padova, Padova, Italy. B. T. Saji, Department of 1st Pediatrics, Division of Pediatric Cardiology, Toho University Medical Center Omori Hospital, Tokyo, Japan. T. Pulido and P. De La Garza, National Heart Institute, Mexico City, Mexico. J. M. Douwes, Center for Congenital Heart Diseases, Paediatric Cardiology, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, The Netherlands. H. Brun, Rikshospitalet, Section for Pediatric Cardiology, Oslo, Norway. L. Moll and K. Michalak, Polish Mothers Hospital Research Institute, Lodz, Poland. W. Kawalec, Department of Cardiology, Children´s Memorial Health Institute, Warsaw, Poland. R. Olgunturk and S. Serdar Kula, Gazi Universitesi Tip Fakultesi, Pediyatrik Kardiyoloji ABD, Ankara, Turkey. A. Dursun, Hacettepe University Ihsan Dogramaci, Tip Fak. Pediyatrik Kardiyoloji, Ankara, Turkey. R. W. Day, Division of Pediatric Cardiology, University of Utah, University Health Care, Salt Lake City, United States of America. G. B. Mallory, Baylor College of Medicine, Texas Children’s Hospital, Houston, United States of America. D. Yung, Children’s Hospital and Regional Medical Center, Seattle, United States of America. D. J. Moore, Division of Cardiology, Vanderbilt Children’s Hospital, Nashville, United States of America. A. M. Atz, Medical University of South Carolina, Charleston, United States of America. J. A. Feinstein, Stanford University Medical Center Packard Children’s Hospital, Palo Alto, United States of America.

References

1. Oudiz, RJ, Galie, N, Olschewski, H, et al. Long-term ambrisentan therapy for the treatment of pulmonary arterial hypertension. J Am Coll Cardiol 2009; 54: 1971–1981.CrossRefGoogle ScholarPubMed
2. Rubin, LJ, Badesch, DB, Fleming, TR, et al. Long-term treatment with sildenafil citrate in pulmonary arterial hypertension: the SUPER-2 study. Chest 2011; 140: 1274–1283.CrossRefGoogle ScholarPubMed
3. Hoeper, MM, Markevych, I, Spiekerkoetter, E, et al. Goal-oriented treatment and combination therapy for pulmonary arterial hypertension. Eur Respir J 2005; 26: 858–863.CrossRefGoogle ScholarPubMed
4. Barst, RJ, Ivy, D, Dingemanse, J, et al. Pharmacokinetics, safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension. Clin Pharmacol Ther 2003; 73: 372–382.CrossRefGoogle ScholarPubMed
5. Beghetti, M, Hoeper, MM, Kiely, DG, et al. Safety experience with bosentan in 146 children 2-11 years old with pulmonary arterial hypertension: results from the European Postmarketing Surveillance program. Pediatr Res 2008; 64: 200–204.CrossRefGoogle ScholarPubMed
6. Humpl, T, Reyes, JT, Holtby, H, et al. Beneficial effect of oral sildenafil therapy on childhood pulmonary arterial hypertension: twelve-month clinical trial of a single-drug, open-label, pilot study. Circulation 2005; 111: 3274–3280.CrossRefGoogle Scholar
7. Barst, RJ, Ivy, DD, Gaitan, G, et al. A randomized, double-blind, placebo-controlled, dose-ranging study of oral sildenafil citrate in treatment-naive children with pulmonary arterial hypertension. Circulation 2012; 125: 324–334.CrossRefGoogle ScholarPubMed
8. Cerro, MJ, Abman, S, Diaz, G, et al. A consensus approach to the classification of pediatric pulmonary hypertensive vascular disease: report from the PVRI Pediatric Taskforce, Panama 2011. Pulm Circ 2011; 1: 286–298.CrossRefGoogle Scholar
9. Berger, RM, Beghetti, M, Humpl, T, et al. Clinical features of paediatric pulmonary hypertension: a registry study. Lancet 2012; 379: 537–546.CrossRefGoogle ScholarPubMed
10. del Cerro Marin, MJ, Sabaté Rotés, A, Rodriguez Ogando, A, et al. Assessing pulmonary hypertensive vascular disease in childhood. Data from the Spanish registry. Am J Respir Crit Care Med 2014; 190: 1421–1429.CrossRefGoogle ScholarPubMed
11. Ivy, DD, Abman, SH, Barst, RJ, et al. Pediatric pulmonary hypertension. J Am Coll Cardiol 2013; 62: D117–D126.CrossRefGoogle ScholarPubMed
12. Consensus statement on the management of pulmonary hypertension in clinical practice in the UK and Ireland. Thorax 2008; 63 (Suppl 2): ii1–ii41.CrossRefGoogle Scholar
13. Tissot, C, Ivy, DD, Beghetti, M. Medical therapy for pediatric pulmonary arterial hypertension. J Pediatr 2010; 157: 528–532.CrossRefGoogle ScholarPubMed
14. Simonneau, G, Galie, N, Rubin, LJ, et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol 2004; 43: 5S–12S.CrossRefGoogle ScholarPubMed
15. Humbert, M, Barst, RJ, Robbins, IM, et al. Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur Respir J 2004; 24: 353–359.CrossRefGoogle ScholarPubMed
16. Kemp, K, Savale, L, O’Callaghan, DS, et al. Usefulness of first-line combination therapy with epoprostenol and bosentan in pulmonary arterial hypertension: an observational study. J Heart Lung Transplant 2012; 31: 150–158.CrossRefGoogle ScholarPubMed
17. Barst, RJ, McGoon, MD, Elliott, CG, et al. Survival in childhood pulmonary arterial hypertension: insights from the registry to evaluate early and long-term pulmonary arterial hypertension disease management. Circulation 2012; 125: 113–122.CrossRefGoogle ScholarPubMed
18. Rich, S, Seidlitz, M, Dodin, E, et al. The short-term effects of digoxin in patients with right ventricular dysfunction from pulmonary hypertension. Chest 1998; 114: 787–792.CrossRefGoogle ScholarPubMed
19. Galie, N, Hoeper, MM, Humbert, M, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J 2009; 34: 1219–1263.Google ScholarPubMed
20. Fuster, V, Steele, PM, Edwards, WD, et al. Primary pulmonary hypertension: natural history and the importance of thrombosis. Circulation 1984; 70: 580–587.CrossRefGoogle ScholarPubMed
21. Olsson, KM, Delcroix, M, Ghofrani, HA, et al. Anticoagulation and Survival in pulmonary arterial hypertension: results from the COMPERA Registry. Circulation 2014; 129: 57–65.CrossRefGoogle ScholarPubMed
22. Blankart, CR, Stargardt, T, Schreyogg, J. Availability of and access to orphan drugs: an international comparison of pharmaceutical treatments for pulmonary arterial hypertension, Fabry disease, hereditary angioedema and chronic myeloid leukaemia. Pharmacoeconomics 2011; 29: 63–82.CrossRefGoogle ScholarPubMed
23. www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm317743.htm.Google Scholar
24. www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAltersforHumanMedicalProducts/usm391152.htm.Google Scholar
25. Beghetti, M, Berger, RM, Schulze-Neick, I, et al. Diagnostic evaluation of paediatric pulmonary hypertension in current clinical practice. Eur Respir J 2013; 42: 689–700.CrossRefGoogle ScholarPubMed