Author + information
- Received August 5, 2015
- Revision received December 2, 2015
- Accepted January 5, 2016
- Published online March 22, 2016.
- Johannes M. Douwes, MDa,
- Tilman Humpl, MD, PhDb,
- Damien Bonnet, MD, PhDc,
- Maurice Beghetti, MDd,
- D. Dunbar Ivy, MDe,
- Rolf M.F. Berger, MD, PhDa,∗ (, )
- TOPP Investigators
- aCentre for Congenital Heart Diseases, Pediatric Cardiology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
- bPediatric Cardiology and Critical Care Medicine, The Hospital for Sick Children University of Toronto, Toronto, Ontario, Canada
- cCentre de Référence Malformations Cardiaques Congénitales Complexes, M3C-Necker Hospital for Sick Children, Assistance Publique des Hôpitaux de Paris, Pediatric Cardiology, University Paris Descartes, Paris, France
- dPediatric Cardiology Unit, Children’s University Hospital, Geneva, Switzerland
- eDepartment of Pediatric Cardiology, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado
- ↵∗Reprint requests and correspondence:
Dr. Rolf M. F. Berger, Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children’s Hospital, University Medical Center Groningen, PO Box 30001, Groningen 9700 RB, the Netherlands.
Background In pulmonary arterial hypertension (PAH), acute vasodilator response testing (AVT) is considered important to identify adult patients with favorable prognosis using calcium-channel blocker (CCB) therapy. However, in pediatric PAH, criteria used to identify acute responders and CCB use are insufficiently studied.
Objectives This study sought to describe current clinical practice of AVT and subsequent treatment decisions in pediatric PAH.
Methods From January 2008 to May 2013, 529 consecutive children with confirmed pulmonary hypertension were enrolled in an international registry. We analyzed those children with evaluable AVT.
Results Of 382 children with evaluable AVT, 212 had idiopathic/familial PAH (IPAH/FPAH) and 105 had PAH associated with congenital heart disease (PAH-CHD). In 70% of the patients, AVT was performed using inhaled nitric oxide; other agents were used in the remaining patients. In IPAH/FPAH patients, 78 (37%) patients were acute responders according to their physician, 62 (30%) according to REVEAL (Registry-to-Evaluate-Early-And-Long-term PAH disease management)-pediatric criteria, and 32 (15%) according to Sitbon criteria. For PAH-CHD patients, the numbers of AVT responders were 38 (36%), 14 (13%), and 7 (7%) respectively. Correlation between AVT responder status as judged by the treating physician and by published response criteria was poor. Moreover, of the IPAH/FPAH patients judged by the treating physician as acute responders, only 23% were treated with CCB without additional PAH-targeted therapy. The Sitbon criteria selected patients with better prognosis who had excellent outcome when treated with CCB.
Conclusions The current practice of identifying responders to AVT and subsequent treatment with CCB therapy demonstrated large discrepancies with current international guidelines. Also, in pediatric IPAH, the Sitbon criteria are the criteria of choice to identify patients with excellent survival when treated with CCB therapy.
- calcium-channel blocker therapy
- congenital heart disease
- mean arterial pressure
- right heart catheterization
The TOPP (Tracking-Outcomes-and-Practice-in-Pediatric-Pulmonary-Hypertension) registry is supported by an unrestricted research grant from Actelion Pharmaceuticals Ltd. Actelion does not participate in the management of the TOPP registry; neither does it have access to the database and the individual site and patient data. All decisions related to the Registry lie solely with the Executive Board of the Association for Pediatric Pulmonary Hypertension. The M3C-Necker contracts with Actelion, Bayer, and Lilly for Dr. Bonnet to perform consultant activities and to participate in steering committees for clinical trials. Dr. Beghetti has received grants from and contracted as consultant for Actelion and Bayer-Schering; and served as a consultant and participated in the steering committee for Actelion, Bayer-Schering, GlaxoSmithKline, Eli Lilly, and Pfizer. The University of Colorado contracts with Actelion, Bayer, Gilead, Lilly, and United Therapeutics for Dr. Ivy to be a consultant. The University Medical Center Groningen contracts with Actelion, GlaxoSmithKline, Bayer, and Lilly for Dr. Berger to perform consultant activities and to participate in steering committees for clinical trials. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received August 5, 2015.
- Revision received December 2, 2015.
- Accepted January 5, 2016.
- American College of Cardiology Foundation