Clinical classification in pediatric pulmonary arterial hypertension associated with congenital heart disease.
Congenital heart disease (CHD) is a frequent cause of pediatric pulmonary arterial hypertension (PAH), with diverse etiology and outcome. We aimed to describe phenotypic heterogeneity in pediatric PAH associated with CHD (PAH-CHD), assess the applicability of the Nice CHD classification, and explore whether this classification accurately reflects patient/disease characteristics and survival. All children with CHD from a contemporary cohort of consecutive pediatric PAH patients followed in three major referral centers (Denver, New York, the Netherlands) were characterized and classified on the basis of the latest proposed clinical classification for PAH-CHD (World Symposium on Pulmonary Hypertension, Nice, 2013). According to this classification, 24% of 134 children were classified into group 1, 14% into group 2, 19% into group 3, and 30% into group 4; 11% could not be classified. Types of CHD and hemodynamic profile differed between groups, with the highest right atrial pressure in group 4 (P < 0.040). Group 3 children had Down syndrome less frequently (P = 0.011) but other (un)defined syndromes most frequently (P = 0.063) and received most intense PAH-targeted therapy (P = 0.003). With 15 deaths and one lung transplant (12%; median follow-up: 4.3 years), survival differences could not be demonstrated between the groups in the Nice CHD classification. Pediatric PAH-CHD is a heterogeneous condition frequently associated with extracardiac, developmental factors that are believed to affect disease development. The Nice CHD classification identifies groups with specific patient/disease characteristics. However, a substantial proportion of children could not be classified. Group 3 forms a distinct disease entity. Its prognostic value could not be determined because of the low number of events. The Nice CHD classification supports clinical characterization of PAH-CHD; however, further refinement is needed to classify all children with PAH-CHD.
Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Willemijn M H
WM
Zijlstra
Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Johannes M
JM
Douwes
Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Mark-Jan
MJ
Ploegstra
College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Usha
U
Krishnan
Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Marcus T R
MT
Roofthooft
Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Hans L
HL
Hillege
Children's Hospital Colorado, Aurora, Colorado, USA.
D Dunbar
DD
Ivy
College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Erika B
EB
Rosenzweig
Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Rolf M F
RM
Berger
Nice congenital heart disease classification; congenital heart disease; pediatrics; pulmonary hypertension; survival
Am J Cardiol. 2010 Nov 1;106(9):1332-8
21029834
J Am Coll Cardiol. 2013 Dec 24;62(25 Suppl):D34-41
24355639
Eur Heart J. 2011 Dec;32(24):3137-46
21893489
J Am Coll Cardiol. 2013 Dec 24;62(25 Suppl):D117-26
24355636
Circulation. 2011 Oct 18;124(16):1755-64
21947294
Eur Heart J. 1998 Dec;19(12):1845-55
9886728
J Am Coll Cardiol. 2002 Jun 19;39(12):1890-900
12084585
Circulation. 1968 May;37(5):805-15
5646864
Pulm Circ. 2014 Jun;4(2):330-41
25006452
Heart. 2009 Feb;95(4):312-7
18952635
Circulation. 2012 Jan 3;125(1):113-22
22086881
Cardiol Young. 2008 Feb;18(1):10-7
18205971
Lancet Respir Med. 2014 May;2(5):348-50
24815801
Pulm Circ. 2011;1(2):286-298
21874158
Circulation. 2005 Aug 9;112(6):828-35
16061735
Eur Respir J. 2013 Jan;41(1):236-9
23277521
Eur Heart J. 1995 May;16(5):698-703
7588904
Prog Cardiovasc Dis. 2002 Sep-Oct;45(2):129-38
12411974
Eur Heart J. 2014 Mar;35(11):716-24
23455361
Circulation. 1984 Apr;69(4):655-67
6697454
Am J Cardiol. 2010 Jul 1;106(1):117-24
20609658
Cardiovasc Res. 1970 Jan;4(1):23-30
5416840
Eur Heart J. 2006 Jul;27(14):1737-42
16793921
Lancet. 2012 Feb 11;379(9815):537-46
22240409
Heart. 2010 Sep;96(17):1401-6
20406768
Paediatr Respir Rev. 2005 Sep;6(3):174-80
16153566
Am J Respir Crit Care Med. 2014 Dec 15;190(12):1421-9
25379685
Am J Cardiol. 2014 Jan 1;113(1):147-55
24176071
J Am Coll Cardiol. 2014 May 27;63(20):2159-2169
24681143
J Pediatr. 2009 Aug;155(2):176-82.e1
19524254