Endothelial Function and Arterial Stiffness Relate to Functional Outcomes in Adolescent and Young Adult Fontan Survivors.
BACKGROUND
Fontan survivors demonstrate diminished vascular function and functional outcomes, but the relationships between these measures have not been established.


RESULTS
We performed a cross-sectional study of 60 Fontan survivors (52% male) with a mean age of 13.9±4.1 years and mean Fontan duration of 9.9±4.2 years. Multimodality assessment of endothelial function (reactive hyperemia index and flow-mediated dilation) and arterial stiffness (augmentation index and baseline pulse amplitude) was performed with peripheral arterial tonometry and brachial flow-mediated dilation. Aerobic capacity was determined using cardiopulmonary exercise testing; mean peak and percentage of predicted oxygen consumption (VO2) were 27.8±7.6 mL/kg per minute and 71.0±21.2%, respectively. Quality of life and physical activity were assessed using the Pediatric Quality of Life Inventory (PedsQL) and the Physical Activity Questionnaire. Vascular measures served as predictor variables, whereas functional measures served as outcome variables. In all cases, worse vascular measures were associated with worse functional measures. Flow-mediated dilation-derived reactive hyperemia index (P<0.05) was positively associated with VO2at anaerobic threshold. Peripheral arterial tonometry-derived baseline pulse amplitude (P<0.05) was negatively associated with the ratio of minute ventilation to carbon dioxide at anaerobic threshold. Flow-mediated dilation-derived reactive hyperemia index and peripheral arterial tonometry-derived augmentation index (P<0.05) were positively and negatively associated, respectively, with peak VO2. Maximum flow-mediated dilation (P<0.05) was positively associated with Physical Activity Questionnaire score. Peripheral arterial tonometry-derived augmentation index and baseline pulse amplitude (P<0.05) were negatively associated with parent-reported PedsQL total and physical heath summary scores.


CONCLUSIONS
Increased arterial stiffness and decreased endothelial function are associated with lower aerobic capacity, physical activity, and quality of life in adolescent and young adult Fontan survivors. Understanding the cause-effect relationship between vascular function and functional outcomes is an important next step.
The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH bryan.goldstein@cchmc.org.
Bryan H
BH
Goldstein
The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Elaine M
EM
Urbina
The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Philip R
PR
Khoury
The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Zhiqian
Z
Gao
The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Michelle A
MA
Amos
The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Wayne A
WA
Mays
The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Andrew N
AN
Redington
Division of Cardiology, Northwestern University Feinberg School of Medicine and Lurie Children's Hospital, Chicago, IL.
Bradley S
BS
Marino
Fontan procedure; arterial stiffness; endothelial function; exercise capacity; quality of life
J Hypertens. 2010 Aug;28(8):1692-8
20647860
J Hypertens Suppl. 1996 Dec;14(5):S147-57
9120672
Lancet. 1992 Nov 7;340(8828):1111-5
1359209
Pediatr Diabetes. 2015 Sep;16(6):434-40
25082568
Int J Obes Relat Metab Disord. 2004 Jul;28(7):852-7
15170465
Med Sci Sports Exerc. 1997 Oct;29(10):1344-9
9346166
N Engl J Med. 1987 Oct 22;317(17):1098
3657876
J Pediatr. 2009 Nov;155(5):678-82
19595374
Eur Heart J. 2006 Nov;27(21):2588-605
17000623
J Am Coll Cardiol. 2008 Jul 8;52(2):85-98
18598886
J Pediatr. 2016 Mar;170:166-72.e1
26685073
Am J Cardiol. 2011 Aug 1;108(3):428-34
21600541
Circulation. 2008 May 13;117(19):2467-74
18458169
Int J Cardiol. 2007 Aug 21;120(2):221-6
17175041
J Thorac Cardiovasc Surg. 2012 Dec;144(6):1307-13; discussion 1313-4
23031685
J Am Coll Cardiol. 2008 Jul 8;52(2):99-107
18598887
Cardiol Young. 2008 Feb;18(1):70-4
18093358
Pediatr Diabetes. 2007 Aug;8(4):193-8
17659060
J Am Coll Cardiol. 2012 Nov 13;60(20):2115-21
23083785
Am J Cardiol. 2004 Mar 15;93(6):792-7
15019898
J Clin Invest. 1994 Jan;93(1):50-5
8282821
Am J Cardiol. 2003 May 15;91(10 ):1286-8
12745126
Heart Vessels. 2013 Jan;28(1):66-75
22331173
Pediatr Hematol Oncol. 2009 Nov;26(8):589-96
19954369
Am Rev Respir Dis. 1984 Feb;129(2 Pt 2):S47-8
6696341
Int J Cardiol. 2013 Aug 20;167(4):1333-8
22525342
Circulation. 2008 Jan 1;117(1):85-92
18071068
Am Heart J. 2008 Aug;156(2):405-10
18657678
J Am Coll Cardiol. 2012 Oct 30;60(18):1778-86
23040568
Int J Cardiol. 2013 Oct 15;168(6):5385-9
24029659
Cardiol Young. 2014 Jun;24(3):469-77
23746330
Med Care. 1999 Feb;37(2):126-39
10024117
J Pediatr. 2008 Apr;152(4):557-62
18346515
Eur Heart J. 2008 Jul;29(13):1681-7
18534975
Am J Cardiol. 2010 Apr 15;105(8):1169-75
20381672
Eur Heart J. 2008 Mar;29(6):792-9
18245115