Published Online
on June 12, 2006

A more recent version of this article appeared on June 20, 2006

This Article Full Text (PDF) All Versions of this Article: 113/24/2796    most recent CIRCULATIONAHA.105.594218v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dimopoulos, K. Articles by Gatzoulis, M. A. Search for Related Content PubMed PubMed Citation Articles by Dimopoulos, K. Articles by Gatzoulis, M. A. Related Collections Other heart failure Exercise testing

Submitted on October 12, 2005
Revised on April 9, 2006
Accepted on April 20, 2006

Abnormal Ventilatory Response to Exercise in Adults With Congenital Heart Disease Relates to Cyanosis and Predicts Survival

Konstantinos Dimopoulos MD, Darlington O. Okonko BSc, MRCP, Gerhard-Paul Diller MD, Craig S. Broberg MD, Tushar V. Salukhe MRCP, Sonya V. Babu-Narayan MRCP, Wei Li MD, PhD, Anselm Uebing MD, Stephanie Bayne BSc, Roland Wensel MD, PhD, Massimo F. Piepoli MD, PhD, Philip A. Poole-Wilson MD, FRCP, Darrel P. Francis MD, MRCP, and Michael A. Gatzoulis MD, PhD^*

From the Adult Congenital Heart Programme (K.D., G.-P.D., C.S.B., S.V.B.-N., W.L., A.U., S.B., M.A.G.), Department of Cardiology, Royal Brompton Hospital, London, United Kingdom; Department of Clinical Cardiology (K.D., D.O.O., G.-P.D., T.V.S., R.W., M.F.P., P.A.P.-W.), National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom; and International Centre for Circulatory Health (T.V.S., D.P.F.), St. Mary’s Hospital & Imperial College, London, United Kingdom.

^* To whom correspondence should be addressed. E-mail: m.gatzoulis{at}rbh.nthames.nhs.uk.

Background--Limited data exist with which to stratify risk in adult congenital heart disease (ACHD). An increased ventilatory response to exercise, expressed as ventilation per unit of carbon dioxide production (VE/VCO₂ slope), is an established predictor of impaired survival in acquired heart disease. We sought to establish the distribution, relation to cyanosis, and prognostic value of the VE/VCO₂ slope across a wide spectrum of ACHD patients.

Methods and Results--Five hundred sixty ACHD patients of varying diagnoses and 50 healthy controls underwent cardiopulmonary exercise testing at a single laboratory between 2001 and 2004. Patient age was 33.2±12.9 years (mean±SD). Peak oxygen consumption was 23.5±9.0 mL · kg^-1 · min^-1. VE/VCO₂ slope for all patients was 36.3±15.3. The slope was raised in all ACHD groups compared with controls and was 73% higher in cyanotic patients. Cyanosis, with or without pulmonary arterial hypertension, was the strongest predictor of abnormal VE/VCO₂ slope. The VE/VCO₂ slope was the most powerful univariate predictor of mortality in the noncyanotic group and the only independent predictor of mortality among exercise parameters on multivariate analysis. In cyanotic patients, no parameter was predictive of death.

Conclusions--Ventilatory response to exercise is abnormal across the spectrum of ACHD. Cyanosis is a powerful stimulus for such exaggerated ventilatory patterns irrespective of the presence of pulmonary arterial hypertension. Increased VE/VCO₂ slope is the strongest exercise predictor of death in noncyanotic ACHD patients.

Key words: congenital heart defects • exercise test • ventilation • prognosis

This article has been cited by other articles:

				K. Dimopoulos, G.-P. Diller, G. Giannakoulas, R. Petraco, A. Chamaidi, E. Karaoli, M. Mullen, L. Swan, M. F. Piepoli, P. A. Poole-Wilson, et al. Anemia in Adults With Congenital Heart Disease Relates to Adverse Outcome. J. Am. Coll. Cardiol., November 24, 2009; 54(22): 2093 - 2100. [Abstract] [Full Text] [PDF]

				A. Gratz, J. Hess, and A. Hager Peak oxygen uptake and exercise capacity: a reliable predictor of quality of life?: reply Eur. Heart J., July 1, 2009; 30(13): 1674 - 1675. [Full Text] [PDF]

				A. Giardini, A. Hager, A. E. Lammers, G. Derrick, J. Muller, G.-P. Diller, K. Dimopoulos, D. Odendaal, G. Gargiulo, F. M. Picchio, et al. Ventilatory efficiency and aerobic capacity predict event-free survival in adults with atrial repair for complete transposition of the great arteries. J. Am. Coll. Cardiol., April 28, 2009; 53(17): 1548 - 1555. [Abstract] [Full Text] [PDF]

				A. Frigiola, V. Tsang, C. Bull, L. Coats, S. Khambadkone, G. Derrick, B. Mist, F. Walker, C. van Doorn, P. Bonhoeffer, et al. Biventricular Response After Pulmonary Valve Replacement for Right Ventricular Outflow Tract Dysfunction: Is Age a Predictor of Outcome? Circulation, September 30, 2008; 118(14_suppl_1): S182 - S190. [Abstract] [Full Text] [PDF]

				S. M. Paridon, P. D. Mitchell, S. D. Colan, R. V. Williams, A. Blaufox, J. S. Li, R. Margossian, S. Mital, J. Russell, J. Rhodes, et al. A Cross-Sectional Study of Exercise Performance During the First 2 Decades of Life After the Fontan Operation J. Am. Coll. Cardiol., July 8, 2008; 52(2): 99 - 107. [Abstract] [Full Text] [PDF]

				J. Meadows, P. Lang, G. Marx, and J. Rhodes Fontan Fenestration Closure Has No Acute Effect on Exercise Capacity but Improves Ventilatory Response to Exercise J. Am. Coll. Cardiol., July 8, 2008; 52(2): 108 - 113. [Abstract] [Full Text] [PDF]

				K. Dimopoulos, G.-P. Diller, E. Koltsida, A. Pijuan-Domenech, S. A. Papadopoulou, S. V. Babu-Narayan, T. V. Salukhe, M. F. Piepoli, P. A. Poole-Wilson, N. Best, et al. Prevalence, Predictors, and Prognostic Value of Renal Dysfunction in Adults With Congenital Heart Disease Circulation, May 6, 2008; 117(18): 2320 - 2328. [Abstract] [Full Text] [PDF]

				National Pulmonary Hypertension Centres of the UK Consensus statement on the management of pulmonary hypertension in clinical practice in the UK and Ireland Heart, March 1, 2008; 94(Suppl_1): i1 - i41. [Full Text] [PDF]

				National Pulmonary Hypertension Centres of the UK Consensus statement on the management of pulmonary hypertension in clinical practice in the UK and Ireland Thorax, March 1, 2008; 63(Suppl_2): ii1 - ii41. [Full Text] [PDF]

				G.-P. Diller, K. Dimopoulos, H. Kafka, S. Y. Ho, and M. A. Gatzoulis Model of chronic adaptation: right ventricular function in Eisenmenger syndrome Eur. Heart J. Suppl., December 1, 2007; 9(suppl_H): H54 - H60. [Abstract] [Full Text] [PDF]

				L. Coats, S. Khambadkone, G. Derrick, M. Hughes, R. Jones, B. Mist, D. Pellerin, J. Marek, J. E. Deanfield, P. Bonhoeffer, et al. Physiological consequences of percutaneous pulmonary valve implantation: the different behaviour of volume- and pressure-overloaded ventricles Eur. Heart J., August 1, 2007; 28(15): 1886 - 1893. [Abstract] [Full Text] [PDF]

				R. Arena, J. Myers, M. A. Williams, M. Gulati, P. Kligfield, G. J. Balady, E. Collins, and G. Fletcher Assessment of Functional Capacity in Clinical and Research Settings: A Scientific Statement From the American Heart Association Committee on Exercise, Rehabilitation, and Prevention of the Council on Clinical Cardiology and the Council on Cardiovascular Nursing Circulation, July 17, 2007; 116(3): 329 - 343. [Full Text] [PDF]

				G.-P. Diller and M. A. Gatzoulis Pulmonary Vascular Disease in Adults With Congenital Heart Disease Circulation, February 27, 2007; 115(8): 1039 - 1050. [Abstract] [Full Text] [PDF]