Six-minute walk test distance and resting oxygen saturations but not functional class predict outcome in adult patients with Eisenmenger syndrome
Introduction
Approximately 5–10% of patients with congenital heart disease develop pulmonary arterial hypertension (PAH), which impacts on quality of life and outcome [1], [2], [3]. Eisenmenger syndrome (ES) represents the extreme manifestation amongst them. Patients with ES are significantly impaired in their exercise capacity and have a relatively high mortality rate, particularly after the third decade of life [4]. However, patients with ES may deny significant limitations in their daily activities and, thus, be classified functional class 2 (or asymptomatic), contrary to objective evidence of severe exercise intolerance [5]. Congenital heart disease is, per definition, present from birth and PAH in patients with ES typically develops early in life, leading to adaptation of daily activities and lifestyle to patient ability [6], and thus masking objective capacity and symptoms. Assessment of functional class is broadly the basis on which physicians decide whether patients warrant initiation or escalation of advanced therapy (AT) for PAH [7]. We submit, however, that in patients with ES functional class is likely to underestimate the extent of exercise intolerance. Moreover, in patients who are already on AT, functional class alone may fail to establish adequacy of treatment and, thus, may be suboptimal for longitudinal follow-up and management of these patients. Timely initiation and escalation of treatment in ES is important, not only for improving exercise and, thus, quality of life, but also in improving prognosis [8], [9]. Objective means of assessing exercise capacity have, therefore, a pivotal role for assessing disease severity, disease progression and response to AT.
The six minute walk test (6MWT) is a simple and reliable test for patients with physical limitation; it is for this reason that it has been widely used as a primary endpoint for clinical trials in the area of PAH [10]. Furthermore, the 6MWT provides a good reflection of functional ability and limitation in everyday life. However, little information is available on the prognostic value of the 6MWT in patients with ES. Our study aimed, therefore, to assess the validity of the 6MWT distance and of other simple clinical variables, such as oxygen saturation (SO2), in predicting outcome in a large, single-centre cohort of adults with ES.
Section snippets
Patients and methods
This was a retrospective study. Data on all adult patients with ES under active follow-up at our centre since 2000 to 2012 were obtained and studied. For the scope of the study we defined the start of adulthood as age > 16 years. We included patients with PAH due to a nonrestrictive intracardiac or extracardiac communication [11], [12], [13]. Patients who underwent previously corrective surgery for CHD were also included [14], provided that they had near-systemic PAH. Patients with Down syndrome
Demographics and mortality
In total, 210 consecutive, adult patients with ES were included in the analysis. Demographic and clinical characteristics of all patients are presented in the Table 1. Mean age at the first 6MWT was 37.1 ± 12.9 years; 33% of patients were male. Most patients had a post-tricuspid lesion (47%) followed by patients with complex cardiac anatomy (37%). Down syndrome was present in 39 (19%). Significant exercise limitation (NYHA functional class III or more) was present in over one third of patients
Discussion
Our data reinforce the validity of the 6MWT distance and resting SO2 in both assessing and risk-stratifying patients with ES. In contrast, functional classification based on subjective reporting of symptoms failed to provide prognostic information in this report. Objective means of assessing functional capacity and deciding management strategy, such as the 6MWT distance and baseline SO2, are thus more suited than functional class alone in this cohort of patients who tend to under-report
Conclusions
The 6MWT distance and SO2 at rest represent objective tools for assessing functional capacity and for risk stratifying patients with ES. In contrast, functional class was not predictive of outcome in this contemporary ES cohort and, thus, cannot be solely relied upon for managing these patients, including initiation and/or escalation of AT.
Disclosures
Dr. Kempny was supported by the Deutsche Herzstiftung e.V. Prof Gatzoulis and the Royal Brompton Hospital Adult congenital Centre and Centre for Pulmonary Hypertension have received support from the British Heart Foundation. Prof Gatzoulis and Dr. Diller and Dr. Dimopoulos acted as consultants for Actelion UK, Pfizer UK and GSK UK and received unrestricted educational grants from Actelion and Pfizer. Dr. Tutarel was supported by the European Society of Cardiology. Dr. Alonso-Gonzalez acted as
Acknowledgements
The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
References (30)
- et al.
Eisenmenger syndrome a clinical perspective in a new therapeutic era of pulmonary arterial hypertension
J Am Coll Cardiol
(2009) The 6-min walk distance in pulmonary arterial hypertension: “Je t'aime, moi non plus”
Chest
(2010)- et al.
Eisenmenger syndrome in adults: ventricular septal defect, truncus arteriosus, univentricular heart
J Am Coll Cardiol
(1999) - et al.
Severe pulmonary hypertension without right ventricular failure: the unique hearts of patients with Eisenmenger syndrome
Am J Cardiol
(2002) - et al.
Longer-term bosentan therapy improves functional capacity in Eisenmenger syndrome: results of the BREATHE-5 open-label extension study
Int J Cardiol
(2008) - et al.
Six-minute walk test in patients with Down syndrome: validity and reproducibility
Arch Phys Med Rehabil
(2009) - et al.
Seeking optimal relation between oxygen saturation and hemoglobin concentration in adults with cyanosis from congenital heart disease
Am J Cardiol
(2011) - et al.
Isolated atrial septal defect with pulmonary vascular obstructive disease–long-term follow-up and prediction of outcome after surgical correction
Circulation
(1987) - et al.
Second natural history study of congenital heart defects. Results of treatment of patients with ventricular septal defects
Circulation
(1993) - et al.
Pulmonary arterial hypertension in adults born with a heart septal defect: the Euro Heart Survey on adult congenital heart disease
Heart
(2007)
Presentation, survival prospects, and predictors of death in Eisenmenger syndrome: a combined retrospective and case-control study
Eur Heart J
Exercise intolerance in adult congenital heart disease: comparative severity, correlates, and prognostic implication
Circulation
Pulmonary arterial hypertension in adults with congenital heart disease: distinct differences from other causes of pulmonary arterial hypertension and management implications
Curr Opin Cardiol
ESC Guidelines for the management of grown-up congenital heart disease (new version 2010)
Eur Heart J
Advanced therapy may delay the need for transplantation in patients with the Eisenmenger syndrome
Eur Heart J
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AK and KD contributed equally to the study.