Six-minute walk test distance and resting oxygen saturations but not functional class predict outcome in adult patients with Eisenmenger syndrome

https://doi.org/10.1016/j.ijcard.2013.07.227Get rights and content

Abstract

Background

Eisenmenger syndrome (ES) represents the extreme manifestation of pulmonary arterial hypertension in patients with congenital heart disease, associated with significant exercise intolerance and mortality. Even though of six-minute-walk-test (6MWT) is routinely used in these patients, little is known about its prognostic value in comparison to functional class.

Methods and results

We included 210 adult patients with ES who underwent a total of 822 6MWTs. Median walking distance (6MWD) was 330 m [IQR 260–395], oxygen saturation (SO2) at baseline 86% [IQR 82–91%] and SO2 at peak-exercise 69% [IQR 60–80%]. In patients commenced on advanced therapy for pulmonary hypertension, but not in the reminder, there was a significant improvement in walking distance (297 ± 97 m vs. 325 ± 87 m,P = 0.0019), SO2 at rest (84.9 ± 7.1 vs. 86.8 ± 5.9%,P = 0.003), SO2 at peak exercise (69.1 ± 12.7 vs. 72.3 ± 12.2%,P = 0.04) and NYHA functional class (P = 0.0047).

During a follow up of 3.3 years, 29 patients died. On time-dependent Cox analysis, 6MWD (HR 0.94 per 10 m, 95%CI: 0.91–0.97,P < 0.001) and baseline SO2 (HR 0.90, 95%CI:0.86–0.94,P < 0.0001) were predictors of death. In contrast, age, functional class, peak-exercise SO2 and SO2 change were not related to mortality. A three-fold increased risk of death was identified in patients not reaching a 6MWD of 350 m or with baseline SO2 below 85%.

Conclusions

The 6MWD and resting SO2, but not functional class were predictive of outcome in this contemporary cohort of Eisenmenger patients and should be incorporated in both risk stratification and management algorithms for these patients.

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)

  • G.P. Diller et al.

    Presentation, survival prospects, and predictors of death in Eisenmenger syndrome: a combined retrospective and case-control study

    Eur Heart J

    (2006)
  • G.P. Diller et al.

    Exercise intolerance in adult congenital heart disease: comparative severity, correlates, and prognostic implication

    Circulation

    (2005)
  • K. Dimopoulos et al.

    Pulmonary arterial hypertension in adults with congenital heart disease: distinct differences from other causes of pulmonary arterial hypertension and management implications

    Curr Opin Cardiol

    (2008)
  • H. Baumgartner et al.

    ESC Guidelines for the management of grown-up congenital heart disease (new version 2010)

    Eur Heart J

    (2010)
  • T. Adriaenssens et al.

    Advanced therapy may delay the need for transplantation in patients with the Eisenmenger syndrome

    Eur Heart J

    (2006)
  • Cited by (43)

    • Heart Failure in Adults With Congenital Heart Disease

      2018, Heart Failure in the Child and Young Adult: From Bench to Bedside
    • Mortality in pulmonary arterial hypertension due to congenital heart disease: Serial changes improve prognostication

      2017, International Journal of Cardiology
      Citation Excerpt :

      Observation of serial changes in these parameters over time may better reflect prognosis. A limited number of studies explored the prognostic value of serial changes in standard clinical parameters [9–12], however, not all parameters have been described, nor the underlying coherence. Knowledge about which serial changes in parameters influence mortality, might improve risk stratification by capturing disease progression in an earlier state.

    • Heart Failure in Adults With Congenital Heart Disease

      2017, Heart Failure in the Child and Young Adult: From Bench to Bedside
    View all citing articles on Scopus
    1

    AK and KD contributed equally to the study.

    View full text