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European Journal of Heart Failure 2006 8(3):321-325; doi:10.1016/j.ejheart.2005.08.006
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© 2005 European Society of Cardiology

Clinical determinants of poor six-minute walk test performance in patients with left ventricular systolic dysfunction and no major structural heart disease

L. Ingle*, A.S. Rigby, S. Nabb, P.K. Jones, A.L. Clark and J.G.F. Cleland

Department of Cardiology, Castle Hill Hospital Castle Road, Cottingham, Hull, HU16 5JQ, UK

* Corresponding author. Tel.: +44 148 262 3732; fax: +44 148 262 4071. E-mail address: L.Ingle{at}hull.ac.uk


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Background: The clinical determinants of six-minute walk test (6-MWT) performance in patients with left ventricular systolic dysfunction (LVSD) have rarely been investigated, and it is not clear whether they differ from patients referred for the assessment of symptoms of heart failure who do not have major structural heart disease (MSHD).

Methods and Results: 571 patients with LVSD enrolled in a chronic disease management programme (79% male; mean age 71±10 years; BMI 28±5) completed a 6-MWT with a mean distance 337±103 m. 688 patients referred with suspected heart failure but in whom MSHD was excluded (49% male; mean age 70±11 years; BMI 28±6) had a mean 6-MWT distance of 391±106 m (P<0.001 compared to patients with LVSD). Relationships with walking distance were determined by calculating odds ratios (ORs) with 95% confidence intervals (CIs) for walking ≤300 versus >300 m. In patients with LVSD, predictors of poor walking distance (≤300 m) included age ≥75 years (OR=4.0, 95% CI=2.4–6.4); low BMI (<20) (OR=3.4, 95% CI=1.6–7.3); anaemia (OR=2.8, 95% CI=1.8–4.2); resting heart rate >80 beats min–1 (OR=2.2, 95% CI=1.3–3.5); and being female (OR=2.0, 95% CI=1.3–3.0). Serum creatinine and NT-proBNP showed dose–response effects, as did self-perceived feelings of depression and anxiety. Determinants of 6-MWT in patients without MSHD were similar including age ≥75 years (OR=6.0, 95% CI=3.4–10.4), anaemia (OR=2.8, 95% CI=1.6–4.9), resting HR >80 beats min–1 (OR=2.5, 95% CI=1.4–4.4) and being female (OR=1.6, 95% CI=1.9–2.4). NT-proBNP and self-perceived feelings of depression and anxiety also showed dose–response effects.

Conclusion: The determinants of poor 6-MWT performance depend on physical–cardiovascular and non-cardiovascular, and psychological factors. Clinical predictors for poor walking performance are similar for patients with LVSD and without MSHD.

Key Words: Clinical determinants • Poor 6-MWT performance • LVSD • No MSHD

Received April 5, 2005; Revised July 20, 2005; Accepted August 25, 2005


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
The six-minute walk test (6-MWT) is used to estimate functional capacity in patients with a variety of medical conditions, and can be performed by those who are unable or unwilling to undertake formal treadmill or bicycle exercise tests [1]. The test is simple to perform, requires inexpensive equipment, is safe because patients are self-paced during exertion, and is fairly reproducible provided it is well standardized [2]. For patients with severe heart failure without locomotor dysfunction, the 6-MWT may be a ‘maximal’ test limited by cardiopulmonary performance [3,4] but other factors including body habitus, locomotor function and psychological well-being are likely to be important. Previous studies have identified that walking <300 m during the 6-MWT is a simple prognostic marker of subsequent cardiac death in patients with mild-to-moderate heart failure [5,6]. However, it is not clear which clinical determinants predict poor 6-MWT performance. Identifying these correlates may allow clinicians to reverse the decline in functional capacity in these patients. Accordingly, we have investigated the determinants of the 6-MWT in all patients referred to our clinic for the investigation of suspected heart failure. This allowed us to compare the determinants of 6-MWT performance inpatients with CHF due to left ventricular systolic dysfunction (LVSD) compared to patients without major structural heart disease (MSHD) in whom a clinical diagnosis of heart failure had been refuted.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
The Hull and East Riding ethics committee approved the study, and all patients provided informed consent for participation. Patients were recruited from referrals with suspected heart failure to a local community heart failure clinic. Two groups of patients were deemed of interest. Those with a diagnosis of heart failure due to LVSD, and those without diagnosis with no MSHD (Table 1). In patients with LVSD, 71% had dysfunction due to ischaemic aetiology and suffered from the condition for at least 6 months. Patients were studied when they were clinically stable, without any changes in medication during the previous three weeks. Patients underwent echocardiographic assessment and left ventricular ejection fraction (LVEF) was calculated using the Simpson's formula from measurements of end-diastolic and end-systolic volumes on apical 2D views [7]. LVSD was diagnosed if LVEF was ≤40% (Table 2). Clinical history, physical examination, 12-lead ECG, blood pressure, spirometry, routine blood samples (anaemia was defined as haemoglobin ≤13 g dl–1 for males and ≤12 g dl–1 for females), and assessment using the EuroHeart Failure symptom and quality of life (QoL) questionnaire [8] were also undertaken. The 6-MWT was conducted following a standardised protocol [9]. Patients were required to walk as far as possible in six minutes along a flat corridor, turning 180° every 15 m. Spirometry was measured via an Oxycon Delta metabolic cart (VIASYS Healthcare Inc., PA, USA). Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) was determined from the best of three efforts.


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  		Table 1 Clinical characteristics

 


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  		Table 2 Co-morbidities and medication

 
2.1. Statistical analysis
Data were analysed using SPSS statistical software for Windows version 11.5 (SPSS Inc, Chicago, Illinois, USA). P<0.05 was taken as being statistically significant. A multivariable model including demographic data, echocardiography, ECG, blood pressure, spirometry, quality of life assessment and routine blood samples was constructed to determine the factors associated with poor 6-MWT performance. Relationships with walking distance were determined by calculating odds ratios (ORs) (odds of walking ≤300 versus >300 m) with 95% confidence intervals (CIs). We carried out a sensitivity analysis by varying the threshold for poor walking distance by ±50 m (i.e., 250 and 350 m).


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
571 patients with LVSD and 688 patients with no MSHD were included. Patients with no MSHD walked significantly further (391±106 v 337±103 m, P=0.01) (Fig. 1). Biochemical markers including creatinine and NT-proBNP were significantly higher in patients with LVSD (P<0.05), and these patients reported significantly higher levels of anxiety (P=0.02) and depression (P=0.03). Self-perceived overall health (P=0.03) and quality of life (P=0.04) were also lower in patients with LVSD.


Figure 1
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  		Fig. 1 Percentage distribution of 6-MWT distance in patients with LVSD and no MSHD.

 
Independent predictors of poor walking performance (≤300 m) included age ≥75 years (OR=4.0, 95% CI=2.4-6.4); low BMI (<20) (OR=3.4, 95% CI=1.6-7.3); anaemia (OR=2.8, 95% CI=1.8-4.2); resting heart rate>80 beats min–1 (OR=2.2, 95% CI=1.3-3.5); and being female (OR=2.0, 95% CI=1.3-3.0) in patients with LVSD (Table 3). Other biochemical markers including serum creatinine and NT-proBNP, and self-perceived feelings of depression and anxiety showed a dose-response relationship (higher/worsening values equated to poorer walking performance) (Table 4).


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  		Table 3 Odds ratios between physical factors and 6-MWT distance

 


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  		Table 4 Odds ratios between psychological factors and 6-MWT distance

 
In patients without MSHD, the clinical predictors of poor 6-MWT performance were age≥75 years (OR=6.0, 95% CI=3.4-10.4), anaemia (OR=2.8, 95% CI=1.6-4.9), resting HR>80 beats.min–1 (OR=2.5, 95% CI=1.4-4.4), prolonged QRS duration (>120 m s–1) (OR=2.5, 95% CI=1.3-4.7); BMI (>30) (OR=1.9, 95% CI=1.2-3.2) and being female (OR=1.6, 95% CI=1.9-2.4) (Fig. 2). NT-proBNP and self-perceived feelings of depression and anxiety showed a similar dose-response relationship to the LVSD group. Worsening feelings of overall health status continued to be associated with poorer 6-MWT distance after adjusting for age, sex, heart rate, BMI, blood pressure, creatinine, NT-proBNP, urea, QRS duration, NYHA class and anaemia. This finding was evident in both groups (Table 5).


Figure 2
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  		Fig. 2 Similar clinical determinants of poor walking performance in patients with LVSD and no MSHD (odds ratio±95% CI).

 


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  		Table 5 Adjusted odds ratios for overall general health and QoL (95% CI)

 
Only two variables that predicted the 6-MWT response in patients with LVSD, low BMI and serum creatinine, did not also predict response in patients without MSHD. Two variables, high BMI and prolonged QRS predicted 6-MWT only in patients without LVSD. After adjusting our threshold of poorer walking performance by ±50 m (250-350 m), similar trends were evident for age, sex, BMI, resting heart rate, creatinine, anaemia, and self-perceived feelings of anxiety and depression in both groups of patients.


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
Our findings indicate that age>75 years, body mass index, anaemia, resting heart rate>80 bpm, being female, QRS width, elevated NT-proBNP levels and self-perceived feelings of anxiety and depression, health and QoL can be used to identify an increased likelihood of poor functional status in patients with LVSD and/or aged-matched patients without MSHD. These similarities are surprising given the differences in cardiac function, co-morbidity, medication, and biochemical and psychological variables that existed between the two groups of patients studied.

Our study highlights the association between self-perceived overall health and QoL and functional capacity status which could not be accounted for by adjusting for other measured variables. These data highlight the importance of the relationship between patients' perception of their health and their functional capacity. However, it is not clear which is cause and which is effect. Indeed, it is possible that this is one more example of a vicious cycle in heart failure. Emerging evidence highlights the importance of exercise training for improving functional capacity and reducing the impact of psychological disorders including anxiety and depression [10,11].

A limitation of the study was the significant difference between males and females with LVSD (males=79%) and those with no MSHD (males=49%). It is known that males walk further than females due to a number of factors including stride length, which is strongly associated with stature. Although we did not measure stride length per se, there were no differences in stature between patient groups, indeed, patients with no MSHD were taller. Other factors that could affect functional capacity including BMI, NYHA classification, haemoglobin concentration and spirometry were also not different between our patient groups.

In conclusion, the determinants of 6-MWT are complex and depend on physical — both cardiovascular and non-cardiovascular, and psychological factors. Clinical determinants of 6-MWT performance are similar in patients with LVSD and age-matched patients without major structural heart disease irrespective of differences in cardiac function, comorbidity, medication, and biochemical and psychological variables. Reversing the effect of these determinants of poor walking performance should be the aim of clinicians — the current study highlights which should be targeted in patients with a reduced functional capacity as a result of the vicious heart failure cycle, and in those patients with no major structural heart disease.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

  1. Woo M.A., Moser D.K., Stevenson L.W., et al. Six-minute walk test and heart rate variability: lack of association in advanced stages of heart failure. Am J Respir Crit Care Med (1997) 6:348–354.
  2. Ingle L., Shelton R.J., Rigby A.S., Nabb S., Clark A.L., Cleland J.G.F. The reproducibility and sensitivity of the 6-minute walk test in elderly patients with chronic heart failure. Eur Heart J (2005) 26:1742–1751.[Abstract/Free Full Text]
  3. Cahalin L.P., Mathier M.A., Semigran M.J., et al. The six-minute walk test predicts peak oxygen uptake and survival in patients with advanced heart failure. Chest (1992) 110:325–332.[CrossRef]
  4. Roul G., Germain P., Bareiss P. Does the 6-minute walk test predict the prognosis in patients with NYHA class II or III chronic heart failure? Am Heart J (1998) 136:449–457.[CrossRef][Web of Science][Medline]
  5. Schiller N.B., Shah P.M., Crawford M., et al. Recommendations for quantification of the left ventricle by two-dimensional echocardiography. J Am Soc Echocardiogr (1989) 2:358–367.[Medline]
  6. Cleland J.G., Swedberg K., Follath F., et al. Study group on diagnosis of the working group on heart failure of the European society of cardiology. The EuroHeart failure survey programme— a survey on the quality of care among patients with heart failure in Europe: Part 1. Patient characteristics and diagnosis. Eur Heart J (2003) 24:442–463.[Abstract/Free Full Text]
  7. Guyatt G.H., Sullivan M.J., Thompson P.L., et al. The six-minute walk: a new measure of exercise capacity in patients with chronic heart failure. Can Med Assoc J (1985) 132:919–923.[Abstract]
  8. Bittner V., Weiner D.H., Yusuf S., et al. Prediction of mortality and morbidity with a 6- minute walk test in patients with left ventricular dysfunction. JAMA (1993) 270:1702–1707.[Abstract/Free Full Text]
  9. Roul G., Germain P., Bareiss P. Does the 6-minute walk test predict the prognosis in patients with NYHA class II or III chronic heart failure? Am Heart J (1998) 136:449–457.[CrossRef][Web of Science][Medline]
  10. Van den Berg-Emons R., Balk A., Bussmann H., Stam H. Does aerobic training lead to a more active lifestyle and improved quality of life in patients with chronic heart failure? Eur J Heart Fail (2004) 6(1):95–100.[Abstract/Free Full Text]
  11. Koukouvou G., Kouidi E., Iacovides A., Konstantinidou E., Kaprinis G., Deligiannis A. Quality of life, psychological and physiological changes following exercise training in patients with chronic heart failure. J Rehabil Med (2004) 36(1):36–41.[CrossRef][Web of Science][Medline]

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