The 6 Minute Walking Test in Chronic Heart Failure: Indications, Interpretation and Limitations from a Review of the Literature

The 6 min walking test (6MWT) was first used to evaluate patients with chronic respiratory diseases such as chronic obstructive pulmonary disease and respiratory failure. The test attracted the attention of cardiologists because it was easy to perform and interpret. For this reason its role in measuring functional limitation, in evaluating the effects of therapy and in the prognostic stratification of patients with chronic heart failure has been widely investigated. The 6MWT is a simple test which does not require expensive equipment or advanced training for technicians. The test involves asking the patient to walk the longest distance possible in a set interval of 6 min, through a walking course (corridor) preferably 30-m long. The patient can stop or slow down at any time and then resume walking, depending on his/her degree of fatigue. Even though other parameters can be monitored during the test, such as arterial pressure and/or heart rate, the number of times the patient has to stop during the test, the speed of walking or even changes in respiratory gases (measured using a portable instrument) and oxygen saturation, the distance walked in 6 min is the parameter usually taken into consideration in clinical practice and also the one that has proven to be most useful in nearly all clinical studies. The first studies on the use of the 6MWT in chronic heart failure were published just over 15 years ago. Guyatt 1 in 1985 and Lipkin 2 in 1986 reported that the distance covered during the 6MWT can identify the most compromised patients and differentiate them from the less severe cases (based on the NYHA classification). The test also showed a good correlation with objective measures of effort tolerance, such as exercise duration and oxygen uptake at the peak of exercise. Furthermore, patients preferred the 6 min walking test to the conventional exercise test because it was similar to the activities of daily living. A few years later Bittner et al. reported that the distance walked during the 6MWT was a strong and independent predictor of morbidity and mortality in patients with left ventricular dysfunction 3. A great number of studies on the 6MWT have been published in the last 10 years, exploring both its physiopathologic determinants and its practical applications. The aim of this paper is to illustrate how the 6MWT can be used in patients with heart failure, based on a review of the existing literature and the guidelines that have recently been published. As previously documented, peak exercise oxygen uptake (Vo2 peak), even for the 6MWT has a poor correlation with the haemodynamic indices recorded at rest. In two studies in which the relation between the distance walked and different haemodynamic and ventricular functional indices was evaluated in patients with chronic heart failure, only right ventricular ejection fraction showed a small but significant correlation with 6MWT 4,5. Several non-cardiovascular parameters showed a correlation with the 6MWT and were good predictors of the distance walked 6–8. Amongst these, the indexes of muscular strength, of postural balance and of reaction time, mood and general health (the latter was evaluated using specific questionnaires) were significantly correlated to the 6MWT. The combination of these variables was found to be responsible for 52.5% 7 and 69% 6, respectively, of the variance of the distance walked during the walking test in two studies carried out on healthy subjects over 62 years. Based on these results, the 6MWT can be considered as a global performance test rather than just a test of cardiovascular performance 6,7. It is thus suggested that the 6MWT may have a wider use than just the evaluation of cardiovascular adaptation to effort, especially in elderly patients. Of interest, the maximum distance walked during the walking test has been shown to correlate significantly with some anthropometric variables, such as gender(less in women), age and weight (inverse relationship), height (direct relationship) 9–11. Therefore, these factors should be taken into consideration when interpreting the results of a single measurement made to determine functional status. The maximum distance walked during the 6MWT has been used in heart failure to identify patients with a greater functional impairment and with a worse prognosis from those that are less compromised. Quartiles of distance, derived from the distribution in a study population, such as SOLVD 3, have generally been employed for this. The lack of 6MWT data in healthy people has, up until now, limited its use in identifying whether there is a reduction in functional capacity and how severe it is. Recently, 6MWT values in relatively large populations of healthy people of different ages have been published 9–12. It has thus been possible to define normal levels (mean values, confidence intervals and lower limits of normal) and predictive equations have been introduced 9,13 taking into account anthropometric variables (gender, age, weight, height) correlated to the walking test (fig. Fig. 1, Table 1). Analysing the values reported in fig. Fig. 1 it could be considered that the same distance of 250 m walked during the 6MWT may indicate a lower limit of normal functional capacity in an 80-year-old man and a severe reduction in effort tolerance in a 45-year-old man, with obvious clinical implications. It has thus been suggested that the results of the test should be expressed not only as an absolute value (the distance walked in meters), which can be useful for example in the same patient when evaluating the effects of therapeutic interventions, but also as a percentage of the predicted value, as is done for other functional capacity indexes, for example the Vo2 peak 14. Because of some of the intrinsic features of the test, such as execution time (max 6 min), simplicity (walking on a flat surface), greater acceptance by patients compared to a conventional exercise test (symptom-limited), the 6MWT has come to be considered a sub-maximal test. The indications to perform a 6MWT could thus differ from those of a maximal exercise test. However, in most studies the longest distance walked during the 6MWT has shown a medium-to-high correlation with the Vo2 measured at the peak of maximal exercise test. It has also been shown that the oxygen uptake at the end of the 6MWT, measured using portable instruments, shows a close correlation with the Vo2 peak 15–17. In some patients, the Vo2 at the end of the walking test was even greater than the Vo2 peak. Consequently, the 6MWT does not seem to have the features of a sub-maximal test. It could instead be used to assess the maximal functional capacity in patients with heart failure 16,17. The degree of reproducibility of a diagnostic or prognostic indicator is one of the factors that can determine its use in clinical practice. The longest distance walked during the 6MWT seems to indicate the effect of a learning curve, because it tends to increase when the test is repeated after a short period of time. It then seems to remain stable from the second/third test onwards. Encouragement given during the test also seems to have a great effect 18, thus indicating the need to use the same protocol during serial measurements 14. Opasich et al. investigated the problem of reproducibility of the 6MWT in a large group of patients with heart failure 19. The authors confirmed that the distance walked tended to increase in the individual patient when two tests were performed 30 min apart (+19 m). It has also been calculated that the minimum variation in the walked distance that can be considered an expression of a real variation of functional capacity is approximately 10% of the average of two consecutive tests 19. As a consequence, when the 6MWT is used as an end-point in intervention studies the clinical relevance of the results must be considered cautiously, if the variation in distance is less than 10% in individuals, even though the results are statistically significant. Many different studies have investigated whether the distance walked during the walking test is a prognostic indicator in chronic heart failure patients. Lower levels of functional capacity (a distance <300 m during 6MWT) have proven to be predictive of mortality (total or cardiovascular) and morbidity (hospitalization for worsening heart failure) both in patients with asymptomatic left ventricular systolic dysfunction and in those with mild-moderate 3,4,20 and advanced heart failure 21,22. In the SOLVD study, total mortality was 10.23% in subjects with a 6MWT<300 m and 2.99% in subjects with a 6MWT≥450 m 3. The difference between the two groups is even more evident when considering hospitalizations for heart failure (22.16% vs. 1.99%). In patients with advanced heart failure that are being evaluated for heart transplantation, the walking test has proven able to predict short term (6 month) mortality or the need for inotropic support, whereas the Vo2 peak has been shown to be a better mid-long term prognostic indicator 21. In some studies, the distance walked during the 6MWT was not an independent prognostic indicator when it was included in models that also considered the Vo2 peak 5,23. On one hand, this confirms that the information given by the 6MWT is very similar to that of the cardiopulmonary exercise test and on the other it seems to indicate that the prognostic relevance of the distance walked is very low or absent when the Vo2 peak is available. However, it should be emphasized that the cardiopulmonary exercise test is not frequently used in chronic heart failure patients for several reasons, including the limited availability of equipment and the inability of patients to perform a maximal effort test 24,25. Furthermore, in studies using the 6MWT for prognostic stratification attention has been concentrated on young, male patients, whose clinical picture is determined by a moderate-to-severe left ventricular systolic dysfunction. There are no data on the prognostic significance of the 6MWT in elderly patients, in women and in patients with left ventricular diastolic dysfunction, who are rarely included in randomized trials. The 6MWT has been used in many studies to assess the effect of therapeutic interventions in patients with heart failure. The variations in the distance walked during the walking test have been reported to identify the short term effects of the tailoring of standard pharmacological therapy (diuretics, vasodilators, digitalis) and of a personalized program of physical training 26,27 (fig. Fig. 2). The 6MWT has also been employed in studies assessing the effectiveness of new drugs, such as beta-blockers, in addition to standard therapy 28, the use of intravenous inotropic drugs 29 and prostaglandin analogues 30,31. The distance walked during the walking test has demonstrated the effects of ventricular assistance devices 16 on functional capacity and more recently the effect of ventricular resynchronization techniques 32,33. The changes in the 6MWT after therapeutic intervention reported in many studies may show large positive or negative variations (from 5–10 to 100–150 m and even more). The meaning of this variance must always be interpreted, both in the single patient and in the trial population, bearing in mind current knowledge on test reproducibility and its capacity to identify real changes in the clinical picture and prognosis (responsiveness). Furthermore, the correct way to express changes in 6 MWT for clinical purposes (absolute value, percentage change from baseline or percentage change of predicted value) is not yet known. Based on the data presented, the 6MWT appears to be a very useful test to evaluate chronic heart failure patients, however, the above-mentioned limitations (and others that may appear once the test is more widely used) must always be considered. The recently published American Thoracic Society Guidelines for the 6MWT 14 support the standardized approach to the 6MWT described in this review and recommend the use of the 6MWT not only in subjects with lung disease but also in those with heart failure as a one-time measure of functional status and for the evaluation of the effects of therapy and prognostic stratification (Table 2). These guidelines, based on a comprehensive Medline literature, other than reviewing the most common indications and limitations of the test, also provide a detailed description of practical aspects to perform a standardized and reproducible test in the clinical setting.