The current study demonstrates that the D.W had a better relationship with VO2 on-kinetics compared to 6MWT-distance and percent-predicted distance in patients with CAD. Moreover, the D.W had a larger effect size than the 6MWT distance in CAD patients with and without LVSD. These findings support the premise that the D.W is an easily applying and potential meaningful measure, in the context of quantifying submaximal exercise performance and physiologic health during exertion, even in patients with less severe impairment.
Field tests have been used to assess exercise capacity in chronic disease populations for a number of years. Submaximal exertion tests enable a greater patient toleration and perhaps had a stronger indication of the ability to perform daily activities[20]. In this context, the 6MWT has been used as a prognostic marker for several diseases, as in cardiac patients, especially in those with LVSD[6,21,22]. Nevertheless, the 6MWT-distance alone is only able to detect the presence of a marked exercise limitation, i.e. in patients unable to walk more than 300 meters. In order to acquire physiological insight, several research groups around the world have simultaneously employed a MOB device during the 6MWT[18,19,23]. The breath-by-breath analysis of cardiopulmonary responses more accurately quantifies physiologic health and of the degree of an exercise limitation. Furthermore, the analysis of VO2 during the initial phase of the 6MWT allows for the assessment of VO2 on-kinetics, as in our study, which is linked to the risk for future adverse events[19,24].
The walking distance in meters had historically been recognized as the primary variable obtained with the 6MWT. Several studies report threshold 6MWT-distance values to predict increased risk of adverse events such as myocardial infarction, stroke, re-hospitalization and mortality[25]. Despite its greater utilization, studies reported only a moderate association between the 6MWT-distance and peak VO2 and other cardiopulmonary exercise testing parameters[8]. In fact, we also found a moderate relationship between 6MWT-distance with VO2SS and wMRT in our CAD patients, explaining the discrepancy from the previously known relation between METS and walking-speed. This finding could suggest that the use of the 6MWT-distance is only able to predict an obvious impairment of functional capacity and then an already very predictable risk of morbidity and mortality.
Additionally, predicted values based on age, gender and body mass index have been studied for populations around the world to obtain normative values of performance. Since reference values are acquired in each country separately, it can be difficult to apply this as a worldwide parameter. Moreover, in the current study, only a modest association was found with VO2 on-kinetics when the percent-predicted values of the 6MWT were used. The lack of a stronger relation could indicate that the functional contribution of participants’ body processes during exercise it not well represented by current prediction models.
The current limitations in the physiological information derived from the 6MWT encourage the search of new parameters that more accurately reflect functional performance[9] and an overall health status. Previous reports have already indicated that the work of walking during the 6MWT can be correlated with the horizontal work on a treadmill (WHO). Since the 6MWT is performed in a horizontal plane and at constant velocity, the work of walking in the 6MWT can be calculated as a product of distance and weight (i.e., D.W)[10]. In our study, we found that all associations with cardiorespiratory responses were greatly improved when the D.W was used rather than walking and percent-predicted distance values. We observed a moderate to modest correlation between both VO2SS and wMRT with walking and percent-predicted distance. However, when the D.W was applied, a strong correlation was observed with VO2SS (r=0.82, p<0.001) and wMRT (r=- 0.70, p<0.001). These results corroborate with other findings in the literature; Chuang, Lin and Wasserman[10] found a modest correlation between 6MWT-distance and peak VO2 (r=0.40, p<0.05) versus a stronger correlation between D.W and peak VO2 (r=0.67, p<0.05). Similarly, Poersch et al[11] found that peak VO2 was modestly correlated with distance (r=0.32, p=0.084) and percent-predicted distance using Soares and Pereira[14] equation (r=0.35, p=0.058), while strongly correlated with D.W (r=0.76, p<0.01). Both aforementioned studies were performed in chronic obstructive pulmonary disease cohorts that underwent cardiopulmonary exercise testing. To the best of our knowledge, this is the first study to evaluate the association between D.W of the 6MWT with VO2 on-kinetics in CAD patients.
It is already well established that CAD exposes the myocardial to a mismatch in oxygen supply and demand. As the time associated with this imbalance elongates, CAD evolves with greater manifestations, leading to a greater impairment in ventricular function, as in LVSD. CAD is the major cause of chronic heart failure leading to progressive degrees of impaired exercise capacity[26]. A limitation of physical activity in this population can be detected by a lower 6MWT performance[6]. In the current study, the LVEF was moderately to strongly correlated to all three 6MWT parameters evaluated in our CAD cohort. As expected based on previous literature[22], our results also revealed that when participants were separated according to LVEF, those with LVSD achieved lower distance and lower D.W during the 6MWT.
In the present study, despite the 6MWT distance already had a large effect size (d=0.84), the D.W effect size was much larger (d=1.32), indicating this as a powerful parameter to discriminate the level of disease impairment. These findings suggest that D.W may be a preferred measure in quantifying submaximal performance. Moreover, the stronger correlation observed to VO2 on-kinetics support the widespread use of D.W, particularly if ventilatory expired gas analysis is not available.
A limitation of this study was that most of the participants were males (80.4%). Women exhibit a lower exercise capacity and as such a gender bias might impact results, especially due to the utilization of a walking test[27,28]. This was a cross-sectional study with a modest number of patients. Future research is necessary to established specific D.W values that could predict clinical outcomes in cardiac patients and reinforced this as superior to walking distance.