Oxygen kinetics during 6-minute walk tests in patients with cardiovascular and pulmonary disease

Abstract

Background: The 6-Minute Walk Test (6MWT) is representative of daily-life activities and reflects the functional capacity of patients. The change of oxygen uptake (VO2) in the initial phase of low-intensity exercise (VO2 kinetics) can be used to assess submaximal exercise performance of patients.The objective of the following study was to analyse VO2 kinetics in patients with different pulmonary and cardiovascular diseases. In addition, we investigated the extent to which VO2 kinetics at the onset of the 6MWT were associated with exercise capacity, morbidity and mortality.

Methods: VO2 kinetics of 204 patients and 16 healthy controls were obtained using mobile telemetric cardiopulmonary monitoring during a 6MWT. A new mean response time (MRT) index (wMRT) was developed to quantify VO2 kinetics by correcting MRT for work rate. The differences in wMRT between disease categories as well as the association between wMRT and patients' exercise capacity and outcome - time to hospitalization/death- were tested.

Results: The assessment of a robust wMRT was feasible in 86% (244/284) patients. wMRT was increased in patients compared to healthy controls (p <0.001). wMRT was largest in patients with pulmonary arterial hypertension (PAH). There were significant associations between wMRT and exercise capacity in all patients. High wMRT was found to be associated with a high rate of death and re-hospitalization in patients with CHF (p = 0.024). In patients with pulmonary diseases and pulmonary hypertension wMRT was not associated with outcome (p = 0.952).

Conclusions: Submaximal exercise performance of patients is reduced. O2 kinetics at the onset of exercise are associated with exercise capacity in all patients. wMRT was found to be an important prognostic factor in patients with congestive heart failure (CHF), but not with pulmonary diseases.

Figure 1

Study exclusions due to technical issues or loss of follow-up. Nine (3%) tests were excluded due to significant patient-related or technical flaws. In thirty-eight (15%) tests it was not possible to fit an acceptable oxygen uptake kinetics curve. Two hundred and twenty tests (82%) were included in the final analysis.

Figure 2

Pre-processing of oxygen uptake during 6MWT and curve fitting. Panel A shows the raw breath-by-breath data. Panel B displays the data after averaging over successive periods of 18 seconds. Panel C depicts the curve fitting (red line) during the 6-minute walk test (6MWT), together with the parameter estimates including the lower limit (y1), the upper limit (y2), and the oxygen deficit (O₂def), from which the mean response time is derived.

Figure 3

Mean response time in the various participants’ categories. The figure shows the box plot distributions of wMRT within the following categories: healthy controls (Healthy); restrictive lung disease (Restrictive); chronic obstructive pulmonary disease (COPD); pulmonary arterial hypertension (PAH); congestive heart failure (CHF). The reparameterized wMRT showed significant differences between patients and healthy controls (p <0.001), the latter showing low wMRT values. Patients suffering from PAH have higher wMRT values than patients with COPD (p = 0.010), restrictive lung disease (p <0.001) and with CHF (p <0.001).

Figure 4

Scatterplot showing the relationship between wMRT and VO _2ss . A Scatterplot showing the relationship between wMRT and VO_2SS in healthy controls (green dots) and in patients (blue dots). B Scatterplot showing the relationship between wMRT and VO_2SS in patients with chronic obstructive pulmonary disease (COPD), restrictive lung disease (Restrictive), pulmonary arterial hypertension (PAH) and congestive heart failure (CHF). The red dots in the scatter plot show the patients who suffered an event (death or re-hospitalization) during the follow-up period.

Figure 5

Reparameterized mean response time and time to death and/or hospitalization during follow-up. The Kaplan-Meier curves depict the time to death and/or hospitalization in non-cardiac (left panel) and cardiac (right panel) patients, as a function of the reparameterized mean response time (wMRT) dichotomized (based on the median wMRT: non- cardiac patients: 1.85V10^-3, cardiac patients: 1.59×10^-3) into low vs. high wMRT categories.