Different testing protocols have been developed for functional testing. Patient capabilities and diagnostic goals generally determine the choice of CPET and protocol modality. However, the principle is similar for all these, and requires the incremental monitored exercise effort until maximal exertion is reached. Some of these include the Balke and Ware, Naughton, and ramp protocols. Irrespective of the one used, it should be individualized and tailored to yield fatigue-limited exercise, which, in ideal circumstances, should occur between 8 and 12 min. Shorter evaluations produce unreliable non-linear relationships between oxygen uptake and work performed. Contrariwise, more protracted regiments may result in testing termination due to specific muscle fatigue, as opposed to cardiopulmonary endpoints. Finally, patients should be discouraged from significant handrail support since it alters the relationship between oxygen uptake and work, by effectively reducing the latter for any given measurement of the former.

During exercise, oxygen uptake (Vo₂) can be estimated by the Fick Equation:

SV represents the stroke volume, HR the heart rate, Cao₂ the arterial oxygen content, and Cvo₂ the mixed venous oxygen. At maximal exercise, this equation would reflect the subject’s ability to take in, exchange, transport, and utilize oxygen for aerobic metabolism. The Vo₂ response to exercise is linear until a maximum is reached, and then begins to plateau. With higher metabolic workloads, the arterio-venous oxygen difference increases, which is a physiologic response best noted in trained athletes. On the other hand, exercise intolerance is evidenced by any changes in the Fick equation that results in an abnormally low Vo₂max, such as suboptimal maximal heart rate response, decrease stroke volume, decrease in Cao₂, or increase in Cvo₂ [3].

Other important estimations include the respiratory exchange ratio (RER) and the ventilatory anaerobic threshold (VAT). The former is calculated by dividing the carbon dioxide output by the oxygen uptake. The RER is determined by the main source of metabolic fuel used; with a ratio of 1 indicative of carbohydrates while <1 represents a mix of carbohydrates and fat, or protein. RER may increase during exercise due to either buffered lactic acid or hyperventilation. Conversely, VAT, or anaerobic threshold, is a determinant of exercise capacity. This principle relies in the fact that at lower workloads metabolism is mostly aerobic whereas there is a shift to lactate production with increasing exercise intensity. The VAT can be determined by directly measuring blood lactic acid or bicarbonate content, or less reliably through non-invasive techniques. Figure 5.2 shows a metabolic test graph report. Normal parameters for CPET and patterns of abnormal results are shown in Tables 5.1 and 5.2, respectively.