Cardiopulmonary testing (CPX) measures exercise tolerance in patients with heart failure: VO, max
V02 max (maximal measured oxygen uptake) is the highest VO, achieved in an exercise protocol to exhaustion involving the major muscle groups; it is the best indicator of aerobic capacity; it can be defined as the plateau reached by maximal oxygen uptake, ie, the point at which uptake does not increase in response to an increase in workload. A failed test is one in which the increase in oxygen uptake is <0.150 L/min or 2.1 mL/kg/min in response to a 25% increase in the treadmill slope. V02 max is the most accurate, reliable, and reproducible functional CPX parameter. It measures the maximal capacity of the cardiovascular, pulmonary and muscular systems. It is an objective measure independent of patient motivation, and dependent on age, gender, and body weight (Table I).
Patients with heart failure rarely achieve VO, max due to rapid symptom onset, low motivation, or concomitant pulmonary, muscular, and musculoskeletal disease. The measure most used then becomes VO, at peak exercise (peak V02), without a plateau phase, and measured in the last 20 to 30 seconds of an exercise protocol to exhaustion.
Peak VO, depends not only on the maximal load reached and exercise duration, but also on motivation and symptom perception by both patient and laboratory physiologist. Peak VO, is more accurate than most commonly used indicators of exercise tolerance, and does not correlate closely with them. This is due partly to the protocols used (the use of 3-minute increments can extend the exercise duration with no change in V02, ie, it can achieve steady state), but mainly to clinical severity. Thus, a reduction in VO, with no change in workload indicates functional impairment as the patient depends increasingly on anaerobic metabolism to maintain exercise capacity.
The CPX data are interpreted by comparing the peak V02 with the 1985 classification by Weber et al (Table II). These levels of dysfunction are still widely applied, and their accuracy and reproducibility in defining functional capacity are superior to alternatives such as New York Heart Association (NYHA) functional class. However, despite the clinical validity and prognostic accuracy of the Weber classification, there are restrictions on the application of peak V02. In heart failure in particular, peak V02 is greatly influenced by the protocol, the exercise modalities, patient motivation, and level of encouragement by physician/physiologist. For example, peak V02 on the treadmill may exceed the cycle ergometer value in the
Ventilatory anaerobic threshold
As V02 max is difficult to determine in heart failure and peak V02 is limited by patient subjectivity and physician involvement, the VAT has been suggested as an alternative index of functional capacity.
The response to exercise includes various phases: preparation, initial phase, stabilization, and completion. The initial phase is characterized by sudden cardiovascular and respiratory adjustment and it ends a few seconds later. Subsequently, if the exercise is sub maximal and constant, the stabilization phase occurs, with minor adjustment to maximize regulatory system synergy. The stabilization phase is followed by a level of physical activity that precedes muscular exhaustion: the VAT. At the VAT, part of the energy required to continue exercising comes from the anaerobic lactic acid system. The VAT is the phase at which anaerobic metabolism is added to aerobic metabolism, causing a significant increase in lactic acid levels. The physiologic determinants of the VAT and increased lactic acid levels during exercise remain debated. Lactic acid accumulation results from a cascade of metabolic events and respiratory adjustments which can be identified by monitoring expired gases during CPX.
VE, V02, and VC02 increase progressively during exercise until the VAT is reached, ie, when a level of exercise is reached at which the oxygen supply to muscles becomes inadequate to meet the demand and the necessary energy must be supplied by anaerobic metabolism. This causes lactic acid and hydrogen ion production, and V02 must increase further to buffer both products (using the bicarbonate/carbonic acid system). But V02 also increases VE. It is still debated whether muscle hypoxia is the main determinant of the increased lactate production. The VAT at the muscle cell level, the onset of lactate accumulation in the blood, and the respiratory threshold may be separate, but related, events. Regarding respiration, there is an increase in ventilation (VE) to the detriment of respiratory rate and an increase in carbon dioxide (âœnon-metabolicâ VC02, produced by the bicarbonate buffers) that is out of proportion to oxygen consumption (V02), so RR inversion occurs. The VAT is identified by multiparametric analysis of VE, V02, VC02 and the ventilatory equivalents (VE/V02, VE/VC02), or using the V-slope method (VC02 vs V02).
It may be expressed as the following:
The V02 value at which VE increases faster than VO, (increase in VE/V02 ratio), while the VE/VC02 ratio and end-expiratory partial oxygen tension (PetC02) remain constant, and the expired 02 fraction FE02 increases without a reduction of the expired C02 fraction (anxiety hyperventilation causes simultaneous increases in VE/V02 and VE/VC02).
The lowest value of VE/V02.
The beginning of the increase in the VE and VC02 slope together with a linear increase in V02, increase in the respiratory ratio and FEOr
The V02 value at the break in the VC02/V02 straight line. This method is not influenced by ventilation.
The threshold occurs at an average of 60% to 70% of V02 max, and is dependent on the same factors that influence maximal exercise tolerance. In clinical and functional terms, VAT is a submaximal parameter, which is reproducible and independent of patient motivation. It validates peak V02 because achieving the threshold requires intense metabolic-muscular commitment. Unfortunately, it is unidentifiable in a substantial proportion of heart failure patients (high NYHA class, severe systolic and diastolic left ventricular dysfunction, high furosemide dose, decreased aerobic capacity, peak V02 <10 mL/kg/min, excessive ventilation during the test, and the same RR during exercise).
Respiratory response to exercise
For the same amount of work and C02 production, heart failure patients have higher values of ventilation (volume/minute), mainly due to an increase in respiratory rate. The severity of this ventilatory abnormality correlates with exercise tolerance in heart failure, but not in health. The mechanisms responsible for the hyperpnea remain debated. Pulmonary dysfunction may be more important than cardiac dysfunction in reducing exercise tolerance. Increased chemosensitiv-ity to hypoxia has been recently demonstrated in heart failure, possibly due to a reduced blood flow to the carotid chemoreceptors or to reduced baroceptor sensitivity. An alternative stimulus of ventilation and dys= pnea may be the exaggerated ergoreflex muscle activity in heart failure. Reducing the respiratory rate by yoga respiratory training enhances exercise capacity and decreases exertional dyspnea.
Oxygen uptake in cm-min divided by heart rate is termed the oxygen pulse. In heart failure, heart rate is generally higher than in healthy subjects with an identical V02. However, drugs such as digoxin, vasodilators, (3-blockers, amiodarone, etc, may affect the chronotropic response to exercise. Another problem is atrial fibrillation, when the average ventricular response is generally higher at rest and more importantly, increases rapidly and markedly during exercise.
Reproducibility of the main cardiopulmonary parameters
Quality control of methodology and measurement, in terms of accuracy and reproducibility, is fundamental in any clinical laboratory. Clinical application of CPX to define severity and progression of disease and the efficacy of therapy depends on documented reproducibility of measurement. Reproducibility has thus been evaluated in duplicate, triplicate, or even in five replicates or more, in individual laboratories and/or multicenter analyses, over the short (weeks) or long term (months), using various parameters: correlation coefficient, percentage deviation from the mean, standard error, and coefficient of variation. Other factors will also influence reproducibility, such as patient lifestyle between tests (diet, smoking, emotion, exercise, or sedentary status).
An incremental CPX is considered reproducible if peak V02 has a variability of Â±10%. Independently of methodological differences, a familiarization test is required to avoid underestimating the aerobic capacity of a heart failure patient. If a training test is not possible, the increase in peak V02 should be interpreted with caution to avoid ascribing improvement, often determined by better psychologic and emotional adjustment to the test, to external factors such as therapy or training.
instrumental finding; cardiopulmonary exercise testing; V02 max; peak V02; aerobic performance; oxygen pulse; reproducibility; prognosis