How does a CPET show a Cardiac Limitation?

Recently a patient was referred to my lab for a CPET by his oncologist. The patient had been complaining of excessive shortness of breath particularly when climbing only a few stairs. The patient recently had a full PFT panel (spirometry, lung volumes, DLCO) and the results had showed mild restriction with a mild gas exchange defect. The patient’s shortness of breath symptoms were far more severe than could be explained by his PFTs however, so he had been referred to Cardiology and had an ECG stress test. The stress test results were normal so Cardiology told the oncologist that the patient’s problems were probably not cardiac.

Because the patient’s PFT results were reduced the patient’s oncologist consulted with a couple of our pulmonary physicians and they suggested a CPET. When I reviewed the patient’s CPET results despite a mildly reduced TLC and DLCO it was quite clear the patient’s primary limitation was in fact cardiac. Why was there such a discrepancy between Cardiology’s ECG stress test and our CPET? The simple answer is that a CPET measures oxygen consumption and a routine ECG stress test does not.

Strictly speaking, during a progressive exercise test any individual with normal heart and lungs usually reaches a cardiac limit before they reach any kind of a pulmonary limit and this is normal. A fit, athletic individual usually has a higher than normal stroke volume (and cardiac output) while a somebody that is out-of-shape has a reduced stroke volume (and cardiac output). This is one of the key differences between being conditioned and being de-conditioned.

So what are the hallmarks of an abnormal cardiac limitation?

There are, of course, many different types of cardiac disease but the common factor (at least in terms of a CPET) is an abnormal decrease in cardiac output. Cardiac output cannot be measured during exercise without specialized equipment or indwelling catheters but there is an intimate connection between cardiac output and VO2 as shown by the Fick equation:

Fick_Equation

Note: CaO2 and CvO2 refer to the oxygen content (in vol%) of arterial and venous blood respectively. I’ve frequently seen CaO2 and CvO2 described as the concentration of oxygen in the blood but although this may be semantically correct I feel it is imprecise because it is easily confused with the partial pressure of oxygen or oxygen saturation when it is actually a function of both of these properties:

O2_Content_Equation

The Fick equation can be restated to make the relationship more obvious:

Fick_Equation_Rearranged

A reduced cardiac output will therefore reduce the maximum VO2 but how do you know when a patient has reached their maximum VO2? This occurs when they reach a plateau in their oxygen consumption. This is also the definition of VO2 Max as opposed to the maximum VO2 that is achieved during a CPET. A VO2 plateau usually requires a motivated patient that is willing to endure discomfort and push themselves however, so it is not seen as often as it should be. There isn’t a precise definition for a VO2 plateau and an apparent VO2 plateau during the final moments of a CPET can also occur when a patient has reduced their exercise effort. Because the indicators of patient effort are somewhat subjective my current working definition is a plateau in VO2 that occurs for at least a minute while VCO2 and Ve continue to increase. A VO2 plateau that occurs at a reduced maximum VO2 is a strong indication of a cardiac output limitation.

The maximum VO2 from a CPET can be reduced for non-cardiac reasons, such as pulmonary mechanical or pulmonary vascular limitations (COPD or IPF for example) but in these instances oxygen saturation is also usually reduced. When cardiac output is reduced SaO2 remains normal which is because:

SaO2 DLO2 equation

Because pulmonary limitations usually decrease the ability of the lung to transfer oxygen SaO2 will decrease as well but as long as the cardiac output is less than the DLO2 then SaO2 remains normal.

As workload increases during a CPET there comes a point at which the amount of oxygen delivered to the exercising muscle is no longer entirely able to meet its needs. This is the point at which lactic acid begins to accumulate, CO2 production increases and is the definition of the Anaerobic Threshold (AT). A reduced cardiac output reduces the delivery of oxygen to the exercising muscles and for this reason not only is the maximum VO2 decreased when there is a cardiac limitation, the VO2 at anaerobic threshold is also usually reduced.

VO2 at AT: Male: Female:
Age: Mean: LLN: Mean: LLN:
20 53% 42 52% 41
30 54% 43 55% 44
40 55% 44 58% 47
50 56% 45 60% 49
60 57% 46 63% 52
70 58% 47 65% 54

A VO2 at AT that is less than the LLN is a strong indication of an abnormal cardiovacular limitation.

Finally for individuals with normal cardiovascular function, there is a linear relationship between VO2 and workload. For individuals with a low cardiac output, a significant proportion of their energy, particularly above anaerobic threshold comes from anaerobic processes. This means that VO2 decreases more slowly for a given increase in workload.

VO2_Workload

Depending on the degree of cardiovascular limitation and the motivation of the individual that is exercising this can either be readily apparent or very subtle.

To summarize, an abnormal cardiac limitation usually has these features:

  • Reduced maximum oxygen consumption
  • Normal SaO2
  • Reduced VO2 at anaerobic threshold
  • A non-linear VO2-workrate relationship

So what did the patient’s results look like and how do they compare to these benchmarks?

AT: %Predicted: Peak Exercise: %Predicted:
VO2 (LPM): 0.65 28% 1.17 49%
RER: 0.95 1.40
SaO2: 96% 96%
Minute Ventilation (LPM): 18.4 23% 53.2 64%
Heart Rate (BPM): 115 69%
O2 Pulse (ml/beat): 10.4 72%

In addition:

  • There was a VO2 plateau during the final minute of exercise (with an increasing VCO2 and Ve).
  • The chronotropic index was 0.72 (0.80 is the LLN).
  • Ve/VCO2 at AT was 30.
  • Ve-VCO2 slope from rest to AT was 23.6.
  • The highest PETCO2 (which occurred slightly after AT) was 39.9.
  • There was a slight downwards inflection of the VO2-workload starting around AT

The RER of 1.40 and VO2 plateau indicates that this was truly a maximal CPET. The low VO2 at anaerobic threshold and low VO2 max without a decrease in SaO2 indicates that the primary limitation was cardiovascular.

The CPET shows at least two reasons for a cardiovascular limitation; One part is chronotropic incompetence (as shown by the reduced chronotropic index, the patient was taking Metoprolol and it’s possible the dosage is too high). The other part is a reduced stroke volume (as shown by the reduced maximum O2 pulse). There are likely other cardiac issues but these are the ones the CPET makes definitive.

It was also clear there were no pulmonary limitations. The minute ventilation of 23% of predicted at AT and maximum minute ventilation of 64% of predicted indicates there wasn’t any pulmonary mechanical limitation. The normal Ve/VCO2 at AT, Ve-VCO2 slope and PETCO2 indicate that there wasn’t pulmonary vascular limitation.

An abnormal cardiac limitation isn’t necessarily accompanied by ECG changes that can be detected with a stress ECG test. Rightly or not, the oncologist felt that they and the patient had been blown off by cardiology. In this instance my PFT lab was able to give a fairly definitive answer for the patient’s shortness of breath but I’d like to stress that what we performed was a cardio-pulmonary exercise test.

CPETs are highly effective at determining the causes for shortness of breath. In many instances, given that it is non-invasive, it is the only reasonable approach as well. Unfortunately cardiopulmonary exercise tests are not as commonly available as they should be. Even when they are available, CPETs are not ordered as frequently as they should be. For these reasons there are many patients with shortness of breath who are forced to go for a prolonged time without a diagnosis and may be end up being “blown off” by any number of specialists.

To a large extent this is a cart and horse problem. Patients don’t have CPETs ordered because they aren’t readily available and CPET programs are not supported because there aren’t enough patients. I could (and frequently do) argue that CPET (and PFT) testing is a solution for institutional cost-effectiveness because it improves patient care with earlier and better diagnoses but producing the numbers to back this up is difficult. Realistically this means that any good CPET program requires a commitment from a hospital’s physicians and administrators who are willing to believe in the effectiveness of CPET testing without being able to prove it.

Cardiopulmonary exercise tests are quite good at differentiating between the pulmonary and cardiac causes of an exercise limitation. In this case, despite a reduced TLC and DLCO and a normal ECG stress test, the patient’s limitations were ultimately due to a cardiac rather than a pulmonary limitation. In one sense this proves the value of cardiopulmonary exercise testing but I also want to take this as a reminder that patients are complex and that the tests we use most routinely always have a limited scope.

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7 thoughts on “How does a CPET show a Cardiac Limitation?

  1. Thank you for this post.

    Question: How do you separate significant deconditioning from mild cardiovascular disease? Perhaps there is no easy way.

    I wonder if the only way to tell or be sure is to put the patient through a graded exercise program and then repeat the VO2 max. Major improvement in the VO2 max suggests the original VO2 max was low because of deconditioning. But have to keep in mind that even cardiovascular diseased patients can have a training effect.

    Also raises the question, how do you/we really define or identify deconditioning?

    • Thomas –

      I think it is deconditioning when the CPET is an adequate test, the VO2 and O2 pulse are low normal and the chronotropic index is high normal (and there are no pulmonary limitations). I like your definition that it is also reversible with training. You have to draw the line between deconditioning and an abnormal cardiac limitation somewhere and that has to be when VO2 is below normal. For us that is <80% of predicted using Wasserman's algorithm for predicted VO2.

      - Richard

  2. Do you have a reference for the table which shows AT as a mean % of peak VO2 by age and gender with LLN? I was curious as to why the mean % increases with age.

    • Amy –

      The table comes from Wasserman’s book on exercise testing. My copy is the 4th edition and it’s on page 171.

      The predicted maximum VO2 decreases with age, so expressed as LPM the predicted VO2 at AT actually decreases slightly with age but not as fast as the max VO2 decreases. The VO2 at AT is a reflection of a physiological requirement and therefore changes less over an individual’s lifetime.

      Regards, Richard

  3. Richard Johnston.Very often patients take beta blockers (bisoprolol, metoprolol et al). Also raises the question, how do you/we really define or identify deconditioning?

    • Andrey –

      The difference between the two is their chronotropic index, which is the slope of the HR-VO2 curve. When a subject takes beta blockers this reduces their ability to increase their heart rate. A long-term adaptation to the use of beta blockers is an increase in cardiac stroke volume. This means that they are able to maintain a near-normal cardiac output and VO2 at a lower maximum heart rate. This lowers the HR-VO2 slope. When an individual is deconditioned by definition this means they have a lower cardiac stroke volume, and therefore even at their maximum heart rate (assuming they can achieve it) their cardiac output and VO2 will be reduced and their HR-VO2 slope will be increased. The normal range for the chronotropic index is 0.80 to 1.30. A chronotropic index below 0.8 is a sign of chronotropic incompetence (the inability to increase heart rate) and is often seen in patients with beta blockers. A chronotropic index above 1.30 is a sign of a low stroke volume which, as mentioned, is a sign (in the absence of other cardiac disease, like diastolic dysfunction or valve disease) of deconditioning.

      Regards, Richard

  4. Hi Richard,
    Your PFT forum archives continue to help and inform me. I reference them frequently. Just wanted you to know that!

    I also want you to know that I think about you and hope you are well. The world needs more generous people like yourself.

    regards,
    Cory Heath, RRT, RPFT
    Berkshire Medical Center
    Pittsfield, MA 01201

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