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Workwell Foundation: Chronotropic Intolerance:An Overlooked Determinant of Symptoms and Activity Limitation in ME


Senior Member

Front. Pediatr., 22 March 2019 | https://doi.org/10.3389/fped.2019.00082
Chronotropic Intolerance: An Overlooked Determinant of Symptoms and Activity Limitation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome?

Todd E. Davenport1,2*, Mary Lehnen1, Staci R. Stevens2, J. Mark VanNess2,3, Jared Stevens2 and Christopher R. Snell2

This literature synthesis supports the presence of abnormally blunted HR responses to activity in people with ME/CFS, at both maximal exertion and submaximal VAT. Pathophysiological processes consistent with autonomic dysregulation should be prioritized for etiologic studies in ME/CFS, independent of distal pathogenic causes and proximal multi-system effects. The abnormal heart rate response to exercise in people with ME/CFS indicates that exercise testing based on a percentage of maximal heart rate cannot be considered “submaximal” in people with ME/CFS and presents a clear risk for supramaximal exertion during “submaximal” exercise tasks in the most severely involved individuals. Pacing self-management plans based on age-predicted heart rate thresholds should be viewed with caution, because the chronotropic response is impaired in people with ME/CFS. Threshold heart rates for effective analeptic management and the etiology of observed CI in people with ME/CFS should be formally established through adequately powered studies that involve serial maximal CPET methodologies.


So the key idea here is our HRs don't bump when we need them to. The dotted line in the graph below

Screen Shot 2019-03-28 at 7.35.07 pm.png

This is a counter-intuitive idea given that our HRs often surge when we don't need them to (orthostatic intolerance)! But it's not impossible. In fact I wear a Fitbit HR monitor and even though it surges when I stand up my HR has never gone over 135. A person like me should be able to hit 190. I've never got close.

The next picture shows that MECFS patients have lower heart rate than controls at maximal exertion in almost all studies.

Screen Shot 2019-03-28 at 7.29.56 pm.png

Standardized mean differences (d) for heart rate at peak exertion during maximal cardiopulmonary exercise testing, comparing patients with ME/CFS (n = 1,053) and matched control subjects (n = 569). Boxes represent point estimates, and whiskers are 95% confidence intervals. Patients with ME/CFS had lower peak heart rates than matched control subjects (large effect size)

When patients do the two day test, the difference is much higher on day two.

The researchers also worry that if you do a "submaximal exertion test" and rely on heart rate to determine whether the exertion is submaximal, you may have mis-designed your test and be actually making subjects do their maximum.


Senior Member
U.S., Earth
So, what the authors are suggesting here is that:

The problem with exercise intolerance in ME may be due to dysautonomia, since the autonomic nervous system controls the heart rate, and the heart rate during exercise in ME patients is much lower than the heart rate during exercise in healthy controls.

The authors call this abnormally reduced heart rate during exercise "chronotropic intolerance". However, it is worth noting that other authors have a much more specific definition of "chronotropic intolerance", and these other authors might suggest that an abnormally reduced heart rate during exercise is insufficient to diagnose "chronotropic intolerance".