Chronotropic incompetence

In healthy people, cardiac output during exercise increases via a rise in both heart rate and stroke volume. When the heart rate does not rise sufficiently, this can lead to exercise intolerance. CI can be detected using a cardiopulmonary exercise test.^[1] People with CI have a higher risk of cardiovascular disease and early death.^[1]

There are different ways to define CI. One common threshold is not being able to reach 80% of age-predicted maximal heart rate (APMHR), which is said to be 220 – age. Another definition is not being able to reach 80% of the expected heart rate reserve, that is, the difference between the individual's resting heart rate and APMHR.^[1]

Chronotropic incompetence occurs in various diseases. Roughly half of people with heart failure experience it, compared to less than 9% of age-matched healthy controls.^[2] When CI occurs alongside issues with stroke volume, it can lead to a strong decrease in functional ability.^[1] It is associated with the activation of the sympathetic nervous system (part of the fight-or-flight response), leading to higher levels of norepinephrine. CI in people with heart failure can further be related to the use of β-blockers, a high resting heart rate or the downregulation of β-adrenergic receptors.^[3]

CI is also observed in people with obstructive sleep apnea.^[4] Similarly to CI in heart failure, it is possibly linked to the autonomic nervous system shift towards the sympathetic nervous system.^[1][4] People with type-2 diabetes often experience CI too,^[5] as do some people with long COVID.^[6] People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) also experience a blunted heart rate response to exercise.^[7] CI in ME/CFS is most evident on the second day of a repeated exercise test, after the first exercise test induces post-exertional malaise.^[8]