In a nutshell:
- Chronotropic incompetence (CI) – the inability of the heart to keep pace with increased activity – is common in myalgic encephalomyelitis (ME/CFS)
- CI is worse in women with ME/CFS but both men and women have a lower than expected heart rate at the anaerobic threshold
- CI is worse in those who have a more severe form of the illness
- CI complicates pacing and will result in inaccurate estimates for the anaerobic threshold when using the age-predicted formula (220 – age)
- In the absence of knowing if you have CI or how severe it is a safer approach to pacing is to keep heart rate below 15 beats above your resting heart rate (RHR + 15 bpm)
- This approach can be further refined by tuning into the immediate, short term, and long term symptoms of post-exertional malaise.
A normal response to exercise is an increase in heart rate. However, in some people, heart rate does not rise according to the predicted levels based on age. The inability of the heart to keep pace with increased activity is called chronotropic incompetence (CI).
CI is a disabling condition that is the main cause or significant contributor to severe, symptomatic exercise intolerance and is an independent predictor of major adverse cardiovascular events and increased mortality. As such, CI may reduce the quality and quantity of life.
According to two meta-analyses from 2019 – one from researchers at Workwell Foundation and the University of the Pacific (UOP) and another from two research groups in Australia – CI is found commonly in people with ME/CFS.
A blunted heart rate contributes to the already low oxygen uptake (VO2) found in ME/CFS (see figure 1), placing further limits on levels of activity. Could CI contribute to the energy metabolism problems seen in ME/CFS? What are the implications of a blunted heart rate for post-exertional malaise (PEM) pacing with a heart rate monitor?
In addition to an inability to reach age-predicted heart rate, many with ME/CFS have a delayed response in reaching maximum heart rate, a low anaerobic threshold (the point at which we switch from aerobic to anaerobic metabolism), a delay in the return to a resting heart rate, and heart rate instability during exertion. All of these are facets of CI and each one affects pacing.
CI in ME/CFS
Workwell Foundation – the pioneers of 2-day cardiopulmonary exercise testing (CPET) for ME/CFS – were ideally suited to synthesize the available data on CI. After seeing this phenomenon for years in both their research and disability testing, they combed the literature to find studies involving 1- and 2-day maximal CPET, which involves exercising to peak exertion. Maximal exercise testing is key for reliably capturing the transition from aerobic to anaerobic metabolism, also called the ventilatory threshold (VAT), and to ensure that maximum heart rate is reached. Overall, they found 36 studies that met their criteria for inclusion in their meta-analysis.
The Australian study had much broader criteria for including studies in their analysis, including studies with submaximal exercise testing and tilt-table testing. Overall, 64 papers were included in their meta-analysis. This paper also looked at cardiac regulation by the autonomic nervous system (ANS) to better understand the possible causes of CI.
Measuring chronotropic incompetence
Chronotropic incompetence is defined as the failure to meet the age-predicted heart rate, defined as 220-age, at maximal exertion. The cutoff for a CI diagnosis ranges from 70-85% of the age-predicted heart rate.
CI is measured as the fraction of heart rate reserve achieved at maximal effort during an exercise test, adjusted for age. Heart rate reserve is the difference between the resting heart rate and maximum heart rate. This information is combined into various indices that may also include age, resting heart rate, age-predicted maximal heart rate, age-predicted heart rate reserve, maximal heart rate observed during exercise testing, and metabolic measures such as the volume of oxygen consumed (VO2 max).
CI is common in ME/CFS in both women and men
The Workwell study found overwhelming evidence for CI in ME/CFS patients, including both men and women, relative to healthy subjects. The matched controls, on average, achieved 94% of age-predicted maximum heart rate whereas the people with ME/CFS only reached 82% of the predicted heart rate. Overall, 92% of the ME/CFS group had a lower peak exercise heart rate relative to controls. According to Mark VanNess, 89% of people with ME/CFS have CI. An older study by Montague and colleagues found a similar result (87% of ME/CFS subjects had CI). See Figure 2.
The Australian meta-analysis also found strong evidence for CI in ME/CFS, with average maximum heart rate being 13 bpm lower compared to controls, despite starting with a higher resting heart rate.
There were some interesting gender differences. Overall, both men and women showed a lower peak heart rate than controls, but men were able to achieve a higher peak heart rate than women (87% of estimated peak HR for men and 83% for women). However, at the anaerobic threshold (AT) – the point at which energy metabolism switches from aerobic to anaerobic – these differences disappeared, with both men and women having a lower than expected heart rate at this threshold. Overall, 63% of people with ME/CFS had a lower heart rate at AT than controls. The Australian meta-analysis also found a moderate difference in AT between ME/CFS subjects and controls (this study did not look at gender differences).
CI worsens on day 2 of repeat testing
In a finding unique to this disease, the study showed that the heart rate response was even lower on the second day of repeat exercise testing at both peak and sub-peak exertion levels. Overall, the ME/CFS subjects in the study performed at 88% of predicted heart rate on day one of testing but then dropped down to 83% on day two. This effect was amplified at AT; controls actually saw an increase relative to predicted HR whereas ME/CFS subjects saw a characteristic decline, putting the oxygen costs of even simple activities above a safe heart rate threshold for many.
CI worsens with disease severity
The magnitude of CI also depends on disease severity, with the most severe patients experiencing even greater differences between actual and predicted maximum heart rate. The percent of predicted heart rate ranged from 83% at the mild end of the spectrum and dropped down to 68% for severely-impacted people. This is likely due to increasing autonomic dysfunction with increasing disease severity, a topic I will probe in a future piece.
The Australian study also included various measures of the autonomic nervous system and found that people with ME/CFS have a higher resting heart rate and lower heart rate variability (HRV) scores relative to controls. This means that there is often a small band between the resting heart rate and heart rate at the AT, placing a severe limit on activities that are safe.
Implications of a blunted heart rate for pacing
A blunted heart rate complicates standard pacing advice. Many people with ME/CFS use an estimated (vs. direct via CPET) measure for AT as the benchmark for pacing. For more information on the anaerobic threshold and its implications for pacing, see my blog on energy metabolism and pacing and 2-day cardiopulmonary testing.
The formula most commonly used by people with ME/CFS to estimate AT is:
Anaerobic threshold = (220 – age) x multiplier
Where 220 – age is the estimated maximum heart rate based on age. The multiplier typically used is 0.55 (another way to think of this is 55% of age-predicted HR).
The assumption behind this equation is that those using it can actually achieve the age-predicted maximum heart rate (220 – age). People with CI do not meet this assumption, invalidating this approach.
What to do in the absence of 2-day CPET, when the extent of CI and AT is unknown? There is no way to estimate CI, other than exercising to maximum capacity and measuring heart rate. Clearly, this is ill-advised for people with ME/CFS! If you have done a 2-CPET, look on your report for the maximum heart rate achieved on day 2. If your value is less than 85% of the maximum heart rate predicted for your age, you likely have CI.
More recently, Workwell advocates for taking an entirely different approach to pacing. Instead of using an estimated AT, they advocate for taking a more conservative, and therefore safer, approach.
A different (and safer) approach to pacing
Workwell’s guidance is to focus on the resting heart rate (RHR) and to use this as the benchmark for pacing.
Anyone can determine their RHR by simply measuring heart rate first thing in the morning while still at rest and before getting up. If your heart rate bounces around a lot, as it does for many with ME/CFS, try to take an average value for each day during the baselining period. For example, if your resting heart rate settles between 70 and 80 bpm, use 75 bpm as the average value for that day. Take the average of a week’s worth of values and use this as your reference point for pacing.
RHR will vary somewhat, especially in response to PEM, which can either elevate or decrease RHR by up to 10 bpm. Note: a drop or increase in RHR can be a sign that you have overdone things and are in PEM. This day-to-day variability is the reason for taking an average of readings over the period of a week or so.
Using average RHR, add 15-20 beats to that measure. For example, my RHR is ~ 55 bpm (range is 42-62 bpm). Using these numbers, my pacing benchmark is ~ 70 bpm, which is very close to the AT measured during my CPET (actual value was 69 bpm). Because of CI, the standard formula overestimates: AT = (220-52)*0.55 = 92 bpm, which is 23 beats above my measured AT.
For some people, this approach may seem exceedingly punishing. The only risk here is that you underestimate your pacing benchmark. This will be the case for people who do not have CI. However, the risk of using an age-predicted maximum heart rate to estimate AT is that you may overestimate your pacing benchmark and experience more PEM, especially if you have CI. While this is a bit of a conundrum, the more conservative pacing approach being advocated by Workwell is certainly safer as a starting point.
Yet another approach to pacing if CI status is unknown
Learning to spot the immediate symptoms of PEM can also help dial in an appropriate pacing benchmark. Workwell has created a handout on the PEM time course, including the symptoms of immediate, short-term, and long-term PEM (Figure 3). Immediate symptoms are related to the body’s response to crossing into anaerobic metabolism and include shortness of breath, dizziness, and nausea. Tuning into these symptoms may allow you to determine if your pacing benchmark is higher than RHR+15 bpm. Once you find the heart rate at which these or similar symptoms occur, it is wise to set your pacing benchmark at 10 beats below this value to avoid crossing into anaerobic metabolism and associated PEM.
For example, let’s say you notice immediate symptoms of PEM (shortness of breath, dizziness) at 100 bpm. Using this information, an appropriate pacing threshold to try is 90 bpm (10 beats below the point at which you first notice symptoms). If you still experience PEM, you may need to revise down on your pacing benchmark.
I will admit that I typically don’t feel the immediate symptoms of PEM until my heart rate is around 85 bpm, a full 15 beats above my actual AT. However, if I stayed 10 beats below 85 bpm I would be close to my AT. To be safe, always set the pacing threshold at least 10 beats below what you think your AT is.
Another refinement to pacing is to wait until your heart rate has settled to resting levels until engaging in the next activity. People with CI may have to wait longer.
Another way to know if you have the right pacing benchmark is whether your PEM is improving. Keep in mind that activities done below AT can also contribute to PEM.
CI combines with other forms of dysautonomia (postural orthostatic tachycardia syndrome, neurally-mediated hypotension, orthostatic intolerance) to make pacing more challenging. With some patience, enhanced ability to spot PEM as it is unfolding, a safe pacing benchmark can be found, even in the absence of a 2-day CPET.
Stay tuned for a future blog exploring the science of what might be driving CI in ME/CFS.