Output Linked to Severe CFS Cases
Article: “Abnormal Impedance Cardiography Predicts
Symptom Severity in Chronic Fatigue Syndrome.” The American Journal of the
Medical Sciences. 2003; 326(2):55-60.
Synopsis: While the cause of chronic fatigue syndrome
(CFS) remains unknown, researchers have noted circulatory irregularities in many
patients. These include autonomic nervous system dysfunction, often manifested
as orthostatic intolerance; neuroendocrine abnormalities (see story on p. 4);
reduced plasma volume; and low red blood cell mass. In combination, some
researchers believe, these factors could create deficiencies in blood flow to
organs and muscles — with resultant symptoms, such as post-exertional fatigue,
that are hallmarks of CFS.
New research from the
Center at the
Medicine and Dentistry of New Jersey
has tested the possible link between CFS symptoms and cardiac output (the amount
of blood pumped by the heart each minute). Thirty-eight CFS patients
participated in the study, along with 27 matched, sedentary controls. All
subjects were tested for cardiac output using impedance cardiography, a
noninvasive procedure based on the principle that electrical impedance of
tissues is proportional to their blood flow. Subjects were tested during a
10-minute resting supine period and a five-minute quiet standing period.
Results showed that patients with severe cases of CFS (those
who had more symptoms and rated them as substantial or greater in severity) had
significantly lower cardiac output than either controls or patients with
less-severe CFS — even though mean arterial blood pressure and heart rate did
not vary significantly among the groups. Moreover, post-exertional fatigue and
flu-like symptoms were predictive of lowered cardiac output (p< 0.0002).
The authors say their work suggests that “in some patients
with CFS, blood pressure is maintained at the cost of restricted flow, possibly
resulting in a low flow circulatory state.” CFS patients with lower cardiac
output may not be able to meet the demands of everyday physical activities,
leading to fatigue and other symptoms.
Q: What led to the hypothesis that CFS patients may have
reduced cardiac output?
Dr. Peckerman: Many of the symptoms of CFS, such
as post-exertional fatigue, are also symptoms of low cardiac output. A person
can have low cardiac output for a number of reasons, but the result is the same
— circulation slows down and some organs may not get enough blood flowing
through them. If cardiac output falls to the point that it is unable to meet
metabolic demands, this is called hypoperfusion. Clinical signs of hypoperfusion
include lowering of pulse pressure, cool extremities, altered mentation, rapid
resting heart rate, breathing that alternates between deep and shallow, and high
blood urea nitrogen relative to creatinine. To be sure, most CFS patients do not
show clinical signs of hypoperfusion, and they couldn’t. If you have symptoms
like these, you get referred for cardiological evaluation and treated
appropriately. You would not be diagnosed with CFS. The point I am making is
that the criteria for defining hypoperfusion are conservative. However, if you
lower the bar, meaning you entertain a possibility that reduction in blood flow
of a lesser degree than that may still be clinically significant, and you pull
together the many indications from different research and clinical observations
in CFS pointing in this direction, it becomes a reasonable question to ask.
Q. The gap in cardiac output between controls and severe
CFS cases was wider when subjects were supine than when they were standing. Why
might that be?
Dr. Peckerman: When you are lying down, blood
flow to the heart (venous return or preload) is generally higher compared to
what it is when you are standing. Normally, having high blood flow to the heart
is good. It helps the heart to work better. But if heart muscle is not working
properly, if it is compromised and may become overloaded. Then you have the
opposite effect. The more blood goes to the heart, the more the function goes
This is what happens with heart failure patients. When they’re
lying down, their heart’s pumping capacity is reduced. When they stand up, the
preload becomes reduced because much of the blood goes to the legs. Normal
people have reduced cardiac performance when standing. In these people, it’s the
opposite; it improves.
In a sense, this is what we found with severe CFS patients.
When we looked at the lying position, the difference between controls and the
severe patients was greater than when they were standing. If you start with the
presumption that these people have orthostatic intolerance due to low blood
volume, you’d expect to see larger deviation from the norm when standing. What
actually happened was the opposite; it was smaller.
Q: Are you saying that some people with severe CFS may
have heart failure?
Dr. Peckerman: Any such conclusion is really
beyond the scope of this study. But what we may be seeing here is a more subtle
form. Present medicine is slowly realizing that there are many people with heart
failure that is not clinically evident but which may be progressing in that
direction. They walk around with an unrecognized disease that is not being
treated. Unfortunately, when the symptoms appear, it already may be
Of course, there could be many other explanations for what we
observed in this study. We could not make a statement about heart failure with
any certainty based on these preliminary findings. More recently we did a
follow-up study that included cardiac stress testing, and the preliminary data
we reported at the Experimental Biology conference in April were consistent with
this possibility. But much more work still remains to be done.
Q. Cognitive dysfunction was not found to be predictive
of reduced cardiac output?
Dr. Peckerman: That’s true. But this does not
mean that cardiac output cannot affect cognitive abilities. It may very well be
happening. In fact, patients with severe CFS who had reduced cardiac output
rated their problems with memory and concentration quite high.
What our analysis did show was that reduced cardiac output was
more likely to be found in patients whose main symptoms were some combination of
post-exertional fatigue and infectious symptoms such as fever and chills. This
was after controlling for headaches, muscle aches, sleep, and other symptoms
included in the case definition.
The same analysis also found that those patients whose main
symptoms related to cognitive functioning had less likelihood of having lowered
cardiac output. The most plausible explanation for this is that primary problem
in those people is not with low cardiac output, but may lie elsewhere, possibly
in the brain.
A major stumbling block in studying CFS has been
heterogeneity, meaning that different patient groups have different causes for
their symptoms — and no reliable means of separating them. This study suggested
one way it possibly can be done. Mind you, we wouldn’t find what we found if we
didn’t separate our patients into the severe and less severe subsets. However,
just looking at symptoms probably would not be sensitive enough. One needs to
look for combinations of clinical and physiological markers. The combination we
identified was that of low cardiac output, plus high post-exertional fatigue,
high fever-chills, and low cognitive problems. This approach seems promising.
Q: Can you see any treatments for CFS arising from your
Dr. Peckerman: Right now, it’s premature to talk
about treatments. We’re looking at a phenomenon that could have a number of
Unless you know the cause, treatment would be a shot in the
dark. In fact, it can do harm. For example, if the problem is with the heart it
is one thing, but if the problem is with low blood volume it is another. In
people with heart failure, blood volume is not low, it is high. So if you assume
that low cardiac output is due to low blood volume, and you give someone
treatment to increase their blood volume, this isn’t going to make matters
better — it may make it worse. Our observations so far have been more consistent
with a problem with the heart, but it is too early to tell for sure.
The good news is that there are ways to treat the problem of
reduced cardiac output if the mechanisms are understood. If you can identify
what’s causing it, it’s certainly possible to treat it. Unfortunately, we are
nowhere near that point yet in CFS cases.