Did you know that you probably have a smaller heart than normal? Four studies suggest that if you have chronic fatigue syndrome (ME/CFS) you probably do.  The word on the small hearts for years has been that they’re probably caused by inactivity or deconditioning. This study suggested that they probably are indeed caused by inactivity – but not by deconditioning at all.

small heart ME/CFS

Small hearts appear to be common on ME/CFS – but not in the way the medical community has thought.

Newton’s earlier small study had found reduced heart mass and significantly reduced blood pumping by the heart, and Miwa in Japan has produced three studies showing that smaller hearts are present in people with chronic fatigue syndrome (ME/CFS).

Mirroring Dr. Cheney’s unpublished findings, both Newton and Miwa have also found reduced diastolic volume (30%).  The diastolic phase of the heart cycle is the filling phase. During diastole, the ventricles relax and then, in an energy intensive process, expand so that they can fill with oxygen enriched blood. Reduced diastolic volume or preload indicates that  the heart is not being filled as much as normal.

Both Newton’s and Miwa’s study published last year found significantly reduced diastolic volume and mass, stroke volume index and cardiac output.  (Miwa targeted and consistently found reduced left ventricular volume and density. He did not measure right ventricular functioning. He or she also appears to be the first Japanese researcher to drop the term CFS and use myalgic encephalomyelitis exclusively throughout the latest paper. )

The Study

Now Newton is back doing more tests with a much larger and better defined cohort (n=41 ME/CFS patients / 10 healthy controls).

Newton measured how much blood entered the heart during the diastolic phase (end-diastolic volume) and systolic phases (end-systolic volume) then how much it spate out (stroke volume). She also assessed the size or mass of the heart.

This time, suspecting that reduced blood volume played a role in the poor cardiac performances, she analyzed blood volume three ways: total blood volume (TV), red blood cell volume (RCV) and plasma volume (PV).

As before, Newton found reduced blood volume during both the diastolic and systolic phases of the heart cycle and not just minor reductions either; ME/CFS patients had a whopping 25% less blood entering their hearts than the healthy controls. They also had about 25% less stroke volume and index and almost 30% smaller heart mass.  These appear to be very large reductions in both heart mass and heart functioning in ME/CFS patients.

Blood pressure was affected as well; ME/CFS patients had significantly lower systolic (125-109) and diastolic (76-70) blood pressures than the healthy controls.  The reduced blood pressure and stroke volumes could result from the poor heart functioning or they could produce the poor heart functioning by not pushing the heart to work harder.

Dr. Cheney appears to believe that reduced heart energetics are interfering with the hearts ability to contract enough to accommodate the blood entering it.  Another possibility is that reductions in blood pressure have resulted in smaller hearts.

Another possibility is that there’s  something wrong with the vascular system leading to the heart which is reducing blood flows to the heart. Reduced blood flows would result in a smaller heart. That’s the option Dr. Newton appears to be most interested in.

Non Compliant Veins?

Dr. Newton questioned whether a problem with “venous compliance” was present.  Since 2/3rd’s of our blood is locked up in our veins the reduced diastolic volume or preload found in ME/CFS could reflect large amounts of blood that has somehow gotten stuck in our veins.

Blood_vessels.svgVenous compliance refers to the ability of veins to “push back” once they get extended with fluid. The more full of fluid they are, the more the veins should – like a rubber band that has been stretched – exert pressure on the fluid to  move. If ME/CFS patients veins are non-compliant; that is, if they’re kind of flaccid in response to filling they may not be moving the blood along as they should.

That could lead to reduced preload (reduced diastolic volume).

Venous compliance can be affected by a number of factors including vasodilators and vasoconstrictors, the muscle tone of the smooth muscle tissue, and the renin–angiotensin system. One wonders if connective tissue problems (eg Ehlers Danlos Syndrome) could come into play as well.

Blood Volume

The blood volume results were assessed according to the norms expected. Blood volume was lower in the ME/CFS patients, but perhaps not to the extent that might have been expected.  About half the ME/CFS patients had normal red blood cell volume and about half fell below the 95th percentile expected. About a third of ME/CFS patients had plasma volumes below the 95th percentile.

On the other hand, statistical analyses suggested that the reduced red blood volumes were strongly associated with reduced ventricular mass in ME/CFS.  That suggests the ventricles may be smaller they’re not getting as much blood as usual.

There’s quite a bit of increased interest in blood volume right now.  Medow’s study on the effects of saline solution on ME/CFS should be published soon. He is currently examining whether the World Health Organization’s oral rehydration formula could be helpful in ME/CFS. His ability to use phenylephrine to increase blood flows to the brain and completely knock out POTS during a tilt test was astonishing.

Dr. Newton proposes to increase the blood volumes of ME/CFS patients and see if the size of their heart’s increase to normal size.

Is Arnold Peckerman Smiling Somewhere?

Arnold Peckerman apparently passed away a couple of years ago but one wonders what he would be thinking of all this.  Peckerman, LeManca and others working at Dr.  Ben Natelson’s NIAID funded ME/CFS research center were hot on the trail of cardiovascular issues when NIAID pulled the plug on its ME/CFS research.

The group had produced some interesting results. The first heart study in 1999 showed increased heart rates and reduced blood flows during a tilt test and presaged the attention on orthostatic intolerance and POTS.  The declines in heart rates and blood pressure during a stressful cognitive test they found may have been the first indication that the autonomic nervous system was prone to poop out under stress.

In 2003 their finding that people with ME/CFS were trying as hard as healthy controls knocked the legs out from under a prominent psychological interpretation. Next, Peckerman showed that people with severe ME/CFS (but not moderate ME/CFS) had a significantly lower stroke volume than healthy controls. Then he showed that the blood pressure responses of ME/CFS patients were off during exercise.


Could reduced heart blood flows after exercise help explain post-exertional malaise?

These results were positive but it was the last study, whose results were never published, which was a potential game-changer.

An MD, Peckerman, had seen post exertional malaise in some of his heart patients after the blood flows through their hearts had been stunted. Peckerman, therefore, decided to measured heart functioning before and after exercise in ME/CFS.

It was a small study – just 16 ME/CFS patients and four healthy controls but the results were astounding, and if they had been published and held up could have produced a simple and effective exercise test. Peckerman didn’t measure VO2 max – he measured blood flows – and it didn’t take him two exhausting exercise tests to get his result; he simply measured heart blood flows at rest, had his subjects exercise, and then measured blood flows at rest again.

In 2003 at the American Physiological Association conference Peckerman reported that 13/16 ME/CFS patients had significantly reduced blood flows at rest after exercise.  WebMD ran a story titled “Tricky Heart May Cause Chronic Fatigue Syndrome” in which Peckerman, obviously no shrinking violet, stated that the reduction of blood flows he had seen was the very definition of heart failure.

An Emory cardiologist in the story agreed. The finding of reduced heart blood flows was, in fact, what he saw in people with serious heart disease:

“Typically we see this in people with three-vessel heart disease. A drop in [blood pumped by the heart] during exercise is not a typical response. It is actually a marker of significant coronary artery obstruction.”

Dr. Natelson described being quite excited at the results but we now know that “heart failure” is not present in ME/CFS.  Heart failure is a progressive condition that ultimately ends in death for just about everyone who has it, and, the fact that ME/CFS patients were not dropping dead from heart failure puzzled both Peckerman and Miller.  They both recommended that further study be done.

The study was never published, however, and we don’t know why.  After one more study on ME/CFS – which did not find differences in cognition before or after exercise – Peckerman was done. He’d participated in 13 studies on ME/CFS and GWS and never published again.

circulatory system ME/CFS

The cardiovascular system is probably causing the heart abnormalities seen

The cardiovascular connection to ME/CFS has never died, however.  As noted above both Newton and Miwa have found significantly reduced blood flows and filling in their studies. It now appears that those issues probably reflect significant problems with the cardiovascular system not the heart.

The outstanding question remaining from Peckerman’s unpublished study, though, is what happened during exercise to so dramatically affect the blood flows to the hearts of his ME/CFS cohort the next day?   The vascular system in ME/CFS and FM is a subject that continues to fascinate.

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