Hollingsworth KG, Hodgson T, Macgowan GA, Blamire AM, Newton JLP
Newcastle Magnetic Resonance Centre, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK
Impaired cardiac function has been confirmed in patients with chronic fatigue syndrome (CFS). Magnetic resonance cardiac tagging is a novel technique that assesses myocardial wall function in vivo. We hypothesized that patients with CFS may have impaired development and release of myocardial torsion and strain.
Cardiac morphology and function were assessed using magnetic resonance imaging and cardiac tagging methodology in 12 CFS patients (Fukuda) and 10 matched controls.
Compared to controls, the CFS group had substantially reduced left ventricular mass (reduced by 23%), end-diastolic volume (30%), stroke volume (29%) and cardiac output (25%). Residual torsion at 150% of the end-systolic time was found to be significantly higher in the patients with CFS (5.3±1.6°) compared to the control group (1.7±0.7°, P=0.0001). End-diastolic volume index correlated negatively with both torsion-to-endocardial-strain ratio (TSR) (r= −0.65, P=0.02) and the residual torsion at 150% end-systolic time (r= −0.76, P=0.004), so decreased end-diastolic volume is associated with raised TSR and torsion persisting longer into diastole. Reduced end-diastolic volume index also correlated significantly with increased radial thickening (r= −0.65, P=0.03) and impaired diastolic function represented by the ratio of early to late ventricular filling velocity (E/A ratio, r=0.71, P=0.009) and early filling percentage (r=0.73, P=0.008).
Patients with CFS have markedly reduced cardiac mass and blood pool volumes, particularly end-diastolic volume: this results in significant impairments in stroke volume and cardiac output compared to controls. The CFS group appeared to have a delay in the release of torsion.
Comment by ME Research UK
Some ME/CFS patients experience heart symptoms, most commonly cardiac arrhythmias including tachycardia (racing heart) or palpitations usually associated with autonomic nervous system dysfunction. In fact, for some patients, these can be the most frightening aspects of their debilitating illness. In the scientific literature, a few reports have confirmed the existence of abnormalities of cardiac function in some patients. For instance, a study in 2006 found that ME/CFS patients had relatively short QT intervals (measures of the time of the heart’s electrical cycle) compared with healthy people. Also, in 2009, Japanese researchers reported cardiac dysfunction with low cardiac output in some oriental patients, and an echocardiographic study from 2010 found that the ability of the heart to contract was reduced. Overall, however, little formal research has been conducted on the presence of heart abnormalities in ME/CFS patients, and what these might mean for the individual patient.
Since 2008, ME Research UK, in conjunction with the John Richardson Research Group and the Irish ME Trust, has funded Professor Julia Newton of the Institute for Ageing and Health, University of Newcastle to explore some of the mechanisms behind autonomic nervous system abnormalities in a large cohort of ME/CFS patients. She and her colleagues Prof. David Jones and senior physicist Dr Kieren Hollingsworth of the Institute of Cellular Medicine have been using state of the art magnetic resonance techniques to investigate whether autonomic nervous system symptoms (which can be found in around three-quarters of patients) are associated with abnormalities in other major organ systems, something we know to be the case in other illnesses.
Their investigations of the heart have been throwing up some intriguing findings. For example, in a previous report they showed that “bioenergetic abnormalities” could be found both in the muscles of the skeleton and in heart muscle, with a correlation between the two suggesting the existence of linked underlying mechanisms. Also, they found that the hearts of the ME/CFS patients had to work harder during prolonged standing than in healthy people. These findings raised the question of whether abnormalities could be detected in the function of the heart, particularly during the heartbeat.
To investigate these aspects, the team have been using cardiac MRI tagging, a complex technique that has been used previously to examine the function of the heart during the ageing process, in which gradual changes might be expected to occur subclinically (before actual symptoms can be observed). The researchers thought it could be the ideal tool to examine the hearts of ME/CFS patients for defects that are not yet clinically apparent. The technique allows accurate assessment of myocardial (heart muscle) movement in three dimensions, and gives detailed information about “myocardial transmural strain” (an indication of the shortening of heart muscle fibres) and torsion (a measure of the “twist” of the heart during the beat), two events that can be affected by energy deficits before they are obvious clinically.
Their experiment involved 12 women with well-defined ME/CFS and 10 closely matched, sedentary healthy women. Each person underwent cardiac examinations using an MRI scanner for cardiac tagging, and cardiac MRI cine imaging to assess cardiac form and structure, as well as systolic and diastolic function. The group’s findings have now been published in the March 2012 issue of the Journal of Internal Medicine (see the results below), and one of the main findings was the dramatic increase in residual torsion in patients compared with controls. This is a measure of the efficiency of the release of torsion and strain during the relaxation phase of the heartbeat. ME/CFS patients had 200% more residual torsion than the matched controls, indicating that their heart muscle was taking longer to relax.
What did the results show?
There were no significant differences in resting heart rate or systolic/diastolic blood pressure between patients and controls.
In the ME/CFS patients, left ventricular mass (the thickness of the heart wall at the ventricle) was substantially reduced (by 23%) compared with controls.
After correction for individual body size, the various measures of ‘blood pool volume’ in the heart were significantly lower in patients than controls:
- stroke volume (the amount of blood pumped by the left ventricle in one contraction) was lower by 26%;
- cardiac output (the output of blood by the heart per minute) was lower by 21%;
- end diastolic volume (the volume of blood in each ventricle at the end of diastole) was lower by 25%.
Intriguingly, residual torsion (at 150% of the end-systolic time) was significantly higher in the patients, indicating a delay in the release of torsion (‘twist’) at the end of the beat.
To put this in context, healthy people have an increase in residual torsion of around 50% between the ages of 22 and 69 years, possibly because ageing affects the lining of the muscle fibres which permit the heart to relax. Why residual torsion is raised even more in people with ME/CFS is unclear, but – because the level of torsion was found to be related to end-diastolic volume – the researchers speculate that low total blood volume might be involved. In fact, the research team says that its overall findings strongly suggest a marked reduction in the total (central) blood volume in ME/CFS patients – since a smaller volume flowing into the heart would lead to a lower amount of blood pumped by the ventricle and a lower cardiac output.
This suggestion is not new: low total blood volume and associated autonomic nervous system dysfunction have been proposed as part of the disease process in subgroups of ME/CFS patients in the past. Indeed, one investigation in 2002 found a 9% lower blood volume in ME/CFS patients than in controls. A further study in 2010 showed that the reductions in cardiac output and end-diastolic volume in ME/CFS could be entirely accounted for by a reduction in the total blood volume, and an accompanying editorial pointed out that the results did not imply heart disease, but rather pointed to “circulatory impairment”.
So, what can be done – or should be done – about correcting low cardiac blood volume? Well, there is anecdotal evidence that ME/CFS patients have had symptomatic improvements with the administration of intravenous fluid as a treatment intervention (although this is not without its drawbacks and risks), and the researchers say that they intend to explore interventions to restore fluid volume in ME/CFS patients. They also point out, however, that ME/CFS patients may indeed have primary myocardial deficits that are not associated with low total blood volume, and this possibility needs to be explored too.
This essay is an extract from our article (pdf 1.4 MB) in the Autumn 2012 issue of Breakthrough.