Cara Tomas, Andreas Finkelmeyer, Tim Hodgson, Laura MacLachlan, Guy A MacGowan, Andrew M Blamire, Julia L Newton
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
Objectives: To explore levels of the brain natriuretic peptide (BNP) and how these associate with the cardiac abnormalities recently identified in chronic fatigue syndrome (CFS).
Methods: Cardiac magnetic resonance examinations were performed using 3T Philips Intera Achieva scanner (Best, Netherlands) in CFS (Fukuda) participants and sedentary controls matched group wise for age and sex. BNP was also measured by using an enzyme immunoassay in plasma from 42 patients with CFS and 10 controls.
Results: BNP levels were significantly higher in the CFS cohort compared with the matched controls (P=0.013). When we compared cardiac volumes (end-diastolic and end-systolic) between those with high BNP levels (BNP >400 pg/mL) and low BNP (<400 pg/mL), there were significantly lower cardiac volumes in those with the higher BNP levels in both end-systolic and end-diastolic volumes (P=0.05). There were no relationships between fatigue severity, length of disease and BNP levels (P=0.2) suggesting that our findings are unlikely to be related to deconditioning.
Conclusion: This study confirms an association between reduced cardiac volumes and BNP in CFS. Lack of relationship between length of disease suggests that findings are not secondary to deconditioning. Further studies are needed to explore the utility of BNP to act as a stratification paradigm in CFS that directs targeted treatments.
Medical Research Council, ME Research UK.
Comment by ME Research UK
An increasing amount of research has revealed heart abnormalities in patients with ME/CFS. For example, people with the illness have been found to have a short QT interval (a measure of the electrical activity of the heart) and a reduced cardiac output (the amount of blood pumped by the heart per minute). These changes may occur before any symptoms are apparent.
Much of the recent work on cardiac dysfunction in ME/CFS has been carried out by Prof. Julia Newton and her team at Newcastle University, including studies funded by ME Research UK.
In 2012, they used magnetic resonance imaging and cardiac tagging technology to asses a group of ME/CFS patients, and found that several measures of the heart were lower in patients than in healthy control subjects:
- left ventricular mass (the thickness of the wall of the left ventricle, the main pumping chamber of the heart),
- stroke volume (the amount of blood pumped by the left ventricle in one contraction),
- cardiac output, and
- end-diastolic volume (the volume of blood in each ventricle after they have refilled).
Then, in 2016, they repeated some of these assessments along with measures of blood volume. The total volume of blood (plasma plus red cells) was slightly less in ME/CFS patients than in controls, but there was a strong association between blood volume and cardiac end-diastolic wall mass.
Continuing their work in this area, the team has recently published a paper in the journal Open Heart looking at levels of brain natriuretic peptide in ME/CFS, and correlating these with measures of cardiac dysfunction.
Despite its name, brain natriuretic peptide (or BNP) is a hormone that is actually secreted by the muscle cells of the heart, and is produced when the ventricles are overstretched to accommodate an increase in blood volume.
Circulating BNP causes a decrease in blood pressure and in cardiac output, and has found use clinically as a diagnostic and prognostic marker of heart failure.
In their current study, the investigators recruited 42 patients with ME/CFS and no other illness, as well as 10 sedentary control subjects matched for age and sex.
The participants’ hearts were examined using magnetic resonance techniques to provide a number of measures of cardiac function, including cardiac volumes at the end of systole (after the ventricles have contracted and pumped out their blood) and at the end of diastole (when the ventricles are relaxed and have refilled with blood).
In addition, blood samples were taken, and plasma BNP levels were measured using an enzyme immunoassay.
The first important finding was that BNP levels were significantly higher in ME/CFS patients than in sedentary control subjects, with mean levels of approximately 500 versus 300 pg/mL, respectively.
Furthermore, both end-systolic and end-diastolic cardiac volumes were significantly lower among patients with high BNP levels (defined as being greater than 400 pg/mL) than in those with low BNP levels.
BNP tends to be a sign of cardiac volume overload, so this association is not what one would normally expect to see. One explanation suggested by the researchers is that the high BNP is causing an excessive production of urine, which reduces the total volume of circulating blood (as seen in their earlier study), leading to a smaller cardiac volume.
It is important to note that none of these measures were related to the patients’ duration of ME/CFS, indicating that the results are unlikely to be due to deconditioning (i.e. they were not the result of the heart adapting to less physical activity).
What might these results mean to patients? One possibility put forward by the investigators is that measurement of BNP levels may be a convenient way by which to identify those ME/CFS patients with cardiac abnormalities who might benefit from specific treatments, although additional studies would be needed to confirm this.
This approach may also be valuable in identifying a specific cardiac subgroup of ME/CFS patients, and better understand the diverse nature of this illness.