CARDIOVASCULAR DYSFUNCTION IN PATIENTS WITH ME/CFS
This is an important section for the Group to be aware of, as the sudden death, particularly of young people with severe ME in their 20’s and early 30’s, is often heart failure. They either collapse, or are found dead in their beds by their carers.
Abnormal Impedance Cardiography Predicts Symptom Severity in CFS
Researchers: Arnold Peckerman, Ben Natelson et al (2003 – USA)6
This is an important research paper that needs to be read. It may well provide some real answers to, if not the majority of ME sufferers, a sub-group of patients. We are also submitting 2 summaries of this paper, which may make it easier to understand the implications of this research. One ‘CFS is Heart Failure Secondary to Mitochondrial Malfunction’ by Dr Sarah Myhill who treats patients in the UK, and one ‘The Heart of the Matter: CFS and Cardiac Issues’ an interview with Dr Paul Cheney7, who has treated patients in the USA for more than 20 years.
This research at the New Jersey Medical Centre was funded by a multi-million dollar grant from the National Institute of Health (NIH). The US Government had wanted the research to try and find a physiological parameter that could be objectively measured and would correlate with the level of disability of the patient.
The researchers identified accumulating evidence to a possible problem with circulation in CFS. The reported findings included autonomic dysfunction, lower plasma volume and/or red cell mass, and abnormalities in neurohormonal systems of circulatory control. Although on their own abnormalities would be insufficient to cause a circulatory dysfunction, cumulatively they could produce significant deficiencies in organ blood flow and symptoms. Previous studies showed reduced blood flow to muscles using magnetic resonance spectroscopy, and nuclear imaging found evidence of post-exercise reduction in brain blood flow in CFS.
The researchers hypothesised that CFS patients have a reduced cardiac output, and they would measure this, using noninvasive impedance cardiography. Early analyses however indicated that reduction in cardiac output was characteristic of the patients most severely affected with CFS, rather than all patients with CFS. To meet the criteria for severe CFS, patients had to meet the more stringent 1988 CDC case definition, which requires >50% reduction in activities and 7 or more of the symptoms listed in the case definition, and at least 7 of those symptoms had to be substantial, or worse in severity, in the previous month. The patients were divided into severe and less severe for this study. The study also wanted to identify whether there are relationships between low cardiac output and specific CFS symptoms, which would be useful for further research.
Patients were tested in a temperature controlled room between 11 am and 1 pm. The study consisted of a 10 minute period of supine rest (laying down) followed by a 5 minute period of quiet standing. Impedance cardiograms were computer scored and edited without the subject group status to provide measures of stroke volume and pre-ejection period. Heart rate was measured from the electrocardiograph. Mean arterial pressure was recorded in synchrony with impedance cardiography.
Statistical analysis of the effects of illness were examined in analysis of variance for the severe, less severe and control groups on measurements taken in supine and standing positions. Symptom patterns descriptive of the severe CFS and their relationships with cardiac output were explored, respectively, with stepwise logistic and multiple regression analyses, using P<0.05 criteria for entry or removal. P<0.05 means there is a possibility that the association between the factor and the outcome is due to chance – so 0.01 means a 1% chance, and 0.0001 a 1 in 10,000 chance.
They found:
Patients with severe CFS had lower supine stroke volume (P<0.03)
Cardiac output (Q) was significantly lower in group with severe CFS, both in supine and standing positions (P0.03). From the graph, controls and less severe CFS patients showed a cardiac output of about 7 litres per minute when supine and about 4.8 on standing. For the severely affected the Q values of cardiac output are just over 5 litres supine and drops to about 3.5 litres standing. (this level is thought to be borderline for organ failure)
Looking at comparisons of reported symptoms of severe and less severe – post-exertional malaise and sore throats emerged as significant differences between the groups – providing correct identification for 88..5% of patients (P0.05 and 0.005)
Lower cardiac output (the mean of supine and standing values) was associated with greater severity ratings for post-exertional fatigue and fever/chills, and lower ratings for a problem with memory and concentration (P<0.0001, 0.008, and 0.006 respectively).
Comparison within the study illustrated the degree to which low levels of cardiac output in CFS patients were specifically related to the symptoms characteristic of severe CFS
As a specific example of the relationship between post-exertional fatigue and cardiac output, increases in tiredness, after the testing, as measured by changes in the AD ACL energy scores, tended to be greater in patients with lower cardiac output (P<0.006)
Conclusions
The correlation coefficient of 0.46 with P value of 0.0002 suggests that the disability level of those that were disabled was exactly proportional to the severity of their Q defect (Q stands for cardiac output in litres per minute)
Results provide initial evidence of reduced cardiac output
Suggests that in some CFS patients, blood pressure is maintained at the cost of restricted flow, possibly resulting in low circulatory state
Therefore at times daily activities and demands for blood flow are not adequately met, compromising metabolic processes, in at least some vascular compartments.
This finding would signify that some cases of CFS might be explained and potentially treated as low circulation problems.
Several deficiencies capable of affecting cardiac output have been reported in CFS, including lower blood volume, impaired venous regulation and changes in autonomic, endocrine and cardiac function
A percentage of patients with symptoms of CFS may in fact have covert heart disease
Abnormalities causing a reduction in cardiac output in CFS may be dispersed over multiple body systems and changes in any of them may be subtle and difficult to detect
This study does suggest interpretations regarding the causes of reduced cardiac output in severe CFS. The reduction in stroke volume was more clearly seen in the supine position and tended to improve during standing, indicating worsened cardiac performance under conditions of augmented preload.
Contractility or diastolic function could affect stroke volume. Although this pattern is consistent with cardiac dysfunction, it could also be due to circulatory, neurogenic and endocrinologic abnormalities.
Lack of heart rate differences does not preclude the possibility patients are moderately hypovolemic
Reduction in cardiac output in CFS patients is unlikely to be due to deconditioning
Secondary analyses, relating cardiac output to specific symptoms, found that post-exertional fatigue and symptoms in the infectious category, were the most characteristic in patients with severe CFS, and severity of these symptoms was associated with lower cardiac output
Ratings of cognitive impairment were not predictive of reduced cardiac output. This suggests that problems outside of circulation produce cognitive deficits in CFS
Reduction in cardiac output in CFS is not likely to fall within abnormal range, but this should not detract from the physiological significance. Even marginal reduction in cardiac output can result in selective under-perfusion of various organs and systems of the body, eg autoregulation, digestion in the gut etc
