relatie tussen hartfunctie-afwijkingen,

spierdysfunctie-/-kracht en

orthostatische intolerantie






In een recente studie hebben Newton (what's in a name) en kollega's aangetoond dat

  • bij een deel van de patiŽnten objektief sprake is van orthostatische intolerantie (32%),
  • het hart van een deel van de patiŽnten veel harder moet werken in een staande positie,
  • bij circa een derde van de patiŽnten sprake is van een verlaagde PCr/ATP-ratio in de hartspier (phosphocreatine of PCr: beschikbare korte termijn-energie: zie afbeelding), en
  • er een duidelijke relatie is tussen enerzijds de beschikbare energie in hart en spieren
  • en anderzijds tussen de mate van (over)werk door het hart en orthostatische intolerantie.




afbeelding: Wikipedia

(van PCr naar ATP en terug: recycling)




Twee slotopmerkingen zijn op zijn plaats:

  • het betrof hier slechts een kleine studiegroep (12 CVS-patiŽnten) en
  • "hartafwijkingen"/orthostatische intolerantie worden slechts bij een deel van de CVS-patiŽnten vastgesteld, hetgeen wederom aangeeft hoe nietszeggend het label "CVS" is.



Citaten uit het studierapport:






We have demonstrated that the skeletal muscle bioenergetic abnormality recently described in patients with CFS [1] associates with a similar cardiac bioenergetic abnormality. This impairment is associated with an increase in cardiac contractility on standing (i.e. the heart has to work harder for the same degree of physiological stress), the severity of which associates with symptoms on standing in those with CFS.


The finding of varying degrees of muscle abnormality may account for the contradictory results in the previous CFS muscle literature [25-29] and underlines the need for a whole organ systematic approach to studies in CFS.




If our CFS patients are considered as a single group, then oxidative muscle metabolism is not significantly impaired compared with controls, as we had previously reported [1], and this would not change by recruiting greater numbers: division by cardiac status, however, suggests the presence of subgroups within the population, one of which has impaired oxidative muscle metabolism.




The relationship between cardiac contractility on standing and symptoms was an important finding as it suggests that symptoms in those with CFS are potentially modifiable by treatment of the underlying cardiac abnormality. These abnormalities were CFS-specific, as there were no such correlations in the control population.




When we considered cardiac energy metabolism in the whole CFS patient group, this appeared to be mixed, with many individuals falling in the normal range with some individuals showing impairment. This suggests that within the symptom complex of CFS, there is a group of patients in whom an actual cardiac abnormality is present (defined by the presence of PCr /ATP ratio < 1.6 [17]).




The heterogeneity of patients included in CFS studies is well recognized, however, despite the usage of specific diagnostic criteria for inclusion, and we could not symptomatically differentiate between the normal and impaired cardiac energetic group. This underlines how important it is to correctly characterize patients with CFS and to study the underlying physiological parameter rather than the symptom complex.




It is unclear what the long-term impact of the cardiac abnormalities will have for those with CFS. However, our findings of reduced survival in those with the fatigue-associated chronic disease and primary biliary cirrhosis [31] and studies confirming a comparable fatigue phenotype between primary biliary cirrhosis and CFS [32] would point to an (as yet) unidentified risk for those with CFS, and our findings of cardiac dysfunction in a proportion of patients may suggest the group at increased risk.




This study has examined the tolerability and diagnostic potential of assess≠ment protocols that examine haemodynamic responses to immediate and prolonged standing in CFS and, for the first time, examines the relationship between measures of cardiovascular function, cardiac energetics at rest and muscle energetics under exercise in CFS patients. HUT is one of the assessment modalities of choice in the evaluation of those with unexplained syncope, and is recommended in national and international guidelines [33-35].


In contrast, the UK NICE CFS guidelines [36] actively discourage the assessment by HUT. This is surprising considering the apparent pathophysiological overlap between neurally mediated hypotension and CFS [37,38,39].




This study has some limitations. The study group could clearly be considered to be self-selected, and as a result biased, as they were recruited via the local patient support group. However, all participants had been seen within a local CFS service within 2 years and been diagnosed with the formal Fukuda criteria. A further limitation is that this study cannot establish a direction of causality for the associations seen in cardiac metabolism, skeletal muscle metabolism and autonomic function.




The findings are, however, consistent with a model in which a cardiovascular impairment might lead to impaired oxidative function, perhaps through impaired venous run-off post-exercise.




Impaired cardiovascular response to standing in chronic fatigue syndrome.

Eur J Clin Invest. Published Online 23 May 2010. doi: 10.1111/j.1365-2362.2010.02310.x.

Hollingsworth KG, Jones DEJ, Taylor R, Blamire AM, Newton JL.








Impaired skeletal muscle metabolism is recognized in chronic fatigue syndrome (CFS).


This study examined the relationship

between skeletal and cardiac muscle function and symptoms on standing in CFS

using magnetic resonance spectroscopy (MRS) and impedance cardiography.



Materials and methods


Phosphocreatine (PCr)/adenosine triphosphate (ATP) ratio by cardiac MRS,

PCr/ADP and proton efflux by muscle MRS

were performed in 12 CFS (Fukuda) and 8 controls.


Head up tilt (HUT) and cardiac contractility (left ventricular work index, LVWI)

(n = 64 CFS and matched controls) were found.


Fatigue impact was accessed by Fatigue Impact Scale and

orthostatic symptoms by Orthostatic Grading Scale (OGS).





Cardiac PCr/ATP correlated with measures of muscle bioenergetic function

(half-time PCr recovery [κ = 0.71, P = 0.005] and half-time ADP recovery [κ = 0.60, P = 0.02])

suggesting that the muscle and cardiac bioenergetic function correlate in CFS.


Four of 12 (33.3%) CFS patients had PCr/ATP values

consistent with significant cardiac impairment.


Those with impaired cardiac energy metabolism

had significantly reduced maximal and initial proton efflux rates (P < 0.05).


Cardiac PCr/ATP ratio correlated with myocardial contractility (LVWI)

in response to standing (P = 0.03).



LVWI on standing was significantly higher in CFS (P = 0.05)

with symptoms on standing (OGS) occurring in 61/64 (95%)

(vs. 25/64 [39%] controls; P < 0.0001).


OGS scores were significantly higher

in those with abnormal LVWI responses to standing (P = 0.04),

with the LVWI on standing

correlating with OGS scores (r2 = 0.1; P = 0.03).


HUT was positive in 19 (32%).





Skeletal muscle and cardiac bioenergetic abnormalities associate in CFS.


Cardiac bioenergetic metabolism

associates with

increase in cardiac contractility on standing.


Haemodynamic assessment in CFS

is well tolerated and safe

with a high diagnostic yield

comparable with unexplained syncope.





Cardiac function, diagnosis, fatigue