Skeletal Muscle Abnormalities and Iron Deficiency in Chronic Heart Failure

[pattismith]

Skeletal Muscle Abnormalities and Iron Deficiency in Chronic Heart Failure

An Exercise 31 P Magnetic Resonance Spectroscopy Study of Calf Muscle
2018

Vojtech Melenovsky 1, Katerina Hlavata 1, Petr Sedivy 2, Monika Dezortova 2, Barry A Borlaug 3, Jiri Petrak 1, Josef Kautzner 4, Milan Hajek 2
Affiliations expand

• PMID: 30354361
• DOI: 10.1161/CIRCHEARTFAILURE.117.004800

Abstract

Background: Heart failure (HF) is often associated with iron deficiency (ID). Skeletal muscle abnormalities are common in HF, but the potential role of ID in this phenomenon is unclear.

In addition to hemopoiesis, iron is essential for muscle bioenergetics.


We examined whether energetic abnormalities in skeletal muscle in HF are affected by ID and if they are responsive to intravenous iron.

Methods and results:

Forty-four chronic HF subjects and 25 similar healthy volunteers underwent 31P magnetic resonance spectroscopy of calf muscle at rest and during exercise (plantar flexions).

Results were compared between HF subjects with or without ID.

In 13 ID-HF subjects, examinations were repeated 1 month after intravenous ferric carboxymaltose administration (1000 mg).
As compared with controls, HF subjects displayed lower resting high-energy phosphate content, lower exercise pH, and slower postexercise PCr recovery.

Compared with non-ID HF, ID-HF subjects had lower muscle strength, larger PCr depletion, and more profound intracellular acidosis with exercise, consistent with an earlier metabolic shift to anaerobic glycolysis.

The exercise-induced PCr drop strongly correlated with pH change in HF group ( r=-0.71, P<0.001) but not in controls ( r=0.13, P=0.61, interaction: P<0.0001). Short-term iron administration corrected the iron deficit but had no effect on muscle bioenergetics assessed 1 month later.

Conclusions:

HF patients display skeletal muscle myopathy that is more severe in those with iron deficiency.

The presence of ID is associated with greater acidosis with exercise, which may explain early muscle fatigue.

Further study is warranted to identify the strategy to restore iron content in skeletal muscle.

 

[pattismith]

in this Heart Failure study , they follow guidelines to select Iron Deficient patients

ID was defined as serum ferritin <100 µg·L−1
or ferritin 100 to 299 µg·L−1 and the transferrin saturation <20%

I wonder if these guidelines may be useful for ME/CFS as well, considering the frequent muscular involvement, the possible hypoperfusion, anoxia and deconditioning process possibly involved in ME/CFS

Here what they say in the discussion part about Chronic heart failure patients:

Iron-deficient HF subjects were more symptomatic, had lower peak muscle strength, larger energetic depletion and more pronounced acidification of the muscle during exercise, consistent with metabolic shift towards anaerobic glycolysis.

Skeletal Myopathy in HF

Patients with chronic HF often complain of diminished skeletal muscle performance. Multiple mechanisms, such as hypoperfusion, deconditioning, inflammation and increased oxidative stress lead to muscle atrophy and weakness, contributing to HF symptoms.13,15 Here we provide an evidence for intrinsic, muscle mass independent, bioenergetic basis of HF-related myopathy. The time constant of PCr recovery (τPCr), an indicator ATP synthesis by oxidative phosphorylation, was more impaired in HF subjects than in controls, confirming previous studies.15,32,33 The reasons for slower PCr recovery could be inherent mitochondrial dysfunction or inadequate delivery of substrates and oxygen to the mitochondria.33–35 We observed a strong correlation between age and Qmax, which may be explained by mitochondrial senescence36 or microvascular dysfunction.37

2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure - Ponikowski - 2016 - European Journal of Heart Failure - Wiley Online Library

 

[pattismith]

I's and older study, but the link between mitochondrial disease with complexe I defect and iron deficiency is interesting (considering association can mean either causal or consequence, or bias of course)

Iron deficiency in children with mitochondrial disease

Hye Eun Kwon 1, Jung Hun Lee, Young Mock Lee, Hoon Chul Kang, Joon Soo Lee, Heung Dong Kim
2010

• DOI: 10.1007/s11011-010-9196-8

Abstract

Mitochondrial disease is an energy metabolic disorder with various organ involvement. Iron is widely known to be one of the most important nutriments required for normal brain development and several essential metabolic functions.

We retrospectively studied the laboratory data on iron deficiency (ID) in 69 children with mitochondrial respiratory chain complex (MRC) defects by biochemical enzyme assay using muscle tissue. We analyzed the differences between groups of mitochondrial disease based on the presence of ID. ID has higher prevalence in children with mitochondrial disease than in the normal population.

There were 6 (9%) patients with low hemoglobin, 12 (17%) with low serum ferrtin, and 22 (32%) with low transferrin saturation levels among children with MRC defects.

In comparisons between the ID and the non-ID group of MRC-defect patients, the frequency of MRC I defect was significantly higher in the ID group while that of MRC IV defect was higher in the non-ID group.

Abnormal brain magnetic resonance imaging (MRI) findings were more frequently detected in the ID group.

The incidence of failure to thrive and gastrointestinal symptoms were significantly higher in the ID group.

Early diagnosis and proper treatment of ID are recommended. Especially in cases with risk factors such as failure to thrive or gastrointestinal manifestation, active evaluation of ID should be encouraged.