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Commonly seen 30% of non hospitalized CHF 50% of hospitalized CHF patients
Increased mortalityIncreased morbidity Hospitalization
Associated
Iron Therapy in Chronic Heart Failure (CHF)
most common causes of CHF
-coronary artery disease (CAD)-hypertensive heart disease -valve disease
In CHF anemia defined as hemoglobin (Hb) levels
<
In CHF, lower Hb values are usually more prevalent in
- older patients ( Low intake of red meat-GIT bleeding)
- patients with poor kidney function ( Low EPO)
- patients in the more advanced stages of the disease (Elevated cytokines) - or presenting with co morbidities ( Diabetes)
Silverberg DS, Wexler D, Blum M et al. The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations. J Am Coll Cardiol 2000;35:1737-1744.
Silverberg DS, Wexler D, Sheps D et al. The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a randomized controlled study. J Am Coll Cardiol 2001;37:1775-1780
The pioneering work of Silverberg et al. has raised interest in the role of anemia in CHF
CHF frequently affects renal function through renal vasoconstriction and renal ischemia, resulting in chronic renal dysfunction and reduced EPO production.
mechanism of anemia in CHF
EPO
renal vasoconstriction
-affecting iron stores (GIT Problems)• Bleeding due to aspirin administration• Polyps – Oesophagitis • Reduced iron absorption resulting from atrophic gastritis
- haemodilution
factors contributing to development of anemia in CHF
Affecting EPO production
-Diabetes• EPO producing cells in kidney may be damaged early by glycosylation
-Anti hypertensive medications It has also been speculated that the use of
•ACE inhibitors•Angiotensin Receptor Blockermay inhibit EPO production
factors contributing to development of anemia in CHF
TNF α - IL6
Cause 4 hematological abnormalities
2 affecting EPO Reduced EPO production in the kidney
Reduced activity of EPO in the bone marrow
2 affecting Iron Hepcidin
induced failure of iron absorbtion from the GIT induced trapping of iron in iron stores in the macrophages
Impaired EPO production induces anemia, which, in turn, exacerbates CHF.
The process may develop into a vicious cycle that Silverberg et al. call
The "cardio-renal syndrome"
Pro-inflammatory cytokines (IL-1, TNFα, IL-6, IFNγ)
EPO production
EPO
+ +
Iron
Fas Ag
Apoptosis
─
HepcidinReleased From liverBy IL6
Fe absorption Fe transport Fe availability(EPO-R, Tf, TfR, Ferriportin, DMT-1)
─ve effect
Erythropoiesis
ACE inhibitors
factors contribute to the development of iron deficiency in CHF
-poor micronutrient supply of diet
-intestinal malabsorption secondary to bowel wall edema
-blood loss inherent to aspirin use
-In CHF patients with chronic kidney failure, proteinuria may further exacerbate iron deficiency
-Besides iron deficiency, insufficient micronutrient supply may also affect folate and vitamin B12 stores.
Anemia contribute to Eccentric LVH
Non-Hematopoietic biological effects of EPO
Reduce apoptosis of the cardiomyocytes oxidative stress and inflammation fibrosis
Prevent hypoxic damage functional impairment of the heart
Increase neovascularization
Improve endothelial dysfunction wound healing
Some of these effects are due to the increase in number and activity Of endothelial progenitor cells (EPCs) from the bone marrow
Eicosanoids influence the state of tension of the smooth muscles. Depending on the impulse that the smooth muscle cells are exposed to, they change from a state of tension to a state of relaxation and vice versa These signaling molecules thereby have a direct effect on important bodily functions, such as
blood pressure regulation breathing intestinal activities.
No
What a body needs iron for
Hormone formation
formation of hormones can only occur if a biochemical impulse for their production is sent. This requires enzymes - substances, also known as catalysts these enzymes need iron to do their job
Serotonin
Dopamine
an endorphin, is also often referred to as the “happy hormone.”
Like serotonin, dopamine is called a “happy hormone”
.8 .8 .8
Melatonin
DSIP (Delta Sleep Inducing Peptide)
regulates the functioning of what is known as our inner clock
produces the deep sleep, an important sleep phase that is responsible for the quality of our nightly recovery.
Energy production
Each body cell contains a large number of mitochondria We consider them our “power plants” and they use adenosine triphosphate (ATP) to produce the necessary chemical cell energy It is the iron-sulfur molecules, which are the central constituents in the cascade of chemical reactions that results in energy being released in the cells
Eicosanoid formation
Eicosanoids are our organism’s iron-containing signaling molecules, which directly influence many of our bodily functions
a) Effect on smooth muscle tension
b) Influence on the stomach
c) Effect on the immune system
c) Effect on the immune system:
The eicosanoids also include leukotrienes.
Those are small acid particles in the white blood cells,
which are
1.effective in connection with allergic and inflammatory reactions.
2.It is also the function of leukotrienes to “attract” the body’s antibodies to the site of an infection.
Before considering using Erythropoietin
Evaluate other causes of anemia (bleeding)
Obtain CBC Hgb - RBCs count - MCV- MCH
Assess for adequate iron stores Ferritin 50 ng/ml or more TS 20% or more
< 10 ng/ml 50 ng/ml 100 ng/ml > 100 ng/ml invalid
Step 1 Insert the TEST CARD
Step 2 Apply the SAMPLE
Step 3 Read the RESULT in 2 min
Restore the iron needed for Erythropoiesis & other functions
Resolution of sever anemia with target Hb 12 g/dl
Reduce need for transfusion and or hospitalization
Enhance quality of life
Initiate therapy with IRON Each 1 gm Hgb require 150 mg of bioavilable iron Calculate iron stors by ferritin test Iron stores should be at least 500 mg
Initiate therapy with Erythropoietin 50 IU/Kg/W Recheck Hgb every 2 weeks Till goals of therapy achieved
ESA Partial responder Hgb increase less than1gm/dl After 4 weeks
check iron stores If iron stores are adequate
Increase Epo dose 25%
Stop Erythropoietin once target HgOf 12 g/dl achieved
ESA responder Hgb increase 1-2 gm/dl/month with Hgb still less than 12g/dl
maintain Epo dose
Stop Erythropoietin once target Hgb of 12g/dl achieved
March 9, 2007
The Hemoglobin Sweet Spot
11 12 139 Hb g/dL
Risk
100%
50%
EfficientAbsorption 23 times greater than iron saltsAbsorption is through the heme receptorsAong the GIT
CompliantTaken with mealsTaken with tea &coffeeNot affected by Gastric acidity as it Does not need to change to Ferrous-Ferric- Ferrous
QualityMade in Sweden
ConstipationCrampingHeartburnNausea
Heme Iron Polypeptide
Absorbed as ferrous
Absorbed from receptors along the GIT
Iron is Coated with the heme molecule in GIT
No constipation
Iron salts
Absorbed after changing from Ferric Ferrous Ferrous
Absorbed from receptors localized at the duodenum
Iron is free in GIT in huge quantity
Usually associated with constipation
Not affected by gastric acidity Affected by gastric acidity
Higher absorption Limited absorption
Heme Iron Polypeptide
Can be taken with food , Tea or Coffee
10 tablet give 60 mg of elemental iron
10 tablets in 5-10 days
No constipation
For a pregnant lady to load iron of 800 mg she will take 134 tablet in 2 month (2 tab/day)
Each 1 gm of hemoglobin need 150 mg of elemental iron = 25 tablet
Can be taken in 13 day
Iron salts
Taken on empty stomach
compared to 60 tablets give 60 mg of elemental iron
60 tablets in 2 month
Usually associated with constipation
For a pregnant lady to load iron of 800 mg she will take 800 tablet in 26 month (1 tab/day)
Each 1 gm of hemoglobin need 150 mg of elemental iron = 150 tablet Can be taken in 5 month
=