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

=