Dr.S.Venkatesan MD

HF is the inability (or reduced ability) to supply oxygen and other nutrients to fulfill the body’s demands. In the process, the heart either fights or flights, and results in symptoms due to hemodynamic alterations, or adversities of neuro-hormonal activation.

Now, what is Anemia? Anemia is a condition with reduced or dysfunctional RBCs. that directly interferes with oxygen delivery to tissues. It is not at all a coincidence, the core functions of the heart and blood are strikingly similar and intertwined. While the heart is the powerhouse of the circulatory system, without good-quality blood, the greatness of this vital organ becomes redundant.

A failing heart & compromised blood, throws up a double challenge, to the fundamental function of the circulatory system and results in impaired cellular oxygen delivery.

Fortunately, RBC and Hemoglobin have an adequate reserve, and real metabolic issues happen only after a 30 %  reduction in hemoglobin. During this time the heart works more to compensate by maintaining high output. When HB falls less than 6 to 7 grams the heart itself suffers from hypoxia and goes for intrinsic failure. So, when anemia coexists with cardiomyopathy imagine the tissue’s plight.

Anemia in Heart failure 

While there are many links between anemia and heart failure few things are worth emphasizing. It can be discussed in 4 categories.

1. Primary anemia that results in heart failure is a separate topic and comes under high-output HF.
2. Anemia as a part of the same disease process as heart failure. (Anemia of chronic illness) 
3. Nutritional anemia associated with common forms of heart failure (Ischemic and non-ischemic DCM) 
4. Anemia of CKD and coexisting heart failure 

*Category 2 is often missed, while category 3 is often ignored

Prevalence of anemia in HF.. Up to 30%. (Iron deficiency anemia is the most common)

Diagnosis: Criteria Ferritin less than100 or 100-299 μg/L with transferrin saturation <20%). 

What is the optimal Hb %?  Should be 13 grams

Iron deficiency is much more than anemia 

It is worthwhile to go back to the basics, anemia is just one aspect of iron deficiency. Humans live their life, essentially inside the breathing chambers of mitochondria in each of the 12 trillion cells.  Without an adequate iron supply, the citric acid cycle will come to a creeping halt. It is now recognized, altered mitochondrial function is one of the key peripheral defects in HF. (Ref 1) Iron deficiency could be an Incidental marker for a more important tissue deficit elsewhere. 

What do the trials say about the role of routine Iron supplements in HF?

As usual, trials blink with data on either side of the truth. Small studies suggested benefits. But large studies with Iron supplements and Erhytopoitn analogs failed to show benefits. IRON-OUT, RED -HF (Ref 2,3) . But in a popular study from the Lancet , showed ferric carboxymaltose improved the outcome. (Ponikowski P,l. Lancet. 2020 Dec 12;396(10266):1895-1904).

Final message

We, as modern-day cardiologists are always pre-occupied with measures to improve LV ejection fraction at any cost (Since we fell into a false knowledge trap of defining HF solely on the basis of  EF% ) To make HF patients walk 30 meters extra in a 6-minute walk test we have complex and costly procedures like CRT, Mitra clips, and IAS flow regulators,  etc.

However, experience tells us there are many parameters other than EF that can improve functional capacity and quality of life. Breathing exercise is the best example. Let’s add one more to this list. A simple correction of anemia with iron can make your cardiac failure patient walk many blocks more. Trials are not consistently confirming this though. Don’t bother them,  just have a try. If prescribing tablet iron without evidence bothers you with scientific guilt, ask your patient to take a diet with rich iron content and see the difference.

For advanced readers

Anemia and  Aortic afterload: The apparent advantage

There is one curious concept. Anemia makes the blood thin. Reason lowered viscosity. As a consequence afterload falls. , hypoxia-induced peripheral vasodilatation and enhanced nitric oxide activity also contribute to this.  Vasodilatation also involves the recruitment of microvessels and, in the case of chronic anemia, stimulation of angiogenesis. So, anemia apparently has a double edge, and one of them seems to be beneficial.

We must also beware, the risk of iron overload is genuine in some of these patients with HF. This makes us wonder, in ancient times venesection was used for so many undisclosed illnesses, which might include heart disease as well.

Reference

1. Melenovsky  V, Petrak  J, Mracek  T,  et al.  Myocardial iron content and mitochondrial function in human heart failure.  Eur J Heart Fail. 2017;19(4):522-530

2. Lewis GD, Malhotra R, Hernandez AF, et al. Effect of Oral Iron Repletion on Exercise Capacity in Patients With Heart Failure With Reduced Ejection Fraction and Iron Deficiency: The IRON OUT HF Randomized Clinical Trial. JAMA. 2017;317(19):1958–1966. doi:10.1001/jama.2017.5427

3. Swedberg K, Young JB, Anand IS, Cheng S, Desai AS, Diaz R, Maggioni AP, McMurray JJ, O’Connor C, Pfeffer MA, Solomon SD, Sun Y, Tendera M, van Veldhuisen DJ; RED-HF Committees; RED-HF Investigators. Treatment of anemia with darbepoetin alfa in systolic heart failure. N Engl J Med. 2013 Mar 28;368(13):1210-9. doi: 10.1056/NEJMoa1214865. Epub 2013 Mar 10. PMID: 23473338.