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Heart failure (HF) is a major chronic condition, affecting nearly 5 million Americans, with about half a million new cases diagnosed annually.¹ Anemia is a common and potentially modifiable comorbidity in patients with heart failure. Studies have shown that the prevalence of anemia in heart failure patients increases with the severity of the heart failure, with prevalence ranging from less than 10% among patients with mild heart failure to more than 50% for those with more advanced disease.²

HF patients with anemia are more likely to be older, have diabetes, chronic kidney disease, greater New York Heart Association (NYHA) functional class, lower exercise capacity, worse health-related quality of life, greater edema, lower blood pressure and greater use of diuretics.³ According to Dr. Ileana Piña, a cardiologist and Professor of Medicine at Case Western Reserve University in Cleveland, “Anemia is dangerous for patients with heart failure. It may exacerbate cardiovascular disease, making the patient’s situation worse. Anemia in these patients should not be ignored.”

Causes of Anemia in HF Patients
Anemia may be incidental, or it may be directly related to HF. A variety of potential causes may contribute to the development of anemia in heart failure patients, but it is most likely caused by a complex interaction of cardiac, hormonal, inflammatory, renal and bone marrow effects.⁴ Some specific potential causes of anemia in HF include inflammation of chronic disease, hemodilutional effects of excess fluid, iron deficiency, renal dysfunction with impaired erythropoietin production, and adverse effect of medications.

Anemia of chronic disease may be the most frequent cause of anemia in HF patients, occurring in as many as 58% of patients.⁵ Proinflammatory cytokine activation, inadequate erythropoietin production, and/or defective iron utilization despite adequate iron stores, have all been found in these patients, suggesting anemia of chronic disease. However, Dr. Piña advises that “Physicians should not simply assume that all anemia in heart failure patients is caused by inflammation and anemia of chronic disease. Their anemia needs to be diagnosed with proper work-up schedule, which may include iron and vitamin levels, erythropoietin levels, and possibly evaluation for blood loss (i.e. colonoscopy and/or endoscopy).”

Anemia in HF patients may also be caused by hemodilution induced “pseudoanemia”, caused by the expansion of plasma volume commonly found in heart failure.³ This hemodilution has been found in as many as 46% of heart failure patients.³ Iron deficiency has also been the reported cause of approximately 20% of anemia in HF patients. Poor nutrition, gastrointestinal malabsorption of iron, chronic aspirin use, and uremic gastritis, can precipitate iron deficiency anemia.

Renal dysfunction, secondary to decreased renal blood flow, is common in patients with HF. However, this renal hypoxia and hypoperfusion should lead to an increase in erythropoietin production. This increase is often lower than expected for the degree of anemia, suggesting blunted erythropoietin production.⁵ Angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) drugs can also contribute to the development of anemia by decreasing renal erythropoietin secretion.³

Anemia-Associated Hemodynamic Changes
Some of the hemodynamic changes that accompany severe anemia include increased cardiac output, decreased peripheral vascular resistance, and increased preload.⁴ These responses may ultimately result in a harmful increase in left ventricular mass, an indicator of poor prognosis. A reduction in oxygen-carrying capacity coupled with increased left ventricular mass and increased wall stress can precipitate myocardial ischemia. Chronically increased myocardial work and the adrenergic stimulation caused by decreased oxygen-carrying capacity can cause worsening of heart failure.⁴

Anemia and Outcomes
Anemia has been shown to be an independent risk factor for severe symptoms in heart failure patients, such as lower functional status, worse exercise capacity, cognitive impairment, and worse quality of life.⁶ In most reported studies, anemia is an independent predictor of increased mortality risk and increased risk of hospitalization for heart failure.

There is a clear association of anemia with hospitalization as a predictor of hospital readmission, and mortality.⁷ However, it is not known whether anemia is just a marker, or if it is actually a mediator of poor outcomes.⁸ With a few important exceptions discussed below, most studies with multivariate adjustment for mortality risk have reported anemia is an independent predictor of mortality risk.⁷ In three large studies of elderly heart failure patients, there was no association between anemia and mortality when adjusted for comorbidities, indicating that the increased mortality may be explained by the severity of the comorbid illnesses rather than the anemia.⁷ However, it is unknown whether anemia may be the cause of the increased mortality with the comorbidities.

Handouts for Your Patients

NAAC also provides information handouts to patients describing anemia caused by specific diseases. The Anemia & Heart Disease handout might be right for your patients - read it today!

Treatment Options
Preliminary studies have demonstrated that erythropoiesis-stimulating agents (ESAs) and IV iron may improve exercise capacity, quality of life, and cardiac and renal function in heart failure patients.⁶ Specifically, a nonsignificant trend was observed toward a lower risk of all cause mortality or first heart failure hospitalization in heart failure patients treated with darbepoetin.⁶ However, a recent double-blind, randomized, placebo-controlled study of darbepoetin in anemic HF patients failed to show improvement in exercise capacity or quality of life.⁶ Iron deficiency is frequently found in anemic HF patients, therefore IV iron therapy may be beneficial in anemic HF patients.³ A few small studies have shown improvement in NYHA functional class, quality of life, and exercise capacity with IV iron.³

Further studies are required to assess the potential benefit of correcting anemia, and the optimal treatment strategy. While preliminary studies show that correction of anemia in HF patients may have beneficial effects, there is still no convincing data regarding the long term efficacy and safety of ESA and IV iron therapy in this patient population.

References

1. National Heart, Lung, and blood Institute Data Fact Sheet. Congestive Heart Failure in the United States: A New Epidemic. Link. Accessed: February 19, 2009.
2. Komajda M. Prevalence of anemia in patients with chronic heart failure and their clinical characteristics. J Card Fail. 2004 Feb;10(1 Suppl):S1-4. Link.
3. Anand IS. Anemia and chronic heart failure implications and treatment options. J Am Coll Cardiol. 2008 Aug 12;52(7):501-11. Link.
4. Dec GW. Anemia in heart failure. Time to rethink its etiology and treatment? J Am Coll Cardiol. 2006 Dec 19;48(12):2490-92. Link.
5. Ezekowitz JA, McAlister FA, Armstrong PW. Anemia is common in heart failure and is associated with poor outcomes: insights from a cohort of 12 065 patients with new-onset heart failure. Circulation. 2003 Jan 21;107(2):223-25. Link.
6. Ghali JK, Anand IS, Abraham WT, Fonarow GC, Greenberg B, Krum H, Massie BM, Wasserman SM, Trotman ML, Sun Y, Knusel B, Armstrong P; Study of Anemia in Heart Failure Trial (STAMINA-HeFT) Group. Randomized double-blind trial of darbepoetin alfa in patients with symptomatic heart failure and anemia. Circulation. 2008 Jan 29;117(4):526-35. Link.
7. Tang Y, Katz SD. The prevalence of anemia in chronic heart failure and its impact on the clinical outcomes. Heart Fail Rev. 2008 Dec;13(4):387-92. Link.
8. Anand I. Introduction: anemia in heart failure. Heart Fail Rev. 2008 Dec;13(4):377-78. Link.
9. Belonje AM, Voors AA, van Gilst WH, van Veldhuisen DJ. Erythropoietin in chronic heart failure. Congest Heart Fail. 2007 Sept-Oct;13(5):289-92. Link.

Last Updated: March 4, 2009