LETTERS TO THE EDITOR
Reply
G. Michael Felker, MD*,
Wendy A. Gattis, PharmD,
Kirkwood F. Adams, MD and
Christopher M. O’Connor, MD
* Duke Clinical Research Institute, 2400 Pratt Street, Room 0311 Terrace Level, Durham, NC 27705 (Email: michael.felker{at}duke.edu).
We appreciate the interest of Drs. Kovacic and Cheng in our report (1) on the relationship between heart failure and anemia. We agree on the need for careful assessment of risks and benefits when evaluating any new therapeutic approach in heart failure. Dr. Kovacic correctly points out that anemia is technically the result of a decrease in red blood cell mass rather than a decreased hemoglobin concentration (2). Because accurate quantification of red cell mass requires labeled red blood cell scanning, hemoglobin concentration is frequently employed as a readily available surrogate in clinical practice. We concede that in states of plasma expansion (such as heart failure, renal failure, or pregnancy), hemoglobin concentration may not accurately reflect red blood cell mass. Our use of the terms "true anemia" and "hemodilution" reflected the terminology used in the study by Androne et al. (3), and we believe this nomenclature accurately describes the two mechanisms for decreased hemoglobin concentration described above.
Dr. Kovacic’s assertion that decreased hemoglobin concentration from plasma expansion in patients with heart failure may represent a "normal adaptation to increased cardiovascular demand" that has a "possible physiologic benefit (reduced blood viscosity)" is not supported by the data from Androne et al., which demonstrated a worse prognosis in patients with "hemodilution" compared to those with "true anemia" (3).
Both Drs. Cheng and Kovacic cite the potentially important role of blood viscosity in understanding the cardiovascular effects of anemia. Dr. Cheng appropriately points out that very elevated hematocrit levels (generally >50%) are associated with increased blood viscosity, which could potentially increase the risk for ischemic cardiac events. However, the studies by Burch and DePasquale cited by Dr. Cheng evaluated "bloodletting" in patients with hematocrit in the upper range of normal or above normal (almost always >50%) (4–6). In contrast, preliminary therapeutic studies using erythropoietin analogs in heart failure have generally targeted a modest rise in hemoglobin with a goal hemoglobin corresponding to a hematocrit below 40% (7,8). Notably, this is still well below the target hematocrit from phlebotomy suggested by Burch of 45% for men and 42% for women (4). Although in vivo evaluation of blood rheology is difficult, in vitro data suggest that optimal oxygen delivery (balancing oxygen delivery and blood viscosity) occurs at hematocrit levels between 38% to 51% (9).
Importantly, different therapies addressing the same target may be associated with a different balance of risks and benefits, and therapies may exert therapeutic or harmful effects through pathways unrelated to their presumed mechanisms. As Dr. Kovacic points out and as we stated in our review, emerging data suggest a role for erythropoietin in cardioprotection from ischemic injury. Such data raises the possibility that erythropoietin analogs may have beneficial effects in cardiovascular disease that are distinct from their effects on erythrogenesis. Conversely, recently published data suggest that red blood cell transfusions are associated with an increase of ischemic events in patients with acute coronary syndromes, possibly due to lack of ability of stored erythrocytes to effectively donate nitric oxide in the microvasculature (10). Given the uncertain balance of risks and benefits of therapy with erythropoietin analogs in patients with heart failure, the clinical equipoise required to proceed with carefully controlled, appropriately powered randomized trials clearly exists. As we stated in our conclusions, we continue to believe "a mixture of optimism and caution" is the appropriate stance until results from such trials are available.
 |
References
|
|---|
1. Felker GM, Adam Jr. KF, Gattis WA, O’Connor CM. Anemia as a risk factor and therapeutic target in heart failure J Am Coll Cardiol 2004;44:959-966.[Abstract/Free Full Text]
2. Schnall SF, Berliner N, Duffy TP, Benz EJ. Approach to the adult and child with anemiaIn: Hoffman R, Benz EJ, Shattil SJ, et al. editors. Hematology. Basic Principles and Practice. New York: Churchill Livingstone; 2000. pp. 367-375.
3. Androne AS, Katz SD, Lund L, et al. Hemodilution is common in patients with advanced heart failure Circulation 2003;107:226-229.[Abstract/Free Full Text]
4. Burch GE, DePasquale NP. Phlebotomyuse in patients with erythrocytosis and ischemic heart disease. Arch Intern Med 1963;111:687-695.[Abstract/Free Full Text]
5. Burch GE, DePasquale NP. The hematocrit in patients with myocardial infarction JAMA 1962;180:62-63.[Medline]
6. Burch GE, DePasquale NP. Hematocrit, viscocity and coronary blood flow Dis Chest 1965;48:225-232.[Web of Science][Medline]
7. 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.[Abstract/Free Full Text]
8. 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 irona randomized controlled study. J Am Coll Cardiol 2001;37:1775-1780.[Abstract/Free Full Text]
9. Stadler AA, Zilow EP, Linderkamp O. Blood viscosity and optimal hematocrit in narrow tubes Biorheology 1990;27:779-788.[Web of Science][Medline]
10. Rao SV, Jollis JG, Harrington RA, et al. Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes JAMA 2004;292:1555-1562.[Abstract/Free Full Text]
Related Article
-
Further Aspects of Anemia, Heart Failure, and Erythropoietin
- Jason C. Kovacic
J. Am. Coll. Cardiol. 2005 45: 1549-1550.
[Full Text]
[PDF]
|
Top
References