Heart failure frequently occurs in patients with a normal ejection fraction (HFNEF) and affected subjects are predominately elderly, women with several co-morbid conditions. Despite the diversity of underlying clinical pathologies and co-morbid conditions present in these patients, a common pathophysiologic explanation is generally applied to explain their clinical symptoms, concentric hypertrophy leading to a small chamber size with decreased diastolic capacitance (decreased volume at a specific filling pressure). In such patients, the high resting left ventricular filling pressure is required for such hearts to maintain normal cardiac output. Our preliminary data revealed that although HFNEF is commonly thought of as being the result of a single hemodynamic mechanism, subgroups exist with distinctly different underlying pathophysiologies. Specifically, we documented that a significant subgroup with HFNEF have increases in ventricular volumes and expanded plasma volumes, consistent with a volume overload state. In the setting of a normal ejection fraction with end diastolic volume increased, stroke volume must increase, indicating a high output state. High output states involve peripheral (i.e.extra-cardiac) mechanisms, including anemia among others. Anemia may be an important, modifiable contributor to exercise intolerance in elderly HFNEF patients, abnormal ventricular remodeling and impaired overall health status and quality of life. Our pilot data suggests that the prevalence of anemia is high (>50%) in elderly patients hospitalized with HFNEF, most of these subjects (76%) have a true anemia by blood volume analysis, which is associated with the glornerular filtration rate, suggesting that inadequate production of erythropoeitin may be a mechanism for their anemia. We have additionally, shown that anemic HFNEF subjects have poorer quality of life, more severe symptoms along with hemodynamic and structural cardiovascular changes compared with elderly subjects with HFNEF without anemia. Finally, preliminary data suggests that erythropoeitin adminstration to anemic HFNEF subjects results in improvements in submaximal and maximal exercise capacity. Concordant with our long-term goal to elucidate the pathophysiologic mechanisms that underlie the the syndrome of HFNEF and to develop effective therapies, we propose to evaluate the impact of treating anemia in elderly subjects with HFNEF.
The specific aims of the current study are to provide a comprehensive and mechanistically based assessment of how correcting anemia in elderly subjects with HFNEF can impact on ventriuclar structure and funciton, functional capacity and overall health status. We propose to perform a randomized, prospective, double bind study in 120 elderly subjects with HFNEF to test the hypothesis that the administration of subcutaneous erythropoietin will be associated with significant reverse ventricular remodeling, increased exercise capacity and improved health status. Principle measurements will include six minute walk, maximal oxygen consumption and ventilatory anaerobic threshold by expired gas analysis;blood volume analysis, mesaures of renal function, health status by standardized questionnaires, and LV volumes, mass and function by three dimensional echocardiography. This study will examine the role of anemia in the pathophysiology of elderly patients with HFNEF and determine whether targeting anemia, one of many extra-cardiac factors that could contribute to the volume overload state that is characteristic of HFNEF, can ventricular remodeling and function, exercise capacity and health status. .

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
Project #
Application #
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Zieman, Susan
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Columbia University (N.Y.)
Internal Medicine/Medicine
Schools of Medicine
New York
United States
Zip Code
Cohen, Laura P; Maurer, Mathew S (2016) Letter by Cohen and Maurer Regarding Article, ""Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis"". Circulation 133:e449
Vullaganti, Sirish; Goldsmith, Jeff; Teruya, Sergio et al. (2014) Cardiovascular effects of hemoglobin response in patients receiving epoetin alfa and oral iron in heart failure with a preserved ejection fraction. J Geriatr Cardiol 11:100-5
Borovka, Margarita; Teruya, Sergio; Alvarez, Julissa et al. (2013) Differences in blood volume components between hyporesponders and responders to erythropoietin alfa: the heart failure with preserved ejection fraction (HFPEF) anemia trial. J Card Fail 19:685-91
Altincatal, Arman; Macarthur, Robert B; Teruya, Sergio et al. (2013) A dosing algorithm for erythropoietin alpha in older adults with heart failure and a preserved ejection fraction. Cardiovasc Ther 31:92-9
Maurer, Mathew S; Teruya, Sergio; Chakraborty, Bibhas et al. (2013) Treating anemia in older adults with heart failure with a preserved ejection fraction with epoetin alfa: single-blind randomized clinical trial of safety and efficacy. Circ Heart Fail 6:254-63
Green, Philip; Babu, Benson A; Teruya, Sergio et al. (2013) Impact of epoetin alfa on left ventricular structure, function, and pressure volume relations as assessed by cardiac magnetic resonance: the heart failure preserved ejection fraction (HFPEF) anemia trial. Congest Heart Fail 19:172-9
Green, Philip; Woglom, Abigail E; Genereux, Philippe et al. (2012) Gait speed and dependence in activities of daily living in older adults with severe aortic stenosis. Clin Cardiol 35:307-14
Bhuiyan, Taslima; Maurer, Mathew S (2011) Heart Failure with Preserved Ejection Fraction: Persistent Diagnosis, Therapeutic Enigma. Curr Cardiovasc Risk Rep 5:440-449
Abramov, Dmitry; He, Kun-Lun; Wang, Jie et al. (2011) The impact of extra cardiac comorbidities on pressure volume relations in heart failure and preserved ejection fraction. J Card Fail 17:547-55
Noumi, Bassel; Teruya, Sergio; Salomon, Say et al. (2011) Blood volume measurements in patients with heart failure and a preserved ejection fraction: implications for diagnosing anemia. Congest Heart Fail 17:14-8

Showing the most recent 10 out of 18 publications