As part of a prospective, single blind, randomized, placebo-controlled study comparing erythropoietin alfa with placebo in older adults (n?=?56) with heart failure and a preserved ejection fraction (HFPEF), we performed blood volume analysis with the use of an indicator dilution technique with 131iodine-labeled albumin. We evaluated differences in plasma volumes and red cell volumes in hyporesponders (eg, <1?g/dL increase in hemoglobin within the first 4?weeks of treatment with erythropoetin alfa) compared with subjects who were responders and controls.
Nine of 28 subjects (32 % ) assigned to ESA were hyporesponders. Hyporesponders did not differ from responders nor control subjects by any baseline demographic, clinical, or laboratory parameter, including hemoglobin. Hyporesponders had a greater total blood volume expansion (1,264.7?¡À?387 vs 229?¡À?206?mL; P?=?.02) but less of a red cell deficit (?96.2?¡À?126 vs ?402.5?¡À?80.6?mL; P?=?.04) and a greater plasma volume expansion (+1,360.8?¡À?264.5 vs?+601.1?¡À?165.5?mL; P?=?.01). Among responders, the increase in hemoglobin with erythropoietin alfa was associated primarily with increases in red cell volume (r?=?0.91; P?<?.0001) as well as a decline in plasma volume (r?=??0.55; P?=?.06).
Among older adults with HFPEF and anemia, hyporesponders to erythropoietin alfa had a hemodilutional basis of their anemia, suggesting that blood volume analysis can identify a cohort likely to respond to therapy.