Hypovolemia and reduced hemoglobin mass in patients with heart failure and preserved ejection fraction

Abstract

A fundamental tenet of heart failure (HF) pathophysiology hinges on a propensity for fluid retention leading to blood volume (BV) expansion and hemodilution. Whether this can be applied to heart failure patients with preserved ejection fraction (HFpEF) remains uncertain. The present study sought to determine BV status and key hormones regulating fluid homeostasis and erythropoiesis in HFpEF patients. BV and hemoglobin mass (Hb_mass ) were determined with high-precision, automated carbon monoxide (CO) rebreathing in 20 stable HFpEF patients (71.5 ± 7.3 years, left ventricular ejection fraction = 55.7 ± 4.0%) and 15 healthy age- and sex-matched control individuals. Additional measurements comprised key circulating BV-regulating hormones such as pro-atrial natriuretic peptide (proANP), copeptin, aldosterone and erythropoietin (EPO), as well as central hemodynamics and arterial stiffness via carotid-femoral pulse wave velocity (PWV). Carotid-femoral PWV was increased (+20%) in HFpEF patients versus control individuals. With respect to hematological variables, plasma volume (PV) did not differ between groups, whereas BV was decreased (-14%) in HFpEF patients. In consonance with the hypovolemic status, Hb_mass was reduced (-27%) in HFpEF patients, despite they presented more than a twofold elevation of circulating EPO (+119%). Plasma concentrations of BV-regulating hormones, including proANP (+106%), copeptin (+99%), and aldosterone (+62%), were substantially augmented in HFpEF patients. HFpEF patients may present with hypovolemia and markedly reduced Hb_mass , underpinned by a generalized overactivation of endocrine systems regulating fluid homeostasis and erythropoiesis. These findings provide a novel perspective on the pathophysiological basis of the HFpEF condition.

Keywords: Blood volume; erythropoietin; heart failure with preserved ejection fraction; hemoglobin mass.

Figure 1

Blood volumes in relative (A) and absolute (B) units in HFpEF patients and control individuals. Data in bars are presented as mean ± SD. *Significantly different (P < 0.05) between HFpEF patients and control individuals. BV, blood volume; HFpEF, heart failure with preserved ejection fraction; PV, plasma volume; RBCV, red blood cell volume.

Figure 2

Blood volume‐regulating hormones in HFpEF patients and control individuals. Data in bars are presented as mean ± SD. *Significantly different (P < 0.05) between HFpEF patients and control individuals. EPO, erythropoietin; HFpEF, heart failure with preserved ejection fraction; proANP, pro‐atrial natriuretic peptide.