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 (Hbmass) 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, Hbmass 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 Hbmass, 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.
Highlights
A fundamental principle of cardiovascular physiology refers to the strict dependence of cardiac reserve upon blood volume (BV), which facilitates venous return, ventricular filling, and stroke volume via the Frank–Starling mechanism (Guyton and Hall 2011; Bonne et al 2014; Montero et al 2015)
heart failure patients with preserved ejection fraction (HFpEF) patients may present with hypovolemia and markedly reduced hemoglobin mass (Hbmass), underpinned by a generalized overactivation of endocrine systems regulating fluid homeostasis and erythropoiesis
The main findings evidence that HFpEF patients may present with: (1) preserved plasma volume (PV), (2) marked reductions in red blood cell volume (RBCV) and Hbmass, resulting in hypovolemia, and (3) augmented levels of BV-regulating hormones including copeptin, aldosterone, and EPO, denoting the activation of negative feedback mechanisms elicited by hypovolemia
Summary
A fundamental principle of cardiovascular physiology refers to the strict dependence of cardiac reserve upon blood volume (BV), which facilitates venous return, ventricular filling, and stroke volume via the Frank–Starling mechanism (Guyton and Hall 2011; Bonne et al 2014; Montero et al 2015). In the presence of a failing heart, acute fluid retention leading to BV expansion is considered a disproportionate compensatory response in the attempt to retrieve cardiac reserve, eventually resulting in clinical congestion (Guyton and Hall 2011). BV may exceed 120 mLÁkgÀ1 in untreated heart failure (HF) patients, a ~1.5-fold increase compared with healthy individuals (Kaplan et al 1954). Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.
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