Blood volume expansion, normovolemia, and clinical outcomes in chronic human heart failure: More is better

Wayne L. Miller, John E. Strobeck, Diane E. Grill, Brian P. Mullan

Research output: Contribution to journalArticlepeer-review


Expansion in blood volume (BV) is a well-recognized response to arterial underfilling secondary to impaired cardiac output in heart failure (HF). However, the effectiveness of this response in terms of outcomes remains inadequately understood. Prospective analysis was undertaken in 110 patients with HF hospitalized and treated for fluid overload. BVs were measured in a compensated state at the hospital discharge using the indicator-dilution methodology. Data were analyzed for composite 1-year HF-related mortality/first rehospitalization. Despite uniform standard of care, marked heterogeneity in BVs was identified across the cohort. The cohort was stratified by BV expansion greater than or equal to þ25% above normal (51% of cohort), mild-moderate expansion (22%), and normal BV (27%). Kaplan–Meier (K-M) survival estimates and regression analyses revealed BV expansion (greater than or equal to þ25%) to be associated with better event-free survival relative to normal BV (P = 0.038). Increased red blood cell mass (RBCm; RBC polycythemia) was identified in 43% of the overall cohort and 70% in BV expansion greater than or equal to þ25%. K-M analysis demonstrated polycythemia to be associated with better outcomes compared with normal RBCm (P < 0.002). Persistent BV expansion to include RBC polycythemia is common and, importantly, associated with better clinical outcomes compared with normal total BV or normal RBCm in patients with chronic HF. However, compensatory BV expansion is not a uniform physiological response to the insult of HF with marked variability in BV profiles despite uniform standard of care diuretic therapy. Therefore, recognizing the variability in volume regulation pathophysiology has implications not only for impact on clinical outcomes and risk stratification but also potential for informing individualized volume management strategies.

Original languageEnglish (US)
Pages (from-to)H1074-H1082
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number6
StatePublished - Dec 2021


  • Blood volume expansion
  • Chronic heart failure
  • Outcomes
  • Plasma volume
  • RBC mass

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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