Persistent Intravascular Volume Expansion is Compensatory, Not Detrimental, in Post-Hospital Chronic Heart Failure Patients and Associated with Better Clinical Outcomes

Abstract

Background Intravascular volume is largely regulated by the kidneys but how the relative extent of volume expansion impacts outcomes in post-hospital chronic heart failure (HF) patients has not been assessed. Our hypothesis was that greater rather than lesser volume expansion is compensatory and associated with better HF-related outcomes. Methods Blood volume (BV) was prospectively measured in 87 HF patients at the time of hospital discharge (post-diuretic therapy) using a standardized nuclear medicine radiolabeled albumin indicator-dilution technique (Daxor Corp., NY, NY). A volume cut-point of ≥+25% above normal BV defined greater from lesser volume expansion. The cohort was analyzed for 1-year composite outcome of HF-related mortality or 1st re-hospitalization. Results BV expansion ≥+25% was present in 53% of the cohort with RBC mass excess (polycythemia) being the predominant contributor (74% of this subgroup). In this volume expanded subgroup (N=46) the risk for the composite endpoint was significantly lower than in the subgroup with less volume expansion (N=41; 56% with normal BV, 44% with mild-moderate BV expansion) [Fig. 1, p=0.017, RR 0.41 (0.20-0.84)]. Further, the evaluation of RBC mass as a component of intravascular volume informs the higher risk associated with true anemia [p=0.006, RR 2.78 (1.37-5.55)], but also importantly the significant reduction in risk associated with RBC polycythemia [p Conclusions The findings of this analysis indicate that persistent intravascular volume expansion (≥+25% above normal volume) is common at the time of hospital discharge despite diuretic intervention in chronic HF patients, and importantly that in post-hospital follow up the greater extent of BV expansion (compared to normal volume or mild-moderate expansion) driven mainly by RBC polycythemia is compensatory, not detrimental, and associated with better HF-related outcomes including reduced mortality. These findings provide additional insight into the pathophysiology of chronic HF and also have implications for a more individualized approach to volume assessment and management in HF patients.