Relation of Intravascular Volume Profiles to Heart Failure Progression and Clinical Outcomes

Author(s):  
Kevin L. Kelly ◽  
Robert J. Wentz ◽  
Bruce D. Johnson ◽  
Wayne L. Miller
2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
W Miller

Abstract Background/Introduction Intravascular volume is regulated by the kidneys but the interconnection of the extent of volume expansion with renal function and outcomes in patients with chronic HF has not been assessed. Therefore, we evaluated how GFR-defined renal function and HF-related clinical outcomes are impacted by the relative extent of intravascular volume expansion. Our hypothesis was that greater rather than lesser volume expansion would be protective of worse renal function and contribute to better clinical outcomes than mild-moderate volume expansion. Purpose Assess the impact of quantitated intravascular volume expansion on heart failure (HF) outcomes in relation to renal function in post-hospital clinically determined “euvolemic” chronic HF patients. Methods Blood volume (BV) was prospectively measured in 87 HF patients considered clinically “euvolemic” post-diuresis at the time of hospital discharge using a standardized radiolabeled albumin indicator-dilution technique (Daxor Corp., NY, NY). A volume cut-point of ≥+25% above normal expected BV was used to define the greater degree of volume expansion from more mild-moderate expansion. These volume subgroups were then stratified by cohort median eGFR (46 mL/min/1.73m2) and analyzed for 1-year outcomes of HF-related mortality or 1st re-hospitalization using the Kaplan-Meier method. Results Volume expansion ≥+25% was demonstrated in 53% of the cohort at the time of hospital discharge despite hospital diuretic therapy. In this subgroup over 1.0 year of follow-up the risk for the composite outcome was significantly lower than in the group with mild-moderate volume expansion (Log-Rank p=0.017). Further, in the clinical setting of greater volume expansion, worse renal function with eGFR below the cohort median (<46 mL/min/1.73m2) was not associated with increased risk for the composite end-point (Figure). In contrast, low eGFR in the presence of mild-moderate volume expansion stratified risk and was associated with worse outcome relative to a higher eGFR above the median (Figure). Figure 1 Conclusions In post-hospital chronic HF patients significant intravascular volume expansion is common, and importantly the extent of BV expansion impacts outcomes including HF-related mortality. However, greater rather than lesser volume expansion appears to favorably mitigate the impact of worse renal function (low eGFR), while normal or mild-moderate expansion does not spare the impact of worse renal function on outcomes. Thus, a favorable degree of volume expansion appears to balance the risks of worse renal function. Volume-kidney interconnections are complex with volume status modulating the impact of impaired renal function on outcomes in chronic HF. Acknowledgement/Funding None


2018 ◽  
Vol 34 (10) ◽  
pp. S93
Author(s):  
J. McConnery ◽  
F. Foroutan ◽  
A. Alba ◽  
H. Ross ◽  
J. MacIver

Author(s):  
Mariana Fernandez-Caggiano ◽  
Philip Eaton

AbstractThe mitochondrial pyruvate carrier (MPC) is the entry point for the glycolytic end-product pyruvate to the mitochondria. MPC activity, which is controlled by its abundance and post-translational regulation, determines whether pyruvate is oxidised in the mitochondria or metabolised in the cytosol. MPC serves as a crucial metabolic branch point that determines the fate of pyruvate in the cell, enabling metabolic adaptations during health, such as exercise, or as a result of disease. Decreased MPC expression in several cancers limits the mitochondrial oxidation of pyruvate and contributes to lactate accumulation in the cytosol, highlighting its role as a contributing, causal mediator of the Warburg effect. Pyruvate is handled similarly in the failing heart where a large proportion of it is reduced to lactate in the cytosol instead of being fully oxidised in the mitochondria. Several recent studies have found that the MPC abundance was also reduced in failing human and mouse hearts that were characterised by maladaptive hypertrophic growth, emulating the anabolic scenario observed in some cancer cells. In this review we discuss the evidence implicating the MPC as an important, perhaps causal, mediator of heart failure progression.


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