Volume-Kidney Interaction in Chronic Heart Failure - Impact of Subclinical Volume Expansion and Chronic Kidney Disease on Clinical Outcomes

Abstract

ObjectivesAssess the impact of volume-kidney interactions on outcomes in clinically “euvolemic” chronic heart failure (HF) patients with co-existing chronic kidney disease (CKD).BackgroundCardio-renal interactions are complex and bi-directional and may in part be mediated by the extent of intravascular volume overload. The impact of subclinical volume expansion on outcomes in HF patients with CKD has not been previously examined.MethodsPlasma volume (PV) was prospectively measured in 110 stable HF patients with varying degrees of CKD using a standardized radiolabeled albumin indicator-dilution technique. To examine the interactive roles of volume expansion and CKD the cohort was dichotomized by median PV and then further stratified by cohort median creatinine (sCr), eGFR, and BUN and analyzed for outcomes of HF-related mortality or 1st hospitalization using Kaplan-Meier method.ResultsSubclinical volume overload was demonstrated in 76% of the cohort. Over 1.5 years, sCr and BUN above and eGFR below (Fig.) cohort median values identified highest risk for the composite end-point but only in severe PV expansion (≥ median expansion of +26%) (p=0.02). In normal to moderate PV expansion (< +26% expansion) worse renal function was not associated with increased risk (p=0.578).ConclusionsIn clinically stable chronic HF patients with co-existing CKD, subclinical PV expansion is common, and importantly the extent of PV expansion impacts outcomes including early HF mortality. However, better kidney function mitigates the deleterious effects of severe PV expansion, while mild-moderate expansion balances the risks of worse renal function. Thus, volume-kidney interactions are complex with volume status modulating the impact of CKD on outcomes in chronic HF. Figures. Risk Stratification by Median eGFR in Chronic Heart Failure Patients with A. Severe Plasma Volume Expansion (PV ≥ Median of +26% Above Normal Volume) B. Mild-Moderate Plasma Volume Expansion (PV < Median of +26% Above Normal Volume) Assess the impact of volume-kidney interactions on outcomes in clinically “euvolemic” chronic heart failure (HF) patients with co-existing chronic kidney disease (CKD). Cardio-renal interactions are complex and bi-directional and may in part be mediated by the extent of intravascular volume overload. The impact of subclinical volume expansion on outcomes in HF patients with CKD has not been previously examined. Plasma volume (PV) was prospectively measured in 110 stable HF patients with varying degrees of CKD using a standardized radiolabeled albumin indicator-dilution technique. To examine the interactive roles of volume expansion and CKD the cohort was dichotomized by median PV and then further stratified by cohort median creatinine (sCr), eGFR, and BUN and analyzed for outcomes of HF-related mortality or 1st hospitalization using Kaplan-Meier method. Subclinical volume overload was demonstrated in 76% of the cohort. Over 1.5 years, sCr and BUN above and eGFR below (Fig.) cohort median values identified highest risk for the composite end-point but only in severe PV expansion (≥ median expansion of +26%) (p=0.02). In normal to moderate PV expansion (< +26% expansion) worse renal function was not associated with increased risk (p=0.578). In clinically stable chronic HF patients with co-existing CKD, subclinical PV expansion is common, and importantly the extent of PV expansion impacts outcomes including early HF mortality. However, better kidney function mitigates the deleterious effects of severe PV expansion, while mild-moderate expansion balances the risks of worse renal function. Thus, volume-kidney interactions are complex with volume status modulating the impact of CKD on outcomes in chronic HF. Figures. Risk Stratification by Median eGFR in Chronic Heart Failure Patients with A. Severe Plasma Volume Expansion (PV ≥ Median of +26% Above Normal Volume) B. Mild-Moderate Plasma Volume Expansion (PV < Median of +26% Above Normal Volume)