Abstract 18594: Plasma Volume Status Calculated Instantaneously from Weight and Hematocrit Relates to Objectively Measured Plasma Volumes and Powerfully Predicts Death and First Morbid Events in Chronic Heart Failure

Abstract

Background: Plasma volume (PV) expansion hallmarks worsening chronic heart failure (CHF) but no non-invasive means of quantifying volume status exists. Because weight and hematocrit are intimately related to PV, we derived an index of relative PV status (PVS) using validated equations based on these simple indices. We tested the validity and prognostic utility of our index in a logical sequence of analyses. Methods: First, we correlated current PV measured using 125 Iodine-human serum albumin to calculated values ([1-hematocrit] x [a + (b x weight)]). Second, we subtracted calculated current PV from ideal PV (c x weight) to derive PVS ([(current-ideal)/ideal] x 100%) in CHF patients (pts). Third, we assessed the prognostic implications of PVS in 5002 pts in the Val-HeFT trial (age 62±11y, LVEF 27±7%, 37% NYHA≥3) and validated this in an accrued ‘real world’ sample of 246 CHF pts (age 67±13y, LVEF 28±8%). Results: Calculated and measured PV correlated at baseline in normal subjects (n=119, r=0.68) with a bias of 78mL, and at baseline (n=22, r=0.44) and over time (r=0.60) in hospitalized CHF pts. In the Val-HeFT cohort, PVS was -10±11% (median [±IQR]) and related to volume biomarkers such as NT-BNP, urea, eGFR, albumin, and sodium (all P<0.01). Over 2 years, 977 (20%) pts died. PVS was associated with death (Fig A ) and first morbid events in a ‘J-shaped’ fashion with the highest and lowest risks seen with a PVS> - 4% and between -12% to -14%, respectively. Stratification into quartiles confirmed this with a PVS> - 4% (versus ≤ - 4%) prognostic (unadjusted HR 1.65, 95% CI 1.44-1.88, χ 2 54, P<0.001, Fig B ) even after adjustment for 22 variables including NT-BNP. These results were mirrored in the validation cohort. Conclusions: PVS calculated from simple clinical indices reliably reflects the degree to which patients have deviated from their ideal PV and independently relates to outcomes. Titrating CHF therapy to keep PVS below - 4% and ideally between -12% to -14% might increment survival.