Background-Overly aggressive diuresis leading to intravascular volume depletion has been proposed as a cause for worsening renal function during the treatment of decompensated heart failure. If diuresis occurs at a rate greater than extravascular fluid can refill the intravascular space, the concentration of such intravascular substances as hemoglobin and plasma proteins increases. We hypothesized that hemoconcentration would be associated with worsening renal function and possibly would provide insight into the relationship between aggressive decongestion and outcomes. Methods and Results-Subjects in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery CatheterizationEffectiveness trial limited data set with a baseline/discharge pair of hematocrit, albumin, or total protein values were included (336 patients). Baseline-to-discharge increases in these parameters were evaluated, and patients with Ն2 in the top tertile were considered to have evidence of hemoconcentration. The group experiencing hemoconcentration received higher doses of loop diuretics, lost more weight/fluid, and had greater reductions in filling pressures (PϽ0.05 for all).Hemoconcentration was strongly associated with worsening renal function (odds ratio, 5.3; PϽ0.001), whereas changes in right atrial pressure (Pϭ0.36) and pulmonary capillary wedge pressure (Pϭ0.53) were not. Patients with hemoconcentration had significantly lower 180-day mortality (hazard ratio, 0.31; Pϭ0.013). This relationship persisted after adjustment for baseline characteristics (hazard ratio, 0.16; Pϭ0.001). Conclusion-Hemoconcentration

Objective We sought to determine if the timing of hemoconcentration influences the associated survival. Background Indicating a reduction in intravascular volume, hemoconcentration during the treatment of decompensated heart failure (HF) has been associated with reduced mortality. However, it is unclear if this survival advantage stems from the improved intravascular volume or if healthier patients are simply more responsive to diuretics. Rapid diuresis early in the hospitalization should similarly identify diuretic responsiveness, but hemoconcentration this early would not indicate euvolemia if extravascular fluid has not yet equilibrated. Methods Consecutive admissions at a single center with a primary discharge diagnosis of HF were reviewed (n=845). Hemoconcentration was defined as an increase in both hemoglobin and hematocrit, then further dichotomized into Early or Late using the midway point of the hospitalization. Results Hemoconcentration occurred in 422 (49.9%) patients; 41.5% Early and 58.5% Late. Patients with Late vs. Early hemoconcentration had similar baseline characteristics, cumulative in-hospital loop diuretic administered, and worsening of renal function. However, patients with Late vs. Early hemoconcentration had higher average daily loop diuretic doses (p=0.001), greater weight loss (p<0.001), later transition to oral diuretics (p=0.03), and shorter length of stay (p<0.001). Late hemoconcentration conferred a significant survival advantage (HR=0.74, 95% CI 0.59–0.93, p=0.009) whereas Early hemoconcentration offered no significant mortality benefit (HR=1.0, 95% CI 0.80–1.3, p=0.93) over no hemoconcentration. Conclusions Only hemoconcentration occurring late in the hospitalization was associated with improved survival. These results provide further support for the importance of achieving sustained decongestion during treatment of decompensated heart failure.

Background-Identifying reversible renal dysfunction (RD) in the setting of heart failure is challenging. The goal of this study was to evaluate whether elevated admission blood urea nitrogen/creatinine ratio (BUN/Cr) could identify decompensated heart failure patients likely to experience improvement in renal function (IRF) with treatment. Methods and Results-Consecutive hospitalizations with a discharge diagnosis of heart failure were reviewed. IRF was defined as ≥20% increase and worsening renal function as ≥20% decrease in estimated glomerular filtration rate. IRF occurred in 31% of the 896 patients meeting eligibility criteria. Higher admission BUN/Cr was associated with inhospital IRF (odds ratio, 1.5 per 10 increase; 95% confidence interval [CI], 1.3-1.8; P<0.001), an association persisting after adjustment for baseline characteristics (odds ratio, 1.4; 95% CI, 1.1-1.8; P=0.004). However, higher admission BUN/Cr was also associated with post-discharge worsening renal function (odds ratio, 1.4; 95% CI, 1.1-1.8; P=0.011). Notably, in patients with an elevated admission BUN/Cr, the risk of death associated with RD (estimated glomerular filtration rate <45) was substantial (hazard ratio, 2.2; 95% CI, 1.6-3.1; P<0.001). However, in patients with a normal admission BUN/Cr, RD was not associated with increased mortality (hazard ratio, 1.2; 95% CI, 0.67-2.0; P=0.59; p interaction=0.03). Conclusions-An elevated admission BUN/Cr identifies decompensated patients with heart failure likely to experience IRF with treatment, providing proof of concept that reversible RD may be a discernible entity. However, this improvement seems to be largely transient, and RD, in the setting of an elevated BUN/Cr, remains strongly associated with death. Further research is warranted to develop strategies for the optimal detection and treatment of these high-risk patients. (Circ Heart Fail. 2013;6:233-239.)

Worsening renal function (RF) and improved RF during the treatment of decompensated heart failure have traditionally been thought of as hemodynamically distinct events. We hypothesized that if pulmonary artery catheter derived measures are relevant in the evaluation of cardiorenal interactions comparison of patients with improved vs. worsening RF should highlight any important hemodynamic differences. All subjects in the ESCAPE trial limited data set with admission and discharge creatinine values available were included (401 patients). There were no differences in baseline, final, or change in pulmonary artery catheter derived hemodynamic variables, inotrope and intravenous vasodilator use, or survival between patients with improved and worsening RF (p=NS for all). Both groups were equally likely to be in the bottom quartile of cardiac index (CI) (p=0.32), have a 25% improvement in CI (p=0.97), or have any worsening in CI (p=0.90). When patients with any significant change in renal function (positive or negative) were compared to patients with stable renal function, strong associations between variables such as reduced CI (OR=2.2, p=0.02), increased intravenous inotrope and vasodilator use (OR=2.9, p<0.001), and worsened all cause mortality (HR=1.8, p=0.01) became apparent. Contrary to traditionally held views, patients with improved RF and worsening RF have similar hemodynamic parameters and outcomes. Combining these groups identifies a hemodynamically compromised population with significantly worse survival than patients with stable renal function. In Conclusion, changes in renal function, regardless of direction, likely identify a population with an advanced disease state and poor prognosis. KeywordsCardio-renal syndrome; worsening renal function; improved renal function; acute heart failure; kidney Corresponding Author: Jeffrey M. Testani, M.D., Hospital of the University of Pennsylvania, 3400 Spruce Street, 8 Gates Pavilion, Philadelphia, PA 19104, Tel: (215) Fax: (215) 349-5734, jeffrey.testani@uphs.upenn.edu. All authors report no conflicts of interest or relationship to industry relevant to this work.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Worsening renal function (RF) complicates approximately one third of acute decompensated heart failure admissions and has been associated with increased length of stay, readmission rate, and decreased short and long term survival (1-4). Traditional teaching has held that the hemodynamic profile associated with worsening RF is that of decreased cardiac output and intravascular volume depletion, concepts which...

AimsOne of the primary determinants of blood flow in regional vascular beds is perfusion pressure. Our aim was to investigate if reduction in blood pressure during the treatment of decompensated heart failure would be associated with worsening renal function (WRF). Our secondary aim was to evaluate the prognostic significance of this potentially treatment-induced form of WRF. Methods and resultsSubjects included in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial limited data were studied (386 patients). Reduction in systolic blood pressure (SBP) was greater in patients experiencing WRF (210.3 + 18.5 vs. 22.8 + 16.0 mmHg, P , 0.001) with larger reductions associated with greater odds for WRF (odds ratio ¼ 1.3 per 10 mmHg reduction, P , 0.001). Systolic blood pressure reduction (relative change . median) was associated with greater doses of in-hospital oral vasodilators (P ≤ 0.017), thiazide diuretic use (P ¼ 0.035), and greater weight reduction (P ¼ 0.023). In patients with SBP-reduction, WRF was not associated with worsened survival [adjusted hazard ratio (HR) ¼ 0.76, P ¼ 0.58]. However, in patients without SBP-reduction, WRF was strongly associated with increased mortality (adjusted HR ¼ 5.3, P , 0.001, P interaction ¼ 0.001). ConclusionDuring the treatment of decompensated heart failure, significant blood pressure reduction is strongly associated with WRF. However, WRF that occurs in the setting of SBP-reduction is not associated with an adverse prognosis, whereas WRF in the absence of this provocation is strongly associated with increased mortality. These data suggest that WRF may represent the final common pathway of several mechanistically distinct processes, each with potentially different prognostic implications.--