Brian D. McCauley

Potential Effects of Aggressive Decongestion During the Treatment of Decompensated Heart Failure on Renal Function and Survival

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 Catheterization Effectiveness 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 ≥2 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 (P<0.05 for all). Hemoconcentration was strongly associated with worsening renal function (odds ratio, 5.3; P<0.001), whereas changes in right atrial pressure (P=0.36) and pulmonary capillary wedge pressure (P=0.53) were not. Patients with hemoconcentration had significantly lower 180-day mortality (hazard ratio, 0.31; P=0.013). This relationship persisted after adjustment for baseline characteristics (hazard ratio, 0.16; P=0.001). Conclusion— Hemoconcentration is significantly associated with measures of aggressive fluid removal and deterioration in renal function. Despite this relationship, hemoconcentration is associated with substantially improved survival. These observations raise the question of whether aggressive decongestion, even in the setting of worsening renal function, can positively affect survival.

Blood Urea Nitrogen/Creatinine Ratio Identifies a High-Risk but Potentially Reversible Form of Renal Dysfunction in Patients With 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 in-hospital 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.

Characteristics of Patients With Improvement or Worsening in Renal Function During Treatment of Acute Decompensated Heart Failure

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 the pulmonary artery catheter-derived measures are relevant in the evaluation of cardiorenal interactions, the comparison of patients with improved versus worsening RF should highlight any important hemodynamic differences. All subjects in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial limited data set with admission and discharge creatinine values available were included (n = 401). No differences were found in the baseline, final, or change in pulmonary artery catheter-derived hemodynamic variables, inotrope and intravenous vasodilator use, or survival between patients with improved versus worsening RF (p = NS for all). Both groups were equally likely to be in the bottom quartile of cardiac index (p = 0.32), have a 25% improvement in cardiac index (p = 0.97), or have any worsening in cardiac index (p = 0.90). When patients with any significant change in renal function (positive or negative) were compared to those with stable renal function, strong associations between variables such as a reduced cardiac index (odds ratio 2.2, p = 0.02), increased intravenous inotrope and vasodilator use (odds ratio 2.9, p <0.001), and worsened all-cause mortality (hazard ratio 1.8, p = 0.01) became apparent. In contrast to traditionally held views, the patients with improved RF and those with worsening RF had similar hemodynamic parameters and outcomes. Combining these groups identified a hemodynamically compromised population with significantly worse survival than patients with stable renal function. In conclusion, the changes in renal function, regardless of the direction, likely identify a population with an advanced disease state and a poor prognosis.

Impact of changes in blood pressure during the treatment of acute decompensated heart failure on renal and clinical outcomes

One 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.

Clinical characteristics and outcomes of patients with improvement in renal function during the treatment of decompensated heart failure.

BACKGROUNDnIn the setting of acute decompensated heart failure, worsening renal function (WRF) and improved renal function (IRF) have been associated with similar hemodynamic derangements and poor prognosis. Our aim was to further characterize IRF and its associated mortality risk.nnnMETHODS AND RESULTSnConsecutive patients with a discharge diagnosis of congestive heart failure at the Hospital of the University of Pennsylvania were reviewed. IRF was defined as a ≥20% improvement and WRF as a ≥20% deterioration in glomerular filtration rate. Overall, 903 patients met the eligibility criteria, with 31.4% experiencing IRF. Baseline venous congestion/right-side cardiac dysfunction was more common (P ≤ .04) and volume of diuresis (Pxa0= .003) was greater in patients with IRF. IRF was associated with a greater incidence of preadmission (odds ratio [OR] 4.2, 95% confidence interval [CI] 2.6-6.7; P < .0001) and postdischarge (OR 1.8, 95% CI 1.2-2.7; Pxa0= .006) WRF. IRF was associated with increased mortality (adjusted hazard ratio 1.3, 95% CI, 1.1-1.7; Pxa0= .011), a finding largely restricted to patients with postdischarge recurrence of renal dysfunction (P interactionxa0= .038).nnnCONCLUSIONSnIRF is associated with significantly worsened survival and may represent the resolution ofxa0venous congestion-induced preadmission WRF. Unlike WRF, the renal dysfunction in IRF patients occurs independently from the confounding effects of acute decongestion and may provide incremental information for the study of cardiorenal interactions.

Worsening renal function defined as an absolute increase in serum creatinine is a biased metric for the study of cardio-renal interactions.

Objectives: Worsening renal function (WRF) during the treatment of decompensated heart failure, frequently defined as an absolute increase in serum creatinine ≧0.3 mg/dl, has been reported as a strong adverse prognostic factor in several studies. We hypothesized that this definition of WRF is biased by baseline renal function secondary to the exponential relationship between creatinine and renal function. Methods: We reviewed consecutive admissions with a discharge diagnosis of heart failure. An increase in creatinine ≧0.3 mg/dl (WRFCREAT) was compared to a decrease in GFR ≧20% (WRFGFR). Results: Overall, 993 admissions met eligibility. WRFCREAT occurred in 31.5% and WRFGFR in 32.7%. WRFCREAT and WRFGFR had opposing relationships with baseline renal function (OR = 1.9 vs. OR = 0.51, respectively, p < 0.001). Both definitions had similar unadjusted associations with death at 30 days [WRFGFR OR = 2.3 (95% CI 1.1–4.8), p = 0.026; WRFCREAT OR = 2.1 (95% CI 1.0–4.4), p = 0.047]. Controlling for baseline renal insufficiency, WRFGFR added incrementally in the prediction of mortality (p = 0.009); however, WRFCREAT did not (p = 0.11). Conclusions: WRF, defined as an absolute change in serum creatinine, is heavily biased by baseline renal function. An alternative definition of WRF should be considered for future studies of cardio-renal interactions.

Impact of worsening renal function during the treatment of decompensated heart failure on changes in renal function during subsequent hospitalization

BACKGROUNDnWorsening renal function (WRF) commonly complicates the treatment of acute decompensated heart failure. Despite considerable investigation in this area, it remains unclear to what degree WRF is a reflection of treatment- versus patient-related factors. We hypothesized that if WRF is significantly influenced by factors intrinsic to the patient, then WRF during an index hospitalization should predict WRF during subsequent hospitalization.nnnMETHODSnConsecutive admissions to the Hospital of the University of Pennsylvania with a discharge diagnosis of congestive heart failure were reviewed. Patients with >1 hospitalization were retained for analysis.nnnRESULTSnIn total, 181 hospitalization pairs met the inclusion criteria. Baseline patient characteristics demonstrated significant correlation between hospitalizations (P ≤ .002 for all) but minimal association with WRF. In contrast, variables related to the aggressiveness of diuresis were weakly correlated between hospitalizations but significantly associated with WRF (P ≤ .024 for all). Consistent with the primary hypothesis, WRF during the index hospitalization was strongly associated with WRF during subsequent hospitalization (odds ratio [OR] 2.7, P = .003). This association was minimally altered after controlling for traditional baseline characteristics (OR 2.5, P = .006) and in-hospital treatment-related parameters (OR 2.8, P = .005).nnnCONCLUSIONSnA prior history of WRF is strongly associated with subsequent episodes of WRF, independent of in-hospital treatment received. These results suggest that baseline factors intrinsic to the patients cardiorenal pathophysiology have substantial influence on the subsequent development of WRF.