Changes in Serum Creatinine during Treatment of Heart Failure and Volume Overload with Ultrafiltration or Intravenous Diuretics

S114 Journal of Cardiac Failure Vol. 12 No. 6 Suppl. 2006 component of HRV, SDANN (Standard Deviation of the 5 minute Average NN intervals) has proven to be a very useful measure as it minimizes the effects of editing, artifact and missed or ectopic beats commonly found with external monitors. Hypothesis: SDANN, collected by a cardiac resynchronization therapy defibrillator (CRT-D) is a good predictor of heart failure (HF) hospitalizations. Methods: Patients enrolled in the DECREASE-HF clinical study were retrospectively analyzed. Enrollment criteria included NYHA III/IV, LVEF ! 35%, QRS O 150 ms and stable drug therapy. Data was collected for HRV analyses in the CRT-D device at 2 weeks, and 3 and 6 months and patients were followed for hospitalizations through 6 months. A Cox Proportional Hazards (PH) model was used to determine if SDANN was a significant predictor of time to first HF hospitalization. Results: The DECREASE-HF Study included 358 (237 male) subjects with NHYA III/IV, mean LVEF 22.4% 6 6.9%, mean QRS 166 6 15ms. 275 patients were successfully implanted and had HRV data available at baseline. A univariate Cox PH indicated that SDANN was a clinically significant predictor of HF hospitalization. An SDANN of ! 73ms quadrupled the likelihood of HF hospitalization within the first six months after implant (hazard ratio 5 4.45, p 5 0.007, 95% confidence interval 5 (1.5,13.2). Conclusions: SDANN is a strong predictor of HF hospitalization within 6 months of CRT-D implantation. HRV data, obtained through implanted CRT devices provides clinicians with daily and weekly trends that allow for early intervention, and the opportunity to prevent HF hospitalization. Further evaluation into early intervention based on SDANN, along with other pertinent clinical information, is recommended. Univariate Cox PH for HF Hospitalization within 6 Months Variable Male % Footprint SDANN % Footprint ! 5 34 SDANN ! 5 73

Hazard Ratio (95% C.I.) 1.29 0.98 0.97 1.35 4.45

(0.60, (0.94, (0.95, (0.57, (1.50,

2.78) 1.02) 0.99) 3.20) 13.23)

P-value 0.52 0.26 0.006 0.50 0.007

374 Enhanced Sodium Extraction with Ultrafiltration Compared to Intravenous Diuretics Syed S. Ali1, Chad C. Olinger1, Paul A. Sobotka2, Steven Bernard2, Thom G. Dahle1, Matthew C. Bunte1, Donnevan Blake1, Scott Campbell2, Andrew J. Boyle1; 1 Medicine, University of Minnesota, Minneapolis, MN; 2CHF Solutions, Brooklyn Park, MN Introduction: Head to head comparisons between ultrafiltration (UF) and intravenous diuretics (IVD) have consistently revealed superior volume removal and weight reduction with UF. However, the impact of these therapies in patients hospitalized with acute decompensated heart failure (ADHF) on total body sodium, potassium, and magnesium has not been described. Hypothesis: UF, beyond removing excessive volume as compared to IVD, also removes more sodium and less potassium and magnesium. Methods: Fifteen hospitalized ADHF patients with presumed diuretic resistance and clinical evidence of volume overload had their urine electrolyte concentrations measured after a dose of IVD. UF was then begun and ultrafiltrate electrolyte concentrations were measured 8 hours later and compared to the initial urine values. Results: The urine sodium in response to IVD (mean 60 6 47 mg/ dL) was less than the sodium in the ultrafiltrate (mean 134 6 8.0 mg/dL) (p 5 0.000025). The urine potassium in response to IVD (mean 41 6 23 mg/dL) was greater than the potassium in the ultrafiltrate (mean 3.7 6 0.6 mg/dL) (p 5 0.000017). The urine magnesium in response to IVD (mean 5.2 6 3.1 mg/dL) was greater than the magnesium in the ultrafiltrate (mean 2.9 6 0.7 mg/dL) (p 5 0.017). Conclusions: In hospitalized patients with ADHF and presumed diuretic resistance, IVD are a poor natriuretic and cause significant losses of potassium and magnesium. In contrast, UF extracts significantly more sodium per liter than IVD while simultaneously removing less potassium and magnesium and reducing the need for supplementation. The reported sustained clinical benefits of UF as compared to IVD may be partly related to their disparate effects on total body sodium, potassium, and magnesium in addition to their differential efficacy of volume removal.

Time to HF hospitalization is significantly different for the two SDANN groups.

375 373 The Effect of Three Biventricular Pacing Methods on HRV and SDANN Measurements Anne Swearingen1, Jill Schafer1, Ross Sample1, David De Lurgio2, James Stone3; 1 Cardiac Rhythm Management, Guidant Corporation, St. Paul, MN; 2Cardiology, Crawford Long Hospital, Atlanta, GA; 3Cardiology, Cardiology Associates of North Mississippi, Tupelo, MS Introduction: Cardiac resynchronization therapy (CRT) utilizes simultaneous or synchronous left and right ventricular stimulation to reduce mechanical dysynchrony, improving left ventricular (LV) function. Heart Rate Variability (HRV) and Standard Deviation Average Normal to Normal (SDANN) measurements are strong predictors of morbidity and mortality in the heart failure population. Hypothesis: Different biventricular pacing methods affect HRV and SDANN through 12 months of follow up. Methods: The DECREASE-HF clinical study enrolled 360 patients. 342 patients were implanted with a CRT-D device (Guidant, RENEWAL 2/4/4 HE, St Paul, USA) with onboard HRV measurement capability and 306 were randomized to one of three CRT modalities (BiV-simultaneous (SIM), BiV sequential (SEQ) or LV CRT). Enrollment criteria included NYHA III/IV, LVEF ! 35%, QRS duration O 150msec. and stable drug therapy. HRV and SDANN data were downloaded from patients at baseline and quarterly thereafter. An ANOVA analysis and paired t- tests were used to determine the effect of the randomized pacing therapy to baseline. Results: HRV and SDANN data were available for 252 patients (86 BiV, 86 sequential BiV, 80 LV) who were characterized as NYHA Class III/IV, 66% male, mean LVEF 22 6 7%, and mean QRS 166 6 15ms. The SDANN measurement significantly improved at all timepoints in the BiV SEQ and BiV SIM arms, but not in the LV arm. The paired six-month change from baseline was significantly different among treatment arms (BiV SIM N 5 80; 17.1 6 27.8ms, BiV SEQ N 5 82; 17.9 6 31.7ms, LV N 5 71; 5.4 6 28.4ms, p 5 0.02). Conclusions: BiV SIM and BiV SEQ, which can be considered similar pacing methods, demonstrated the largest change in SDANN from baseline in HF patients at the 6-month visit. The changes were not as large in the LV CRT arm. This improvement in SDANN is encouraging. The results of the DECREASE HF trial will be instrumental in determining how well changes in SDANN correlate with other functional measures. Fututre studies will be needed to find the best way to integrate the HRV feature into the routine management of the heart failure patient.

Changes in Serum Creatinine during Treatment of Heart Failure and Volume Overload with Ultrafiltration or Intravenous Diuretics Bradley A. Bart1, John R. Teerlink2, Maria Rosa Costanzo3, Mitchell T. Saltzberg3, Paul A. Sobotka4; 1Department of Medicine, Hennepin County Medical Center, Minneapolis, MN; 2Department of Medicine, San Francisco Veteran Affairs Medical Center, San Francisco, CA; 3Midwest Heart Foundation, Naperville, IL; 4 CHF Solutions, Brooklyn Park, MN Background: Worsening renal function during therapy for volume overload (VO) in heart failure (HF) patients (pts) is associated with increased morbidity/mortality. The Ultrafiltration versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Heart Failure (UNLOAD) trial showed that among 200 HF pts with VO (63 6 15 yrs, 69% male, 71% LVEF ! / 5 40%) the ultrafiltration (UF) group, compared to the intravenous (IV) diuretic group, had greater weight (5.0 6 3.1 vs 3.1 6 3.5 Kg; p 5 0.001) and net fluid loss (4.6 vs 3.3 L; p 5 0.001) at 48 hours after randomization. Changes in serum creatinine (SCr) levels, % of pts with rises in SCr O 0.3 mg/dl, the relationship between net fluid removed and changes in SCr and changes in SCr /L of fluid removed were compared between groups. Methods: Differences in SCr between treatment groups were evaluated using the Wilcoxon’s rank sum test. Change over time in SCr levels within groups was tested using Wilcoxon’s matched pairs signed ranks test. Correlations between changes in SCr and fluid loss were calculated using Spearman’s rho. P-values (2-tailed) ! 0.05 were considered statistically significant. Results: Change in SCr levels were similar in the UF and IV diuretics groups at all time intervals: 24 hours (0.04 6 0.30 vs 0.01 6 0.21; p 5 0.841); 48 hours (0.12 6 0.42 vs 0.07 6 0 .41; p 5 0.356) and discharge (0.19 6 0.76 vs 0.07 6 0.37; p 5 0.528). The % of pts with rises in SCr O 0.3 mg/dl was similar: 24 h(14.4% vs 7.7%; p 5 0.163); 48 h (26.5% vs 20.3%; p 5 0.430) and discharge (22.6% vs 19.8%; p 5 0.709). There was no correlation between net fluid removed and changes in SCr in the UF (r 5 -0.050; p 5 0.695) or in the IV diuretics group (r 5 0.028; p 5 0.820). Changes in SCr/L of net fluid removed were similar in the UF and in the IV diuretics groups at 48 h (0.02 6 0.13 vs 0.07 6 0.31; p 5 0.804 and at 72 h (0.04 6 0.16 vs 0.02 6 0.25; p 5 0.244). Conclusions: UF produces greater VO reduction than IV diuretics in HF pts without greater increases in SCr or in the % of pts with rises in SCr O 0.3 mg/dl. The lack of correlation in both groups between amount of fluid removed and SCr increases suggests that mechanisms other than volume depletion cause worsening renal function in HF pts during VO treatment.