Effects on congestion, natriuretic peptides, diuretic efficiency, and renal function during different dose and administration of intravenous loop diuretic: preliminary data of DIUR-AHF Trial

Background Although loop diuretic is the cornerstone of treatment in acute heart failure (AHF) there is no consensus about the best modality and amount to be used during acute phase. Current Guidelines do not provide specific insights regarding timing course and target dose. Usually physicians double the oral domestic amount when they start intravenous infusion, but a precise algorithm does not exist. Aims To compare admission and pre discharge clinical congestion and BNP trend in relation to furosemide amount and modality administration; 2- to evaluate diuretic efficiency and renal function in the four arms and the potential effects on outcome. Methods This is a multicentre prospective Trial (DIUR-AHF) designed in order to clarify the correct loop diuretic target avoiding potential side effects. The study enrolled patients with AHF BNP level >100 pg/ml and congestion signs. Patients were divided in four arms in accordance with modality administration: Continuous (Ci) vs Bolus (Bi) and dose administered Low (LD) vs High (HD) considering a cutoff 125 mg/die. All patients executed a clinical congestion evaluation and Chest radiography at admission and pre discharge, BNP sample and renal function were measured during the first 12 hours and before discharge. Diuretic efficiency (DE) defined as weight change per 40 mg of furosemide during infusional period. DE was estimated as the net fluid output produced per 40 mg of furosemide equivalents, Follow up were obtained by direct visit or phone contact at 30 and 60 days after discharge Results We included 268 hospitalized patients with a mean BNP level 987±440 pg /ml, mean congestion score (3.5±2) creatinine and GFR value were 1.6±0.7 mg/dl; and 48±20 ml/min/m2 respectively. At admission BNP and Creatinine were modestly increased in HD (P<0.01) compared with all other groups. Pre discharge Congestion score were increased in Bi and HD groups (2.5±1 vs 1±1), similarly BNP levels were increased in Bi and HD with respect to Ci and LD (454±215 and 413±223 vs 288±170 and 312±248 p<0.05). Whereas DE were significantly increased in Ci compared with the other arms (−1.23 vs −0.55 p<0.01). In all groups, low DE, residual congestion and BNP reduction <30% resulted in escalation of diuretic strategies and impaired outcome (HR 1.88 [1.16–204]; 2.1 [1.4–2.8]; 1.3 [0.88–2.1]). A significant correlation between poor DE and residual congestion was recruited (r=0.76). Worsening Renal function (WRF) occurred much more in HD and Ci compared to LD and Bi (HD 44%, Ci 35% vs LD 33% and Bi 23% p<0.01) without significant effects on outcome. Conclusions HD and Bi of furosemide are both related with reduced congestion and invreased BNP level before discharge. In all groups low DE residual congestion and poor BNP reduction appear associated with higher rate of adverse events. Current data provide additional features for AHF patients during intravenous loop diuretic administration Funding Acknowledgement Type of funding source: None

Comparing Diuresis Patterns in Hospitalized Patients With Heart Failure With Reduced Versus Preserved Ejection Fraction: A Retrospective Analysis

Background: Congestion predominates in exacerbations of heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF), but evidence suggests that excess volume may be distributed differently in these 2 subgroups. Methods and Results: In this retrospective study, diuretic efficiency (DE, or net urine output per 40-mg of intravenous furosemide equivalent) during the first 72 hours was compared between patients hospitalized with HFrEF (n = 121) versus HFpEF (n = 120). Multivariate analysis was used to compare the 2 groups based on expected baseline differences (e.g., demographics, heart failure etiology, concomitant therapy). During the first 72 hours, mean daily diuretic doses were higher in patients with HFpEF versus HFrEF (172.0 vs. 159.9 mg, respectively, p = 0.026) but urine output was not significantly different (2603.3 mL vs. 2667.5 mL, respectively, adjusted p = 0.100). Similarly, mean cumulative DE did not differ (−673.5 vs. −637.8 mL/40-mg in the HFrEF and HFpEF groups, respectively, adjusted p = 0.884). An exploratory analysis of propensity-matched cohorts yielded similar findings. Correlations between the components of DE varied considerably and only became weak to moderately correlated toward the end of the observation period. Conclusions: Although cumulative DE did not differ between patients with HFrEF and HFpEF, variable correlations in the components of DE suggest there may be differences in diuretic response that warrant future analysis.

Early Spot Urinary Sodium and Diuretic Efficiency in Acute Heart Failure and Concomitant Renal Dysfunction

Objective: In acute heart failure (AHF), early assessment of spot urinary sodium (UNa) has emerged as a useful biomarker for risk stratification and monitoring. The objective of this study was to investigate (a) whether early spot UNa predicts 24-h diuretic efficiency and (b) the clinical factors associated with early spot UNa in patients with AHF and concomitant renal dysfunction (RD). Methods: This is a post hoc analysis of the IMPROVE-HF trial, in which 160 patients with AHF and RD (estimated glomerular filtrate rate [eGFR] <60 mL/min/1.73 m2) were included. Diuretic efficiency was calculated as the net fluid output produced per 40 mg of furosemide equivalents in 24 h. The association between early spot UNa and diuretic efficiency and clinical variables associated with UNa were evaluated using multivariate linear regression analysis. The contribution of the exposures in the predictability of the models was assessed with the coefficient of determination (R2). Results: The mean age of the study population was 78 ± 8 years. The median (interquartile range) diuretic efficiency, early spot UNa, aminoterminal pro-brain natriuretic peptide, and eGFR were 747 (490–1,167) mL, 90 mmol/L (65–111), 7,765 pg/mL (3,526–15,369), and 33.7 ± 11.3 mL/min/1.73 m2, respectively. In a multivariate setting, lower UNa was significantly and nonlinearly associated with lower diuretic efficiency (p = 0.001), explaining the 44.4% of the model predictability. Natremia and surrogates of congestion emerged as the main factors related to UNa. Conclusions: In patients with AHF and RD at presentation, early spot UNa was inversely related to 24-h diuretic efficiency.

Measures of Loop Diuretic Efficiency and Prognosis in Chronic Kidney Disease

<b><i>Background:</i></b> The evolution and prognostic impact of loop diuretic efficiency according to chronic kidney disease (CKD) severity is unclear. <b><i>Methods:</i></b> This retrospective cohort study includes 783 CKD patients on oral loop diuretic therapy with a 24-h urine collection available. Acute kidney injury and history of renal replacement therapy were exclusion criteria. Patients were stratified according to Kidney Disease Improving Global Outcomes (KDIGO) glomerular filtration rate class. Loop diuretic efficiency was calculated as urine output, natriuresis, and chloruresis, each adjusted for loop diuretic dose, and compared among strata. Risk for onset of dialysis and all-cause mortality was evaluated. <b><i>Results:</i></b> Loop diuretic efficiency metrics decreased from KDIGO class IIIB to IV in furosemide users and from KDIGO class IV to V with all loop diuretics (<i>p</i> value &#x3c;0.05 for all comparisons). The correlation between loop diuretic efficiency and creatinine clearance was moderate at best (Spearman’s <i>ρ</i> 0.298–0.436; <i>p</i> value &#x3c;0.001 for all correlations). During median follow-up of 45 months, 457 patients died (58%) and 63 received kidney transplantation (8%), while dialysis was started before in 328 (42%). All loop diuretic efficiency metrics were significantly and independently associated with both the risk for dialysis and all-cause mortality. In KDIGO class IV/V patients, low loop diuretic efficiency (i.e., urine output adjusted for loop diuretic dose ≤1,000 mL) shortened median time to dialysis with 24 months and median time to all-cause mortality with 23 months. <b><i>Conclusion:</i></b> Low loop diuretic efficiency is independently associated with a shorter time to dialysis initiation and a higher risk for all-cause mortality in CKD.

Serum and Urine Albumin and Response to Loop Diuretics in Heart Failure

Background and objectivesDiuretic resistance can limit successful decongestion of patients with heart failure. Because loop diuretics tightly bind albumin, low serum albumin and high urine albumin can theoretically limit diuretic delivery to the site of action. However, it is unknown if this represents a clinically relevant mechanism of diuretic resistance in human heart failure.Design, setting, participants, & measurementsIn total, 208 outpatients with heart failure at the Yale Transitional Care Center undergoing diuretic treatment were studied. Blood and urine chemistries were collected at baseline and 1.5 hours postdiuretic administration. Urine diuretic levels were normalized to urine creatinine and adjusted for diuretic dose administered, and diuretic efficiency was calculated as sodium output per doubling of the loop diuretic dose. Findings were validated in an inpatient heart failure cohort (n=60).ResultsSerum albumin levels in the outpatient cohort ranged from 2.4 to 4.9 g/dl, with a median of 3.7 g/dl (interquartile range, 3.5–4.1). Serum albumin had no association with urinary diuretic delivery (r=−0.05; P=0.52), but higher levels weakly correlated with better diuretic efficiency (r=0.17; P=0.02). However, serum albumin inversely correlated with systemic inflammation as assessed by plasma IL-6 (r=−0.35; P<0.001), and controlling for IL-6 eliminated the diuretic efficiency-serum albumin association (r=0.12; P=0.12). In the inpatient cohort, there was no association between serum albumin and urinary diuretic excretion (r=0.15; P=0.32) or diuretic efficiency (r=−0.16; P=0.25). In the outpatient cohort, 39% of patients had microalbuminuria, and 18% had macroalbuminuria. There was no correlation between albuminuria and diuretic efficiency after adjusting for kidney function (r=−0.02; P=0.89). Results were similar in the inpatient cohort.ConclusionsSerum albumin levels were not associated with urinary diuretic excretion, and urinary albumin levels were not associated with diuretic efficiency.

Lack of Diuretic Efficiency (but Not Low Diuresis) Early in An Acutely Decompensated Heart Failure Episode Is Associated with Increased 180-Day Mortality

Introduction: The assessment of the amount of urine produced by the dose of administered diuretic has been proposed as the main signal of interest in diuretic responsiveness - diuretic efficiency (DE). The main aim of our study is to determine if a low DE is associated with 180-day all-cause mortality (ACM). Methods: During a 3-year period, we retrospectively studied patients with acutely decompensated heart failure (ADHF) and respiratory insufficiency admitted to the emergency room of a tertiary university hospital in Porto, Portugal. A total of 170 patients (age 76.2 ± 10.3 years) were included. The outcome of ACM occurred in 43 (25.3%) patients during the 180-day follow-up period. DE was evaluated for a maximum of 3 h after emergency room admission. The lowest DE was defined as ≤140 mL of diuresis per 40 mg of furosemide equivalents. Results: No significant differences in age, comorbidities, baseline HF symptoms, or disease-modifying medication were found between the lowest and highest DE groups. The lowest DE group had higher blood urea and lower estimated glomerular filtration rate (eGFR) levels (41.3 ± 24.5 vs. 56.7 ± 23.2 mL/min/1.73 m2, p < 0.001). The patients with the lowest DE had significantly higher rates of ACM during the 180-day follow-up, even after adjustment for other clinically relevant variables: hazard ratio (HR) [95% CI] = 2.31 [1.16-4.58], p = 0.016. The lowest diuresis (≤300 mL) and the highest intravenous furosemide dose (>80 mg) alone were not significantly associated with the outcome. After adjustment for N-terminal prohormone of brain natriuretic peptide, the association between the lowest DE and the outcome lost strength (HR [95% CI] = 1.53 [0.75-3.13], p = 0.240). Conclusion: A low DE (≤140 mL/40 mg of furosemide) in the first 3 h after an ADHF episode was associated with increased mid-term mortality rates.