Insufficient natriuretic response to continuous intravenous furosemide is associated with poor long-term outcomes in acute decompensated heart failure

Abstract

Background: Treatment of acute decompensated heart failure (ADHF) with loop diuretics, such as furosemide, is frequently complicated by insufficient urine sodium excretion. We hypothesize that insufficient natriuretic response to diuretic therapy, characterized by lower urine sodium (UNa) and urine furosemide, is associated with subsequent inadequate decongestion, worsening renal function, and adverse long term events.

Methods and results: We enrolled 52 consecutive patients with ADHF and measured serum and urine sodium (UNa), urine creatinine (UCr), and urine furosemide (UFurosemide) levels on a spot sample taken after treatment with continuous intravenous furosemide, and followed clinical and renal variables as well as adverse long-term clinical outcomes (death, rehospitalizations, and cardiac transplantation). We observed similar correlations between UNa:UFurosemide ratio and UNa and fractional excretion of sodium (FENa) with 24-hour net urine output (r = 0.52-0.64, all P < .01) and 24-hour weight loss (r = 0.44-0.56; all P < .01). Interestingly, FENa (but not UNa or UNa:UFurosemide) were influenced by estimated glomerular filtration rate (eGFR). We observed an association between lower UNa:UFurosemide with greater likelihood of worsening renal function (hazard ratio [HR] 3.01; P = .02) and poorer adverse clinical outcomes (HR 1.63, P = .008) after adjusting for age and eGFR. Meanwhile, both diminished weight loss and net fluid output over 24 hours of continuous intravenous furosemide were observed when UNa:UFurosemide ratios were <2 mmol/mg or when UNa <50 mmol.

Conclusion: In patients with ADHF receiving continuous furosemide infusion, impaired natriuretic response to furosemide is associated with greater likelihood of worsening renal function and future adverse long-term outcomes, independently from and incrementally with decreasing intrinsic glomerular filtration.

Keywords: Acute decompensated heart failure; furosemide; natriuresis; urine sodium.

Figure 1. Diuretic Response to Continuous Intravenous Furosemide and Clinical Outcomes According to U_Na: U_Furosemide Ratio

Caption: Panel A: Comparison across tertiles of U_Na: U_Furosemide ratio on net fluid output; Panel B: Comparison across tertiles of U_Na: U_Furosemide ratio on net weight loss; Panel C: Kaplan-Meier Analysis of adverse clinical outcomes (all-cause mortality, cardiac transplantation or heart failure re-hospitalization) in patients with acute decompensated heart failure receiving continuous intravenous furosemide (n=52) stratified according to optimal U_Na:U_Furosemide cut-off (2.27 mmol/mg) and median estimated glomerular filtration rate (eGFR 50 ml/min/1.73m²).

Figure 2. Diuretic Response to Continuous Intravenous Furosemide According to Urine Sodium Excretion (U_Na) and Fractional Excretion of Urine Sodium (FE_Na)

Caption: Panel A: Comparison across tertiles of U_Na on net fluid output; Panel B: Comparison across tertiles of FE_Na on net fluid output; Panel C: Comparison across tertiles of U_Na on net weight loss; Panel D: Comparison across tertiles of FE_Na on net weight loss