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 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 transplant). We observed comparable correlations between UNa:UFurosemide ratio as well as UNa and fractional excretion of sodium (FENa) with 24-hour net urine output (r=0.52–0.64, all p<0.01) and 24-hour weight loss (r=0.44–0.56, all p<0.01). 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 (HR 3.01, p=0.02) and poorer adverse clinical outcomes (HR 1.63, p=0.008) 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 that is independent and incremental to intrinsic glomerular filtration.

Determinants and impact of the natriuretic response to diuretic therapy in heart failure with reduced ejection fraction and volume overload

“…Importantly, the fact that diuretic efficacy incorporates aspects of both cardiac and renal function, makes it an attractive parameter to represent decongestion in decompensated HF. In a more mechanistic study, which assessed urinary sodium over urinary furosemide concentrations during continuous intravenous administration, our group has reported the incremental value of natriuresis over classic measurements of kidney function 10 . In that study of 52 decompensated HF patients, poor natriuretic response to furosemide was associated with low urine output, worsening renal function and adverse clinical outcome 10 .…”

“…In a more mechanistic study, which assessed urinary sodium over urinary furosemide concentrations during continuous intravenous administration, our group has reported the incremental value of natriuresis over classic measurements of kidney function 10 . In that study of 52 decompensated HF patients, poor natriuretic response to furosemide was associated with low urine output, worsening renal function and adverse clinical outcome 10 . The current study reaffirms the concept of diuretic efficacy as an important prognostic marker in decompensated HF, providing more insight in its determinants.…”

Effects of Additive Tolvaptan vs. Increased Furosemide on Heart Failure With Diuretic Resistance and Renal Impairment ― Results From the K-STAR Study ―

“…3, 4 Although loop diuretics continue to comprise the mainstay therapy to remove volume overload, it has been found that patients with diuretic resistance have lower underlying glomerular filtration rates (GFRs). 4 The potential pharmacokinetic causes of diuretic resistance could be addressed by increasing the dose of the loop diuretic.…”

“…3, 4 Although loop diuretics continue to comprise the mainstay therapy to remove volume overload, it has been found that patients with diuretic resistance have lower underlying glomerular filtration rates (GFRs). 4 The potential pharmacokinetic causes of diuretic resistance could be addressed by increasing the dose of the loop diuretic. 5 In the Diuretic Optimization Strategies Evaluation (DOSE) trial, the use of higher doses of furosemide (FUR) was associated with higher net fluid and weight loss at the cost of an increased incidence of rising serum creatinine in acute HF.…”

Management of the Cardiorenal Syndrome in Decompensated Heart Failure

“…However, patients with CRS regularly present with so-called diuretic resistance and congestion signs refractory to adequately dosed intravenous loop diuretics. Interestingly, loop diuretic efficiency, defined as urine output per diuretic dose, has recently been identified as an important prognostic indicator in decompensated HF, independent of the underlying kidney function [63,64] . The most obvious explanation for this finding is that characteristics of more advanced cardiac and renal disease are contributing to decreased diuretic efficiency.…”