Dhssraj Singh1, Kevin Shrestha2, Jeffrey M Testani3, Frederik H Verbrugge4, Matthias Dupont5, Wilfried Mullens4, W H Wilson Tang6. 1. Division of Cardiovascular Diseases, Department of Medicine, University of Kansas, Kansas City, Kansas. 2. Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio. 3. Department of Internal Medicine and Program of Applied Translational Research, Yale, University School of Medicine, New Haven, Connecticut. 4. Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium; Doctoral School for Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium. 5. Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium. 6. Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address: tangw@ccf.org.
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.
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.
Authors: Clyde W Yancy; Mariell Jessup; Biykem Bozkurt; Javed Butler; Donald E Casey; Mark H Drazner; Gregg C Fonarow; Stephen A Geraci; Tamara Horwich; James L Januzzi; Maryl R Johnson; Edward K Kasper; Wayne C Levy; Frederick A Masoudi; Patrick E McBride; John J V McMurray; Judith E Mitchell; Pamela N Peterson; Barbara Riegel; Flora Sam; Lynne W Stevenson; W H Wilson Tang; Emily J Tsai; Bruce L Wilkoff Journal: Circulation Date: 2013-06-05 Impact factor: 29.690
Authors: Frederik H Verbrugge; Matthias Dupont; Zhili Shao; Kevin Shrestha; Dhssraj Singh; Michael Finucan; Wilfried Mullens; W H Wilson Tang Journal: J Card Fail Date: 2013-09 Impact factor: 5.712
Authors: G Michael Felker; Kerry L Lee; David A Bull; Margaret M Redfield; Lynne W Stevenson; Steven R Goldsmith; Martin M LeWinter; Anita Deswal; Jean L Rouleau; Elizabeth O Ofili; Kevin J Anstrom; Adrian F Hernandez; Steven E McNulty; Eric J Velazquez; Abdallah G Kfoury; Horng H Chen; Michael M Givertz; Marc J Semigran; Bradley A Bart; Alice M Mascette; Eugene Braunwald; Christopher M O'Connor Journal: N Engl J Med Date: 2011-03-03 Impact factor: 91.245
Authors: Frederik H Verbrugge; Matthias Dupont; Paul Steels; Lars Grieten; Quirine Swennen; W H Wilson Tang; Wilfried Mullens Journal: Eur J Heart Fail Date: 2013-12-09 Impact factor: 15.534
Authors: Bradley A Bart; Steven R Goldsmith; Kerry L Lee; Michael M Givertz; Christopher M O'Connor; David A Bull; Margaret M Redfield; Anita Deswal; Jean L Rouleau; Martin M LeWinter; Elizabeth O Ofili; Lynne W Stevenson; Marc J Semigran; G Michael Felker; Horng H Chen; Adrian F Hernandez; Kevin J Anstrom; Steven E McNulty; Eric J Velazquez; Jenny C Ibarra; Alice M Mascette; Eugene Braunwald Journal: N Engl J Med Date: 2012-11-06 Impact factor: 91.245
Authors: João Pedro Ferreira; Nicolas Girerd; Pedro Bettencourt Medeiros; Miguel Bento Ricardo; Tiago Almeida; Alexandre Rola; Faiez Zannad; Patrick Rossignol; Irene Aragão Journal: Cardiorenal Med Date: 2017-01-21 Impact factor: 2.041
Authors: Jozine M ter Maaten; Mattia A E Valente; Kevin Damman; Hans L Hillege; Gerjan Navis; Adriaan A Voors Journal: Nat Rev Cardiol Date: 2015-01-06 Impact factor: 32.419
Authors: Justin L Grodin; Dianne Gallup; Kevin J Anstrom; G Michael Felker; Horng H Chen; W H Wilson Tang Journal: Am J Cardiol Date: 2017-03-29 Impact factor: 2.778
Authors: João Pedro Ferreira; Nicolas Girerd; Pedro Bettencourt Medeiros; Mário Santos; Henrique Cyrne Carvalho; Paulo Bettencourt; David Kénizou; Javed Butler; Faiez Zannad; Patrick Rossignol Journal: Clin Res Cardiol Date: 2015-11-28 Impact factor: 5.460