Author + information
- Received January 1, 2019
- Revision received February 14, 2019
- Accepted February 20, 2019
- Published online April 29, 2019.
- Pieter Martens, MDa,b,
- Matthias Dupont, MDa,
- Frederik Hendrik Verbrugge, MD, PhDa,
- Kevin Damman, MD, PhDc,
- Nicolas Degrysea,
- Petra Nijst, MD, PhDa,
- Carmen Reynders, MSSCd,
- Joris Penders, MD PhDd,
- W.H. Wilson Tang, MDe,
- Jeffrey Testani, MDf and
- Wilfried Mullens, MD, PhDa,g,∗ ()
- aDepartment of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium
- bDoctoral School for Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium
- cDepartment of Cardiology, University of Groningen, University Medical Centrum Groningen, the Netherlands
- dDepartment of Laboratory Medicine, Ziekenhuis Oost-Limburg, Genk, Belgium
- eDepartment of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio
- fDepartment of Cardiovascular Medicine, Yale University, New Haven, Connecticut
- gBiomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium
- ↵∗Address for correspondence:
Dr. Wilfried Mullens, Department of Cardiology, Ziekenhuis Oost-Limburg, Schiepse Bos 6, 3600 Genk, Belgium.
Objectives This study sought to determine the relationship between urinary sodium (Una) concentration and the pathophysiologic interaction with the development of acute heart failure (AHF) hospitalization.
Background No data are available on the longitudinal dynamics of Una concentration in patients with chronic heart failure (HF), including its temporal relationship with AHF hospitalization.
Methods Stable, chronic HF patients with either reduced or preserved ejection fraction were prospectively included to undergo prospective collection of morning spot Una samples for 30 consecutive weeks. Linear mixed modeling was used to assess the longitudinal changes in Una concentration. Patients were followed for the development of the clinical endpoint of AHF.
Results A total of 80 chronic HF patients (71 ± 11 years of age; an N-terminal pro–B-type natriuretic peptide [NT-proBNP] concentration of 771 [interquartile range: 221 to 1,906] ng/l; left ventricular ejection fraction [LVEF] 33 ± 7%) prospectively submitted weekly pre-diuretic first void morning Una samples for 30 weeks. A total of 1,970 Una samples were collected, with mean Una concentration of 81.6 ± 41 mmol/l. Sodium excretion remained stable over time on a population level (time effect p = 0.663). However, interindividual differences revealed the presence of high (88 mmol/l Una [n = 39]) and low (73 mmol/l Una [n = 41]) sodium excreters. Only younger age was an independent predictor of high sodium excretion (odds ratio [OR]: 0.91; 95% confidence interval [CI]: 0.83 to 1.00; p = 0.045 per year). During 587 ± 54 days of follow-up, 21 patients were admitted for AHF. Patients who developed AHF had significantly lower Una concentrations (F[1.80] = 24.063; p < 0.001). The discriminating capacity of Una concentration to detect AHF persisted after inclusion of NT-proBNP and estimated glomerular filtration rate (eGFR) measurements as random effects (p = 0.041). Furthermore, Una concentration dropped (Una = 46 ± 16 mmol/l vs. 70 ± 32 mmol/l, respectively; p = 0.003) in the week preceding the hospitalization and returned to the individual’s baseline (Una = 71 ± 22 mmol/l; p = 0.002) following recompensation, while such early longitudinal changes in weight and dyspnea scores were not apparent in the week preceding decompensation.
Conclusions Overall, Una concentration remained relatively stable over time, but large interindividual differences existed in stable, chronic HF patients. Patients who developed AHF exhibited a chronically lower Una concentration and exhibited a further drop in Una concentration during the week preceding hospitalization. Ambulatory Una sample collection is feasible and may offer additional prognostic and therapeutic information.
Dr. Martens is supported by a doctoral fellowship from Research Foundation-Flanders grant 1127917N. Drs. Martens and Mullens perform research for the Limburg Clinical Research Program UHasselt-ZOL-Jessa, supported by the Limburg Sterk Merk Foundation, Hasselt University, Ziekenhuis Oost-Limburg, and Jessa Hospital. Dr. Tang has consulted for Sequana Medical Inc. and MyoKardia Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received January 1, 2019.
- Revision received February 14, 2019.
- Accepted February 20, 2019.
- 2019 American College of Cardiology Foundation
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