Aims Most studies examined spot urine sodium's (sUNa + ) prognostic utility during the early phase of acute heart failure (AHF) hospitalization. In AHF, sodium excretion is related to clinical status; therefore, we investigated the differences in the prognostic information of spot UNa + throughout the course of hospitalization for AHF (admission vs. discharge). Methods and resultsThe study population were AHF patients (n = 172), who survived the index hospitalization. We compared the relationship between early (on admission, at 24 and 48 h) and discharge sUNa + measurements with post-discharge study endpoints: composite of 1 year all-cause mortality and AHF rehospitalization (with time to first event analysis) as well as with each event in separation. There were 49 (28.5%) deaths, 40 (23.3%) AHF rehospitalizations, while the composite endpoint occurred in 69 (40.1%) during 1 year follow-up. The sUNa + had prognostic significance for the composite endpoint when assessed on admission, at 24 and at 48 h: hazard ratios (HRs) with 95% confidence intervals (CIs) (per 10 mmol/L) were 0.88 (0.82-0.94); 0.87 (0.81-0.91); 0.90 (0.84-0.96), all P < 0.005. In contrast to early, active decongestion phase, discharge sUNa + had no prognostic significance HR (95% CI) (per 10 mmol/L): 0.99 (0.93-1.06) P = 0.79 for the composite endpoint, which was independent from the dose of oral furosemide prescribed at that timepoint (average causal mediation effects: À0.38; P = 0.71). Similarly, discharge sUNa + was neither associated with 1 year mortality HR (95% CI) (per 10 mmol/L): 0.97 (0.89-1.05) P = 0.48 nor with AHF rehospitalizations HR (95% CI) (per 10 mmol/l): 1.03 (0.94-1.12), P = 0.56. The comparison of longitudinal profiles of sUNa + during hospitalization showed significantly higher values within the early, active decongestive phase in those who did not experience composite endpoint when compared with those who did: admission: 94 ± 34 vs. 76 ± 35; Day 1: 85 ± 36 vs. 65 ± 37; Day 2: 84 ± 37 vs. 67 ± 35, all P < 0.005 (mmol/L), respectively. There was no difference between those groups in discharge sUNa + : 73 ± 35 vs. 70 ± 35 P = 0.82 (mmol/L). Conclusions Spot UNa + assessed at early phase of hospitalization and at discharge have different prognostic significance, which confirms that it should be always interpreted along with clinical context.

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With its complicated pathophysiology, high incidence and prevalence, heart failure remains a major public concern. In hopes of improving diagnosis, treatment and prognosis, the utility of many different biomarkers is researched vigorously around the world. In this review, biomarkers of myocardial remodeling and fibrosis (galectin-3, soluble isoform of suppression of tumorigenicity 2, matrix metalloproteinases, osteopontin, interleukin-6, syndecan-4, myostatin, procollagen type I C-terminal propeptide, procollagen type III N-terminal propeptide, vascular endothelial growth factor, nitric oxidase synthetase and asymmetric dimethylarginine), myocyte injury (heart-type fatty acid-binding protein, glutathione S-transferase P1 and heat shock protein 60), as well as iron metabolism (ferritin, transferrin saturation, soluble transferrin receptor and hepcidin), are considered in terms of possible clinical applicability and significance. Our short review consists of a summary of the aforementioned cardiovascular biomarkers’ clinical relevance and perspectives.

AimsDiuretic response in heart failure is blunted when compared to healthy individuals, but the pathophysiology underlying this phenomenon is unclear. We aimed to investigate whether the diuretic resistance mechanism is related to insufficient furosemide tubular delivery or low tubular responsiveness.Methods and resultsWe conducted a prospective, observational study of 50 patients with acute heart failure patients divided into two groups based on previous furosemide use (furosemide naïve: n = 28 [56%] and chronic furosemide users: n = 22 [44%]). Each patient received a protocol‐derived, standardized furosemide dose based on body weight. We measured diuretic response and urine furosemide concentrations. The furosemide naïve group had significantly higher urine volumes and natriuresis when compared to chronic users at all timepoints (all p < 0.05). Urine furosemide delivery was similar in furosemide naïve versus chronic users after accounting for differences in estimated glomerular filtration rate (28.02 [21.03–35.89] vs. 29.70 [18.19–34.71] mg, p = 0.87). However, the tubular response to delivered diuretic was dramatically higher in naïve versus chronic users, that is the urine volume per 1 μg/ml of urine furosemide at 2 h was 148.6 ± 136.1 versus 50.6 ± 56.1 ml (p = 0.005).ConclusionsPatients naïve to furosemide have significantly better diuresis and natriuresis when compared to chronic furosemide users. The blunted diuretic response in patients with chronic loop diuretic exposure is driven by decreased tubular responsiveness rather than insufficient furosemide tubular delivery.