Counterpoint: Natriuresis-Guided Diuresis in Patients Admitted to Hospital With Heart Failure - Barking Up the Wrong Tree? Towards Direct Insights Into the Efficacy of Diuretic Therapy

Abstract

Despite significant advancements in chronic heart failure management over the past 3 decades, the treatment and outcomes of patients hospitalized with acute heart failure (AHF) have remained relatively unchanged. Recent years have seen growing interest in personalizing diuretic therapy based on measures of diuretic or natriuretic response as approximately 40% of AHF patients exhibit an inadequate response to loop diuretics, the only Class IÀrecommended decongestive treatment. 1 The absence of a standard definition for diuretic resistance suggests this number could be even higher. Consequently, early identification of diuretic resistance or insufficient response is essential. Traditional methods such as assessing weight loss, net fluid loss, or diuresis are commonly used to evaluate diuretic therapy response. However, these measures are difficult to obtain precisely in hospitalized patients with AHF and have inherent limitations, leading to inconsistent reliability and reproducibility. For example, the correlation between fluid loss and weight loss during decongestive therapy in AHF is modest at best, with studies showing correlations of around 0.50 and wide 95% limits of agreement. 2 Additionally, there is a large variation in the measured weight depending on the method used to assess weight, with an astonishing mean bias of 1.42 kg between bed scale and standing scale assessment. 3 In 2019, HF experts proposed a novel approach by assessing urinary sodium excretion as a proxy for diuretic efficacy, based on the pharmacologic mechanism of diu-retics promoting sodium excretion. 4 At that time, the data supporting this approach were scarce and largely observational , mainly highlighting associations between reduced natriuretic response and poor outcomes. 5 Since then, this approach has sparked renewed interest in AHF research, yielding valuable insights into contemporary AHF management. First, the notion that water retention is the primary issue for all AHF patients is increasingly being questioned. Evidence points to the variety of AHF phenotypes, with pressure not necessarily equating to volume overload. 6,7 Emerging studies also implicate sodium storage via glyco-saminoglycans as a key mechanism. 8 For example, using 23 Na-magnetic resonance imaging, patients with HF were found to have elevated skin sodium levels comparable to those in hemodialysis patients. 9 Similarly, a study of AHF patients undergoing loop diuretic therapy showed reductions in sodium content in skin and muscle, whereas water content remained unchanged despite significant weight loss of 3.6 kg. 10 These findings underscore the role of desalination over simple fluid loss in AHF. The inability of hypertonic saline to increase natriuresis does not negate urinary sodium's utility as a marker of loop diuretic response. Rather, it emphasizes the sodium avidity of HF and the neutral effects of hypertonic saline in unselected AHF populations. Moreover, data from the ROSE-AHF trial revealed that even with negative fluid balance, insufficient natriuresis (below 2 g/day dietary intake) was linked to higher mortality risk. 11 Second, spot urine does not perfectly correlate with 24-hour natriuresis. Its primary utility lies in its ability to quickly and easily identify patients at risk of poor response to diuretic therapy. These limitations are currently being addressed with predictive tools such as the natriuretic response prediction equation, now under evaluation in From the