Assessing intrinsic renal sodium avidity in acute heart failure: implications in predicting and guiding decongestion

Martens, Pieter; Chen, Horng H.; Verbrugge, Frederik H.; Testani, Jeffrey; Mullens, Wilfried; Tang, W.H. Wilson

doi:10.1002/ejhf.2662

Cited by 17 publications

(17 citation statements)

References 34 publications

(83 reference statements)

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“…112 The lack of a meaningful effect on total blood volume may explain why SGLT2 inhibition did not reduce NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels in the 5 placebo-controlled trials in patients with heart failure summarized in Table 1, whereas NT-proBNP levels are reduced by loop diuretics. 113,114 In large-scale heart failure trials, SGLT2 inhibition for 3 months produces only modest changes in natriuretic peptides and left ventricular filling pressures (even in patients with volume overload), with little correlation between changes in natriuretic pep-tides and metrics of decongestion. 105,[115][116][117] Even in acutely decompensated heart failure, changes in NT-proBNP are not apparent 79 or are modest and not sustained.…”

Section: Table 1 Continuedmentioning

confidence: 99%

Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes

2023

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SGLT2 (sodium-glucose cotransporter 2) inhibitors interfere with the reabsorption of glucose and sodium in the early proximal renal tubule, but the magnitude and duration of any ensuing natriuretic or diuretic effect are the result of an interplay between the degree of upregulation of SGLT2 and sodium-hydrogen exchanger 3, the extent to which downstream compensatory tubular mechanisms are activated, and (potentially) the volume set point in individual patients. A comprehensive review and synthesis of available studies reveals several renal response patterns with substantial variation across studies and clinical settings. However, the common observation is an absence of a large acute or chronic diuresis or natriuresis with these agents, either when given alone or combined with other diuretics. This limited response results from the fact that renal compensation to these drugs is rapid and nearly complete within a few days or weeks, preventing progressive volume losses. Nevertheless, the finding that fractional excretion of glucose and lithium (the latter being a marker of proximal sodium reabsorption) persists during long-term treatment with SGLT2 inhibitors indicates that pharmacological tolerance to the effects of these drugs at the level of the proximal tubule does not meaningfully occur. This persistent proximal tubular effect of SGLT2 inhibitors can be hypothesized to produce a durable improvement in the internal set point for volume homeostasis, which may become clinically important during times of fluid expansion. However, it is difficult to know whether a treatment-related change in the volume set point actually occurs or contributes to the effect of these drugs to reduce the risk of major heart failure events. SGLT2 inhibitors exert cardioprotective effects by a direct effect on cardiomyocytes that is independent of the presence of or binding to SGLT2 or the actions of these drugs on the proximal renal tubule. Nevertheless, changes in the volume set point mediated by SGLT2 inhibitors might potentially act cooperatively with the direct favorable molecular and cellular effects of these drugs on cardiomyocytes to mediate their benefits on the development and clinical course of heart failure.

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Section: Table 1 Continuedmentioning

confidence: 99%

Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes

2023

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“…weight loss, visual analogue scale improvement, NT‐proBNP decrease, natriuretic response), had lower total natriuresis, exhibited more oedema at 72 h and had a longer length of stay. An increase in loop diuretic dose after >24 h was associated with better natriuretic response in the high IRSA group, even if cumulative natriuresis still remained lower at 72 h 36 …”

Section: Acute Heart Failurementioning

confidence: 84%

October 2022 at a glance: focus on clinical trials

Tomasoni

Adamo

Metra

2022

European J of Heart Fail

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Assessment of biomarkers is a cornerstone of heart failure (HF) management. [1][2][3][4] A review from the Biomarkers Working Group of the Heart Failure Association summarizes the utility of biomarkers for defining and managing congestion on top of clinical evaluation, haemodynamics, and imaging. 5 The same group also reviewed the use of circulating biomarkers in clinical trials. They may be used as inclusion criteria, as surrogate endpoints, or as safety endpoints. 6 Focus on clinical trials SGLT2 inhibitorsSodium-glucose cotransporter 2 (SGLT2) inhibitors are recommended as foundational therapy for patients with HF and reduced ejection fraction (HFrEF) for their effects on mortality and HF hospitalizations. [7][8][9][10] They also improved quality of life in randomized controlled trials but their effects on exercise capacity, a measurement not changed by neurohormonal modulators, are less studied. 11 In the multicentre randomized double-blind DAPA-VO 2 trial, dapagliflozin, compared with placebo, significantly improved peak oxygen consumption at 1 and 3 months in stable patients with HFrEF. 12 Administration of SGLT2 inhibitors is associated with an initial decline in estimated glomerular filtration rate (eGFR). Changes in eGFR from randomization to week 4 were assessed in the EMPEROR-Reduced trial. On average, empagliflozin induced a leftward shift of the distribution of the initial eGFR changes, i.e. a greater decrease, of -2.5 ml/min/1.73 m 2 versus placebo in patients with HFrEF. 13 The initial mild decline in eGFR was not associated with a higher risk of HF, mortality, or kidney safety events. 13 Similarly, in the EMPULSE trial, including patients hospitalized for acute HF with an eGFR >20 ml/min/1.73 m 2 , empagliflozin caused an initial decline in eGFR of -2 ml/min/1.73 m 2 at day 15 compared to placebo that was no longer evident at day 90. The clinical benefit of empagliflozin was independent of baseline eGFR. 14 Liver dysfunction is a marker of more severe HF and an independent predictor of poor prognosis. 15 In the Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA-HF) trial, patients with the highest bilirubin tertile had more severe HFrEF

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“…9,61,62 Randomized prospective clinical trials are ongoing to assess the impact of these measurements on post-discharge outcomes. [63][64][65][66][67] Myocardial, kidney and liver injury should be monitored during hospitalization with the use of traditional biomarkers (e.g., cardiac troponin, creatinine, cystatin C, transaminases, bilirubin, gamma-glutamyl transpeptidase). 9,38,42,44 The significance of trajectories in serum creatinine measurements during hospitalization and their relationship with concomitant treatment have been recently reviewed in position papers by the HFA as well as in the ESC HF guidelines.…”

Section: Laboratory Measurementsmentioning

confidence: 99%

“…Diuretic response may be assessed through urinary sodium and/or urine volume measurements as recommended by the guidelines for the first 24 h to guide diuretic dosing 9,61,62 . Randomized prospective clinical trials are ongoing to assess the impact of these measurements on post‐discharge outcomes 63–67 …”

Section: Pre‐discharge Assessmentmentioning

confidence: 99%

Pre‐discharge and early post‐discharge management of patients hospitalized for acute heart failure: A scientific statement by the Heart Failure Association of the ESC

Metra

Adamo

Tomasoni

et al. 2023

European J of Heart Fail

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Acute heart failure is a major cause of urgent hospitalizations. These are followed by marked increases in death and rehospitalization rates, which then decline exponentially though they remain higher than in patients without a recent hospitalization. Therefore, optimal management of patients with acute heart failure before discharge and in the early post‐discharge phase is critical. First, it may prevent rehospitalizations through the early detection and effective treatment of residual or recurrent congestion, the main manifestation of decompensation. Second, initiation at pre‐discharge and titration to target doses in the early post‐discharge period, of guideline‐directed medical therapy may improve both short‐ and long‐term outcomes. Third, in chronic heart failure, medical treatment is often left unchanged, so the acute heart failure hospitalization presents an opportunity for implementation of therapy. The aim of this scientific statement by the Heart Failure Association of the European Society of Cardiology is to summarize recent findings that have implications for clinical management both in the pre‐discharge and the early post‐discharge phase after a hospitalization for acute heart failure.

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Assessing intrinsic renal sodium avidity in acute heart failure: implications in predicting and guiding decongestion

Cited by 17 publications

References 34 publications

Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes

Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes

October 2022 at a glance: focus on clinical trials

Pre‐discharge and early post‐discharge management of patients hospitalized for acute heart failure: A scientific statement by the Heart Failure Association of the ESC

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