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Structural basis for human NKCC1 inhibition by loop diuretic drugs.
EMBO J
January 2025
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, 84112-5650, USA.
Na-K-Cl cotransporters functions as an anion importers, regulating trans-epithelial chloride secretion, cell volume, and renal salt reabsorption. Loop diuretics, including furosemide, bumetanide, and torsemide, antagonize both NKCC1 and NKCC2, and are first-line medicines for the treatment of edema and hypertension. NKCC1 activation by the molecular crowding sensing WNK kinases is critical if cells are to combat shrinkage during hypertonic stress; however, how phosphorylation accelerates NKCC1 ion transport remains unclear.
View Article and Find Full Text PDFClinical profile of an unselected population with heart failure treated with vericiguat in real life: differences with the VICTORIA trial.
Front Cardiovasc Med
January 2025
Cardiology Service, Hospital Universitario de La Princesa, Madrid, Spain.
Introduction: Vericiguat, an oral stimulator of soluble guanylate cyclase, reduces cardiovascular mortality and hospitalisations in patients with heart failure (HF) and reduced ejection fraction, as demonstrated in the VICTORIA trial. This study assessed the real-world use of vericiguat.
Material And Methods: This cross-sectional, prospective and multicenter registry (VERISEC) included 776 patients from 43 centres in Spain between December 2022 and October 2023.
Therapeutic novelties in acute heart failure and practical perspectives.
Anaesth Crit Care Pain Med
January 2025
City Cardiological Center, Almaty, Kazakhstan.
Acute Heart Failure (AHF) is a leading cause of death and represents the most frequent cause of unplanned hospital admission in patients older than 65 years. Since the past decade, several randomized clinical trials have highlighted the importance and pivotal role of certain therapeutics, including decongestion by the combination of loop diuretics, the need for rapid goal-directed medical therapies implementation before discharge, risk stratification, and early follow-up after discharge therapies. Cardiogenic shock, defined as sustained hypotension with tissue hypoperfusion due to low cardiac output and congestion, is the most severe form of AHF and mainly occurs after acute myocardial infarction, which can progress to multiple organ failure.
View Article and Find Full Text PDFUtility of loop diuretics as a marker of risk in clinical trials of heart failure with preserved ejection fraction: Analysis from the Swedish Heart Failure Registry.
Eur J Heart Fail
January 2025
Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Aims: It is common in heart failure (HF) trials, especially in HF with preserved (HFpEF) and mildly reduced ejection fraction (HFmrEF), to select for increased risk of outcomes ('enrichment'). We investigated the association between loop diuretic use and common trial outcomes.
Methods And Results: Patients in the Swedish HF Registry with HFmrEF and HFpEF were divided into three groups: no loop diuretic use, 1-40 mg furosemide equivalent, and >40 mg.
Canagliflozin reduces oral loop diuretic intensification in patients with type 2 diabetes: A participant-level pooled analysis of the CANVAS and CREDENCE trials.
Eur J Heart Fail
January 2025
The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
Aims: The sodium-glucose cotransporter 2 inhibitor canagliflozin reduces the risk of heart failure (HF) hospitalization or cardiovascular death and chronic kidney disease (CKD) progression among patients with type 2 diabetes at high cardiovascular risk or with CKD. Patients with type 2 diabetes commonly have coexisting HF or CKD that require treatment with loop diuretics; however, the prognostic implications of oral loop diuretic intensification are not well characterized.
Methods And Results: In this participant-level pooled analysis of the CREDENCE and CANVAS trials (not including CANVAS-R), 1454/8731 (16.
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