Hypochloraemia in Patients with Heart Failure: Causes and Consequences
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REVIEW
Hypochloraemia in Patients with Heart Failure: Causes and Consequences Joseph J. Cuthbert
. Sunil Bhandari
. Andrew L. Clark
Received: July 3, 2020 Ó The Author(s) 2020
ABSTRACT Hypochloraemia is a common electrolyte abnormality in patients with heart failure (HF). It has a strong association with adverse outcome regardless of HF phenotype and independent of other prognostic markers. How hypochloraemia develops in a patient with HF and how it might influence outcome are not clear, and in this review we explore the possible mechanisms. Patients with HF and hypochloraemia almost invariably take higher doses of loop diuretic than patients with normal chloride levels. However, renal chloride and bicarbonate homeostasis are closely linked, and the latter
Digital features To view digital features for this article go to https://doi.org/10.6084/m9.figshare.12674555. J. J. Cuthbert (&) A. L. Clark Department of Academic Cardiology, Hull York Medical School, Hull and East Yorkshire Medical Research and Teaching Centre, Castle Hill Hospital, Cottingham, Kingston upon Hull HU16 5JQ, UK e-mail: [email protected] S. Bhandari Department of Academic Nephrology, Hull University Teaching Hospitals NHS Trust and Hull York Medical School, Anlaby Road, Kingston upon Hull HU3 2JZ, UK
may be influenced by neurohormonal activation: it is likely that the etiology of hypochloraemia in patients with HF is multifactorial and due to more than just diuretic-induced urinary losses. There are multiple proposed mechanisms by which low chloride concentrations may lead to an adverse outcome in patients with HF: by increasing renin release; by a stimulatory effect on the with-no-lysine kinases which might increase renal sodium-chloride co-transporter activity; and by an adverse effect on myocardial conduction and contractility. None of these proposed mechanisms are proven in humans with HF. However, if true, it might suggest that hypochloraemia is a therapeutic target that might be amenable to treatment with acetazolamide or chloride supplementation.
Keywords: Acetazolamide; Chloride; Diuretics; Diuretic resistance; Heart failure; Hypochloraemia; Metabolic alkalosis; Outcome; Prognosis; Sudden death
Cardiol Ther
Key Summary Points Low serum chloride levels are associated with adverse prognosis in patients with acute or chronic heart failure (HF) regardless of left ventricular ejection fraction and independently of other prognostic markers such as N-terminal pro-B-type natriuretic peptide levels. It is not clear how hypochloraemia develops in patients with HF but it may be linked to neurohormonal activation, high-dose loop diuretic usage, and metabolic alkalosis. It is not known whether hypochloraemia is a marker or mediator of adverse outcome in patients with heart failure, although there are several putative mechanisms that might suggest the latter. For example, hypochloraemia might be linked to increased neurohormonal activation, diuretic resistance, and increased risk of sudden cardiac death. Acetazolamide may increase na
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