Chloride in Heart Failure: The Neglected Electrolyte

Arietje J.L. Zandijk, BSC; Margje R. van Norel, BSC; Florine E.C. Julius, BSC; Nariman Sepehrvand, MD, PHD; Neesh Pannu, MD, SM; Finlay A. McAlister, MD, MSC; Adriaan A. Voors, MD; Justin A. Ezekowitz, MBBCH, MSC


JACC Heart Fail. 2022;9(12):904-915. 

In This Article

The Existing Published Data on Chloride Abnormalities in HF

Sixteen studies have shown that low serum chloride level is associated with adverse outcomes (Table 1) in patients who are hospitalized with acute HF (6,787 patients)[1,7,10–16] as well as in outpatients with chronic HF (18,757 patients).[6,9,10,17–20]

A few studies suggested that both hypochloremia and hyperchloremia were associated with adverse outcomes in a U-shaped correlation.[6,10,19,20] Others either did not study hyperchloremia[9,13–17,21] or studied it but did not find a correlation between hyperchloremia and adverse outcomes.[7,11,12,18]

In some studies, serial measurements, instead of a single measurement, were used to see whether a change in chloride concentration was related to the outcome of interest. Kataoka[17] looked at the change of chloride levels in patients with HF and reported an increase in chloride concentration during worsening HF, which was decreased after HF treatment with conventional diuretic agents. A few studies explored the effect of chloride change in hospital on clinical outcomes and the majority showed higher risk of mortality in those with either progressive or persistent hypochloremia during hospital stay.[11,14,16]

It is suggested that sodium and chloride should be assessed together in patients with decompensated HF. The majority of studies,[1,6,7,10,17] but not all,[16] have reported a correlation between chloride and sodium, although the observed correlation was very modest in 2 studies.[9,20] Some studies showed a link between hypochloremia and mortality in the context of hyponatremia, but the association attenuated at higher sodium levels.[1,10] Whether sodium or chloride have any effect on clinical outcomes independent of each other remains uncertain and requires further research. Although studies suggested a link between hyponatremia and clinical outcomes in the univariate analysis, this link often disappeared with adjustment for covariates including chloride level.[6,7,9,12,14,16,20,21]

The changes in chloride concentration were shown to be relatively greater than the changes in sodium concentration in 1[17] of 3 studies[14,16,17] reporting the change of both electrolytes during the course of treatment. The risk of adverse outcomes is shown to be increased in higher baseline sodium/chloride ratios.[1]