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

Possible Role of Chloride in HF Pathophysiology

Chloride is frequently tested in patients with HF and although there is no universal consensus on the normal chloride level ranges, hypochloremia and hyperchloremia are often defined as <96 mmol/L and >105 mmol/L, respectively.[6]

Electrolytes are important for signaling in the heart and contribute to cellular excitability in the cardiovascular system. Activation of cardiac chloride channels affects the membrane potential and action potential duration in the sino-atrial node, which can result in arrhythmias.[8] This arrhythmogenesis resulted from abnormal chloride levels, which are partly mediated by the dysregulated myocyte intracellular pH and K+ levels, and can lead to sudden cardiac death.[6] Patients with HF have shown a 50% decline in the presence of chloride transfer regulator called the cystic fibrosis transmembrane conductance regulator in an adaptive mechanism during the HF progression.[8] Consequently, this may lead to an instability of repolarization and a higher tendency to arrhythmias. Moreover, this electrolyte imbalance can cause dysregulation of myocyte intracellular pH, which is shown to be an arrhythmogenic factor.[6] The above-mentioned adaptive remodeling of chloride channels can contribute to the progression of myocardial hypertrophy and subsequent HF.[8]

More importantly, chloride is well known to play an important role in fluid homeostasis, neurohormonal activation, and diuretic resistance,[3,9] which are generally recognized as major factors in the development and progression of HF. These factors will be discussed in greater detail in this review.