Chloride Dynamics in Heart Failure: Clinical Implications of Serum Levels and the Emerging Significance of Urinary Chloride

Heart failure remains a prevalent, high-risk condition particularly common among the elderly population. Impairment of systolic function, secondary dysregulation of maladaptive neurohormonal systems and HF therapies lead to electrolyte disturbances with hyponatremia being considered a robust marker of adverse prognosis in HF. Serum chloride has emerged as a promising prognostic marker, accurately predicting adverse outcomes in acute and chronic HF. Hypochloremia reflects a compound of maladaptive neurohormonal, renal, and acid–base mechanisms, frequently worsened by diuretic therapy, and is independently associated with increased cardiovascular mortality, HF hospitalization, and diuretic resistance. uCl⁻ has recently been shown to serve as a dynamic biomarker of HF severity, RAAS activation, and poor outcomes, offering incremental prognostic value. Our review synthesizes the latest evidence on serum and urinary chloride disturbances in HF, framing key distinctions between acute versus persistent electrolyte disturbances. We also explore the interrelationship between chloride and sodium, the differential impact of hypochloremia in HFpEF versus HFrEF, and clinical outcomes stratified by the temporal vs persistent nature of chloride imbalance. We have as well included practical, visual flowcharts for classifying and managing hypochloremia based on underlying etiology.