Low serum chloride in patients with chronic heart failure: clinical associations and prognostic significance

Background Low serum chloride is common in patients with chronic heart failure (CHF) and is associated with worse outcomes. We investigated the clinical and prognostic associations, including cause of death associations, of low serum chloride in patients referred to a secondary care clinic with suspected heart failure. Methods and results Patients with echocardiogram and serum chloride were evaluated (n=5613). CHF was defined as signs and symptoms of the disease and either left ventricular systolic dysfunction (LVSD) worse than mild [heart failure with reduced ejection fraction (HFrEF)] or LVSD mild or better and raised amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (>125 ng/L) [heart failure with preserved ejection fraction (HFpEF)]. Hypochloraemia was defined as greater than two standard deviations below the mean in the local normal distribution (<96 mmol/L). Of the 5613 patients referred, 908 patients did not have CHF, 1988 had HFrEF, and 2717 had HFpEF. Compared to patients in the fourth quartile (median chloride 106 mmol/L), patients in the first quartile (median chloride 96 mmol/L) had more severe symptoms (38% New York Heart Association class III or IV vs. 25%, P < 0.001) and were more likely to take loop diuretics (79% vs. 55%, P < 0.001). The annual mortality rate for patients with CHF was 11%. Hypochloraemia was associated with an increased risk of death independent of NT-proBNP. Patients in the first quartile had a two-fold increased risk of death compared to patients in the fourth quartile (P < 0.001). Sudden death was a common mode of death amongst patients with hypochloraemia. Conclusions Hypochloraemia is strongly related to an adverse prognosis and may be a therapeutic target in patients with CHF.