Effect of renal function on the prognostic importance of chloride in patients with heart failure

Hypochloremia has recently gained interest as a potential marker of outcomes in patients with heart failure (HF). The exact pathophysiologic mechanism linking hypochloremia to HF is unclear but is thought to be mediated by chloride-sensitive proteins and channels located in kidneys. This analysis aimed to understand whether renal dysfunction (RD) affects the association of hypochloremia with mortality in patients with HF. Using data from a nationwide registry, 438 cases with complete data on serum chloride concentration and 1-year survival were included in the analysis. Patients with an estimated glomerular filtration rate of <60 mL/min/m² at baseline were accepted as having RD. Hypochloremia was defined as a chloride concentration <96 mEq/L at baseline. For HF patients without RD at baseline, patients with hypochloremia had a significantly higher 1-year all-cause mortality than those without hypochloremia (41.6% vs 13.0%, log-rank p < 0.001) and the association remained significant after multivariate adjustment (odds ratio (OR): 2.55, 95% confidence interval (CI): 1.25-5.21). The evidence supporting the association was very strong in this subgroup (Bayesian Factor (BF)₁₀: 48.25, log OR: 1.56, 95% CI: 0.69-2.43). For patients with RD at baseline, there was no statistically significant difference for 1-year mortality for patients with or without hypochloremia (36.3% vs 29.7, log-rank p = 0.35) and there was no evidence to support an association between hypochloremia and mortality (BF₁₀: 1.18, log OR :0.66, 95% CI: -0.02 to 1.35). In patients with HF, the association between low chloride concentration and mortality is limited to those without RD at baseline.