Impact of Hypochloremia on Mortality in Heart Failure Patients: Systematic Review and Metanalysis

Abstract Background Electrolyte imbalances are common in patients with heart failure (HF). Several studies have shown that low serum chloride level is associated with adverse outcomes in patients who are hospitalised with acute HF as well as in outpatients with chronic HF, however the exact prognostic value of hypochloremia has not been quantified. Objectives We performed a systematic review and meta-analysis to assess the impact of hypochloremia on all-cause mortality in HF patients. Methods Data search was conducted from inception through February 1, 2023, using the following MeSH terms: ("chloride" OR "hypochloremia") AND "heart failure". Studies reporting serum chloride measurement and cardiovascular outcomes in HF patients were included. The pre-defined primary outcome was all-cause mortality. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used as effect estimates and calculated with a random-effect model; fixed-effect model and leave-one-out sensitivity analysis were also performed. Results A total of fifteen studies, involving 25,848 patients, were included for quantitative analysis. Prevalence of hypochloremia ranged from 7.4% to 26.1%. Median follow-up time ranged from 6 to 67 months. Hypochloremia as a categorical variable was associated with an increased risk of all-cause mortality (HR 1.56; 95% CI: 1.38 to 1.75; p < 0.001; figure 1). As a continuous variable, serum chloride was associated with all-cause mortality (HR per mmol/l decrease in serum chloride: 1.06; 95% CI 1.05 to 1.07; p < 0.001; figure 2). Fixed-effect model and leave-one-out sensitivity analyses confirmed such findings. Conclusions Hypochloremia exhibits a substantial prognostic value in HF patients. Serum chloride can be used as an effective tool for risk stratifying patients with HF.Hypochloremia and all-cause mortalitySerum chloride and all-cause mortality