Heart failure & cardiomyopathies

Prognostic and exploratory neurohormonal correlates of hypochloraemia in heart failure: a multicentre cohort study

HeartPublished multicentre prospective cohort study

Main finding · All-cause mortalityResult — go to the resultAdjusted hazard ratio 2.09 95% CI 1.64–2.67

Authors' conclusion

Hypochloraemia identified patients with heart failure at substantially increased cardiovascular risk independent of established prognostic markers. Exploratory analyses suggested a potential association between circulating UCN2 and chloride homeostasis that warrants mechanistic investigation.

Study context

Population
Patients discharged after hospitalisation for acute or worsening heart failure with available serum chloride measurementspatients included, exploratory UCN2 analyses in a predefined subset of 499 patients · UCN2 exploratory subset 499
Participants
3,941 patients
Exposure
Associations between chloride status and 2-year outcomes
Outcome
All-cause mortality
Follow-up
2-year

Main finding

As reported in the abstract

Adjusted hazard ratio

2.09

95% CI 1.64–2.67

P < 0.001

Hypochloraemia
adjusted HR 2.09 (95% CI 1.64–2.67); P < 0.001

Observational data: associations, not effects.

Further findings

Cardiovascular mortality · 2-year

Adjusted HR (95% CI)P value
HypochloraemiaComparator not stated · multivariable adjustment2.29 (1.64–3.20)P < 0.001

Heart failure rehospitalisation · 2-year

Adjusted HR (95% CI)P value
HypochloraemiaComparator not stated · multivariable adjustment1.30 (1.02–1.67)P = 0.04

Composite outcome · 2-year

Adjusted HR (95% CI)P value
HypochloraemiaComparator not stated · multivariable adjustment1.46 (1.20–1.78)P < 0.001

Competing risk analysis of mortality

Excess mortality risk associated with hypochloraemia was predominantly cardiovascular

All-cause mortality in models including both serum chloride and sodium

Chloride remained independently associated with all-cause mortality whereas sodium did not

Circulating UCN2 concentrations vs serum chloride levels (exploratory)

B
−0.37
95% CI
−0.72 to −0.02
p
P = 0.04
  • Modest inverse association
  • Adjusted for sodium, renal function, nutritional status and clinical severity
  • Exploratory

Original publication

Prognostic and exploratory neurohormonal correlates of hypochloraemia in heart failure: a multicentre cohort study. Heart. Published 20 August 2026. doi:10.1136/heartjnl-2026-328053

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