Serum chloride and the response to combining loop and thiazide diuretics for acute heart failure: the ALCALOTIC study

Chloride may play an important role in the pathophysiology of heart failure (HF) as it is associated with HF prognosis and diuretic resistance. This study evaluates the diuretic response across serum chloride in patients admitted with acute heart failure (AHF) and treated with loop and thiazide diuretics. This is a subanalysis of the ALCALOTIC study, a prospective, multicentre, observational cohort study that included 665 patients admitted for AHF at 30 clinical sites in Spain. We analysed 386 patients after excluding those without baseline chloride or in-hospital weight loss data. The endpoint was in-hospital weight loss across the spectrum of baseline serum chloride. Mean age was 82 years and 59% were women. Hypochloraemia (< 96 mmol/L) and hyperchloraemia (> 106 mmol/L) were present in 59 (15%) and 65 (17%), respectively. Compared to those with chloraemia ≥ 96 mmol/L, hypochloraemia was independently associated with smaller weight loss at discharge (β coefficient - 0.78, CI 95%: - 1.53 to - 0.21, p = 0.044). Add-on thiazide to loop diuretics was associated with higher weight loss in the overall population (β Coefficient 1.23, CI 95%: 0.38 to 2.09, p = 0.005). However, a differential between-treatment association was found across serum chloride (p value for interaction = 0.020). Thiazides were associated with a greater weight loss in patients with normo- or hyperchloraemia but not in those with hypochloraemia. Hypochloraemia was associated with a worse diuretic response (measured by weight loss during hospitalization). Treatment with thiazides was associated with a better diuretic response only in patients with normo- and hyperchloraemia but not in those with hypochloraemia.