Prognostic significance of serum chloride level in heart failure patients with preserved ejection fraction

Abstract

AimsThe prognostic value of serum chloride level has been reported primarily in patients with heart failure with reduced ejection fraction, and hence, there is limited evidence in patients of heart failure with preserved ejection fraction (HFpEF). This study was conducted to clarify the relationship between serum chloride level and clinical outcomes in patients with HFpEF with acute decompensated heart failure (ADHF). Methods and resultsPatient data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT HFpEF) study, a prospective multicentre observational registry for ADHF-HFpEF in Osaka. The data of 870 patients were analysed after excluding patients with in-hospital death, missing follow-up data, missing data of serum chloride level, or on chronic dialysis therapy. The primary endpoint of this study was all-cause mortality. At discharge, right ventricular systolic dysfunction was significantly associated with the lowest tertile of serum chloride level after multivariable adjustment (P = 0.0257). During a mean follow-up period of 1.8 ± 1.0 years, 186 patients died. Cox multivariable analysis showed that serum chloride level at discharge (P = 0.0017) was independently associated with all-cause mortality after multivariable adjustment of major confounders, whereas serum sodium level was no longer significant (P = 0.6761). Kaplan-Meier survival curve analysis revealed a significantly increased risk of mortality stratified by the tertile of serum chloride level [29% vs. 19% vs. 16%, P = 0.0002; hazard ratio (HR): 2.09 (95% confidence interval, CI: 1.31 to 3.34), HR: 1.03 (95% CI: 0.65 to 1.64)]. Conclusions Serum chloride level was useful for the prediction of poor outcome in ADHF patients with preserved ejection fraction.

Prognostic significance of plasma chloride in elderly patients hospitalized for acute heart failure

“…The hypochloraemia that we observed in our patients can be explained both using diuretics and by the activation of the RAAS and vasopressin. We attribute less importance to other drugs given that only 50% of the patients were taking angiotensin‐converting enzyme inhibitor (ACE‐I)/angiotensin receptor blocker (ARB) and 15% mineralocorticoid receptor antagonist (MRA) and none tolvaptan, unlike other studies where this percentage was higher 14 …”

“…The pathophysiology of chloride in HF is not fully understood. It is known that chloride plays a key role in the alterations of the RAAS, in the maintenance of the acid–base balance, and in the renal transporters on which diuretics act 14,18 . There are two main mechanisms that reduce chloride levels in HF: the use of diuretics and the activation of RAAS and/or vasopressin 9 .…”

“…The prognostic value of plasma chloride was described before, but the studies were performed using plasma chloride at discharge 1,14 or admission, 7,8 in younger populations, 7,8,14,15 the majority with HF with reduced ejection fraction (HFrEF) 8,9 or chronic HF. 15 In the current study, we measured plasma chloride during the acute congestive phase (24-48 h from the admission) in a very old European cohort hospitalized in an Internal Medicine Department, with HFpEF mainly (80%).…”

“…It is known that chloride plays a key role in the alterations of the RAAS, in the maintenance of the acid-base balance, and in the renal transporters on which diuretics act. 14,18 There are two main mechanisms that reduce chloride levels in HF: the use of diuretics and the activation of RAAS and/or vasopressin. 9 The hypochloraemia that we observed in our patients can be explained both using diuretics and by the activation of the RAAS and vasopressin.…”

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

“…7,8 After the publication of these two studies, several other groups confirmed these initial findings and also found that they extend to other HF phenotypes, such as patients with preserved ejection fraction. 18,19 Interestingly, despite the strong association of serum chloride with HF outcomes, the addition of chloride on top of prognostic models is either associated with little improvement in the predictive ability of the models or is not associated with an improvement at all. 9,20 This latter finding suggests that the incremental usefulness of chloride over existing models might only be valid for some subgroups, and indeed Ferreira et al have found that the usefulness of hypochloremia as a risk marker is limited to those with low sodium at baseline.…”