Title : The prognostic role of serum chloride in acute decompensated heart failure and cardiorenal syndrome: A retrospective cohort study
Abstract:
Introduction: Heart failure (HF) is a highly prevalent disease worldwide, contributing to significant morbidity and mortality, with a substantial burden on healthcare systems. Despite extensive research on HF, chloride has not been a primary investigational target in most studies (1). Chloride has been identified as a key electrolyte for tubuloglomerular feedback and an important regulator of neurohormonal system activity (2). A growing body of evidence suggests a strong link between low serum chloride levels and poor outcomes in heart failure, particularly increased mortality and longer hospital stay (3). Cardiorenal syndrome (CRS) is a condition in which heart failure and renal dysfunction coexist. It is classified into five types based on the primary organ dysfunction and the acuity or chronicity of the dysfunction (4). Acute CRS, a subset of acute kidney injury (AKI), is defined as CRS type 1 when acute renal dysfunction follows acute heart failure (4). AKI in acute heart failure is a common clinical occurrence, associated with adverse outcomes, including increased mortality and prolonged hospital stays (5). The pathophysiology of CRS is complex, as cardiac and renal dysfunction are interconnected. Current research is focused on identifying biomarkers that can help predict and manage CRS (5). Neurohormonal dysregulation through activation of the renin-angiotensin-aldosterone system (RAAS) is a major contributor to organ dysfunction in CRS (5). Although recent studies have highlighted the role of chloride as a key regulator of the neurohormonal system, its potential as a biomarker in CRS remains unexplored.
Methods: This single-center retrospective cohort study examined patients aged 18 to 80 years who were admitted with acute decompensated heart failure (ADHF) to medical or cardiology wards between 2020 and 2021. Patients on renal replacement therapy were excluded. The primary outcome was the risk of CRS type 1 in ADHF patients with hypochloremia (serum chloride <96 mEq/L). Secondary outcomes included one-year mortality, 30-day readmission, need for ICU admission, and need for inotropic support. Continuous data were reported as means ± SD or medians, as appropriate. Categorical data were presented as percentages. Statistical significance was set at p-value <0.05. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 22.
Results: During the study period, a total of 187 `study eligible patients with ADHF were admitted to the general cardiology and internal medicine wards .Patients were classified as having either hypochloremia (<96 mEq/L) or normochloremia (96-110 mEq/L), with only a few exhibiting hyperchloremia (>110 mEq/L). The average age in our cohort was 65 years, with 49% female and 51% male. Medical comorbidities included hypertension (64%), coronary artery disease (51%), valvular heart disease (45%), and chronic kidney disease (48%). Based on ejection fraction (EF), patients were categorized as having HFrEF (53%), HFpEF (39%), or HFmrEF (8.1%). Serum chloride levels on admission were not associated with acute kidney injury (p-value = 0.2). However, chloride levels on day 3 were significantly associated with increased one-year mortality (p-value = 0.018), though no significant association was found with 30-day readmission. Hypochloremia on admission was significantly associated with ICU admission (p-value = 0.004), and hypochloremia on admission and day 7 was associated with the need for inotropic support (p-values = 0.007 and 0.016, respectively).
Conclusions: The study’s primary outcome of an increased risk of CRS type 1 in patients with hypochloremia during ADHF admission was not statistically significant. However, the study demonstrated that hypochloremia in ADHF patients was associated with an increased risk of one-year mortality, need for inotropic support, and ICU admission. The study had several limitations, including its retrospective observational design, being conducted at a single tertiary center, and an underpowered sample size for detecting statistically significant results. Larger multicenter studies are needed to validate our findings and explore mechanistic pathways linking chloride to HF and CRS outcomes.
