Chloride and Cardiorenal Interactions in Heart Failure

The cardiorenal literature has long been dominated by a sodium-centric view. However, mechanisms affecting sodium homeostasis in patients with heart failure (HF) commonly lead to concurrent changes in the serum levels of chloride as well. There is a growing body of evidence on a strong link between low serum chloride levels and adverse outcomes in HF, which might be even more potent than that of sodium. Maladaptive neurohormonal activation and unresponsiveness to diuretics have been proposed as potential mechanisms to explain this phenomenon. In parallel with accumulating evidence on the predictive value of chloride in various HF populations, the limited available interventional studies that were aimed at increasing serum chloride levels have also shown promising results. Ongoing studies are designed to elucidate the role of chloride as a key cardiorenal connector and whether hypochloremia represents a modifiable risk factor (i.e., target of therapy) or a mere marker of disease severity and poor prognosis.