Despite significant advances in management, heart failure continues to impose a significant epidemiologic burden with high prevalence and mortality rates. For decades, sodium has been the serum electrolyte most commonly associated with outcomes; however, challenging the conventional paradigm of sodium's influence, recent studies have identified a more prominent role in serum chloride in the pathophysiology of heart failure. More specifically, hypochloremia is associated with neurohumoral activation, diuretic resistance, and a worse prognosis in patients with heart failure. This review examines basic science, translational research, and clinical studies to better characterize the role of chloride in patients with heart failure and additionally discusses potential new therapies targeting chloride homeostasis that may impact the future of heart failure care.
© 2023 The Authors.