Chloride in Heart Failure Syndrome: Its Pathophysiologic Role and Therapeutic Implication

Until recently, most studies of heart failure (HF) focused on body fluid dynamics through control of the sodium and water balance in the body. Chloride has remained largely ignored in the medical literature, and in clinical practice, chloride is generally considered as an afterthought to the better-known electrolytes of sodium and potassium. In recent years, however, the important role of chloride in the distribution of body fluid has emerged in the field of HF pathophysiology. Investigation of HF pathophysiology according to the dynamics of serum chloride is rational considering that chloride is an established key electrolyte for tubulo-glomerular feedback in the kidney and a possible regulatory electrolyte for body fluid distribution. The present review provides a historical overview of HF pathophysiology, followed by descriptions of the recent attention to the electrolyte chloride in the cardiovascular field, the known role of chloride in the human body, and recent new findings regarding the role of chloride leading to the proposed 'chloride theory' hypothesis in HF pathophysiology. Next, vascular and organ congestion in HF is discussed, and finally, a new classification and potential therapeutic strategy are proposed according to the 'chloride theory'.