Effects of heart failure pharmacotherapy on natriuresis and diuresis: A narrative review

Neurohormonal overactivation and the resulting sodium avidity, driving sodium retention, are important mechanisms underlying the signs and symptoms of heart failure (HF). Blockade of the renin-angiotensin-aldosterone and adrenergic systems therefore represents a central therapeutic target and cornerstone of HF pharmacotherapy, theoretically counteracting sodium avidity. Paradoxically, evidence on how neurohormonal blockade affects markers of sodium avidity, natriuresis, and diuresis remains fragmented, with no integrated summary to date. This review aims to synthesize available evidence on the impact of guideline-directed medical therapy and other HF therapies on sodium excretion/diuresis in HF [Fig. 1]. Here we present comprehensive review of available data on this topic. The scarcity of high-quality studies, small sample sizes, and conflicting results preclude definitive conclusions; accordingly, we refrain from formulating any. Interpretation is further limited by the lack of a standardized method for assessing sodium excretion independent of confounders such as renal function and dietary sodium intake, which restricts reproducibility across studies.