Sodium Chloride Versus Glucose Solute as a Volume Replacement Therapy for More Effective Decongestion in Acute Heart Failure (SOLVRED-AHF): A Prospective, Randomized, Mechanistic Study

AIMS: We questioned the long-standing paradigm that sodium/chloride restriction is essential for effective decongestion in acute heart failure (AHF). This study compared the decongestive effects of two isotonic infusion strategies: 5% glucose (for intravascular volume repletion only) versus 0.9% NaCl (providing additional sodium/chloride supplementation), both added to protocolized diuretic therapy. METHODS AND RESULTS: This single-centre, prospective, randomized, single-blind study included patients with fluid overload who were randomized 1:1 to continuous infusions (83.3 ml/h) of either 0.9% NaCl or 5% glucose for 48 h. Co-primary endpoints included 24- and 48-h urine output, natriuresis within 48 h, and total furosemide dose up to 48 h. The NaCl group (n = 25) significantly outperformed glucose group (n = 25) in all co-primary endpoints: the median urine output was higher in the NaCl group versus glucose group at 24 and 48 h (cumulative during 48 h: 9500 vs. 7395 ml, p = 0.001), the NaCl group had higher natriuresis during 48 h of decongestion (p < 0.05), which was achieved with lower cumulative doses of furosemide (220 vs. 280 mg, p = 0.02). The fractional excretion of lithium was higher in the NaCl versus glucose group (19.0 ± 8.9% vs. 14.7 ± 9.6%, p = 0.030), indicating inhibited proximal tubular sodium reabsorption. There was no difference in absolute distal reabsorption, but relative distal sodium reabsorption in the NaCl group was lower (86.9 ± 12.3% vs. 91.5 ± 9.3%, p < 0.001). CONCLUSIONS: The infusion of NaCl compared to glucose added to diuretic therapy led to significantly higher diuresis, natriuresis, and lower loop diuretic use, driven by lower sodium avidity and inhibition of proximal tubular sodium reabsorption. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT05962255.