Tackling Congestion in Acute Heart Failure: Is It the Primetime for "Combo Diuretic Therapy?"

Symptoms and signs of congestion are the primary reason for hospitalization of patients with acute heart failure. Efficient fluid and sodium removal remain the main goals of therapy, and loop diuretics are the recommended agents in this setting. However, the therapeutic response to these medications is known to be variable, and a significant subset of patients is discharged from the hospital with residual fluid overload. Therefore, sequential blockade of the nephron has been proposed as a more effective decongestive strategy. Pilot studies have suggested significant increase in diuresis and natriuresis with combination diuretic therapy. Recently, two groups of investigators examined this hypothesis on a larger scale in randomized placebo-controlled trials; one targeted the proximal tubules upstream of the loop of Henle (Acetazolamide in Decompensated Heart Failure with Volume Overload - ADVOR), while the other one blocked sodium-chloride cotransporters in the distal convoluted tubules (Combination of Loop with Thiazide Diuretics for Decompensated Heart Failure - CLOROTIC). Herein, we discuss the results of these two trials with special focus on their impact on extraction of sodium, i.e., the main determinant of extracellular volume, and put them in the context of previous studies of combination diuretic therapy as well as extracorporeal ultrafiltration.