Diagnosing and Targeting Mechanisms of Diuretic Resistance in Heart Failure

Summary

Effective diuresis is the primary goal of most acute decompensated heart failure hospitalizations, but diuretic resistance is common and our ability to detect it is limited. Further, there are therapeutically distinct groups of diuretic-resistant patients. These are not easily distinguished using currently available methods, leading to trial-and-error based treatment that promotes lengthy hospitalizations. The aims of this study are: 1. To develop inexpensive and efficient tools to predict diuretic response 2. To understand the prevalence of therapeutically targetable mechanisms of diuretic resistance using endogenous lithium clearance 3. To develop methodology to differentiate diuretic resistance mechanisms using common/inexpensive laboratory tests 4. To provide proof of concept that mechanistically tailored diuretic therapy can improve natriuresis

Timeline

Start

2015-08-31

Primary completion

2020-01-23

Completion

2020-01-23

Publications

• Rao VS, Cox ZL, Ivey-Miranda JB, Moreno-Villagomez J, Ramos-Mastache D, Maulion C, Bellumkonda L, Turner J, Wilson FP, Shilpak MG, Estrella MM, Welling P, Wilcox CS, Ellison DH, Forbush B, Testani JM. Loop Diuretic Dose Intensification versus Adjuvant Thiazide for Diuretic Resistance in Acute Heart Failure: Mechanistic Randomized Controlled Trial. J Am Soc Nephrol. 2026 Mar 1;37(3):533-544. doi: 10.1681/ASN.0000000887. Epub 2025 Sep 12.
• Ivey-Miranda JB, Rao VS, Cox ZL, Moreno-Villagomez J, Mahoney D, Maulion C, Bellumkonda L, Turner JM, Collins S, Wilson FP, Krumholz HM, Testani JM. In-Hospital Observation on Oral Diuretics After Treatment for Acute Decompensated Heart Failure: Evaluating the Utility. Circ Heart Fail. 2023 Apr;16(4):e010206. doi: 10.1161/CIRCHEARTFAILURE.122.010206. Epub 2023 Mar 10.

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