Diagnosing and Targeting Mechanisms of Diuretic Resistance in Heart Failure

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

This study is a minimal-risk observational open-label single center study with randomization between two standard of care interventions. Approximately 500 patients admitted to the hospital (Yale New Haven Health System) with a clinical diagnosis of heart failure will be enrolled in the overall study. Patients will undergo sampling of their blood and collection of urine at a minimum of 4 timepoints (called "visits"), or a minimum of 5 in the interventional arm. Patients with a low urine sodium output (\<100 mmol) on Visit 1 will be eligible for 1:1 randomization to either an increased dose of their Visit 1 loop diuretic or addition of IV chlorothiazide to their Visit 1 loop diuretic.