Mechanisms of Diuretic Resistance in Heart Failure, Aim 2 (MsDR 2)

Inclusion Criteria: Chronic clinical diagnosis of HF with a documented ejection fraction <40%. Use of beta blocker, ACE, ARB or neprilysin inhibitor (sacubitril/valsartan), aldosterone antagonist, and SGLT2 inhibitor at ≥50% guideline directed doses for 30 days with no plan for titration/change during the study period. Chronic stable use of ≥80mg furosemide equivalents per day for ≥ 30 days Peak FENa < 5% following 10mg IV bumetanide challenge at the screening visit Absence of hospitalizations in the previous 3 months. At optimal volume status by symptoms, exam, and dry weight. Serum potassium ≤ 5.0 mmol/L Serum sodium ≥ 130 mEq/L Age > 18 years Exclusion Criteria: GFR <20 ml/min/1.73m2 Use of any non-loop type diuretic in the last 14 days with the exclusion of low dose aldosterone antagonist (e.g., spironolactone ≤50 mg) History of flash pulmonary edema or a "brittle" volume sensitive HF phenotype such as amyloid cardiomyopathy Hemoglobin < 8 g/dL Pregnant or breastfeeding Inability to give written informed consent or comply with study protocol or follow-up visits