Mechanisms of Diuretic Resistance in Heart Failure, Aim 2

Eligibility Criteria

• 1. Chronic clinical diagnosis of HF with a documented ejection fraction \<40%.
• 2. 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.
• 3. Chronic stable use of ≥80mg furosemide equivalents per day for ≥ 30 days
• 4. Peak FENa \< 5% following 10mg IV bumetanide challenge at the screening visit
• 5. Absence of hospitalizations in the previous 3 months.
• 6. At optimal volume status by symptoms, exam, and dry weight.
• 7. Serum potassium ≤ 5.0 mmol/L
• 8. Serum sodium ≥ 130 mEq/L
• 9. Age \> 18 years
• 1. GFR \<20 ml/min/1.73m2
• 2. 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)
• 3. History of flash pulmonary edema or a "brittle" volume sensitive HF phenotype such as amyloid cardiomyopathy
• 4. Hemoglobin \< 8 g/dL
• 5. Pregnant or breastfeeding
• 6. Inability to give written informed consent or comply with study protocol or follow-up visits