Mechanisms of Diuretic Resistance in Heart Failure, Aim 2

Prior treatment

• History of flash pulmonary edema requiring hospitalization and treatment with biphasic positive airway pressure or mechanical ventilation or a "brittle" volume sensitive HF phenotype such as an infiltrative or restrictive cardiomyopathy (i.e. amyloid cardiomyopathy, etc).
• On Lithium therapy

Other illness

• Diagnosis of liver failure
• Contraindications or allergy to sulfonamides
• Any contraindication to thiazide diuretic or allergy to thiazide or bendroflumethiazide

Lab values

• GFR \<20 ml/min/1.73m2 using the CKD-EPI equation or use of renal replacement therapies
• Hemoglobin \< 8 g/dL or symptomatic anemia

Other

• Use of any non-loop type diuretic in the last 7 days or 5 half lives, with the exclusion of low dose aldosterone antagonist (e.g., spironolactone or eplerenone ≤50 mg). Examples of non-loop diuretics include but may not be limited to acetazolamide (oral or IV, not ophthalmic), metolazone, HCTZ, chlorthalidone, chlorothiazide, indapamide, triamterene, amiloride, finerenone, spironolactone dose \> 50mg day, eplerenone \> 50mg/day,
• Pregnant or breastfeeding
• Inability to give written informed consent or comply with study protocol or follow-up visits
• Chronic urinary retention limiting ability to perform timed urine collection procedures
• On pimozide or thioridazine

• Clinical diagnosis of HF
• No plan for titration/change of heart failure medical or device therapies during the study period.
• Absence of non-elective hospitalizations in the previous 2 weeks
• At optimal volume status by symptoms, exam, and dry weight.
• Serum potassium ≤ 5.0 mmol/L
• Serum sodium ≥ 130 mEq/L
• Age \> 18 years
• Hemoglobin ≥8 g/dL
• Objective evidence of diuretic resistance to a 10mg bumetanide challenge, defined as:
  • FENa \<10% and total sodium output \<150mmol and
  • At least one of the following criteria:
  • 1\. Chronic home furosemide dose \> or equal to 80mg furosemide equivalents daily 2. eGFR \< 60ml/min 3. Serum chloride \<100mmol/L 4. FENa \<5% and total sodium output \<75mmol on the 2 hour screening