Mechanism and Effects of Manipulating Chloride Homeostasis in Stable Heart Failure

Inclusion Criteria:

• Meticulous history of medical compliance and attendance of appointments

• Stable heart failure as defined by:

1. Absence of hospitalizations for 90 days

2. Stable diuretic and medical therapy for 30 days

3. Opinion of the patient's treating physician (Heart Failure Cardiologist) thatthe patient is at optimal volume status

• Evidence based heart failure treatment with maximally-tolerated doses of a betablocker, ACE/ARB/neprilysin inhibitor and aldosterone antagonist

• Chronic loop diuretic therapy with ≥ 40 mg of furosemide equivalents

• Serum chloride <102 mmol/L

Exclusion Criteria:

• Inability to commit to or comply with the rigorous study protocol

• Use of a thiazide diuretic in the last 30 days

• History of metabolic or respiratory acidosis

• Use of metformin, acetazolamide, or any other agent that could predispose toacidosis. Patients who are on metformin may be enrolled if their metformin can besafely discontinued for the randomized periods in each arm. Any participants whohave consistently elevated Blood glucose readings > 200 mg/dL while inpatient willnot be enrolled.

• Serum bicarbonate level <24mmol/L

• Serum pH <7.3

• Estimated glomerular filtration rate <30 mL/min or prior or current history of renalreplacement therapy

• Anemia, as defined by Hemoglobin <8.0 g/dL at screening visit

• Urinary incontinence or significant bladder dysfunction (post-void residual atscreening >300 mL)

• Use of chloride containing medications that provide more than 5 mmol/day of chlorideif the medication cannot be discontinued or substituted

• Appears unlikely, or unable to participate in the required study procedures, asassessed by the study PI or research RN (ex: clinically-significant psychiatric,addictive, or neurological disease)

• Inability to give written informed consent or follow study protocol