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:

Absence of hospitalizations for 90 days
Stable diuretic and medical therapy for 30 days
Opinion of the patient's treating physician (Heart Failure Cardiologist) that the patient is at optimal volume status
Evidence based heart failure treatment with maximally-tolerated doses of a beta blocker, ACE/ARB/neprilysin inhibitor and aldosterone antagonist
Ejection fraction <40%
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 outpatient or inpatient 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 to acidosis. Patients who are on metformin may be enrolled if their metformin can be safely discontinued for the inpatient randomized periods in each arm. Any participants who have consistently elevated Blood glucose readings > 200 mg/dL while inpatient will not be enrolled.
Serum bicarbonate level <24mmol/L
Estimated glomerular filtration rate <30 mL/min or prior or current history of renal replacement therapy
Anemia, as defined by Hemoglobin <8.0 g/dL at screening visit
Urinary incontinence or significant bladder dysfunction (post-void residual at screening >100 mL
Use of chloride containing medications that provide more than 5 mmol/day of chloride if the medication cannot be discontinued or substituted
Appears unlikely, or unable to participate in the required study procedures, as assessed 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