Mechanism and Effects of Manipulating Chloride Homeostasis in Stable Heart Failure

Prior treatment

• Estimated glomerular filtration rate \<30 mL/min or prior or current history of renal replacement therapy
• Use of chloride containing medications that provide more than 5 mmol/day of chloride if the medication cannot be discontinued or substituted

Other illness

• History of metabolic or respiratory acidosis
• 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)

Lab values

• 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 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
• Serum pH \<7.3
• Anemia, as defined by Hemoglobin \<8.0 g/dL at screening visit

Other

• Inability to commit to or comply with the rigorous study protocol
• Use of a thiazide diuretic in the last 30 days
• Urinary incontinence or significant bladder dysfunction (post-void residual at screening \>300 mL)
• Inability to give written informed consent or follow study protocol

• 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
• Chronic loop diuretic therapy with ≥ 40 mg of furosemide equivalents
• Serum chloride \<102 mmol/L