Unmitigated Aldosterone Signaling During Standard Clinical MRA Dosing

Inclusion criteria

• Chronic stable heart failure at optimal volume status. Inclusion will require participants to be NYHA class I or II.
• eGFR \> 30 ml/min/1.73m2
• Serum potassium ≤5.0 meq/L and ≥3.5 meq/L
• Stable heart failure medications without need or expectation for changes during the 8-week study period
• Free from heart failure decompensation for the preceding 60 day
• Systolic blood pressure \>90 mmHg if not taking an MRA at screening. If patients are already taking an MRA at the time of screening a systolic blood pressure needs to be \>80 mmHg.

Exclusion criteria

• Uncontrolled hypertension (SBP \> 160 mmHg)
• Severe bladder dysfunction
• Current MRA dose \> 50mg spironolactone or equivalent or non MRA potassium sparing diuretic such as amiloride
• Contraindication to initiation or withdrawal of spironolactone per study procedures
• History of severe hyperkalemia (K\>6.0 meq/l)
• Brittle volume sensitive heart failure, recurrent flash pulmonary edema, restrictive cardiomyopathy or other pathology that would make aldosterone infusion high risk
• Pregnant or breastfeeding
• Women of childbearing potential that are not receiving a highly effective form of contraception. Females of childbearing potential must agree to use a highly effective method of birth control until 14 days after the last dose of study drug. The following are highly effective methods for this study:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal
• Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, or implantable
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
• Vasectomized partner
• Sexual abstinence