Inclusion Criteria:

• Subject provides written informed consent prior to study participation.
• Age at least 18 years or greater.
• Current New York Heart Association (NYHA) Class II–IV.
• Left ventricular ejection fraction ≤ 40%, measured by any echocardiographic, radionuclide, magnetic resonance imaging (MRI), angiographic, or computerized tomography method in the last 12 months (without subsequent measured ejection fraction > 40% duringReceiving any dose of a beta blocker (BB) for the treatment of HF or unable to tolerate BB (reason documented).
• Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m^2 at Screening (based on a single local laboratory analysis of serum creatinine and calculation using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation).
• Hyperkalemia at Screening (defined by 2 local serum K+ values of > 5.0 mEq/L each obtained from a separate venipuncture; e.g., one in each arm or two separate venipunctures in the same arm) while receiving ACEi, ARB, ARNi, and/or MRA OR Normokalemia at Screening (defined by 2 local serum K+ ≥4.0-≤5.0 mEq/L each obtained from a separate venipuncture; e.g., one in each arm or two separate venipunctures in the same arm) but with a history of hyperkalemia documented by a usual care serum K+ measurement > 5.0 mEq/L while on RAASi treatment in the 12 months prior to Screening leading to a subsequent and permanent dose decrease or discontinuation of one or more RAASi medications.
• Females of child-bearing potential must be non-lactating, must have a negative pregnancy test at Screening, and must agree to continue using contraception throughout the study and for 4 weeks after study completion.
• With hospitalization for HF or equivalent (e.g., emergency room or outpatient visit for worsening HF during which the patient received intravenous medications for the treatment of HF) within the last 12 months before Screening:
  • Without atrial fibrillation at Screening, BNP level must be greater than 150 pcg/mL (18 pmol/L) or N-terminal pro b-type BNP (NT-proBNP) must be greater than 600 pcg/mL (71 pmol/L);
  • With atrial fibrillation at Screening, BNP level must be greater than 300 pcg/mL (35 pmol/L) or NT-proBNP must be greater than 1,200 pcg/mL (142 pmol/L); OR
  • Without hospitalization for HF or equivalent (e.g., emergency room or outpatient visit for worsening HF during which the subject received intravenous medications for the treatment of HF) within the last 12 months before Screening:
    • Without atrial fibrillation at Screening, BNP level must be greater than 300 pcg/mL (35 pmol/L) or NT-proBNP must be greater than 1,200 pcg/mL (142 pmol/L);
    • With atrial fibrillation at Screening, BNP level must be greater than 600 pcg/mL (71 pmol/L) or NT-proBNP must be greater than 2400 pcg/mL (284 pmol/L) this interval).

Exclusion Criteria:

• Current acute decompensated HF within 4 weeks before Screening. Subjects with a discharge from a hospitalization for acute decompensation of HF longer than 4 weeks before Screening may be included.
• Symptomatic hypotension or systolic blood pressure 5 times upper limit of normal at Screening based on the local laboratory.
• Diagnosis or treatment of a malignancy in the past 2 years, excluding non-melanoma skin cancer and carcinoma in situ of the cervix, prostate cancer with Gleason score < 7, or a condition highly likely to transform into a malignancy during the study.
• Presence of any condition (e.g., drug/alcohol abuse; acute illness), in the opinion of the Investigator, that places the subject at undue risk, or prevents complete participation in the trial procedures, or potentially jeopardizes the quality of the study data.
• Use of any investigational product for an unapproved indication within 4 weeks prior to Screening or currently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
• Known hypersensitivity to patiromer (RLY5016) or its components.
• Subjects currently being treated with or having taken any one of the following medications in the 7 days prior to Screening: sodium or calcium polystyrene sulfonate or sodium zirconium cyclosilicate, or patiromer.
• An employee, spouse, or family member of the Sponsor (Relypsa, Vifor Pharma), investigational site or the Contract Research Organization (CRO)