Mechanistic Clinical Trial Comparing the Pharmacokinetics/Pharmacodynamics of Metoprolol in Heart Failure With Reduced Ejection Fraction Patients With Low vs. High Polygenic Score

Inclusion Criteria: * Heart Failure with Reduced Ejection Fraction (HFrEF) * Has not taken a beta-blocker within the past 6 months (preferred), or if needed to meet enrollment target, patients that have not taken a beta-blocker in the past 3 months, or only taken a low dose of beta-blocker within the past 6 months (i.e., \< 50% of the guideline-recommended HFrEF target dose, or for beta-blockers that are not approved for HFrEF, \<50% of the maximum dose) * Genetic data already available to calculate the polygenic score (e.g., through participation in the Michigan Genomics Initiative (MGI) or other genetic tests) or willingness to provide a deoxyribonucleic acid (DNA) sample for genetic analysis * White race * Has been prescribed a stable dose (including no dose) of angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), ARB-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 (SGLT-2) inhibitor, or mineralocorticoid receptor antagonist (MRA) for at least the past 4 weeks * Has been prescribed a stable dose (including no dose) of diuretic(s) for at least the past 2 weeks * For women of child-bearing potential: the participant is willing to perform a pregnancy test and use a highly effective contraceptive method for at least 4 weeks prior to the start of metoprolol treatment, during the entire metoprolol treatment period, and for at least 5 days after the discontinuation of metoprolol treatment * Ability to understand and willing to sign a written informed consent Exclusion Criteria: * Prior heart transplant or left ventricular assist device (LVAD) or planned within treatment period * Planned implantation of a pacemaker or Cardiac Resynchronization Therapy (CRT) during treatment period * Patients with a pacemaker that does not allow their heart rate to change in response to exercise per protocol * Pregnant * Systolic blood pressure \< 95 millimeters of mercury (mmHg) * Heart rate \< 60 beats per minute * Second (Mobitz II)- or third-degree heart block * Cardiogenic shock * Patients with acute decompensated heart failure requiring current hospitalization or immediate medical intervention. * Sick sinus syndrome * Pheochromocytoma * Known hypersensitivity to the metoprolol succinate oral tablet used in the trial * Hypertrophic obstructive cardiomyopathy * Active myocarditis * Acute coronary syndrome within the past month * Active or uncorrected severe mitral or aortic valvular dysfunction * Patients with known severe congenital heart disease per protocol * Child-Pugh Class C liver disease * Patients with end-stage renal disease (ESRD) requiring hemodialysis * Concomitant disease that prohibits participating in Cardiopulmonary Exercise Test (CPET) per protocol * Concomitant disease with expected survival less than the duration of the study (e.g., metastatic cancer) * Current or planned treatment with cardiotoxic medications, including interferons and the cancer therapies per protocol * Concurrent participation in another clinical trial that may affect participant safety or validity of data collected in this clinical trial * Inability to take oral medication * Unwilling or unlikely to adhere to the study procedures, as determined at the discretion of the study team, including but not limited to the following reasons: 1. Psychiatric illness or other comorbidities 2. Substance abuse 3. Social or logistical circumstances