The purpose of this trial is to better understand how the beta-blocker metoprolol works in people with Heart Failure with Reduced Ejection Fraction (HFrEF) according to participants genetics. Participants will have the beta-blocker (BB) polygenic score calculated from genotype data. The score will be used to stratify the patients in the low and high polygenic score groups in the study.
The hypotheses for this trial are:
* HFrEF patients with high polygenic score will have weaker cardiovascular responses to metoprolol succinate than HFrEF patients with low polygenic score. * HFrEF patients with high polygenic score have lower steady-state plasma concentrations of metoprolol succinate than HFrEF patients with low polygenic score. * HFrEF patients with high polygenic score require higher metoprolol succinate plasma concentrations to achieve similar cardiovascular effects as those with low polygenic score.
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
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
University of Michigan
Lead sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Collaborator