Using genetic scores to guide beta-blocker treatment for heart failure with mildly reduced ejection fraction

Using Polygenic Scores to Guide Beta-blocker Therapy for Heart Failure With Mildly Reduced Ejection Fraction

This study will test whether a genetic (polygenic) score can help predict which adults with heart failure and an ejection fraction of 41–50% will benefit from beta-blocker (metoprolol) treatment.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years to 89 Years
• Sex: All
• Sponsor: Henry Ford Health System (Academic / other)
• Locations: 1 site (Detroit, Michigan)
• Trial ID: NCT07054489 on ClinicalTrials.gov

What this trial studies

This interventional study uses a polygenic score—a summary of many genetic variants—to guide use of beta-blocker therapy in adults with heart failure and mildly reduced ejection fraction (41–50%). Participants will have genetic testing and receive metoprolol-based beta-blocker therapy with cardiac MRI used to measure changes in left ventricular end-systolic volume index. The aim is to see whether the genetic score identifies patients who experience greater improvements in cardiac structure and function while avoiding unnecessary exposure in those unlikely to benefit. The protocol excludes patients already on high-dose beta-blockers, those with clear contraindications, or those with prior very reduced EF.

Who should consider this trial

Good fit: Adults aged 18–89 with a clinical diagnosis of heart failure within the past year and a most-recent ejection fraction of 41–50% who can undergo study procedures and are not already on high-dose beta-blocker are ideal candidates.

Not a fit: Patients with prior documented EF ≤35%, those already on ≥25% target beta-blocker dose, those with contraindications to beta-blockers, active cancer treatment, dialysis dependence, or limited life expectancy are unlikely to benefit from enrollment.

Why it matters

Potential benefit: If successful, the approach could help personalize beta-blocker use so people likely to benefit get treatment while others avoid side effects.

How similar studies have performed: Prior work by the principal investigator validated a polygenic score that predicted beta-blocker mortality benefit in European-ancestry heart failure patients, but prospective use of such scores to guide therapy—especially in diverse populations—remains largely untested.

Eligibility criteria

Inclusion Criteria:

* Age 18-89 years
* Ejection Fraction (EF) \>40% and =\<50% by any modality within 1 year (must be most recent)
* Clinical diagnosis of HF within 1 year, evidenced by any one: Hospital discharge with primary or secondary HF diagnosis, ER discharge with primary diagnosis of HF, ambulatory diagnostic code for HF and diuretic use, BNP\>35 ng/L or NTproBNP \>125 ng/L at any time
* Expected ability to fully participate in study (can tolerate study processes, no long travel)

Exclusion Criteria:

* Unable to provide informed consent
* Previous documented EF =\< 35%
* Currently on BB =\>25% target dose
* Uncontrolled hypertension (systolic BP \> 180 at enrollment)
* Has contraindications to all BB or intolerance to metoprolol
* Systolic BP \< 100 or heart rate \<70
* Current cancer requiring active treatment
* Heart transplant or LVAD or expected in the next year
* Life expectancy \< 1 year for any reason
* Dialysis dependence or ESRD
* MI/ PCI or other cardiac surgery within 90 days prior to enrollment or planned in the future
* Absolute indication for BB other than heart failure (e.g. tachyarrhythmia required BB for rate control, angina)
* If PI decides for any reason participation in trial is not in best interest of the patient
* Has a contraindication to completing MRI procedures

Where this trial is running

Detroit, Michigan

• Henry Ford Health — Detroit, Michigan, United States (Recruiting)

Study contacts

• Principal investigator: David Lanfear, MD — Henry Ford Health
• Study coordinator: Whitney Cabral, MS

Conditions Heart Failure; Polygenic Score; Beta blocker; Metoprolol