Fast Induced Remodeling in Heart Failure with Preserved Ejection Fraction (FIRE-HFpEF)

Medtronic

Status: Enrolling

Conditions: Concentric Hypertrophy; Heart Failure with Preserved Ejection Fraction

Treatments: Device: Pacemaker PLR + TRT ON; Device: Pacemaker non-pacing mode or an exertional rate-adaptive pacing mode with no planned pacing at rest.

Study type: Interventional

Funder types: Industry

Identifiers

NCT05839730

MDT20060

Details and patient eligibility

About

FIRE-HFpEF is a multi-center, prospective, randomized, single-blinded, clinical feasibility study. This study will enroll up to 105 subjects with heart failure with preserved ejection fraction in the United States. Data will be collected to evaluate whether pacing therapies can lead to improvements in exercise capacity and health status of subjects.

Full description

After enrollment, baseline data will be collected, and subjects will then have a pacemaker implanted. After 6 weeks, subjects will have a follow up visit with a blood draw and a cardiac MRI. At this visit, subjects will be randomized 2:1 for pacing therapy or as a control (programmed into either a non-pacing mode or an exertional rate-adaptive pacing mode with no planned pacing at rest). After 3, 6 and 9 months after randomization, subjects will return for a follow up visit. At the 9-month visit therapy modifications will be made based on initial pacing randomization assignment: pacing therapy will be terminated in the original therapy group and enabled in the control group. After an additional 3-months of follow-up, subjects will return for their final visit, therapies will be disabled in all subjects and subjects will be exited. Echocardiographic, functional, and health status endpoints will be collected and analyzed to assess therapy efficacy.

Enrollment: 105 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of Heart Failure, Left Ventricular Ejection Fraction (LVEF) ≥ 55% (this and other measurements must be made within the last year).

• New York Heart Association (NYHA) Functional Class I-III

• Stable on guideline-directed medical therapy (GDMT) heart failure medications as determined by the investigator, for at least 1 month, with the exception of loop diuretic therapy. GDMT should be in accordance with current American Heart Association (AHA)/American College of Cardiology (ACC)/Heart Failure Society of America (HFSA) Guidelines and include consideration of Sodium/glucose cotransporter-2 inhibitors (SGLT2i) therapy.

• V End Diastolic Volume indexed to body surface area (BSA) ≤ 80 mL/m^2.

• Concentric remodeling or concentric hypertrophy defined as at least one of the following criteria:

  • Left ventricular (LV) posterior or lateral wall thickness > 11mm
  • Relative wall thickness (RWT) > 0.42
  • Male and LV mass indexed to BSA ≥115 g/m2
  • Male and LV mass indexed to height ≥ 49.2 g/m2.7
  • Female and LV mass indexed to BSA ≥ 95 g/m2
  • Female and LV mass indexed to height ≥ 46.7 g/m2.7

Exclusion criteria

• Unable or unwilling to undergo contrast MRI.
• Class I indication for permanent pacing, except for symptomatic chronotropic incompetence
• Current permanent or persistent Atrial fibrillation (A-fib)
• Structural heart disease requiring intervention
• Aortic valve replacement procedure less than 12 months prior to enrollment
• Known pericardial constriction, genetic hypertrophic cardiomyopathy, or infiltrative cardiomyopathy
• Severe aortic or mitral valve disease, defined as severe regurgitation or a valve area < 1cm^2
• Exertional angina
• Severe pulmonary disease including severe Chronic obstructive pulmonary disease (COPD) (i.e., requiring home oxygen, chronic nebulizer therapy, or chronic oral steroid therapy or hospitalized for pulmonary decompensation within 12 months)
• Estimated glomerular filtration rate (eGFR) < 25 ml/min/1.73m^2 as calculated by the Modification in Diet in Renal Disease (MDRD) formula
• Uncontrolled blood pressure, defined as systolic pressure outside the range of 100 to 160 mmHg despite anti-hypertensive medication.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Double Blind

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105 participants in 2 patient groups

Pacemaker with multiple pacing therapies enabled

Experimental group

Description:

Device will be programmed for personalized lower rate pacing (PLR) and tachycardiac remodeling pacing (TRT).

Treatment:

Device: Pacemaker PLR + TRT ON

Pacemaker with no pacing therapies enabled

Active Comparator group

Description:

Device will be programmed to a non-pacing mode or an exertional rate-adaptive pacing mode with no planned pacing at rest.

Treatment:

Device: Pacemaker non-pacing mode or an exertional rate-adaptive pacing mode with no planned pacing at rest.