Pacemaker Therapy for Heart Failure

(FIRE-HFpEF Trial)

Recruiting at 11 trial locations

Overseen By Scott A Sarazin

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medtronic Cardiac Rhythm and Heart Failure

Must be taking: Heart failure medications

Disqualifiers: Atrial fibrillation, Structural heart disease, Severe COPD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

105 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if certain pacemaker therapies can enhance exercise capacity and overall well-being in people with a specific type of heart failure. It compares two approaches: one where the pacemaker remains inactive and another where it uses special settings to assist the heart. Individuals with heart failure and normal pumping ability (preserved ejection fraction) who manage their condition with medication may qualify for this study. As an unphased trial, it offers patients the chance to explore innovative treatment options that could improve their quality of life.

Will I have to stop taking my current medications?

The trial requires participants to be stable on their current heart failure medications for at least one month before joining, except for loop diuretics. This means you should continue taking your prescribed medications as directed by your doctor.

What prior data suggests that this pacemaker therapy is safe for heart failure patients?

Previous studies have shown that personalized lower rate pacing (PLR) is safe for people with heart failure who have pacemakers. Patients reported a better quality of life, and researchers found no major safety issues. This personalized pacing uses a special program to set the heart rate, which has been tested and is well-tolerated.

For the pacemaker with PLR and tachycardiac remodeling pacing (TRT), specific safety data is limited. However, the safety of personalized pacing methods in similar situations provides some reassurance. Overall, evidence suggests that these pacemaker therapies are generally safe and well-tolerated by patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these pacemaker treatments for heart failure because they explore innovative pacing strategies. Unlike traditional pacemakers that provide consistent pacing, the "Pacemaker PLR + TRT ON" arm combines personalized lower rate pacing (PLR) with tachycardiac remodeling pacing (TRT), aiming to tailor the pacing to individual needs and potentially improve heart function more effectively. The "Pacemaker PLR ON" arm offers exertional, rate-adaptive pacing, focusing on optimizing the heart's response during physical activity without pacing at rest, which could enhance exercise capacity and quality of life. These approaches are distinct from standard pacemaker settings by emphasizing personalization and adaptability, offering new hope for heart failure patients.

What evidence suggests that this trial's pacemaker therapies could be effective for heart failure?

Research shows that customizing pacemaker settings can improve life for people with heart failure. Studies have found that adjusting the pacemaker to match a person's natural heart rate greatly enhances health outcomes. In this trial, one group will receive a pacemaker with multiple pacing therapies enabled, including personalized lower rate pacing (PLR) and tachycardiac remodeling pacing (TRT). This method, known as Pacemaker with PLR + TRT ON, may improve exercise ability. Reviews on heart function and pacing suggest these methods could benefit heart health and daily activities for those with heart failure. ^{1 5 6 7 8}

Who Is on the Research Team?

Tom Mullen

Principal Investigator

Medtronic

Are You a Good Fit for This Trial?

This trial is for people with heart failure who still have normal or near-normal heart pumping function (LVEF ≥ 55%), specifically those in NYHA Functional Class I-III without severe symptoms. Participants should show signs of a thickened heart muscle and be stable on standard heart failure meds, except diuretics, for at least a month. They can't join if they need a pacemaker for other reasons, have severe chest pain during exercise, permanent A-fib, recent valve surgery, serious lung disease like COPD, very low kidney function (eGFR < 25), uncontrolled high blood pressure despite treatment, or certain types of cardiomyopathy.

Inclusion Criteria

My heart's size is within the normal range for my body size.

My heart's pumping ability is normal or above normal.

My heart condition allows me to perform daily activities with minimal to moderate difficulty.

Exclusion Criteria

I experience chest pain when I exert myself.

I have severe lung disease such as advanced COPD.

I had an aortic valve replacement less than a year ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline and Implantation

Baseline data collection and pacemaker implantation

6 weeks

1 visit (in-person)

Randomization and Initial Follow-up

Randomization to pacing therapy or control, with follow-up visits at 3, 6, and 9 months

9 months

3 visits (in-person)

Therapy Modification

Therapy modifications based on initial randomization; pacing therapy terminated in original group and enabled in control group

3 months

1 visit (in-person)

Final Follow-up

Final follow-up visit with therapy cessation and exit from the study

3 months

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Pacemaker PLR ON
• Pacemaker PLR + TRT ON

Trial Overview The FIRE-HFpEF study is testing whether special pacing therapies from pacemakers can improve the ability to exercise and overall health in patients with Heart Failure with Preserved Ejection Fraction (HFpEF). It's comparing two different pacemaker settings to see which might work better. Up to 105 participants will be randomly assigned to one of these treatments at multiple centers.

How Is the Trial Designed?

Group I: Pacemaker with multiple pacing therapies enabled Experimental Treatment 1 Intervention

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

Group II: Pacemaker with no pacing therapies enabled Active Control 1 Intervention

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

Who Is Running the Clinical Trial?

Medtronic Cardiac Rhythm and Heart Failure

Lead Sponsor

Trials

206

Recruited

137,000+

Geoff Martha

Medtronic Cardiac Rhythm and Heart Failure

Chief Executive Officer since 2020

MBA from University of Minnesota

Dr. Kweli Thompson

Medtronic Cardiac Rhythm and Heart Failure

Chief Medical Officer since 2022

MD from Harvard Medical School

Published Research Related to This Trial

The Micra AV leadless pacemaker, approved by the FDA in early 2020, was successfully implanted in a 38-year-old female patient with a complete AV block, demonstrating its safety and efficacy in treating AV blocks.

After experiencing complications with a traditional dual chamber pacemaker, the patient was safely transitioned to the Micra AV pacemaker, suggesting it may be a viable option for young patients facing device-related issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The implantation of AV leadless pacemaker - a case report. Warwas, S., Jędrzejczyk-Patej, E., Jagosz, M., et al.[2022]

The combination of the Micra AV pacemaker and WiSE-CRT systems allows for completely leadless cardiac resynchronization therapy, demonstrating feasibility in clinical practice.

This case report provides a 1-year follow-up on the first use of these leadless systems together in the United States, indicating potential for innovative treatment options in cardiac care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Outcome of the First Completely Leadless Cardiac Resynchronization Therapy in the United States. Mehlhorn, D., Patel, S., Verghese, D., et al.[2023]

Biventricular resynchronization therapy significantly improves cardiac function and reduces symptoms in most patients with systolic heart failure, as evidenced by improved ejection fraction and decreased NYHA class after treatment.

In a study of 17 patients with prolonged QRS intervals and severe heart failure, the majority experienced better walking distances and reduced hospital stays, although a few patients did not respond to the treatment and two patients died from unrelated complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Resynchronisation therapy in patients with heart failure: our results]. Milasinović, G., Jelić, V., Petrović, M., et al.[2019]

Pacemakers are effective for patients with symptomatic bradyarrhythmias, complete atrioventricular (AV) block, and type II second-degree AV block, but their use in type I second-degree AV block and first-degree AV block is more controversial and generally not recommended unless specific symptoms are present.

Cardiac resynchronization therapy significantly improves outcomes in patients with severe heart failure (NYHA class III or IV) and a QRS duration of 150 milliseconds or greater, but it is not supported for patients with class I heart failure or those with a QRS duration of 120 to 150 milliseconds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Common questions about pacemakers. Denay, KL., Johansen, M.[2014]

In a study of 157 pacemaker-dependent patients with left ventricular dysfunction, those with significant coronary artery disease (CAD) experienced a higher risk of appropriate shocks from CRT-defibrillators, with a shocking rate of 1 per 26 person-years compared to 1 per 362 person-years in patients without CAD.

Patients without CAD had better overall survival and fewer comorbidities, suggesting that CRT-pacemakers may be a safer and equally effective option for these patients, as they showed similar improvements in heart function without the increased risk of shocks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes in pacemaker-dependent patients upgraded from conventional pacemakers to cardiac resynchronization therapy-defibrillators. Adelstein, E., Schwartzman, D., Bazaz, R., et al.[2016]

Pacemaker therapy is widely used, with around 900,000 patients receiving treatment each year, primarily for conditions like sinus node dysfunction and atrioventricular block, which can significantly improve symptoms and quality of life.

Biventricular pacing has been shown to effectively treat advanced heart failure, particularly in patients with left bundle branch block, highlighting its role in improving survival in specific populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indications and recommendations for pacemaker therapy. Gregoratos, G.[2007]

Biologics, including TNF, IL-12/23, and IL-17 antagonists, have been shown to be safe for both short- and long-term use, based on a review of phase 3 clinical trials and biologics registries.

While these treatments have similar safety profiles regarding infections and cardiovascular events, specific risks such as tuberculosis activation with TNF antagonists can be managed through screening, and IL-17 blockade may lead to mild infections or inflammatory bowel disease issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Trial and Registry Data. Gooderham, M., Papp, K.[2019]

Long-term safety concerns have emerged regarding TNF blocker therapy, including risks of infections, cytopenias, lymphoma, and other serious conditions, necessitating careful monitoring of patients.

Regular evaluations and tuberculin skin testing are recommended before starting TNF inhibitors to assess the risk of infections, particularly tuberculosis, ensuring the safety and efficacy of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laboratory monitoring of biologic therapies. Cush, JJ., Yazici, Y.[2017]

In a study of 50 patients with unavoidable right ventricular pacing and left ventricular systolic dysfunction, cardiac resynchronization therapy (CRT) significantly improved left ventricular ejection fraction (LVEF) compared to standard RV pacing, with a median increase of 9% versus a decrease of 1.5% in the RV-PGR group after 6 months.

Patients receiving CRT also experienced better exercise capacity, improved quality of life, and lower NT-proBNP levels, along with fewer hospital days compared to those with standard RV pacing, highlighting the benefits of CRT even in patients with mild or no symptoms of heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac resynchronization therapy in pacemaker-dependent patients with left ventricular dysfunction. Gierula, J., Cubbon, RM., Jamil, HA., et al.[2021]

In a study of 199 psoriasis patients on long-term biologic treatments, significant changes were observed in neutrophil counts and triglyceride levels, particularly during the first 180 days of treatment, indicating the need for careful monitoring of these parameters.

Despite recording 15 serious laboratory adverse events related to liver enzymes, only 2 cases required a change in treatment, suggesting that routine monitoring of many laboratory parameters may not be necessary during long-term biologic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Routine Laboratory Parameter Dynamics and Laboratory Adverse Events in Psoriasis Patients on Long-term Treatment with Adalimumab, Etanercept, and Ustekinumab. Hoffmann, JH., Knoop, C., Enk, AH., et al.[2017]

Citations

1. withpower.com withpower.com/trial/phase-concentric-hypertrophy-4-2023-09181

Pacemaker Therapy for Heart Failure (FIRE-HFpEF Trial) Device will be programmed for personalized lower rate pacing (PLR) and tachycardiac remodeling pacing (TRT). Group II: Pacemaker with no pacing therapies ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9902309/

Rate adaptive pacing in people with chronic heart failure ... The purpose of this systematic review is to determine the efficacy of RAP in people with CHF, with respect to peak HR and exercise capacity.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11203142/

Cardiac Remodeling and Ventricular Pacing: From Genes ... This review explores the intricate relationship between cardiac remodeling and ventricular pacing, spanning from the molecular underpinnings to biomechanical ...

4. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0259450

A phase II randomised, controlled clinical trial | PLOS One Personalised pacemaker reprogramming was guided by a published protocol. Primary outcome was change in LV ejection fraction on echocardiography after 6 months.

5. academic.oup.com academic.oup.com/europace/article/15/11/1609/505431

Cardiac resynchronization therapy in pacemaker-dependent ... The aim was to determine if cardiac resynchronization therapy (CRT) at the time of pulse generator replacement (PGR) is of benefit in patients with unavoidable ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9996402/

Effect of Personalized Accelerated Pacing on Quality of Life ... In this study, among patients with HFpEF and pacemakers, treatment with a moderately accelerated, personalized pacing rate was safe and improved ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8859799/

Personalized pacing for diastolic dysfunction and heart failure ... The study uses a novel personalized heart rate algorithm to provide a customized lower rate setting for pacemaker patients. ▫. The findings ...

8. cardioaragon.com cardioaragon.com/wp-content/uploads/The-myPACE-Randomized-Clinical-Trial.jamacardiology2023.pdf

The myPACE Randomized Clinical Trial The personalized accelerated pacing heart rate was calculated using a resting heart rate algorithm based on height and modified by ejection.