Pacing Rates for Atrial Fibrillation

(OPT-RATE AF Trial)

Recruiting at 6 trial locations

Overseen By Sarahfaye Dolman

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medstar Health Research Institute

Disqualifiers: Severe CAD, ESRD, Pulmonary disease, others

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

Compensation: Varies

Number of Visits: 2

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether setting a pacemaker to 80 beats per minute (bpm) helps individuals with atrial fibrillation (irregular heartbeat) walk longer distances. Participants will have their pacing rate set to either 60 bpm or 80 bpm for three months and then switch. Ideal candidates have experienced atrial fibrillation for some time, have a pacemaker or similar device implanted, and have a history of limited exercise ability due to their condition. As an unphased trial, this study provides participants the chance to contribute to innovative research that could enhance exercise capacity for those with atrial fibrillation.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that these pacing rates are safe for atrial fibrillation patients?

Research has shown that heart pacing rates of 60 and 80 beats per minute (bpm) are generally safe and well-tolerated. Specifically, no evidence of harmful effects has been found for the 60 bpm rate, suggesting its safety, especially since it is often used in heart treatments.

For the 80 bpm rate, studies indicate that a slightly faster pace can improve the quality of life for some patients, confirming its safety with no major problems reported.

Both pacing rates are commonly used in treatments and have not raised significant safety concerns, providing confidence in their tolerance by patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how different pacing rates might influence atrial fibrillation treatment outcomes. Unlike traditional approaches that often rely on medication or more invasive procedures, this method uses a non-invasive technique to adjust heart rhythms. By testing two pacing rates—60 bpm and 80 bpm—researchers aim to discover if changing the heart's pacing can improve symptoms or reduce complications associated with atrial fibrillation. This could offer a more tailored and potentially safer option for patients, providing new insights into managing this common heart condition.

What evidence suggests that this trial's pacing rates could be effective for improving exercise tolerance in atrial fibrillation?

Research shows that the speed at which the heart is paced can impact heart health in people with atrial fibrillation (AF). This trial will compare two pacing strategies: one group will start at 60 beats per minute (bpm) for the first 3 months, then switch to 80 bpm for the next 3 months, while another group will start at 80 bpm and then switch to 60 bpm. Studies suggest that setting the pace at 80 bpm can enhance heart function and improve quality of life. For example, one study found that slightly faster pacing rates led to better heart health and overall well-being. In contrast, pacing the heart at 60 bpm has less evidence supporting its benefits for AF patients. While both pacing rates are used, research suggests that 80 bpm might offer better advantages for heart function and exercise ability. ^{4 6 7 8 9}

Who Is on the Research Team?

Athanasios Thomaides, MD

Principal Investigator

MedStar Health

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a history of atrial fibrillation, heart failure or NYHA class II or higher. They must have had CRT or pacing system implantation within the last 3-5 years and not be pregnant, in palliative care, or have life-threatening conditions like severe cardiomyopathy, end-stage renal disease, uncontrolled hypertension, significant lung disease on oxygen therapy, end stage cancer diagnosis.

Inclusion Criteria

LVEF ≥ 50%

N-terminal pro-B-type natriuretic peptide (NT-proBNP) >400 pg/mL in the last 24 months

Able to provide informed consent

Exclusion Criteria

Ventricular ectopy >15% premature ventricular contractions (PVC)

Hemoglobin <7 g/dL

I have been diagnosed with infiltrative cardiomyopathy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Participants receive a pacing rate of either 60 bpm or 80 bpm for the first 3 months

3 months

1 visit (in-person) at baseline, 1 visit (in-person) at 3 months

Treatment Phase 2

Participants switch to the alternate pacing rate (80 bpm or 60 bpm) for the next 3 months

3 months

1 visit (in-person) at 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Pacing rate of 60 bpm
• Pacing rate of 80 bpm

Trial Overview The study aims to see if setting a cardiac pacemaker to work at 80 beats per minute (bpm) improves patients' quality of life compared to the standard rate of 60 bpm. Participants will experience both rates for three months each in a randomized order to compare effects.

How Is the Trial Designed?

Group I: 80 bpm, then 60 bpm Experimental Treatment 2 Interventions

Pacing rate of 80 bpm for the first 3 months, then switch to 60 bpm for the next 3 months.

Group II: 60 bpm, then 80 bpm Experimental Treatment 2 Interventions

Pacing rate of 60 bpm for the first 3 months, then switch to 80 bpm for the next 3 months.

Pacing rate of 60 bpm is already approved in European Union, United States for the following indications:

Approved in European Union as Cardiac Resynchronization Therapy (CRT) for:

• Heart failure with reduced ejection fraction
• Left bundle branch block

Approved in United States as Cardiac Resynchronization Therapy (CRT) for:

• Heart failure with reduced ejection fraction
• Left bundle branch block

Who Is Running the Clinical Trial?

Medstar Health Research Institute

Lead Sponsor

Trials

202

Recruited

187,000+

Medtronic

Industry Sponsor

Trials

627

Recruited

767,000+

Geoff Martha

Medtronic

Chief Executive Officer since 2020

Finance degree from Penn State University

Dr. Richard Kuntz

Medtronic

Chief Medical Officer since 2023

MD, MSc

Published Research Related to This Trial

In patients with atrial fibrillation receiving cardiac resynchronization therapy, achieving over 98% biventricular pacing is associated with significant improvements in heart function and reduced mortality.

Continuous monitoring of biventricular pacing has enhanced the management of these patients and raised new questions regarding the need for anticoagulant therapy, particularly for those at high risk of thromboembolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous monitoring of atrial fibrillation in heart failure. Herweg, B., Barold, SS., Steinberg, JS.[2013]

In a study of 16 patients with congestive heart failure and permanent atrial fibrillation, upgrading to biventricular pacing significantly improved heart function and symptoms after a mean follow-up of 20 months.

Key improvements included a 5% reduction in cardiothoracic ratio, an 8% decrease in end-systolic diameter, and a 40% reduction in mitral regurgitation area, indicating enhanced left ventricular performance despite unchanged exercise test results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of upgrading to biventricular pacing in patients with right ventricular pacing and congestive heart failure after atrioventricular junctional ablation for chronic atrial fibrillation. Valls-Bertault, V., Fatemi, M., Gilard, M., et al.[2007]

In a study of 50 heart failure patients using biventricular pacing, those receiving cardiac resynchronization therapy (CRT) showed significantly higher heart rate variability (HRV) compared to those not receiving therapy, indicating improved autonomic control of heart rate.

The increase in HRV suggests that CRT enhances cardiac autonomic balance, making it less reliant on sympathetic activation, which could lead to better overall heart function and patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac resynchronization therapy improves heart rate variability in patients with symptomatic heart failure. Adamson, PB., Kleckner, KJ., VanHout, WL., et al.[2016]

In a study of 379 patients receiving cardiac resynchronization therapy (CRT), a history of atrial fibrillation (AF) was common and linked to worse outcomes, but it did not independently predict mortality or heart transplantation.

Achieving biventricular pacing (BivP) of more than 98% during the first year of CRT treatment is crucial, as BivP levels at or below this threshold were associated with a significantly higher risk of death or heart transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atrial fibrillation incidence and impact of biventricular pacing on long-term outcome in patients with heart failure treated with cardiac resynchronization therapy. Jacobsson, J., Reitan, C., Carlson, J., et al.[2020]

A high percentage of biventricular pacing (BIV%) is crucial for improving mortality rates in patients with atrial fibrillation (AF) undergoing cardiac resynchronization therapy (CRT), with the optimal BIV% cut-point identified as 98.7%. Patients with BIV% >99.6% experienced a significant 24% reduction in mortality.

The CERTIFY trial supports the effectiveness of AV junctional (AVJ) ablation in CRT patients with AF, showing that this procedure can improve mortality rates to levels similar to those in patients with normal sinus rhythm, although it carries risks such as device failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac Resynchronization in Patients with Atrial Fibrillation. Barold, SS., Herweg, B.[2020]

In a study of 174 heart failure patients treated with cardiac resynchronization therapy (CRT), those who experienced device-detected atrial fibrillation (AF) had significantly lower optimal biventricular (BiV) pacing (42.1%) compared to those without AF (75.2%), indicating that AF negatively impacts pacing effectiveness.

Patients with device-detected AF also faced worse clinical outcomes, including higher rates of heart failure hospitalization, cardiovascular death, and all-cause mortality, highlighting the importance of managing AF in heart failure patients undergoing CRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Implications of Device-Detected Atrial Fibrillation in Cardiac Resynchronization Therapy. Yoon, M., Oh, J., Chun, KH., et al.[2023]

In a study involving 12 patients with non-ischemic heart failure, increasing the pacing rate from DDD-60 to DDD-80 for 3 months significantly reduced sympathetic nerve activity, indicating a potential benefit for autonomic function.

Despite the reduction in sympathetic activity with DDD-80 pacing, patients reported better quality of life scores with the lower pacing rate (DDD-60), suggesting that higher pacing rates may not be as well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal Cardiac Resynchronization Therapy Pacing Rate in Non-Ischemic Heart Failure Patients: A Randomized Crossover Pilot Trial. Ghotbi, AA., Sander, M., Køber, L., et al.[2018]

The PEGASUS CRT study is a large multicenter trial involving approximately 1200 heart failure patients with CRT defibrillators, aimed at evaluating the clinical benefits of empiric atrial support pacing over one year.

Patients will be randomized to different pacing modes to assess impacts on mortality, heart failure events, quality of life, and exercise capacity, providing insights into the effectiveness of atrial pacing in improving outcomes for heart failure patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pacing Evaluation-Atrial SUpport Study in Cardiac Resynchronization Therapy (PEGASUS CRT): design and rationale. Martin, DO., Stolen, KQ., Brown, S., et al.[2007]

In a study of 40 patients with permanent atrial fibrillation undergoing triple-site (Tri-V) pacing Cardiac Resynchronization Therapy (CRT), the responder rate increased to 79% after 12 months, which is significantly higher than typical response rates for standard CRT.

Tri-V CRT also improved patients' quality of life and heart function, with a notable increase in ejection fraction from 26% to 41% over one year, and a survival rate free from heart failure hospitalization of 87.9%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triple-site pacing for cardiac resynchronization in permanent atrial fibrillation: follow-up results from a prospective observational study. Marques, P., Nobre Menezes, M., Lima da Silva, G., et al.[2019]

In a study of 96 patients with heart failure undergoing cardiac resynchronization therapy (CRT), those who responded to CRT showed a significant reduction in left atrial size and a decrease in the incidence of persistent atrial fibrillation (AF) after six months.

CRT responders had a shorter mean duration of AF compared to non-responders, indicating that effective CRT can lead to improvements in atrial remodeling and potentially reduce AF duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac resynchronization therapy response is associated with shorter duration of atrial fibrillation. Lellouche, N., De Diego, C., Vaseghi, M., et al.[2007]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5135194/

Cardiac Resynchronization in Patients with Atrial Fibrillation The greatest mortality reduction in CRT patients with AF occurs with BIV% pacing ≥ 97-98%. One should always aim for a BIV% pacing of 100%.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2666501821001653

Atrial fibrillation in cardiac resynchronization therapy Significant improvements in biventricular pacing percentage, LV ejection fraction, and NYHA class were demonstrated and 67% of patients were free from AF at 24 ...

3. heartrhythmjournal.com heartrhythmjournal.com/article/S1547-5271(24)02910-2/fulltext

Ineffective cardiac resynchronization pacing is associated ... While it is well known that decreased pacing percentage is associated with decreased survival in patients with CRT devices, ineffective pacing ...

4. innovationsincrm.com innovationsincrm.com/cardiac-rhythm-management/2011/december-2011/165-maximizing-cardiac-resynchronization-therapy-af-patientss

Maximizing Cardiac Resynchronization Therapy in Patients ... As expected, patients with atrial fibrillation (AF) had a worse outcome than those without AF. However, this was lessened if the high percentage of BiV pacing ...

5. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.123.067465

Arrhythmic Risk in Biventricular Pacing Compared With Left ... Left bundle branch area pacing was also associated with significantly lower incidence of new-onset atrial fibrillation compared with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06445439

Optimal Pacing Rate for Cardiac Resynchronization Therapy Pacing rate of 60 bpm for the first 3 months, then switch to 80 bpm for the next 3 months. Pacing rate of 80 bpm for the first 3 months, then switch to 60 bpm ...

7. heartrhythmjournal.com heartrhythmjournal.com/article/S1547-5271(23)02026-X/fulltext

2023 HRS/APHRS/LAHRS guideline on cardiac ... Patients undergoing pacemaker implant who are expected to require substantial ventricular pacing (≥ 20%–40%) may be considered for CPP to reduce ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3382419/

Biventricular Pacing (Cardiac Resynchronization Therapy) The goal of treatment with BiV pacing is to improve cardiac output for people in heart failure (HF) with conduction defect on ECG (wide QRS interval)

9. sciencedirect.com sciencedirect.com/science/article/pii/S1547527124029102

Ineffective cardiac resynchronization pacing is associated ... This study aims to determine whether loss of effective CRT pacing is associated with adverse outcomes in CRT recipients.