Pacing Rates for Atrial Fibrillation

(OPT-RATE AF Trial)

Recruiting at 4 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

Trial Summary

What is the purpose of this trial?

This is a prospective, randomized crossover study. The objective of the study is to determine if a pacing rate of 80 beats per minute (bpm) improves exercise tolerance during the 6-minute walk test. The investigators will randomly assign half of the participants to a starting rate of 60 bpm and then switch them to a rate of 80 bpm for 3 months, and vice versa.

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 data supports the effectiveness of the treatment Pacing Rates for Atrial Fibrillation?

Research shows that effective biventricular pacing (pacing both sides of the heart) is crucial for the success of cardiac resynchronization therapy (CRT) in patients with heart failure. A high percentage of biventricular pacing, especially over 98%, is linked to better outcomes and reduced mortality, even in patients with atrial fibrillation. ^{1 2 3 4 5}

Is biventricular pacing safe for humans?

Biventricular pacing, used in cardiac resynchronization therapy (CRT), has been studied in patients with heart failure and atrial fibrillation. While the studies focus on effectiveness, they suggest that maintaining a high percentage of biventricular pacing is important for positive outcomes, indicating it is generally safe when properly managed. ^{1 3 6 7 8}

How does the pacing rate treatment for atrial fibrillation differ from other treatments?

This treatment uses specific pacing rates (60 bpm and 80 bpm) as part of Cardiac Resynchronization Therapy (CRT) to improve heart function in patients with atrial fibrillation (AF) and heart failure. It focuses on achieving a high percentage of biventricular pacing, which is crucial for the success of CRT, especially in patients with AF, where maintaining effective pacing can be challenging. ^{1 3 4 9 10}

Research Team

Athanasios Thomaides, MD

Principal Investigator

MedStar Health

Eligibility Criteria

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

Hemoglobin <7 g/dL

Ventricular ectopy >15% premature ventricular contractions (PVC)

I have been diagnosed with infiltrative cardiomyopathy.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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 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 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 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]

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]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Clinical Implications of Device-Detected Atrial Fibrillation in Cardiac Resynchronization Therapy. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Cardiac resynchronization therapy improves heart rate variability in patients with symptomatic heart failure. [2016]

3. England 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. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Cardiac Resynchronization in Patients with Atrial Fibrillation. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Pacing Evaluation-Atrial SUpport Study in Cardiac Resynchronization Therapy (PEGASUS CRT): design and rationale. [2007]

6. England 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. [2007]

7. United States pubmed.ncbi.nlm.nih.gov

Continuous monitoring of atrial fibrillation in heart failure. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Optimal Cardiac Resynchronization Therapy Pacing Rate in Non-Ischemic Heart Failure Patients: A Randomized Crossover Pilot Trial. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Triple-site pacing for cardiac resynchronization in permanent atrial fibrillation: follow-up results from a prospective observational study. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Cardiac resynchronization therapy response is associated with shorter duration of atrial fibrillation. [2007]