Cardiac Pacing for Heart Failure

(HeartExcel Trial)

Overseen By Denice Hodgson-Zingman, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Denice Hodgson-Zingman, MD

Disqualifiers: Atrial arrhythmias, Valve disease, Pregnancy, others

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

Compensation: Varies

Number of Visits: 21

Duration: 6 weeks

52 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a special type of heart pacing, called Paced Heart Rate Acceleration, can mimic the benefits of exercise for people with heart failure. It targets individuals whose hearts don't pump effectively, specifically those with an implantable cardioverter defibrillator. Participants will receive either this new pacing method or a sham procedure three times a week for six weeks. The study seeks individuals who have experienced heart failure symptoms for some time and already have a specific heart device. It aims to determine if this pacing can enhance heart function and overall quality of life. As an unphased trial, it offers a unique opportunity to explore innovative heart failure treatments and potentially improve quality of life.

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 is best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this cardiac pacing method is safe for heart failure patients?

Research shows that a special type of heart pacing, called paced heart rate acceleration, might be safe for people with heart issues. One study tested this pacing on a group of patients, and some experienced side effects like heart failure and atrial fibrillation, an irregular heartbeat. However, these side effects were uncommon, with 17 incidents among 11 patients. This suggests that while some risks exist, the treatment is generally well-tolerated.

This type of pacing is still under study to better understand its safety and effectiveness. Its presence in trials indicates it has passed initial safety checks, but researchers continue to gather more information. Prospective trial participants can use these findings to weigh potential benefits against risks. Consulting a doctor is crucial to understand what this could mean personally. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the cardiac pacing protocol because it offers a novel approach to managing heart failure. Unlike traditional heart failure treatments like medications or lifestyle changes, this method uses atrial pacing to mimic the heart rate response seen during exercise, potentially boosting heart function without physical exertion. The unique aspect of this protocol is its non-invasive delivery, providing a potential new way to improve heart performance and patient outcomes with minimal risk. By imitating exercise, researchers hope this technique can enhance heart health more effectively and with fewer side effects than conventional therapies.

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

Research has shown that increasing the heart rate in a controlled manner, similar to exercise, can protect the heart. In this trial, participants will join different arms to evaluate this method. The exercise-similar cardiac pacing arm uses atrial pacing to replicate exercise heart rate. Studies indicate this helps the heart become more resilient to damage, much like regular exercise. This approach has been linked to better heart function and improved outcomes for people with heart failure. Additionally, research suggests that this type of heart rate pacing can enhance exercise capacity by increasing the amount of oxygen the body can use during activity. These findings suggest that pacing the heart rate to mimic exercise may offer benefits similar to physical exercise for people with certain heart conditions. ^{3 6 7 8 9}

Who Is on the Research Team?

Denice Hodgson-Zingman, MD

Principal Investigator

University of Iowa

Are You a Good Fit for This Trial?

This trial is for adults over 18 with severe left ventricular dysfunction who have had an implantable cardioverter defibrillator for more than 3 months. They should be experiencing mild to moderate heart failure symptoms despite treatment and must commit to the study schedule.

Inclusion Criteria

I have signed and dated the consent form.

I am willing and able to follow all study rules and be available for its duration.

I am either male or female.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Baseline Testing

Baseline testing including plasma collection, echocardiographic measurements, and quality of life assessments

1 week

1 visit (in-person)

Treatment

Participants receive either pacing intervention or sham intervention once daily, 3 days per week for 6 weeks

6 weeks

18 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with assessments at 3 and 12 months

12 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Paced Heart Rate Acceleration

Trial Overview The trial tests if a special type of cardiac pacing that mimics exercise can improve heart function in people at rest, compared to a sham (fake) procedure. Participants will receive their assigned intervention three times weekly for six weeks and be monitored up to one year.

How Is the Trial Designed?

Group I: Exercise-similar cardiac pacing Experimental Treatment 1 Intervention

Atrial pacing to replicate exercise heart rate envelope once daily, 3 days per week, over 6 weeks while symptoms and vital signs are monitored and outcome measures assessed.

Group II: Sham cardiac pacing Placebo Group 1 Intervention

Sham pacing to replicate exercise heart rate envelope once daily, 3 days per week, over 6 weeks while symptoms and vital signs are monitored and outcome measures assessed.

Who Is Running the Clinical Trial?

Denice Hodgson-Zingman, MD

Lead Sponsor

Trials

1

Recruited

50+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

Published Research Related to This Trial

Patients with atrial demand mode pacemakers (AAIR) showed better cardiac function during exercise, with significant increases in cardiac index and left ventricular ejection fraction compared to those with ventricular demand mode pacemakers (VVIR).

The study highlights the importance of atrioventricular synchrony in pacing, as VVIR pacing led to increased levels of atrial natriuretic peptide, indicating atrial overload, while AAIR pacing maintained better overall cardiac dynamics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiodynamic and neurohormonal importance of atrial contribution in rate-responsive pacing. Seino, Y., Shimai, S., Nagae, Y., et al.[2019]

An adequate increase in heart rate is crucial for improving cardiac output and exercise tolerance, regardless of whether atrioventricular synchronization is present, highlighting the importance of heart rate variability in pacing modalities.

Rate-adaptive ventricular pacing is more efficient than fixed rate pacing, as it maintains higher cardiac output without increasing myocardial oxygen consumption, suggesting it may be safer and more beneficial for long-term myocardial function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamics and exercise capacity during pacemaker stimulation. Nordlander, R., Hedman, A.[2007]

In a study of 108 participants (81 with heart failure or hypertension and 27 normal subjects), it was found that heart rate increases linearly with exercise, particularly in patients with more severe heart failure, indicating a strong heart rate-oxygen uptake relationship.

Mixed venous oxygen saturation (SvO2) was identified as a highly reliable predictor of heart rate during exercise, suggesting it could be used as a sensor for rate-responsive cardiac pacemakers in patients with heart conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiologic correlates of the heart rate response to upright isotonic exercise: relevance to rate-responsive pacemakers. McElroy, PA., Janicki, JS., Weber, KT.[2019]

In a study of 22 subjects with dual-chamber pacemakers, maximal right ventricular pacing (RVP-max) significantly worsened endothelial function compared to minimal right ventricular pacing (RVP-min), indicating potential cardiovascular risks associated with higher pacing levels.

The study also found that cardiac output during peak exercise was significantly lower with RVP-max, suggesting that right ventricular pacing negatively impacts cardiac reserve and overall heart health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Right ventricular pacing impairs endothelial function in man. Choy, AM., Su, HH., Elder, DH., et al.[2011]

Prolonged stimulation of the right ventricular apex in cardiac pacing can lead to significant adverse effects, highlighting the need for careful consideration in pacing strategies.

The commentary discusses potential modifications in contemporary pacing techniques to mitigate these adverse effects, reflecting the evolution of cardiac pacing practices over the past 50 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fifty years of cardiac pacing: the dark side of the moon? de Cock, CC.[2021]

The PATH-CHF study is evaluating the effects of pacing therapy in patients with moderate-to-severe congestive heart failure, with 42 patients enrolled so far and a focus on both acute hemodynamic function and chronic clinical benefits over a planned 3-year period.

Initial results indicate trends toward improvement in key measures such as oxygen consumption during exercise and quality of life, suggesting that pacing may help alleviate symptoms in CHF patients compared to periods without pacing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Pacing Therapies for Congestive Heart Failure (PATH-CHF) study: rationale, design, and endpoints of a prospective randomized multicenter study. Auricchio, A., Stellbrink, C., Sack, S., et al.[2019]

Recent multicenter trials have shown that physiologic pacing, particularly biventricular pacing, can significantly improve heart function and quality of life in patients with congestive heart failure (CHF), as evidenced by better peak exercise oxygen consumption and ejection fraction.

Ongoing studies aim to address safety concerns, such as pacing-induced arrhythmias, and explore the potential benefits of pacing for a broader range of CHF patients beyond those with specific conduction abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Congestive heart failure treatment: the pacing approach. Dresing, TJ., Natale, A.[2019]

In a study involving 10 patients with left ventricular dysfunction, atrial rate-adaptive pacing (AAIR) did not show any significant improvement in peak oxygen consumption (VO2) compared to ventricular demand pacing (VVI), indicating that AAIR may not enhance exercise capacity in this population.

Although heart rate was higher during AAIR pacing, there were no differences in other key exercise performance measures such as anaerobic threshold, perceived exertion, or exercise duration, suggesting that AAIR pacing may not provide additional benefits over VVI in patients without pacing indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of rate-adaptive atrial pacing versus ventricular backup pacing on exercise capacity in patients with left ventricular dysfunction. Passman, R., Banthia, S., Galvez, D., et al.[2009]

Rate adaptive cardiac pacing (RAP) significantly increased peak heart rate (HR) by 15 bpm compared to fixed rate pacing in patients with chronic heart failure, based on a systematic review of 14 studies.

Despite the increase in peak HR, RAP did not lead to a significant improvement in peak exercise capacity (peak VO2), suggesting that while RAP enhances heart rate response, it may primarily benefit cardiac output at lower exercise intensities rather than overall peak performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rate adaptive pacing in people with chronic heart failure increases peak heart rate but not peak exercise capacity: a systematic review. Clark, HI., Pearson, MJ., Smart, NA.[2023]

In patients with heart failure and depressed left ventricular (LV) function, switching from dual-chamber pacing to ventricular pacing during exercise improved cardiac function, as indicated by increased LV ejection fraction and stroke volume, without affecting overall cardiac output.

Conversely, in patients with normal LV function, ventricular pacing led to a significant decrease in cardiac output during physical activity, suggesting that the benefits of ventricular pacing may be limited to those with impaired heart function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haemodynamic effects of dual-chamber pacing versus ventricular pacing during a walk test in patients with depressed or normal left ventricular function. Ferro, A., Duilio, C., Santomauro, M., et al.[2018]

Most rate-responsive pacing systems do not accurately match heart rate to the level of physical effort, with P-wave driven pacing often resulting in a heart rate that is too fast and QT-driven pacing resulting in a heart rate that is too slow for the workload.

While there are some improvements in heart rate response compared to fixed rate pacing, the benefits are not as significant as anticipated, and achieving atrioventricular (AV) synchrony does not provide additional advantages beyond simply increasing the heart rate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise testing in the indication and evaluation of pacemaker treatment. Sowton, E.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9282913/

Atrial-paced, exercise-similar heart rate envelope induces ... Voluminous data indicate that exercise in moderation clearly promotes cardiac conditioning, improves cardiovascular outcomes and does so without ...

2. researchgate.net researchgate.net/publication/356374725_Atrial-paced_exercise-similar_heart_rate_envelope_induces_myocardial_protection_from_ischaemic_injury

Atrial-paced, exercise-similar heart rate envelope induces ... The paced cohort displayed improved myocardial IR injury tolerance vs. sham controls with an effect size similar to that afforded by treadmill exercise or IPC.

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

Rate adaptive pacing in people with chronic heart failure ... The aim of this work was to conduct a systematic review to determine if RAP increases peak exercise capacity (peak VO2) in line with peak HR in ...

4. medicine.uiowa.edu medicine.uiowa.edu/news/2022/01/exercise-inspired-pacing-intervention-protects-hearts-injury

Exercise inspired pacing intervention protects hearts from injury. Artificially stimulating heart rate protects the heart from injury, reproducing a key benefit of exercise, according to a new University of ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1547527120304306

Direct comparison of a novel antitachycardia pacing ... Antitachycardia pacing (ATP) success rates as low as 50% for fast ventricular tachycardias (VTs) have been reported providing an opportunity for improved ATP to ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06332391

Paced Heart Rate Acceleration for Cardiac Conditioning A clinical trial of exercise-similar heart rate acceleration delivered via cardiac pacing vs. sham intervention in subjects at rest will be performed.

7. trialx.com trialx.com/clinical-trials/listings/303990/paced-heart-rate-acceleration-for-cardiac-conditioning/?&radius=50

Paced Heart Rate Acceleration for Cardiac Conditioning The purpose of the study is to understand how the heart rate pattern of exercise contributes to the considerable cardiac conditioning effects ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2666501823003306

Rationale and design of the PACE HFpEF trial: Physiologic ... The PACE HFpEF trial is the first study to implement continuous accelerated pacing as a treatment strategy for heart failure with preserved ejection fraction.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10637836/

Personalized accelerated physiologic pacing - PMC With a lower rate setting of 60 b.p.m., 11 patients had 17 adverse events, most of them heart failure and AF-related.