Catheter Ablation + HF Therapies for Heart Failure and Atrial Fibrillation

(TAP-CHF Trial)

Recruiting at 9 trial locations

Overseen By Sanjeev Saksena, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Electrophysiology Research Foundation

Must be taking: Heart failure drugs

Must not be taking: ACE inhibitors, ARBs

Disqualifiers: Uncontrolled hypertension, Recent stroke, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

360 Participants Needed

Trial Summary

What is the purpose of this trial?

Heart failure (HF) with preserved left ventricular function (pEF) is difficult clinical syndrome to treat effectively with few evidence based therapies. Atrial fibrillation (AF) is now an important co-morbidity being observed in 43% of patients with HFpEF. Rhythm control has not been studied in this population. Catheter ablation and antiarrhythmic drugs are rhythm control therapies that have been used for treatment of AF without HF or HF with reduced systolic function but have not been widely applied in HFpEF. No controlled comparative evaluation has been performed in HFpEF. The introduction of wireless pulmonary artery hemodynamic monitoring has permitted optimization of HF therapy in patients with chronic HF with reduced and preserved EF. Reduction in HF hospitalizations has been observed in post hoc analyses of HFpEF patients but has not been systematically applied in AF patients with HFpEF. In this study, we propose to study both rhythm control and optimized HF therapeutic approaches in an AF with HFpEF study population in a pilot study using a sequential two phase randomized controlled clinical trial design.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications. However, you must be on standard heart failure drug therapy for at least 30 days before joining the study.

What data supports the effectiveness of catheter ablation treatment for heart failure and atrial fibrillation?

Research shows that catheter ablation, a treatment that uses energy to make small scars in your heart tissue to stop abnormal electrical signals, is more effective than drugs at maintaining normal heart rhythm in patients with both heart failure and atrial fibrillation. It has been associated with improved clinical outcomes, such as reduced hospitalizations and mortality, compared to drug treatments. ^{1 2 3 4 5}

Is catheter ablation safe for treating atrial fibrillation in heart failure patients?

Catheter ablation is generally considered safe for treating atrial fibrillation, especially in patients with heart failure, and is often preferred over antiarrhythmic drugs due to fewer side effects. However, the long-term impact on overall health and survival is still being studied. ^{4 5 6 7 8}

How is catheter ablation different from other treatments for atrial fibrillation and heart failure?

Catheter ablation is unique because it directly targets and removes the heart tissue causing abnormal rhythms, which can be more effective than drugs in maintaining normal heart rhythm and reducing heart failure-related mortality. Unlike antiarrhythmic drugs, which can have side effects, catheter ablation has shown higher success rates in restoring and maintaining sinus rhythm, especially in patients with heart failure. ^{1 2 3 4 9}

Research Team

Sanjeev Saksena, MD

Principal Investigator

Electrophysiology Research Foundation

Andrea Natale, MD

Principal Investigator

Electrophysiology Research Foundation

Eligibility Criteria

This trial is for outpatients over 50 with heart failure and preserved cardiac function (HFpEF) who also have atrial fibrillation. They must be on heart failure drugs for at least a month, eligible for catheter ablation, antiarrhythmic drug therapy, and long-term anticoagulation. Excluded are those with reversible cardiomyopathies, recent acute coronary issues or myocardial infarction, contraindications to anticoagulants, life expectancy under a year, uncontrolled hypertension or significant other medical conditions.

Inclusion Criteria

I have heart failure with preserved ejection fraction and irregular heartbeats.

I was hospitalized for heart failure or atrial fibrillation in the last year and have high NT-pro BNP levels.

Your heart has certain measurements that show it may not be working properly.

Exclusion Criteria

I have heart failure with preserved ejection fraction and either am not on heart failure drugs or have very high blood pressure despite treatment.

I cannot take blood thinners due to health risks or bad reactions in the past.

You haven't been following medical instructions or have social issues that make it hard for you to have regular check-ups, or you have had alcohol or drug problems in the past year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Participants undergo either catheter ablation or antiarrhythmic drug therapy for atrial fibrillation with preserved systolic function

9 months

Multiple visits for procedure and monitoring

Phase 2 Treatment

Participants receive either guided heart failure therapy with hemodynamic monitoring or empiric heart failure therapy

9 months

Multiple visits for monitoring and therapy adjustment

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• Catheter ablation
• Empiric heart failure drug therapy
• Insertion of CardioMems Hemodynamic monitor
• Rate or Rhythm control antiarrhythmic drugs for atrial fibrillation

Trial Overview The study tests rhythm control therapies like catheter ablation and antiarrhythmic drugs against optimized heart failure treatments in patients with both HFpEF and atrial fibrillation. It uses wireless pulmonary artery monitoring to optimize treatment. The design is a two-phase randomized controlled pilot trial comparing these approaches.

Participant Groups

Group I: Phase 1 Catheter Ablation Active Control 1 Intervention

Patients with atrial fibrillation and heart failure with preserved systolic function will be enrolled after informed consent. They randomly assigned to catheter ablation as one arm. They will undergo a catheter ablation procedure within 14 days of randomization. This procedure will include isolation of all four pulmonary veins in the antrum using catheter delivered radiofrequency current, cryothermal or laser ablation energy with standard FDA approved ablation catheter systems used in atrial fibrillation ablation. Patients will be monitored for a minimum period of 9 months after the catheter ablation intervention.

Group II: Phase 1 Antiarrhythmic drug therapy Active Control 1 Intervention

Patients with atrial fibrillation and heart failure with preserved systolic function will be enrolled after informed consent. They will be randomly assigned to antiarrhythmic drug therapy for Rate or Rhythm control in this arm. They will undergo drug dose titration within 14 days of randomization. . Patients will be monitored for a minimum period of 9 months after the AAD therapy initiation

Group III: Phase 2 Guided Heart Failure Therapy Active Control 1 Intervention

Patients with atrial fibrillation and heart failure with preserved systolic function will be enrolled after informed consent and completion of Phase 1. They will be randomly assigned to insertion of an implantable hemodynamic monitor in this arm and heart failure therapy guided by wireless hemodynamic monitoring. Patients will be monitored for a minimum period of 9 months after the implantable hemodynamic monitor insertion on guided drug therapy

Group IV: Phase 2 Empiric Heart Failure Therapy Active Control 1 Intervention

Patients with atrial fibrillation and heart failure with preserved systolic function will be enrolled after informed consent and completion of Phase 1. They will be randomly assigned to heart failure management with empirical selection of heart failure therapy. Patients will be monitored for a minimum period of 9 months after the initiation of empirically selected heart failure drug therapy

Catheter ablation is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Catheter ablation for:

• Atrial fibrillation
• Supraventricular tachycardia
• Ventricular tachycardia

Approved in United States as Catheter ablation for:

• Atrial fibrillation
• Supraventricular tachycardia
• Ventricular tachycardia

Approved in Canada as Catheter ablation for:

• Atrial fibrillation
• Supraventricular tachycardia
• Ventricular tachycardia

Approved in Japan as Catheter ablation for:

• Atrial fibrillation
• Supraventricular tachycardia
• Ventricular tachycardia

Who Is Running the Clinical Trial?

Electrophysiology Research Foundation

Lead Sponsor

Trials

2

Recruited

370+

Findings from Research

In a study involving 411 patients with high-burden atrial fibrillation and heart failure, ablation-based rhythm control showed a trend towards improved clinical outcomes compared to rate control, although it did not reach statistical significance for all-cause mortality or heart failure events.

Patients receiving ablation-based rhythm control experienced significant improvements in left ventricular ejection fraction, walking distance, and quality of life measures, suggesting potential benefits in heart function and patient well-being despite the overall primary outcome not being statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Ablation-Based Rhythm-Control Versus Rate-Control Trial in Patients With Heart Failure and Atrial Fibrillation: Results from the RAFT-AF trial. Parkash, R., Wells, GA., Rouleau, J., et al.[2022]

Recent evidence indicates that the treatment strategy for atrial fibrillation (AF) can significantly affect the survival of patients with heart failure (HF), suggesting that rhythm control may be more beneficial than previously thought.

Catheter ablation of AF in HF patients has been associated with a reduction in HF-related mortality, making it a preferred treatment option over traditional medical therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Catheter ablation of atrial fibrillation-A key role in heart failure therapy? Tose Costa Paiva, B., Fischer, TH., Brachmann, J., et al.[2021]

Catheter ablation is a more effective treatment for maintaining sinus rhythm in patients with atrial fibrillation and heart failure compared to traditional antiarrhythmic drug treatments, which do not show superior results.

While some trials indicate that catheter ablation may reduce hospitalization and mortality rates, further studies are necessary to fully understand its benefits and address existing gaps in research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Clinical Trials of Catheter Ablation of Atrial Fibrillation in Congestive Heart Failure: Knowns and Unmet Needs. Terricabras, M., Piccini, JP., Verma, A.[2019]

Catheter ablation of atrial fibrillation (AF) in patients with heart failure and reduced ejection fraction (HFrEF) significantly improves clinical outcomes compared to pharmacological rhythm control, which shows no added benefit over rate control.

The higher success rates of catheter ablation in restoring and maintaining normal heart rhythm, along with the side effects associated with antiarrhythmic drugs, highlight the need for optimizing ablation techniques for better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Outcome of Pulmonary Vein Isolation Versus Amiodarone Therapy in Patients with Coexistent Persistent AF and Congestive Heart Failure. Faggioni, M., Della Rocca, DG., Mohanty, S., et al.[2020]

Both rhythm control and rate control strategies are acceptable for managing atrial fibrillation (AF), with no clear superiority of one over the other, especially in patients with heart failure.

Catheter ablation techniques, such as radiofrequency and cryotherapy, have shown to be more effective in maintaining sinus rhythm and reducing symptoms compared to antiarrhythmic drugs, particularly in younger patients, although their long-term impact on morbidity and mortality remains to be established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cardiac rhythm management of patients with atrial fibrillation]. Tréguer, F.[2021]

A systematic review of five trials involving 994 patients showed that catheter ablation significantly reduces the recurrence of atrial tachyarrhythmias and symptomatic atrial fibrillation compared to anti-arrhythmic drugs, with odds ratios of 0.36 and 0.32 respectively.

Catheter ablation also led to fewer hospitalizations (odds ratio 0.25) without a significant increase in symptomatic bradycardia, indicating it is a more effective first-line treatment for rhythm control in patients with symptomatic atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Catheter Ablation is Superior to Antiarrhythmic Drugs as First-Line Treatment for Atrial Fibrillation: a Systematic Review and Meta-Analysis. Cardoso, R., Justino, GB., Graffunder, FP., et al.[2022]

Atrial fibrillation (AF) is the most common arrhythmia, especially in older patients, and typically requires oral anticoagulants and rate-control treatments to manage heart rate and reduce cardiovascular risks.

For patients not adequately controlled with rate-control therapy, rhythm-control treatments such as antiarrhythmic drugs, cardioversion, or catheter ablation are recommended, with safety being a key factor in choosing the appropriate therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Atrial fibrillation: current recommendations for diagnosis and treatment]. Kirchhof, P.[2021]

Catheter ablation is being increasingly considered as a treatment option for patients with atrial fibrillation and heart failure with reduced ejection fraction, as traditional antiarrhythmic drugs often show limited efficacy and higher risks of side effects.

Current evidence suggests that catheter ablation may improve outcomes in these patients, although careful patient selection is crucial for maximizing its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Catheter ablation of atrial fibrillation in heart failure with reduced ejection fraction. Malhi, N., Hawkins, NM., Andrade, JG., et al.[2019]

Catheter ablation has become a promising alternative to traditional antiarrhythmic drugs for rhythm control in patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF), showing superior outcomes in recent clinical trials.

Patients with HFrEF and AF face higher risks of stroke and mortality, and the advancements in catheter ablation technology over the past decade have made it a more effective treatment option compared to pharmacological methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Atrial Fibrillation in Patients with Co-existing Heart Failure and Reduced Ejection Fraction: Time to Revisit the Management Guidelines? Baher, A., Marrouche, NF.[2020]

References

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

Randomized Ablation-Based Rhythm-Control Versus Rate-Control Trial in Patients With Heart Failure and Atrial Fibrillation: Results from the RAFT-AF trial. [2022]

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

Catheter ablation of atrial fibrillation-A key role in heart failure therapy? [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Randomized Clinical Trials of Catheter Ablation of Atrial Fibrillation in Congestive Heart Failure: Knowns and Unmet Needs. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Long-term Outcome of Pulmonary Vein Isolation Versus Amiodarone Therapy in Patients with Coexistent Persistent AF and Congestive Heart Failure. [2020]

5. France pubmed.ncbi.nlm.nih.gov

[Cardiac rhythm management of patients with atrial fibrillation]. [2021]

6. Brazil pubmed.ncbi.nlm.nih.gov

Catheter Ablation is Superior to Antiarrhythmic Drugs as First-Line Treatment for Atrial Fibrillation: a Systematic Review and Meta-Analysis. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

[Atrial fibrillation: current recommendations for diagnosis and treatment]. [2021]

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

Catheter ablation of atrial fibrillation in heart failure with reduced ejection fraction. [2019]

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

Treatment of Atrial Fibrillation in Patients with Co-existing Heart Failure and Reduced Ejection Fraction: Time to Revisit the Management Guidelines? [2020]