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Pulmonary Vein Isolation Alone or in Combination With Substrate Modulation After Electric Cardioversion Failure (PACIFIC)

E

Elsan

Status

Enrolling

Conditions

Persistent Atrial Fibrillation

Treatments

Procedure: Pulmonary Vein Isolation (PVI) alone
Procedure: PVI procedure associated with substrate modulation

Study type

Interventional

Funder types

Other

Identifiers

NCT05264831
2021-A02291-40 (Other Identifier)
PACIFIC

Details and patient eligibility

About

This study aims at assessing whether electric cardioversion can act as a discriminant factor between patients requiring Pulmonary Vein Isolation (PVI) procedure alone or PVI procedure combined with substrate modulation.

All included patients will undergo an electric cardioversion, then:

  • Patients with electric cardioversion success will be treated as per Standard of Care and according to ESC recommendations (2020). A prospective registry will be implemented for these patients.

  • Patients with electric cardioversion failure will be randomized in the study between 2 ablative procedures:

    • PVI procedure alone
    • PVI procedure combined with substrate modulation

Full description

Atrial fibrillation (AF) is the most common heart rhythm disorder. It is the result of uncoordinated action of the atrial myocardial cells, causing rapid and irregular contraction of the heart's atria.

The AF prevalence in adults is currently estimated to be between 2% and 4% and is expected to increase by a factor of 2.3 in the next few years, due to the increased longevity of the general population and the increased search for undiagnosed AF. Increased age is an important risk factor for AF, but other increased comorbidities, including hypertension, diabetes, heart failure, coronary artery disease, chronic renal failure, obesity, and obstructive sleep apnoea syndrome, are also important; modifiable risk factors contribute strongly to the development and progression of AF (ESC Guideline, 2020).

The European Society of Cardiology (ESC) recommended pulmonary vein isolation (PVI) (Class IA) as first-line ablative strategy for persistent AF (Class IA) (ESC Guideline, 2020). However, PVI alone is only effective in treating about 40% to 60% of patients with persistent AF in the general population (unselected). If we apply this strategy to all patients (PVI alone), we accept to re-do ablative procedure in up to 60% of patients.

The second feasible strategy is to treat patients with persistent AF by PVI combined with substrate modulation (ESC Class IIb). This strategy, when done well, by creating irreversible lesions (Marshall-PLAN) can effectively treat 70% to 80% of AF patients. But this implies that the investigator will be doing unnecessary substrate modulation in up to 40% of patients, which can lead to increased risks associated with the ablative procedure, longer procedure times, multiple lesions, etc... In addition, incorrect or incomplete substrate modulation is pro-arrhythmic and leads to recurrences in the form of left atrial flutters, tolerance of which, is generally poor.

Both ablative strategies have been widely validated in large numbers of published studies.

The problem is to know when and for which patients to apply one or the other of the two strategies. Electric cardioversion could help in selecting the most appropriate strategy.

Enrollment

450 estimated patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Criteria to be validated for patients included before performing electric cardioversion:

  1. Persistent AF (continuous for at least 7 days without interruption according to information transmitted by the cardiologist and the patient), symptomatic and resistant to at leat one anti-arrhythmic drug treatment including amiodarone;

Criteria to be validated for patients included after performing electric cardioversion :

  1. Patient treated by electric cardioversion for persistent AF, symptomatic and resistant to anti-arrhythmic treatment including amiodarone and whom ablative procedure is planned in the following 4-6 weeks after electric cardioversion

    Criteria to be validated for all patients included:

  2. Life expectancy > 5 years;

  3. Female or male between 18 and 80 years of age at the electric cardioversion time

  4. Affiliation to a health insurance system;

  5. Patient informed of the study and having signed informed consent

    Criteria to be validated prior to randomization on the day of ablation (these patients may be randomized):

  6. Patient with failed electric cardioversion i.e. in AF, confirmed by ECG.

Exclusion criteria

Criteria to be validated before or after performing electric cardioversion (the study cannot be proposed to patients corresponding to these criteria):

  1. Current hyperthyroidism;

  2. Pregnant or breastfeeding woman;

  3. Patient with a Body Mass Index (BMI) greater than 35;

  4. Patient with severe Chronic Obstructive Pulmonary Disease (COPD);

  5. Patient with hypertrophic heart disease;

  6. Patient with a mechanical or biological mitral valve;

  7. Contraindications to anticoagulants;

  8. Transient Ischemic Attack (TIA) /stroke less than 6 months old;

  9. Psychiatric illness affecting follow-up;

  10. Left Ventricular Ejection Fraction (LVEF) < 40% ;

  11. Uncontrolled ischaemic heart disease (angina, myocardial ischaemia)

  12. Patients under legal protection

  13. Cardiac surgery on left atrium

  14. Inflammatory status in progress (cancer, rheumatoid arthritis, PPRZ, acute or chronic periodontitis, Crohn's disease, RCUH)

  15. Pulmonary embolism or phlebitis less than 6 months old

  16. Prior atrial fibrillation ablation

  17. Active cancer

    Criteria to be validated before randomization, on the day of ablation (these patients cannot be randomized):

  18. Patient in sinus rhythm 4-6 weeks after electric cardioversion: these patients are included in the study registry.

  19. Patient with complete absence of sinus rhythm (less than 10 seconds) after 3 electric cardioversion attempts: these patients will discontinue from the study.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

450 participants in 2 patient groups

PVI procedure alone
Active Comparator group
Description:
If the patient presents with AF (= failure of electric cardioversion, approximately 30% of patients), randomization will be carried out according to : - Group 1: PVI procedure alone in accordance with ESC recommendations
Treatment:
Procedure: Pulmonary Vein Isolation (PVI) alone
PVI procedure combined with substrate modulation
Experimental group
Description:
If the patient presents with AF (= failure of electric cardioversion, approximately 30% of patients), randomization will be carried out according to : - Group 2: PVI procedure associated with substrate modulation
Treatment:
Procedure: PVI procedure associated with substrate modulation

Trial contacts and locations

13

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Central trial contact

Agustín Bortone, MD

Data sourced from clinicaltrials.gov

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