Persistent Atrial Fibrillation
Conditions
Keywords
atrial fibrillation, mapping, substrate, ablation
Brief summary
In this study, the investigators aim to identify and characterize, by means of an EnSite Velocity Research Software, the electrophysiological characteristics of substrates that sustain AF in patients with persistent AF and to test whether ablation of such patient-specific substrates might improve the acute and long-term success of conventional catheter ablation therapy.
Detailed description
This study is a prospective, single center, randomized, single-blind, controlled, 2-arm parallel group trial in Milan, Italy. The total duration of the study is expected to be 24 months with \ 12 months of enrollment. Approximately 80 subjects suffering from persistent AF will be randomized in a 1:1 fashion to the following investigation arms: * Modified circumferential pulmonary vein ablation alone (mCPVA); * Substrate-targeted ablation guided by AF substrate mapping, followed by completion of modified circumferential pulmonary vein ablation (Substrate+ mCPVA) * Ablate the areas that have fast and regular electrical activities, starting from the fastest cycle length (defined by Mean CL in the range of 120-250 milliseconds, and SD CL in the range of 1-30 milliseconds * Ablate the areas that have consistent rotational or focal propagation pattern (defined by conduction velocity vectors) * Ablate the areas that comprises the slow conduction zone of possible arrhythmia circuits * If AF terminates during RF ablation, stimulation protocol will be used to examine if AF is re-inducible. If AF sustains or is re-inducible and physician decides to remap, mapping will be performed again for substrate-targeted ablation. If AF is not re-inducible, mCPVA will be completed Subjects will be followed up at 3, 6, 12 months. The primary objective of the study is to assess acute and long-term outcome of patient-tailored substrate-targeted ablation (Substrate) plus modified circumferential pulmonary vein ablation (Substrate+mCPVA) versus modified circumferential pulmonary vein ablation alone (mCPVA). The secondary objective of the study is to map and characterize electrophysiological substrates during AF, including regular and fast activities, complex fractionated electrograms, wave front propagation directions, and fibrosis.
Interventions
DEVICESubstrate+mCPVA
The intervention in the experimental arm includes using a research software (investigational device) to map AF substrate and guide ablation.
DEVICEmCPVA
The intervention in the active comparator arm includes using the commercially available EnSite Velocity mapping and ablation system for modified circumferential pulmonary vein ablation.
Sponsors
Abbott Medical Devices
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* 18 - 85 years of age * Persistent AF scheduled to undergo catheter ablation with approved standard indication by ESC/EHRA guidelines * First or second time ablation for persistent AF * Ability to provide written informed consent for study participation and be willing and able to comply with the study evaluations and follow up schedule
Exclusion criteria
* Had two or more previous AF ablation procedures * Secondary AF * Hyperthyroidism * Left ventricular ejection fraction \<30% * NYHA functional class IV * Left atrial area \> 35 cm2 * Uncorrected severe valvular heart disease * Contraindication to anticoagulation * Presence of left atrial thrombus * Recent (\<6 Months) myocardial Infarction or unstable angina or coronary artery by-pass * Thoracic surgery for congenital, valvular or aortic disease * History of cerebrovascular accidents * Pregnancy * Significant comorbidities such as cancer, severe renal insufficiency requiring hemodialysis, severe obstructive lung disease, cirrhosis, with a life expectancy less than 2 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Long-term Clinical Success Rate | 12 months | Freedom from symptomatic AF off antiarrhythmic drug therapy assessed from the end of the 3 months blanking period to 12 months following the ablation procedure, documented by implantable loop recorder (ILR) monitoring or trans-telephonic (TT) ECG monitoring. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute Ablation Procedure Outcome | During Ablation | Acute AF termination or significant AF cycle length slowing during RF application in ablation procedure |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| mCPVA Subjects in the mCPVA arm will undergo intervention called modified circumferential pulmonary vein ablation, which is considered to be the standard ablation treatment for AF.
mCPVA: The intervention in the active comparator arm includes using the commercially available EnSite Velocity mapping and ablation system for modified circumferential pulmonary vein ablation. | 40 |
| Substrate+mCPVA Subjects in the Substrate+mCPVA arm will undergo intervention of substrate mapping and substrate-targeted ablation guided by the investigational device, followed by completion of modified circumferential pulmonary vein ablation.
Substrate+mCPVA: The intervention in the experimental arm includes using a research software (investigational device) to map AF substrate and guide ablation. | 41 |
| Total | 81 |
Baseline characteristics
| Characteristic | Total | Substrate+mCPVA | mCPVA |
|---|---|---|---|
| AF persistency, mo | 6.1 months STANDARD_DEVIATION 1.4 | 5.8 months STANDARD_DEVIATION 1.3 | 6.5 months STANDARD_DEVIATION 1.8 |
| Age, Continuous | 61.7 years STANDARD_DEVIATION 10.6 | 63.5 years STANDARD_DEVIATION 10.4 | 59.5 years STANDARD_DEVIATION 10.8 |
| Diabetes mellitus, n | 8 Participants | 4 Participants | 4 Participants |
| Hypertenstion, n | 48 Participants | 22 Participants | 26 Participants |
| LA area, cm2 | 24.5 cm2 STANDARD_DEVIATION 5.5 | 24.5 cm2 STANDARD_DEVIATION 6.1 | 24.8 cm2 STANDARD_DEVIATION 4.8 |
| Left Ventricle Ejection Fraction (%) | 54.6 % STANDARD_DEVIATION 6.6 | 55.5 % STANDARD_DEVIATION 7.3 | 53.5 % STANDARD_DEVIATION 5.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 81 Participants | 41 Participants | 40 Participants |
| Region of Enrollment Italy | 81 participants | 41 participants | 40 participants |
| Sex: Female, Male Female | 21 Participants | 12 Participants | 9 Participants |
| Sex: Female, Male Male | 60 Participants | 29 Participants | 31 Participants |
| Years AF diagnosed, y | 4.5 years STANDARD_DEVIATION 5.3 | 5.4 years STANDARD_DEVIATION 5.3 | 3.8 years STANDARD_DEVIATION 5.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 41 |
| other Total, other adverse events | 0 / 40 | 0 / 41 |
| serious Total, serious adverse events | 0 / 40 | 0 / 41 |
Outcome results
Primary
Long-term Clinical Success Rate
Freedom from symptomatic AF off antiarrhythmic drug therapy assessed from the end of the 3 months blanking period to 12 months following the ablation procedure, documented by implantable loop recorder (ILR) monitoring or trans-telephonic (TT) ECG monitoring.
Time frame: 12 months
Population: Success rate of patient's undergoing radiofrequency catheter ablation during follow up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| mCPVA | Long-term Clinical Success Rate | 30 Participants |
| Substrate+mCPVA | Long-term Clinical Success Rate | 21 Participants |
Secondary
Acute Ablation Procedure Outcome
Acute AF termination or significant AF cycle length slowing during RF application in ablation procedure
Time frame: During Ablation
Population: Success rate of radiofrequency catheter ablation to terminate atrial fibrillation during the ablation procedure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| mCPVA | Acute Ablation Procedure Outcome | 12 Participants |
| Substrate+mCPVA | Acute Ablation Procedure Outcome | 25 Participants |