Atrial Fibrillation
Conditions
Keywords
atrial fibrillation, ablation, adenosine
Brief summary
The purpose of this study is to determine if additional ablation during the first procedure as the result of the ability to medically induce quiet atrial arrhythmias will improve clinical outcome in patients with atrial fibrillation thus decreasing the need for additional ablation procedures.
Detailed description
Hypothesis: 1. Adenosine reveals incomplete conduction block due to partial tissue injury/stunning during catheter ablation of atrial fibrillation. 2. Identification of incomplete conduction block by adenosine improves clinical outcomes including an increase in efficacy and a decrease in need for repeat procedures after catheter ablation of atrial fibrillation. Objectives: 1. In patients with paroxysmal Atrial Fibrillation (AF), the prevalence of Pulmonary Vein (PV) reconnection during adenosine infusion after complete PV isolation using conventional techniques will be determined. 2. Patients will be randomized to further ablation to achieve complete isolation during adenosine infusion vs to no further ablation. 3. Primary endpoint of the study will be freedom from any atrial arrhythmias 6 months after a single ablation procedure in the absence of antiarrhythmic drug therapy. 4. Secondary endpoints will include number of repeat ablation procedures because of documented recurrence of symptomatic AF or atrial flutter/tachycardia, outcome after 2 ablation procedures; Proportion of patients with AF or atrial flutter/tachycardia occuring during the first three months post ablation, prevalence of recovery of conduction into PVs during repeat ablation procedures in both groups, procedure duration, and incidence of peri-procedural complications including stroke, PV stenosis, cardiac perforation, atrio-esophageal fistulae, and death.
Interventions
DRUGAdenosine
Subject will receive 6-24 mg of intravenous adenosine given rapidly for each PV in order to assess dormant PV conduction. Subjects in this group will also receive isoproterenol to assess inducibility of AF with re-isolation of PVs and targeting non PV sources of AF if necessary.Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate.
DRUGIsoproterenol
Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to\<85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol.
Sponsors
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patients \>18 and \<75 who are able to give informed consent undergoing atrial fibrillation ablation procedure. 2. Paroxysmal Atrial fibrillation lasting = 7 days which is self-terminating. It is considered recurrent if two or more episodes occur. 3. Failure or unwilling to take class I or III anti-arrhythmic drugs
Exclusion criteria
1. History of asthma 2. Patients with severe coronary artery disease, stable/unstable angina, or ongoing myocardial ischemia 3. Previous cardiac surgery ( excluding CABG and mitral valve surgery) 4. Symptomatic congestive heart failure including but not limited to NYHA III/IV and/or documented ejection fraction \<40% measured by acceptable cardiac testing, 5. Left atrial diameter \>55mm 6. Moderate to severe mitral or aortic valve disease 7. Myocardial infarction within three months of enrollment 8. Congenital heart disease where it increases the risk of an ablative procedure 9. Prior ASD/PFO closure with a device using a percutaneous approach 10. Hypertrophic cardiomyopathy (LV wall thickness \>1.5mm) 11. Pulmonary Hypertension (mean or systolic PA pressure\> 50mmHg on Doppler echocardiography 12. Any prior ablation of atrial fibrillation 13. Enrollment in any other arrhythmia protocol 14. Any ventricular arrhythmia being treated where the arrhythmia or management may interfere with this study 15. Active infection or sepsis 16. Any history of cerebrovascular disease including stroke or TIAs 17. Pregnancy or lactation 18. Left atrial thrombus at the time of ablation 19. Untreatable allergy to contrast media 20. Any diagnosis of atrial fibrillation secondary to electrolyte disturbance, thyroid disease, or any other reversible or non-cardiovascular causes 21. History of blood clotting(bleeding or thrombotic) abnormalities 22. Known sensitivities to heparin or warfarin 23. Severe COPD (defined as FEV1 \<1) 24. Severe comorbidity or poor general physical/mental health that, in opinion of the investigator, will not allow the patient to be a good study candidate (i.e. other disease processes, mental capacity, substance abuse, shortened life expectancy)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Freedom From Any Atrial Arrhythmias | 2- 14 months after Ablation procedure | Primary endpoint of the study will be number of participants who are free from any atrial arrhythmias after a single ablation procedure in the absence of antiarrhythmic drug therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With AF or Atrial Flutter/Tachycardia Occurring During the First Three Months Post Ablation | first three months post ablation | — |
| Number of Pulmonary Veins That Recovered Conduction During Repeat Ablation Procedures in Both Groups | post-procedure (6 months) | Prevalence of recovery of conduction into pulmonary veins during repeat ablation procedures in both groups. This is determined by surgeon assessment using a circular mapping catheter to identify recovery of conduction into the pulmonary veins. |
| Incidence of Stroke | peri-procedural (0 to 30 days after procedure) | Number of subjects who develop stroke within 30 days after procedure. |
| Number of Subjects Who Need Repeat Ablations | date of ablation to 6 months after procedure | Number of participants who had one or more repeat ablation procedures due to documented recurrence of Symptomatic AF or atrial flutter/tachycardia. |
| Incidence of Cardiac Perforation | within 24 hours | Number of subjects who develop perforation of heart during ablation |
| Incidence of Atrio-esophageal Fistula | within 4 weeks | Number of subjects who develop connection between heart and the esophagus |
| Incidence of Death | with 90 days of the procedure | Number of deaths within 90 days of the procedure. |
| Incidence of Pulmonary Vein Stenosis | 6 months post-procedure | Number of subjects who develop Symptomatic pulmonary vein stenosis |
Countries
United States
Participant flow
Pre-assignment details
Two subjects were not randomized.
Participants by arm
| Arm | Count |
|---|---|
| Adenosine and Isoproterenol Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction.
Adenosine: Subject will receive 6-24 mg of intravenous adenosine given rapidly for each PV in order to assess dormant PV conduction.
Subjects in this group will also receive isoproterenol to assess inducibility of AF with re-isolation of PVs and targeting non PV sources of AF if necessary.Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate.
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to\<85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol. | 61 |
| Isoproterenol This group will not receive adenosine during the procedure.
Isoproterenol: Isoproterenol will be infused through a femoral vein at rates of 5, 10, 15, and 20 μg/min for 2 minutes at each infusion rate. The isoproterenol infusion will be discontinued upon induction of AF, a decrease in systolic blood pressure to\<85 mmHg, complaints of severe chest tightness, electrocardiographic changes suggestive of ischemia, or upon completion of the infusion protocol. | 68 |
| Total | 129 |
Baseline characteristics
| Characteristic | Isoproterenol | Total | Adenosine and Isoproterenol |
|---|---|---|---|
| Age, Continuous | 58.9 years STANDARD_DEVIATION 10.7 | 59.3 years STANDARD_DEVIATION 13.8 | 59.7 years STANDARD_DEVIATION 8.7 |
| Cerebrovascular accident | 4 Participants | 6 Participants | 2 Participants |
| CHADS2 Score ( Congestive heart failure, Hypertension, Age > 75 years, Diabetes Mellitus, Stroke | 0.7 units on a scale STANDARD_DEVIATION 0.7 | 0.75 units on a scale STANDARD_DEVIATION 0.9 | 0.8 units on a scale STANDARD_DEVIATION 0.7 |
| Diabetes Mellitus | 8 Participants | 14 Participants | 6 Participants |
| Hypertension | 28 Participants | 61 Participants | 33 Participants |
| left atrial diameter | 41.2 milli meters STANDARD_DEVIATION 6.4 | 41.1 milli meters STANDARD_DEVIATION 8.3 | 41.0 milli meters STANDARD_DEVIATION 5.3 |
| Left ventricular ejection fraction | 59.3 Percentage STANDARD_DEVIATION 5.6 | 59.5 Percentage STANDARD_DEVIATION 7.8 | 59.7 Percentage STANDARD_DEVIATION 5.4 |
| Obstructive sleep apnea | 19 Participants | 34 Participants | 15 Participants |
| Region of Enrollment United States | 68 Participants | 129 Participants | 61 Participants |
| Repeat procedure | 23 Participants | 43 Participants | 20 Participants |
| Sex: Female, Male Female | 15 Participants | 39 Participants | 24 Participants |
| Sex: Female, Male Male | 53 Participants | 90 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 61 | 0 / 68 |
| other Total, other adverse events | 0 / 61 | 0 / 68 |
| serious Total, serious adverse events | 4 / 61 | 3 / 68 |
Outcome results
Primary
Freedom From Any Atrial Arrhythmias
Primary endpoint of the study will be number of participants who are free from any atrial arrhythmias after a single ablation procedure in the absence of antiarrhythmic drug therapy
Time frame: 2- 14 months after Ablation procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adenosine and Isoproterenol | Freedom From Any Atrial Arrhythmias | 24 Participants |
| Isoproterenol | Freedom From Any Atrial Arrhythmias | 23 Participants |
p-value: 0.83Log Rank
Secondary
Incidence of Atrio-esophageal Fistula
Number of subjects who develop connection between heart and the esophagus
Time frame: within 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adenosine and Isoproterenol | Incidence of Atrio-esophageal Fistula | 0 Participants |
| Isoproterenol | Incidence of Atrio-esophageal Fistula | 0 Participants |
Secondary
Incidence of Cardiac Perforation
Number of subjects who develop perforation of heart during ablation
Time frame: within 24 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adenosine and Isoproterenol | Incidence of Cardiac Perforation | 0 Participants |
| Isoproterenol | Incidence of Cardiac Perforation | 0 Participants |
Secondary
Incidence of Death
Number of deaths within 90 days of the procedure.
Time frame: with 90 days of the procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adenosine and Isoproterenol | Incidence of Death | 0 Participants |
| Isoproterenol | Incidence of Death | 0 Participants |
Secondary
Incidence of Pulmonary Vein Stenosis
Number of subjects who develop Symptomatic pulmonary vein stenosis
Time frame: 6 months post-procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adenosine and Isoproterenol | Incidence of Pulmonary Vein Stenosis | 0 Participants |
| Isoproterenol | Incidence of Pulmonary Vein Stenosis | 0 Participants |
Secondary
Incidence of Stroke
Number of subjects who develop stroke within 30 days after procedure.
Time frame: peri-procedural (0 to 30 days after procedure)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adenosine and Isoproterenol | Incidence of Stroke | 0 Participants |
| Isoproterenol | Incidence of Stroke | 0 Participants |
Secondary
Number of Pulmonary Veins That Recovered Conduction During Repeat Ablation Procedures in Both Groups
Prevalence of recovery of conduction into pulmonary veins during repeat ablation procedures in both groups. This is determined by surgeon assessment using a circular mapping catheter to identify recovery of conduction into the pulmonary veins.
Time frame: post-procedure (6 months)
Population: Only 21 participants had repeat ablations; each participant has four pulmonary veins therefore the number of connections measured is based 4 x the number of participants
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Adenosine and Isoproterenol | Number of Pulmonary Veins That Recovered Conduction During Repeat Ablation Procedures in Both Groups | 29 pulmonary veins |
| Isoproterenol | Number of Pulmonary Veins That Recovered Conduction During Repeat Ablation Procedures in Both Groups | 28 pulmonary veins |
p-value: 0.09t-test, 2 sided
Secondary
Number of Subjects Who Need Repeat Ablations
Number of participants who had one or more repeat ablation procedures due to documented recurrence of Symptomatic AF or atrial flutter/tachycardia.
Time frame: date of ablation to 6 months after procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adenosine and Isoproterenol | Number of Subjects Who Need Repeat Ablations | 12 Participants |
| Isoproterenol | Number of Subjects Who Need Repeat Ablations | 9 Participants |
p-value: 0.35t-test, 2 sided
Secondary
Number of Subjects With AF or Atrial Flutter/Tachycardia Occurring During the First Three Months Post Ablation
Time frame: first three months post ablation
Population: This data was not collected.