Adenosine to Assess Complete Conduction Block During Catheter Ablation of Paroxysmal Atrial Fibrillation

Study Overview
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Brief Summary
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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
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Hypothesis: Adenosine reveals incomplete conduction block due to partial tissue injury/stunning during catheter ablation of atrial fibrillation. 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: 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. Patients will be randomized to further ablation to achieve complete isolation during adenosine infusion vs to no further ablation. 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. 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.

Official Title
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Adenosine Study in Paroxysmal Atrial Fibrillation

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: Adenosine
* Drug: Isoproterenol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients >18 and <75 who are able to give informed consent undergoing atrial fibrillation ablation procedure. Paroxysmal Atrial fibrillation lasting = 7 days which is self-terminating. It is considered recurrent if two or more episodes occur. Failure or unwilling to take class I or III anti-arrhythmic drugs Exclusion Criteria: History of asthma Patients with severe coronary artery disease, stable/unstable angina, or ongoing myocardial ischemia Previous cardiac surgery ( excluding CABG and mitral valve surgery) Symptomatic congestive heart failure including but not limited to NYHA III/IV and/or documented ejection fraction <40% measured by acceptable cardiac testing, Left atrial diameter >55mm Moderate to severe mitral or aortic valve disease Myocardial infarction within three months of enrollment Congenital heart disease where it increases the risk of an ablative procedure Prior ASD/PFO closure with a device using a percutaneous approach Hypertrophic cardiomyopathy (LV wall thickness >1.5mm) Pulmonary Hypertension (mean or systolic PA pressure> 50mmHg on Doppler echocardiography Any prior ablation of atrial fibrillation Enrollment in any other arrhythmia protocol Any ventricular arrhythmia being treated where the arrhythmia or management may interfere with this study Active infection or sepsis Any history of cerebrovascular disease including stroke or TIAs Pregnancy or lactation Left atrial thrombus at the time of ablation Untreatable allergy to contrast media Any diagnosis of atrial fibrillation secondary to electrolyte disturbance, thyroid disease, or any other reversible or non-cardiovascular causes History of blood clotting(bleeding or thrombotic) abnormalities Known sensitivities to heparin or warfarin Severe COPD (defined as FEV1 <1) 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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adenosine and Isoproterenol<br>Patients in this group will receive 12-24mg of adenosine for each PV in order to assess dormant PV conduction. | Drug: Adenosine<br>* 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.<br>Drug: Isoproterenol<br>* 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.<br>* Other names: Isuprel;|
| Other: Isoproterenol<br>This group will not receive adenosine during the procedure. | Drug: Isoproterenol<br>* 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.<br>* Other names: Isuprel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 2- 14 months after Ablation procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | date of ablation to 6 months after procedure | 
| 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 | 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. | post-procedure (6 months) | 
| Incidence of Stroke | Number of subjects who develop stroke within 30 days after procedure. | peri-procedural (0 to 30 days after procedure) | 
| Incidence of Pulmonary Vein Stenosis | Number of subjects who develop Symptomatic pulmonary vein stenosis | 6 months post-procedure | 
| Incidence of Cardiac Perforation | Number of subjects who develop perforation of heart during ablation | within 24 hours | 
| Incidence of Atrio-esophageal Fistula | Number of subjects who develop connection between heart and the esophagus | within 4 weeks | 
| Incidence of Death | Number of deaths within 90 days of the procedure. | with 90 days of the procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atrial fibrillation, ablation, adenosine