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

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.

• Adenosine (Drug): 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 (Drug), also known as Isuprel: 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.

Primary outcomes

• 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 outcomes

• 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.
• 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.
• Incidence of Pulmonary Vein Stenosis [6 months post-procedure]: Number of subjects who develop Symptomatic pulmonary vein stenosis
• 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.

Sex: All, ages: 18 Years to 75 Years

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)

Participant flow

Outcome results

• Freedom From Any Atrial Arrhythmias (Primary), Count of participants, Participants: Adenosine and Isoproterenol 24; Isoproterenol 23 (p .83)
• Number of Subjects Who Need Repeat Ablations (Secondary), Count of participants, Participants: Adenosine and Isoproterenol 12; Isoproterenol 9 (p .35)
• Number of Subjects With AF or Atrial Flutter/Tachycardia Occurring During the First Three Months Post Ablation (Secondary)
• Number of Pulmonary Veins That Recovered Conduction During Repeat Ablation Procedures in Both Groups (Secondary), Count of units, pulmonary veins: Adenosine and Isoproterenol 29; Isoproterenol 28 (p 0.09)
• Incidence of Stroke (Secondary), Count of participants, Participants: Adenosine and Isoproterenol 0; Isoproterenol 0
• Incidence of Pulmonary Vein Stenosis (Secondary), Count of participants, Participants: Adenosine and Isoproterenol 0; Isoproterenol 0
• Incidence of Cardiac Perforation (Secondary), Count of participants, Participants: Adenosine and Isoproterenol 0; Isoproterenol 0
• Incidence of Atrio-esophageal Fistula (Secondary), Count of participants, Participants: Adenosine and Isoproterenol 0; Isoproterenol 0
• Incidence of Death (Secondary), Count of participants, Participants: Adenosine and Isoproterenol 0; Isoproterenol 0

Adverse events

Time frame: within 24 hours of procedure

Serious adverse events by term

• Hamid Ghanbari, MD, Principal investigator, University of Michigan