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

• Sponsor: University of Michigan (Other)
• Overall Status: Completed
• CT.gov ID: NCT03032965
• Collaborator: (none)
• Enrollment: 131
• Location: 1
• Arms: 2
• Duration (Months): 45
• Patients Per Site Per Month: 2.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation	Drug: Adenosine; Drug: Isoproterenol	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 131 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Adenosine Study in Paroxysmal Atrial Fibrillation
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. Number of Subjects With AF or Atrial Flutter/Tachycardia Occurring During the First Three Months Post Ablation [first three months post ablation]

3. 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.

4. Incidence of Stroke [peri-procedural (0 to 30 days after procedure)]

   Number of subjects who develop stroke within 30 days after procedure.

5. Incidence of Pulmonary Vein Stenosis [6 months post-procedure]

   Number of subjects who develop Symptomatic pulmonary vein stenosis

6. Incidence of Cardiac Perforation [within 24 hours]

   Number of subjects who develop perforation of heart during ablation

7. Incidence of Atrio-esophageal Fistula [within 4 weeks]

   Number of subjects who develop connection between heart and the esophagus

8. Incidence of Death [with 90 days of the procedure]

   Number of deaths within 90 days of the procedure.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan	Ann Arbor	Michigan	United States	48109

Sponsors and Collaborators

• University of Michigan

Investigators

• Principal Investigator: Hamid Ghanbari, MD, University of Michigan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hamid Ghanbari, Assistant Professor of Internal Medicine, University of Michigan
• ClinicalTrials.gov Identifier: NCT03032965
• Other Study ID Numbers: HUM00048922
• First Posted: Jan 26, 2017
• Last Update Posted: Dec 13, 2017
• Last Verified: Nov 1, 2017

• Keywords provided by Hamid Ghanbari, Assistant Professor of Internal Medicine, University of Michigan: atrial fibrillation; ablation; adenosine
• Additional relevant MeSH terms: Atrial Fibrillation; Adenosine; Isoproterenol

Study Results

Participant Flow

Pre-assignment Detail	Two subjects were not randomized.

Arm/Group Title	Adenosine and Isoproterenol	Isoproterenol
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	61	68
COMPLETED	61	68
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Adenosine and Isoproterenol	Isoproterenol	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	61	68	129
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.7 (8.7)	58.9 (10.7)	59.3 (13.8)
Sex: Female, Male (Count of Participants)
Female	24 39.3%	15 22.1%	39 30.2%
Male	37 60.7%	53 77.9%	90 69.8%
Region of Enrollment (Count of Participants)
United States	61 100%	68 100%	129 100%
Left ventricular ejection fraction (Percentage) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage]	59.7 (5.4)	59.3 (5.6)	59.5 (7.8)
left atrial diameter (milli meters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milli meters]	41.0 (5.3)	41.2 (6.4)	41.1 (8.3)
Hypertension (Count of Participants)
Count of Participants [Participants]	33 54.1%	28 41.2%	61 47.3%
Diabetes Mellitus (Count of Participants)
Count of Participants [Participants]	6 9.8%	8 11.8%	14 10.9%
Obstructive sleep apnea (Count of Participants)
Count of Participants [Participants]	15 24.6%	19 27.9%	34 26.4%
Cerebrovascular accident (Count of Participants)
Count of Participants [Participants]	2 3.3%	4 5.9%	6 4.7%
Repeat procedure (Count of Participants)
Count of Participants [Participants]	20 32.8%	23 33.8%	43 33.3%
CHADS2 Score ( Congestive heart failure, Hypertension, Age > 75 years, Diabetes Mellitus, Stroke (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	0.8 (0.7)	0.7 (0.7)	0.75 (0.9)

Outcome Measures

1. Primary Outcome

Title	Freedom From Any Atrial Arrhythmias
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Adenosine and Isoproterenol	Isoproterenol
Arm/Group Description	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.	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.
Measure Participants	61	68
Count of Participants [Participants]	24 39.3%	23 33.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adenosine and Isoproterenol, Isoproterenol
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.83
	Comments
	Method	Log Rank
	Comments	Kaplan Meier log rank

2. Secondary Outcome

Title	Number of Subjects Who Need Repeat Ablations
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Adenosine and Isoproterenol	Isoproterenol
Arm/Group Description	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.	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.
Measure Participants	61	68
Count of Participants [Participants]	12 19.7%	9 13.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adenosine and Isoproterenol, Isoproterenol
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.35
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Number of Subjects With AF or Atrial Flutter/Tachycardia Occurring During the First Three Months Post Ablation
Time Frame	first three months post ablation

Outcome Measure Data

Analysis Population Description

This data was not collected.

Arm/Group Title	Adenosine and Isoproterenol	Isoproterenol
Arm/Group Description	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.	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.
Measure Participants	0	0

4. Secondary Outcome

Title	Number of Pulmonary Veins That Recovered Conduction During Repeat Ablation Procedures in Both Groups
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Adenosine and Isoproterenol	Isoproterenol
Arm/Group Description	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.	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.
Measure Participants	12	9
Measure pulmonary veins	48	36
Count of Units [pulmonary veins]	29	28

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adenosine and Isoproterenol, Isoproterenol
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.09
	Comments
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

Title	Incidence of Stroke
Description	Number of subjects who develop stroke within 30 days after procedure.
Time Frame	peri-procedural (0 to 30 days after procedure)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Adenosine and Isoproterenol	Isoproterenol
Arm/Group Description	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.	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.
Measure Participants	61	68
Count of Participants [Participants]	0 0%	0 0%

6. Secondary Outcome

Title	Incidence of Pulmonary Vein Stenosis
Description	Number of subjects who develop Symptomatic pulmonary vein stenosis
Time Frame	6 months post-procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Adenosine and Isoproterenol	Isoproterenol
Arm/Group Description	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.	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.
Measure Participants	61	68
Count of Participants [Participants]	0 0%	0 0%

7. Secondary Outcome

Title	Incidence of Cardiac Perforation
Description	Number of subjects who develop perforation of heart during ablation
Time Frame	within 24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Adenosine and Isoproterenol	Isoproterenol
Arm/Group Description	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.	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.
Measure Participants	61	68
Count of Participants [Participants]	0 0%	0 0%

8. Secondary Outcome

Title	Incidence of Atrio-esophageal Fistula
Description	Number of subjects who develop connection between heart and the esophagus
Time Frame	within 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Adenosine and Isoproterenol	Isoproterenol
Arm/Group Description	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.	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.
Measure Participants	61	68
Count of Participants [Participants]	0 0%	0 0%

9. Secondary Outcome

Title	Incidence of Death
Description	Number of deaths within 90 days of the procedure.
Time Frame	with 90 days of the procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Adenosine and Isoproterenol	Isoproterenol
Arm/Group Description	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.	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.
Measure Participants	61	68
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Time Frame	within 24 hours of procedure
Arm/Group Title	Adenosine and Isoproterenol		Isoproterenol
Arm/Group Description	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.		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.
All Cause Mortality
	Adenosine and Isoproterenol		Isoproterenol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/61 (0%)		0/68 (0%)
Serious Adverse Events
	Adenosine and Isoproterenol		Isoproterenol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/61 (6.6%)		3/68 (4.4%)
Respiratory, thoracic and mediastinal disorders
Transient phrenic nerve paralysis	0/61 (0%)		1/68 (1.5%)
Vascular disorders
Site hematoma	2/61 (3.3%)		2/68 (2.9%)
Pericardial Effusion	1/61 (1.6%)		0/68 (0%)
A V Fistula	1/61 (1.6%)		0/68 (0%)
Other (Not Including Serious) Adverse Events
	Adenosine and Isoproterenol		Isoproterenol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/61 (0%)		0/68 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.