The investigator-initiated, Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation (CABANA) Trial will test the hypothesis that the treatment strategy of percutaneous left atrial catheter ablation for the purpose of eliminating atrial fibrillation (AF) is superior to current state-of-the-art pharmacologic therapy with either rate control or rhythm control drugs for reducing total mortality (primary endpoint) and decreasing the composite endpoint of total mortality, disabling stroke, serious bleeding and cardiac arrest (secondary endpoint) in patients with untreated or incompletely treated AF warranting therapy. Additional secondary endpoints will include AF recurrence and quality of life and cost effectiveness. The need for this trial arises out of 1) the rapidly increasing number of patients >60 years of age with AF accompanied by symptoms and morbidity, 2) the failure of anti-arrhythmic drug therapy in multiple recent trials to maintain sinus rhythm and reduce mortality, 3) the rapidly increasing application of radiofrequency catheter ablation for AF without appropriate evidence-based validation, and 4) the resulting impact of AF on national health care costs. This 140-center mortality study will randomize 3000 patients over 3 years to a strategy of catheter ablation (n=1500) vs. state-of-the-art rate or rhythm control drug therapy (n=1500). Each patient will have 1) characteristics similar to AFFIRM patients (age >65, or <65 with >1 risk factor for stroke, 2) documented AF warranting treatment, and 3) eligibility for both catheter ablation and >2 anti-arrhythmic or >3 rate control drugs. Patients will be followed every 6 months for >2 yrs (median 3.5 yrs) and will undergo repeat trans-telephonic monitoring, Holter monitoring, and CT/MR studies to assess the impact of treatment. The primary and secondary endpoints will be examined in pts with paroxysmal, persistent, or permanent AF, without regard to age or underlying heart disease. With an anticipated 3.5 year mortality rate of >12% in drug treated patients, 1500 patients in each treatment arm will provide 90% power for detecting a 30% relative reduction in overall mortality and >90% power for detecting a 25% reduction in the composite secondary endpoint. The CABANA trial will disclose the role of medical and ablative therapies for an ever-escalating national healthcare dilemma, ascertain the cost and influence of therapy on quality of life, establish the impact of therapy on atrial morphology and function, and will help determine if AF is a modifiable risk factor for cardiovascular mortality. CABANA will be a landmark trial that will guide therapy and shape health care policy in the AF arena for years to come.

Public Health Relevance

The rapidly increasing incidence of cardiac arrhythmias, and particularly atrial fibrillation (AF), in an aging population has become a major public health problem. Current prevalent treatments for atrial fibrillation are medication (pharmaceuticals), pacemakers, catheter-based myocardial ablation, and open chest heart surgery. Pacemakers are ineffective in many patients, especially those with AF, and due to the risk and morbidity of surgery, the potential for effective, less invasive treatments has become of high interest. However, no compelling quantitative comparison of performance and outcomes for pharmaceutical versus ablative treatment has been accomplished. This proposal, one of four linked in a synergistic coalition to conduct a large clinical trial, will provide exactly the quantitative measures required to settle the issue and produce a winner. That method will become the compelling first choice for effective minimally invasive treatment for millions of people who have serious atrial fibrillation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL089645-04
Application #
8232076
Study Section
Special Emphasis Panel (ZHL1-CSR-R (O3))
Program Officer
Mascette, Alice
Project Start
2009-02-01
Project End
2015-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
4
Fiscal Year
2012
Total Cost
$261,781
Indirect Cost
$88,531
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Rettmann, M E; Holmes 3rd, D R; Johnson, S B et al. (2015) Analysis of Left Atrial Respiratory and Cardiac Motion for Cardiac Ablation Therapy. Proc SPIE Int Soc Opt Eng 9415:
Sun, Deyu; Rettmann, Maryam E; Packer, Douglas et al. (2015) Simulated evaluation of an intraoperative surface modeling method for catheter ablation by a real phantom simulation experiment. Proc SPIE Int Soc Opt Eng 9415:
Rettmann, Maryam E; Holmes 3rd, David R; Breen, Jerome F et al. (2015) Measurements of the left atrium and pulmonary veins for analysis of reverse structural remodeling following cardiac ablation therapy. Comput Methods Programs Biomed 118:198-206
Sun, Deyu; Rettmann, Maryam E; Holmes Iii, David R et al. (2014) Anatomic surface reconstruction from sampled point cloud data and prior models. Stud Health Technol Inform 196:387-93
Rettmann, M E; Holmes 3rd, D R; Linte, C A et al. (2014) Toward Standardized Mapping for Left Atrial Analysis and Cardiac Ablation Guidance. Proc SPIE Int Soc Opt Eng 9036:
Linte, Cristian A; Camp, Jon J; Rettmann, Maryam E et al. (2013) Image-based Modeling and Characterization of RF Ablation Lesions in Cardiac Arrhythmia Therapy. Proc SPIE Int Soc Opt Eng 8671:
Linte, Cristian A; Camp, Jon J; Holmes 3rd, David R et al. (2013) Toward online modeling for lesion visualization and monitoring in cardiac ablation therapy. Med Image Comput Comput Assist Interv 16:9-17
Rettmann, Maryam E; Gunawan, Mia S; Holmes 3rd, David R et al. (2012) Centerline tracking for quantification of reverse structural remodeling of the pulmonary veins following cardiac ablation therapy. Acad Radiol 19:1332-44
Linte, Cristian A; Rettmann, Maryam E; Dilger, Ben et al. (2012) Calibration and Evaluation of a Magnetically Tracked ICE Probe for Guidance of Left Atrial Ablation Therapy. Proc SPIE Int Soc Opt Eng 8316: