September 26, 2008
Steve Phurrough, M.D.
Director, Coverage and Analysis Group
Centers for Medicare & Medicaid Services
U. S. Department of Health and Human Services
Mailstop: C1-09-06
7500 Security Blvd.
Baltimore, MD 21244
Re: CMS Posting of Potential NCD Topics
Dear Dr. Phurrough,
Biosense Webster, a Johnson & Johnson Company, is pleased to provide comments to the Centers for
Medicare and Medicaid Services' (CMS) request for information and relevant evidence regarding the use
of cardiac ablation for atrial fibrillation (AF). Biosense Webster is an industry leader in the technology
used for the diagnosis and treatment of cardiac arrhythmias. The primary focus of our clinical research
has been on patients undergoing radiofrequency ablation procedures using our technologies.
We share CMS' commitment to assuring that Medicare beneficiaries receive access to evidencesupported
medical services and technologies. We appreciate the opportunity to provide comments
regarding the evidence of health benefits in the patients who receive cardiac ablation for the treatment of
AF. In the comments below we provide information regarding the current state of evidence for this
important procedure and of the further clinical trials that are underway. We also provide details on the
characteristics of those patients that benefit most from the procedure. Under separate cover, Johnson &
Johnson's corporate policy group is providing additional comments regarding the process used to identify
and prioritize National Coverage Determination topics.
I. AF Background
AF is a common supraventricular arrhythmia that is defined by uncoordinated atrial activation, resulting in
progressive electrophysiological and structural remodeling of the atria.1, 2, 3 There are several
classifications of AF. Paroxysmal AF is characterized by recurrent AF symptoms (> 2 episodes) that
terminate spontaneously within seven days.2 Persistent AF is used to describe patients with AF that lasts
beyond seven days, or lasting less than seven days but requiring therapeutic intervention.2 Included
within the category of persistent AF is "longstanding persistent AF" which is defined as continuous AF of
greater than one-year duration.2 Permanent (or chronic) AF is used to describe patients in whom
cardioversion has either failed or not been attempted.2
A range of treatment options for AF is available, including drug therapies, electrical cardioversion, surgical
interventions, and ablation therapy. For patients in whom ablation therapy is the recommended course of
treatment, appropriately trained and experienced physicians may choose between several energy
sources for the ablation, including radiofrequency and cryothermy.
II. Current State of Evidence for Cardiac Ablation
Strong evidence exists in peer-reviewed literature that demonstrates the benefit of cardiac ablation for AF
treatment, leading to the development of evidence-based clinical guidelines and expert consensus
statements. In 2006, the American College of Cardiology (ACC), the American Heart Association (AHA),
and the European Society of Cardiology (ESC), in collaboration with the Heart Rhythm Society (HRS)
released a comprehensive set of clinical guidelines outlining treatment pathways for patients with AF.
The guidelines report on the cumulative study experience of over 4,000 ablation patients, with high success rates in patients with paroxysmal and persistent AF, and provide recommendations for the use of
ablation therapy for the treatment of AF, noting that "catheter ablation is a reasonable alternative to
pharmacologic therapy to prevent recurrent AF in symptomatic patients with little or no left atrial
enlargement."1 The guidelines further support ablation as a second-line therapy for all categories of
patients for the maintenance of sinus rhythm.2
In 2007, an expert consensus statement that provided a state-of-the-art review of the field of catheter and
surgical ablation of AF was published by HRS, in partnership with the European Heart Rhythm
Association (EHRA) and the European Cardiac Arrhythmia Society (ECAS), and in collaboration with the
ACC, AHA, and the Society of Thoracic Surgeons (STS), which reported the findings of a task force
convened to define patient selection, techniques and outcomes for the procedures. The task force
supported the recommendations of the 2006 guidelines on AF ablation.2 Similarly, the organizers of
VeniceArrythmias2007 assembled world-recognized experts in the field to develop the Venice Chart
International Document, a synthesis of the consensus on AF management reached by these experts.
The document also notes "AF ablation appears to be an effective therapy over both the short- and longerterm,
with an acceptably low incidence of complications."4
There are a number of key randomized, controlled trials (RCTs) reported in the literature that provide
evidence that in select patients, ablation therapy provides superior clinical outcomes relative to alternative
existing therapies, primarily in demonstrating clinically relevant, statistical differences in freedom from AF
recurrence over varied time periods. Typically, these trials evaluated ablation therapy as a second-line
therapy to antiarrhythmic drug (AAD) therapies in patients who had failed at least one antiarrhythmic
drug. A smaller number of studies investigated the benefit of using ablation therapy as a first-line
treatment for AF.5, 6
The Catheter Ablation for the Cure of Atrial Fibrillation Study (CACAF) study demonstrated that ablation
therapy, combined with an AAD, was superior to an AAD alone in preventing atrial arrhythmia in patients
with paroxysmal or persistent AF whom had already failed AAD therapy. The CACAF trial found that 61.1
percent of patients did not experience further atrial arrhythmia recurrence, with a median follow-up of 18
months.7 Additionally, the study found that after 12 months of follow-up, 63/69 (91.3%) control group
patients had at least one AF recurrence, whereas 30/68 (44.1%) (P < 0.001) of ablation group patients
had atrial arrhythmia recurrence.7 Similarly, the Atrial Fibrillation Ablation versus Antiarrhythmic Drugs
(A4) study found that 75 percent of ablation patients were free of AF recurrence at one-year follow-up.8
These results are consistent with the findings of the Ablation for Paroxysmal Atrial Fibrillation (APAF) trial,
which showed that a single circumferential pulmonary vein ablation (CPVA) procedure is more effective
than AAD therapy in preventing AF relapses in patients with paroxysmal atrial fibrillation (PAF).6
Specifically, the study showed that 86 percent of patients in the ablation study group demonstrated no
recurrence of AF at one-year follow-up. Oral et al. demonstrated that sinus rhythm can be maintained
long term in the majority of patients with chronic AF by means of CPVA independently of the effect of
AAD therapy, cardioversion, or both.9 Analysis from this study showed 74 percent of patients in sinus
rhythm at one year, without additional AAD therapy required. Lastly, the Radiofrequency Ablation for
Atrial Fibrillation Trial (RAAFT) investigated the use of radiofrequency ablation as first-line therapy for
patients with symptomatic AF. Results from the study suggest that the rate of symptomatic AF recurrence
for patients receiving ablation therapy (13 percent) was lower than in those receiving AAD therapy (63
percent).8
Three recent systematic literature reviews and meta-analyses of available clinical data for cardiac
ablation provide a broader review of the evidence by including data from multiple study designs, including
the RCTs discussed in the preceding paragraph. The results from these analyses, assessing hundreds of
patients, further substantiate that radiofrequency ablation for the treatment of AF results in higher efficacy
and lower rates of complications than AAD therapies.10, 11, 12
The current body of evidence also demonstrates improvement in quality of life (QoL) and other outcome
measures for patients undergoing ablation therapy for AF.13, 14, 15 Reynolds et al. reported on quality of
life from major AF interventions. Each of the nonrandomized studies reported positive changes in all or
nearly all SF-36 subscales in patients following ablation. The magnitude of change was typically significant in mental and physical summary scores. The randomized studies likewise showed large
improvements in QoL following ablation, which in one of the studies were significantly larger than the
gains achieved with antiarrhythmic drugs.15 Weerasooriya et al. reported that ablation patients exhibited
significant improvements in all eight subscales of the SF-36 questionnaire, with the greatest (36-point)
improvements in the role physical subscale, which reflects the patient-perceived disability stemming from
physical limitations (patients that received ablation for treatment of their AF reporting less perceived
physical limitation) and in the physical pain (31-point improvement) subscale.16 The study also showed
complementary improvement in Symptom Checklist (SCL) severity and frequency scores, with a baseline
SCL frequency score of 25 } 3 that was reduced to 15 + 2 (P < .05). The baseline SCL severity score
was 10 + 2 and was improved to 5 + 1(P < .05).16 Health utility analysis results from the A4 trial provide further evidence of the benefits of ablation. A statistically significantly greater improvement in health state utility was seen after ablation than after treatment with an alternative AAD.17 Preliminary analysis has
also shown that for certain patients, ablation results in decreased office, emergency department, and
hospital visits, and results in decreased healthcare costs.13
Although the evidence-base for ablation is larger in younger patients, positive outcomes have also been
demonstrated in elderly AF patients. Studies show that the use of catheter ablation therapy in elderly
patients results in freedom from recurrent AF, with low rates of complications and adverse events, at a
level comparable to that found in younger patients.18, 19 Additional data collection in the Medicare
population is ongoing.
We have included in Appendix A a list of publications supporting the use of ablation therapy for AF for
your reference, in addition to those cited here. Biosense Webster is pleased to provide CMS with this list
and would welcome further dialogue on the existing body of evidence.
III. Ongoing Studies and Clinical Trials
In addition to the currently available body of evidence, research continues to strengthen the evidencebase
for this procedure. A primary focus of current research is on refining ablation techniques, defining
methods and intervals of follow-up, and establishing a consistent approach to achieving and reporting
success rates. And while no catheter today has an FDA-approved indication for ablation of AF, a number
of trials intended to demonstrate the safety and effectiveness of specific ablation catheters for AF
treatment are nearing completion, including an Investigational Device Exemption (IDE) study sponsored
by Biosense Webster. Appendix B provides public information from www.ClinicalTrials.gov on the 15
studies specific to radiofrequency ablation of AF, along with information as to the purpose of the study,
the specific intervention, age inclusion/exclusion criteria, study population size, study type, and expected
start and completion dates.
Additionally, the Catheter Ablation versus Antiarrhythmic Drug for Atrial Fibrillation (CABANA) Trial will
compare pharmacologic rate and rhythm control to catheter ablation to study the mortality benefit of
ablation and gather information on the therapeutic impact to patient quality of life and healthcare resource
utilization. The study will also investigate other outcomes of AF ablation and drug therapy including
cardiovascular death, occurrence of disabling stroke, serious bleeding and cardiac arrest.2 This study has
completed pilot phase enrollment, and funding for the pivotal phase is under review at the National
Institutes of Health (NIH).
IV. Patient Selection for Ablation Therapy
According to AHA/ACC/ESC guidelines, "catheter ablation is a reasonable alternative to pharmacological
therapy to prevent recurrent AF in symptomatic patients with little or no atrial enlargement."1 Typically,
appropriate patients have symptomatic AF and are refractory or intolerant to at least one Class 1 or 3
antiarrhythmic medication.2, 7 Other considerations for patient selection include age, left atrium diameter,
duration of AF and presence or absence of co-morbid conditions.2 A recent study has shown significant
improvement in cardiac function, symptoms, exercise capacity and quality of life in patients with both AF
and congestive heart failure.20
V. Summary
The current body of evidence supports the health benefits of cardiac ablation for AF in appropriately
selected patients. Ongoing clinical studies will add to the existing evidence-base and provide important
additional data to guide patient-specific decision-making and clinical practice. Biosense Webster
supports the HRS/EHRA/ECAS Expert Consensus Statement, which provides parameters for technical
competence and training requirements.2 We believe that physicians who are trained and technically
competent are essential components to achieving the best possible clinical outcomes.
As with all clinical decisions, patients and providers should continue to have the ability to consider all
relevant factors when determining the most appropriate course of therapy for their specific circumstances,
including the existing evidence, unique patient characteristics, clinician experience, and the risks and
benefits of AAD therapy. Catheter ablation is a reasonable alternative to AAD therapy in certain patients,
where the evidence supports the use of ablation therapy to achieve optimal clinical outcomes.12, 21
Biosense Webster appreciates the opportunity to provide comments to CMS on this potential NCD topic
and we welcome further discussion. Please feel free to contact me at 909-839-8998 or Jamie March,
Director, Global Health Policy, at 909-839-8543, if you wish to discuss our comments in further detail.
Sincerely yours,
Marcia S. Yaross, Ph.D.
Vice President, Clinical, Regulatory, and Health Policy
Biosense Webster, Inc.
References
1 Fuster, V.; Ryden, L.; Cannom, D.S.; Crijns, H.J.; Curtis, A.B.; Ellenbogen, K.A.; Haperin, J.L.; Le
Heuzey, J-Y.; Kay, N.K.; Lowe, J.E.; Olsson, S.B.; Prystowsky, E.N.; Tumargo, J.L.; Wann, S.; Smith,
S.C.; Jacobs, A.K.; Adams, C.D.; Anderson, J.L.; Antman, E.L.; Hunt, S.A.; Nishimura, R.; Ornato, J.P.;
Page, R.L.; Riegel, B.; Priori, S.G.; Blanc, J-J.; Budaj, A.; Camm, A.J.; Dean, V.; Deckers, J.W.;
Despres, C.; Dickstein, K.; Lekakis, J.; McGregor, K.; Metra, M.; Morais, J.; Osterspey, A.; Tamargo,
J.L.; Zumorano, J.L. "ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial
Fibrillation . Executive Summary. A Report to the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines." Circulation. 114 (August 15, 2006): 700-752.
2 Calkins, H.; Brugada, J.; Packer, D.; Cappato, R.; Chen, S.; Crijns, H.; Damiano, R.; Davies, W.;
Haines, D.; Haissaguerre, M.; Iesaka, Y.; Jackman, W.; Jais, P.; Kottkamp, H.; Kuck, K.; Lindsay, B.;
Marchlinski, F.; McCarthy, P.; Mont, J.; Morady, F.; Nademanee, K.; Natale, A.; Pappone, C.;
Prystowsky, E.; Raviele, A.; Ruskin, J.; Shemin, R. "HRS/EHRA/ECAS Expert Consensus Statement on
Catheter and Surgical Ablation of Atrial Fibrillation: Recommendations for Personnel, Policy,
Procedures and Follow-Up." Heart Rhythm. 4(6) (June 2007): 1-46.
3 Van Wagoner, D.R. "Electrophysiological Remodeling in Human Atrial Fibrillation." PACE. 26 (2003):
1572-1575.
4 Natale, A.; Raviele, A.; Arentz, T.; Calkins, H.; Chen, S.; Haissaguerre, M.; Hindricks, G.; Ho, Y.; Kuck,
K.; Marchlinski, F.; Napolitano, C.; Packer, D.; Pappone, C.; Prystowsky, E.; Schilling, R.; Shah, D.; Themistoclakis, S.; Verma, A. "Venice Chart International Consensus Document on Atrial Fibrillation
Ablation." Journal of Cardiovascular Electrophysiology. 18(5) (May 2007): 560-580.
5 Wazni, O.; Marrouche, N.; Martin, D.; et al. "Radiofrequency Ablation vs. Antiarrhythmic Drugs as Firstline
Treatment of Symptomatic Atrial Fibrillation: A Randomized Trial." JAMA. 293(21) (2005): 2634-
2640.
6 Pappone, C.; Augello, G.; Sala, S.; Gugliotta, F.; Vicedomini, G.; Gulletta, S.; Paglino, G.; Mazzone, P.;
Sora, N.;: Greiss, I.; Santagostino, A.; LiVolsi, L.; Pappone, N.; Radinovice, A.; Manguso, F,; Santinelli,
V. "A Randomized Trial of Circumferential Pulmonary Vein Ablation Versus Antiarrhythmic Drug
Therapy in Paroxysmal Atrial Fibrillation." Journal of the American College of Cardiology. 48(11) (2006):
2340-2347.
7 Stabile, G.; Bertaglia, E.; Senatore, G.; De Simone, A.; Zoppo, F.; Donnici, G.; Turco, P.; Pascotto, P.;
Fazzari, M.; Vitale, D.F. "Catheter Ablation Treatment in Patients With Drug-Refractory Atrial
Fibrillation: A Prospective, Multi-Centre, Randomized, Controlled Study (Catheter Ablation for the Cure
of Atrial Fibrillation Study)." European Heart Journal. 27 (2006): 216-221.
8 Jais, P.; Packer, D. "Ablation Versus Drug Use for Atrial Fibrillation." European Heart Journal
Supplements. 9(Supplement G) (2007): G26-G34.
9 Oral, H.; Pappone, C.; Chugh, A.; Good, E.; Bogun, F.; Pelosi, F.; Bates, E.; Lehmann, M.; Vicedomini,
G.; Augello, G.; Agricola, E.; Sala, S.; Santinelli, V.; Morady, F. "Circumferential PulomonaryVein
Ablation for Chronic Atrial Fibrillation." The New England Journal of Medicine. 354(9) (2006): 934-941.
10 Calkins, H.; Reynolds, M.R.; Spector, P.; Sondhi1, M.; Xu1, Y.; Martin, A.; Williams, C.J.; Sledge, I.
"Treatment of Atrial Fibrillation with Antiarrhythmic Drugs or Radiofrequency Ablation: Two Systematic
Literature Reviews and Meta-analyses." (Submitted to peer-reviewed journal on May 28, 2008): 1-32.
11 Nair, G.; Nery, P.; Diwakaramenon, S.; Healey, J.; Connolly, S.; Morillo, C. "A Systematic Review of
Randomized Trials Comparing Radiofrequency Ablation with Antiarrhythmic Medications in Patients
with Atrial Fibrillation." Journal of Cardiovascular Electrophysiology. Published Electronically.
(September 3, 2008): 1-7.
12 Noheria, A.; Kumar, A.; Wylie, J.V.; Josephson, M.E. "Catheter Ablation vs. Antiarrhythmic Drug
Therapy for Atrial Fibrillation." Archives of Internal Medicine. 168(6) (March 24, 2008): 581-586.
13 Goldberg, A.; Menen, M.; Mickelsen, S.; MacIndoe, C.; Binder, M.; Nawman, R.; West, G.; Kusumoto,
F.M. "Atrial Fibrillation Ablation Leads to Long-Term Improvement of Quality of Life and Reduced
Utilization of Healthcare Resources." Journal of Interventional Cardiac Electrophysiology. 8(1) (2003):
59-64.
14 Morady, F. "Radiofrequency Ablation as Treatment for Cardiac Arrhythmias." The New England Journal
of Medicine. 340(7) (February 18, 1999): 534-544.
15 Reynolds, M.; Ellis, E.; Zimetbaum, P. "Quality of Life in Atrial Fibrillation; Measurement Tool and
Impact of Interventions." Journal of Cardiovascular Electrophysiology. Published Electronically 19(7)
(July 2008): 762-768.
16 Weerasooriya, R.; Jais, P.; Hocini, M.; Scavee, C.; MacLe. L.; Hsu, L.; Sandars, P.; Garrigue, S.;
Clementy, J.; Haissaguerre, M. "Effect of Catheter Ablation on Quality of Life of Patients with
Paroxysmal Atrial Fibrillation." Heart Rhythm. 2(6) (2005): 619-623.
6
17 Reynolds, M.; Cauchemez, B.; Macle, L.; Daoud, E.G.; Jais, P. "Health State Utilities Improve with
Catheter Ablation for AF More Than with Drug Therapy: Analysis From a Randomized Trial (abstract)."
Circulation. 115(21) (2007):e574-5.
18 Corrado, A.; Patel, D.; Riedlbauchova, L.; Fahmy, T.; Themistoclakis, S.; Bonso, A.; Rossillo, A.; Hao,
S.; Schweikert, R.; Cummings, J.; Bhargava, M.; Burkhardt, D.; Saliba, W.; Raviele, A.; Natale, A.
"Efficacy, Safety, and Outcome of Atrial Fibrillation Ablation in Septuagenarians." Journal of
Cardiovascular Electrophysiology. 19(8) (2008): 807-811.
19 Zado, E.; Callans, D.; Riley, M.; Hutchinson, M.; Garcia, F.; Bala, R.; Lin, D.; Cooper, J.; Verdino, R.;
Russo, A.; Dixit, S.; Gerstenfeld, E.; Marchlinski, F. "Long-Term Clinical Efficacy and Risk of Catheter
Ablation for Atrial Fibrillation in the Elderly." Journal of Cardiovascular Electrophysiology. 19(6) (2008):
621-626.
20 Hsu, L.; Jais, P.; Sandars, P.; Garrigue, S.; Hocini, M.; Sacher, F.; Takahashi, Y.; Rotter, M.; Pasquie,
J.; Scavee, C.; Bordachar, P.; Clementy, J.; Haissaguerre, M. "Catheter Ablation For Atrial Fibrillation In
Heart Failure." The New England Journal of Medicine. 351(23) (2004): 2373-2383.
21 Biosense Webster. "Biosense Webster's Response To The Agency For Health Care Research And
Quality's (AHRQ) Research Review On The Effectiveness Radiofrequency Catheter Ablation
(ABLATION THERAPY) For Atrial Fibrillation." Submitted via AHRQ Web Site. (January 2, 2008): 1-3.
Appendix A: Additional Published Literature
| Primary Author | Year | Citation |
|---|
| Fassini | 2005 | Fassini G, Riva S, Chiodelli R, Trevisi N, Berti M, et al . Left mitral isthmus ablation associated with PV isolation: Long-term results of a prospective randomized study.Journal of Cardiovascular Electrophysiology 2005; 16: 1150-6. | | Hocini | 2005 | Hocini M, Jais P, Sanders P, Takahashi Y, Rotter M, Rostock T, et al. Techniques, evaluation, and consequences of linear block at the left atrial roof in paroxysmal atrial fibrillation: A prospective randomized study. Circulation 2005; 112: 3688-96. | | Karch | 2005 | Karch MR, Zrenner B, Deisenhofer I, Schreieck J, Ndrepepa G, Dong J, et al. Freedom from atrial tachyarrhythmias after catheter ablation of atrial fibrillation: A randomized comparison between two current ablation strategies. Circulation 2005; 111: 2875-80. | | Kumagai | 2005 | Kumagai K, Ogawa M, Noguchi H, Nakashima H, Zhang B, Miura S-I, et al. Comparison of two mapping strategies for pulmonary vein isolation. Circulation 2005; 69: 1496-502. | | Liu | 2006 | Liu X, Dong J, Mavrakis HE, Hu F, Long D, Fang D, et al. Achievement of pulmonary vein isolation in patients undergoing circumferential pulmonary vein ablation: A randomized comparison between two different isolation approaches. Journal of Cardiovascular Electrophysiology 2006; 17: 1263-70. | | Liu | 2006 | Liu X, Long D, Dong J, Hu F, Yu R, Tang R, et al. Is circumferential pulmonary vein isolation preferable to stepwise segmental pulmonary vein isolation for patients with paroxysmal atrial fibrillation. Circulation 2006; 70: 1392. | | Nilsson | 2006 | Nilsson B, Chen X, Pehrson S, Kober L, Hilden J, Svendsen JH. Recurrence of pulmonary vein conduction and atrial fibrillation after pulmonary vein isolation for atrial fibrillation: A randomized trial of the ostial versus the extraostial ablation strategy.American Heart Journal 2006; 152: 537.e1-e8. | | Oral | 2006 | Oral H, Chugh A, Good E, Sankaran S, Reich SS, Igic P, et al. A tailored approach to catheter ablation of paroxysmal atrial fibrillation. Circulation 2006; 113: 1824-31. | | Pappone | 2004 | Pappone C, Manguso F, Vicedomini G, Gugliotta F, et al . Prevention of iatrogenic atrial tachycardia after ablation of atrial fibrillation: A prospective randomized study comparing circumferential pulmonary vein ablation with a modified approach. Circulation 2004; 110: 3036-42. | | Calo | 2006 | Calo L, Lamberti F, Loricchio ML, De Ruvo E, Colivicchi F, Bianconi L, et al. Left atrial ablation versus biatrial ablation for persistent and permanent atrial fibrillation. A prospective and randomized study. Journal American College of Cardiology 2006; 47: 2504-12. | | Tondo | 2005 | Tondo C, Mantica M, Russo G, Karapatsoudi E, Lucchina A, Nigro F, et al. A new nonfluoroscopic navigation system to guide pulmonary vein isolation.Pacing and Clinical Electrophysiology 2005; 28 Suppl 1: S102-5. | | Arentz | 2007 | Arentz T, Weber R, Burkle G, Herrera C, Blum T, Stockinger J, et al. Small or large isolation areas around the pulmonary veins for the treatment of atrial fibrillation? Results from a prospective randomized study. Circulation 2007; 115(24): 3057-63. | | Dixit | 2006 | Dixit S, Gerstenfeld EP, Callans DJ, Cooper JM, Lin D, Russo AM, et al. Comparison of cool tip versus 8-mm tip catheter in achieving electrical isolation of pulmonary veins for long-term control of atrial fibrillation: a prospective randomized pilot study. Journal of Cardiovascular Electrophysiology 2006; 17(10): 1074-9. | | Haissaguerre | 2004 | Haissaguerre M, Sanders P, Hocini M, Hsu LF, Shah DC, Scavee C, et al. Changes in atrial fibrillation cycle length and inducibility during catheter ablation and their relation to outcome. Circulation 2004; 109(24): 3007-13. | | Kanj | 2007 | Kanj MH, Wazni O, Fahmy T, Thal S, Patel D, Elay C, et al. Pulmonary vein antral isolation using an open irrigation ablation catheter for the treatment of atrial fibrillation: a randomized pilot study. Journal American College of Cardiology 2007; 49(15): 1634-41. | | Katritsis | 2004 | Katritsis DG, Ellenbogen KA, Panagiotakos DB, Giazitzoglou E, Karabinos I, Papadopoulos A, et al. Ablation of superior pulmonary veins compared to ablation of all four pulmonary veins. Journal of Cardiovascular Electrophysiology 2004; 15(6): 641-5. | | Krittayaphong | 2003 | Krittayaphong R, Raungrattanaamporn O, Bhuripanyo K, Sriratanasathavorn C, Pooranawattanakul S, Punlee K, et al. A randomized clinical trial of the efficacy of radiofrequency catheter ablation and amiodarone in the treatment of symptomatic atrial fibrillation. Journal of Medical Association of Thailand 2003; 86 Suppl 1:S8-16. | | Lee | 2000 | Lee SH, Cheng JJ, Chen SA. A randomized, prospective comparison of anterior and posterior approaches to atrioventricular junction modification of medically refractory atrial fibrillation. Pacing Clin Electrophysiology 2000; 23(6): 966-74. | | Liu | 2005 | Liu X, Wang XH, Gu JN, Zhou L, Qiu JH. Electroanatomical systems to guided circumferential pulmonary veins ablation for atrial fibrillation: initial experience from comparison between the Ensite/NavX and CARTO system. Chinese Medical Journal (Engl) 2005; 118(14): 1156-60. | | Marrouche | 2007 | Marrouche NF, Guenther J, Segerson NM, Daccarett M, Rittger H, Marschang H, et al. Randomized comparison between open irrigation technology and intracardiac-echo-guided energy delivery for pulmonary vein antrum isolation: procedural parameters, outcomes, and the effect on esophageal injury. Journal of Cardiovascular Electrophysiology 2007; 18(6): 583-8. | | Oral | 2005 | Oral H, Chugh A, Good E, Igic P, Elmouchi D, Tschopp DR, et al. Randomized comparison of encircling and nonencircling left atrial ablation for chronic atrial fibrillation. Heart Rhythm 2005; 2(11): 1165-72. | | Oral | 2004 | Oral H, Chugh A, Lemola K, Cheung P, Hall B, Good E, et al. Noninducibility of atrial fibrillation as an end point of left atrial circumferential ablation for paroxysmal atrial fibrillation: a randomized study. Circulation 2004; 110(18): 2797-801. | | Rotter | 2005 | Rotter M, Takahashi Y, Sanders P, Haissaguerre M, Jais P, Hsu LF, et al. Reduction of fluoroscopy exposure and procedure duration during ablation of atrial fibrillation using a novel anatomical navigation system. European Heart Journal 2005; 26(14): 1415-21. | | Sheikh | 2006 | Sheikh I, Krum D, Cooley R, Dhala A, Blanck Z, Bhatia A, et al. Pulmonary vein isolation and linear lesions in atrial fibrillation ablation. Journal of Interventional Cardiology and Electrophysiology 2006; 17(2): 103-9. | | Sra | 2007 | Sra J, Narayan G, Krum D, Malloy A, Cooley R, Bhatia A, et al. Computed tomography-fluoroscopy image integration-guided catheter ablation of atrial fibrillation.Journal of Cardiovascular Electrophysiology 2007; 18(4): 409-14. | | Stabile | 2001 | Stabile G, De Simone A, Turco P, La Rocca V, Nocerino P, Astarita C, et al. Response to flecainide infusion predicts long-term success of hybrid pharmacologic and ablation therapy in patients with atrial fibrillation. Journal American College of Cardiology 2001; 37(6): 163944. | | Tang | 2008 | Tang K, Ma J, Zhang S, Zhang JY, Wei YD, Chen YQ, et al. A randomized prospective comparison of CartoMerge and CartoXP to guide circumferential pulmonary vein isolation for the treatment of paroxysmal atrial fibrillation. Chinese Medical Journal (Engl) 2008; 121(6): 508-12. | | Turco | 2007 | Turco P, De Simone A, La Rocca V, Iuliano A, Capuano V, Astarita C, et al. Antiarrhythmic drug therapy after radiofrequency catheter ablation in patients with atrial fibrillation.Pacing Clinical Electrophysiology 2007; 30 Suppl 1: S112-5. | | Wang | 2007 | Wang XH, Liu X, Sun YM, Gu JN, Shi HF, Zhou L, et al. Early identification and treatment of PV re-connections: role of observation time and impact on clinical results of atrial fibrillation ablation. Europace 2007; 9(7): 481-6. | | Wazni | 2005 | Wazni O, Marrouche NF, Martin DO, Gillinov AM, Saliba W, Saad E, et al. Randomized study comparing combined pulmonary vein-left atrial junction disconnection and cavotricuspid isthmus ablation versus pulmonary vein-left atrial junction disconnection alone in patients presenting with typical atrial flutter and atrial fibrillation. Circulation 2003; 108(20): 2479-83. | | Willems | 2006 | Willems S, Klemm H, Rostock T, Brandstrup B, Ventura R, Steven D, et al. Substrate modification combined with pulmonary vein isolation improves outcome of catheter ablation in patients with persistent atrial fibrillation: a prospective randomized comparison.European Heart Journal 2006; 27(23) 2871-8. |
Appendix B: Clinical Trials For Radiofrequency Catheter Ablation Therapy
For The Treatment Of Atrial Fibrillation (AF)
| Study One | | NCT ID | NCT00272636 | | Title | Radiofrequency Catheter Ablation for Chronic Atrial Fibrillation | | Status | Completed | | Condition(s) | Atrial Fibrillation | | Intervention(s) | Procedure: Radiofrequency Catheter Ablation; Drug: Amiodarone and Cardioversion | | Study Population Size | 140 | | Ages Eligible for Study | 18 years to 70 years | | Sponsor(s) | University of Michigan, Section of Electrophysiology (Arrhythmia Research); Dept of Electrophysiology, San Raffaele University Hospital, Milan, Italy | | Funded By | Other | | Study Type | Interventional | | Study Design | Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study | | Other IDs | 2002-0480 | | Start Date | November 2002 | | Expected Completion Date | February 2005 | | Last Updated | January 3, 2006 |
| Study Two |
| NCT ID | NCT00315068 | | Title | Usefulness of Markers to Predict Recurrence of Atrial Fibrillation After Radiofrequency Catheter Ablation | | Status | Active, Not Recruiting | | Condition(s) | Atrial Fibrillation | | Intervention(s) | N/A | | Study Population Size | 180 | | Ages Eligible for Study | 18 years to 80 years | | Sponsor(s) | University Hospital, Geneva | | Funded By | Other | | Study Type | Observational | | Study Design | Screening, Longitudinal, Defined Population, Prospective Study | | Other IDs | PRD-03-I-03 | | Start Date | April 2004 | | Expected Completion Date | August 2007 | | Last Updated | April 19, 2007 |
| Study Three |
| NCT ID | NCT00540787 | | Title | A Comparison of Antiarrhythmic Drug Therapy and Radiofrequency Catheter Ablation in Patients With Paroxysmal Atrial Fibrillation | | Status | Completed | | Condition(s) | Atrial Fibrillation | | Intervention(s) | Device: RF Ablation, AAD | | Study Population Size | N/A | | Ages Eligible for Study | 18 years and older | | Sponsor(s) | Biosense Webster, Inc. | | Funded By | Industry | | Study Type | Interventional | | Study Design | Randomized, Open Label, Parallel Assignment | | Other IDs | A4 | | Start Date | N/A | | Expected Completion Date | N/A | | Last Updated | October 5, 2007 |
| Study Four |
| NCT ID | NCT00116428 | | Title | NAVISTAR® THERMOCOOL® Catheter for the Treatment of Atrial Fibrillation | | Status | Active, Not Recruiting | | Condition(s) | Heart Disease, Arrhythmia; Atrial Fibrillation | | Intervention(s) | Device: NAVISTAR® THERMOCOOL® Catheter | | Study Population Size | 230 | | Ages Eligible for Study | 18 years and older | | Sponsor(s) | Biosense Webster, Inc. | | Funded By | Industry | | Study Type | Interventional | | Study Design | Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study | | Other IDs | BWI03130 | | Start Date | October 2004 | | Expected Completion Date | N/A | | Last Updated | July 25, 2008 |
| Study Five |
| NCT ID | NCT00434694 | | Title | A Study of Strategies for Electrical Isolation of Pulmonic Veins for Curative Treatment of Atrial Fibrillation | | Status | Completed | | Condition(s) | Atrial Fibrillation | | Intervention(s) | Procedure: Pulmonary Vein Isolation (Radiofrequency Catheter Ablation) | | Study Population Size | 300 | | Ages Eligible for Study | 40 years and older | | Sponsor(s) | University of Pennsylvania | | Funded By | Other | | Study Type | Interventional | | Study Design | Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study | | Other IDs | Penn: PVI Strategies | | Start Date | July 2003 | | Expected Completion Date | February 2006 | | Last Updated | November 19, 2007 |
| Study Six |
| NCT ID | NCT00674401 | | Title | Radiofrequency Ablation of Drivers of Atrial Fibrillation (RADARAF) | | Status | Not Yet Recruiting | | Condition(s) | Atrial Fibrillation | | Intervention(s) | Procedure: Radiofrequency Catheter Ablation | | Study Population Size | 232 | | Ages Eligible for Study | 18 years and older | | Sponsor(s) | Hospital General Universitario Gregorio Marañon; Centro Nacional de Investigación Cardiovascular (CNIC) | | Funded By | Other | | Study Type | Interventional | | Study Design | Treatment, Randomized, Single Blind (Subject), Parallel Assignment, Safety/Efficacy Study | | Other IDs | CNIC-13 | | Start Date | January 2009 | | Expected Completion Date | January 2012 | | Last Updated | May 6, 2008 |
| Study Seven |
| NCT ID | NCT00408200 | | Title | A Study of the Effectiveness of Antiarrhythmic Medications After Atrial Fibrillation Ablation | | Status | Completed | | Condition(s) | Atrial Fibrillation | | Intervention(s) | Drug: Propafenone, Flecainide, Sotalol, Dofetilide; Device: Radiofrequency Catheter Ablation | | Study Population Size | 168 | | Ages Eligible for Study | 18 years and older | | Sponsor(s) | University of Pennsylvania | | Funded By | Other | | Study Type | Interventional | | Study Design | Treatment, Randomized, Open Label, Uncontrolled, Parallel Assignment, Efficacy Study | | Other IDs | 805346HUP | | Start Date | November 2006 | | Expected Completion Date | June 2008 | | Last Updated | July 21, 2008 |
| Study Eight |
| NCT ID | NCT00729911 | | Title | Ablation Versus Amiodarone for Treatment of Atrial Fibrillation in Patients With Congestive Heart Failure and an Implanted Implantable Cardioverter-Defibrillator (ICD) | | Status | Not Yet Recruiting | | Condition(s) | Heart Failure | | Intervention(s) | Procedure: Atrial Fibrillation Ablation; Drug: Amiodarone | | Study Population Size | 120 | | Ages Eligible for Study | 18 years and older | | Sponsor(s) | Texas Cardiac Arrhythmia Research Foundation; Casa Sollievo della Sofferenza IRCCS; Catholic University, Italy; Southlake Regional Health Centre; Stanford University; University of Kansas; The University of Texas, Galveston; University of Foggia; Sutter Health | | Funded By | Other | | Study Type | Interventional | | Study Design | Treatment, Randomized, Open Label, Parallel Assignment, Efficacy Study | | Other IDs | AATAC-AF | | Start Date | August 2008 | | Expected Completion Date | August 2011 | | Last Updated | August 7, 2008 |
| Study Nine |
| NCT ID | NCT00643188 | | Title | Catheter Ablation Versus Standard Conventional Treatment in Heart Failure Patients With Atrial Fibrillation | | Status | Recruiting | | Condition(s) | Atrial Fibrillation; Heart Failure | | Intervention(s) | Procedure: Radiofrequency Ablation; Other: Conventional Treatment | | Study Population Size | 420 | | Ages Eligible for Study | 18 years and older | | Sponsor(s) | Biotronik GmbH & Co. KG | | Funded By | Industry | | Study Type | Interventional | | Study Design | Treatment, Randomized, Open Label, Parallel Assignment, Efficacy Study | | Other IDs | EP020 | | Start Date | January 2008 | | Expected Completion Date | January 2013 | | Last Updated | June 6, 2008 |
| Study Ten |
| NCT ID | NCT00721149 | | Title | NAVISTAR® THERMOCOOL® Catheter for the Treatment of Atrial Fibrillation -TX | | Status | Not Yet Recruiting | | Condition(s) | Heart Diseases; Arrhythmia; Atrial Fibrillation | | Intervention(s) | Device: Radiofrequency Ablation | | Study Population Size | 100 | | Ages Eligible for Study | 18 years and older | | Sponsor(s) | Biosense Webster, Inc. | | Funded By | Industry | | Study Type | Interventional | | Study Design | Other, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study | | Other IDs | BWI03130TXA | | Start Date | July 2008 | | Expected Completion Date | June 2010 | | Last Updated | July 22, 2008 |
| Study Eleven |
| NCT ID | NCT00587899 | | Title | Prophylactic Pulmonary Vein Isolation Study | | Status | Recruiting | | Condition(s) | Atrial Fibrillation | | Intervention(s) | Procedure: Pulmonary Vein Isolation | | Study Population Size | 154 | | Ages Eligible for Study | 18 years and older | | Sponsor(s) | Mayo Clinic | | Funded By | Other | | Study Type | Interventional | | Study Design | Prevention, Randomized, Single Blind (Outcomes Assessor), Historical Control, Parallel Assignment, Safety/Efficacy Study | | Other IDs | 06-005543 | | Start Date | January 2007 | | Expected Completion Date | December 2009 | | Last Updated | July 29, 2008 |
| Study Twelve |
| NCT ID | NCT00227344 | | Title | CACAF2 Study: Catheter Ablation for Cure of Atrial Fibrillation | | Status | Active, Not Recruiting | | Condition(s) | Atrial Fibrillation | | Intervention(s) | Device: RF Ablation; Drug: Drug Therapy | | Study Population Size | 126 | | Ages Eligible for Study | 18 years to 70 years | | Sponsor(s) | Biosense Webster EMEA | | Funded By | Industry | | Study Type | Interventional | | Study Design | Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study | | Other IDs | CACAF2 | | Start Date | December 2004 | | Expected Completion Date | March 2011 | | Last Updated | February 12, 2008 |
| Study Thirteen |
| NCT ID | NCT00392054 | | Title | First Line Radiofrequency Ablation Versus Antiarrhythmic Drugs for Atrial Fibrillation Treatment (The RAAFT Study) | | Status | Recruiting | | Condition(s) | Atrial Fibrillation | | Intervention(s) | Procedure: Pulmonary Vein Isolation; Drug: Control Group receives Anti-Arrhythmic Drugs per ACC/AHA 2006 Guidelines for the Management of Patients with AF | | Study Population Size | 400 | | Ages Eligible for Study | 19 years and older | | Sponsor(s) | Population Health Research Institute; Johnson & Johnson | | Funded By | Other / Industry | | Study Type | Interventional | | Study Design | Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study | | Other IDs | USMay1/07CANAug1/06EUJan1/07 | | Start Date | August 2006 | | Expected Completion Date | December 2009 | | Last Updated | October 10, 2007 |
| Study Fourteen |
| NCT ID | NCT00133211 | | Title | Radiofrequency Ablation (RFA) Versus Antiarrhythmic Drug Treatment in Paroxysmal Atrial Fibrillation (MANTRA-PAF) | | Status | Recruiting | | Condition(s) | Atrial Fibrillation | | Intervention(s) | Procedure: Radiofrequency Ablation | | Study Population Size | 300 | | Ages Eligible for Study | 18 years to 71 years | | Sponsor(s) | Danish Heart Foundation | | Funded By | Other | | Study Type | Interventional | | Study Design | Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study | | Other IDs | sks2005psh01 (MANTRA-PAF) | | Start Date | September 2005 | | Expected Completion Date | March 2009 | | Last Updated | November 6, 2007 |
| Study Fifteen |
| NCT ID | NCT00379301 | | Title | Efficacy of Different Ablation Strategies for Controlling Atrial Fibrillation | | Status | Recruiting | | Condition(s) | Atrial Fibrillation | | Intervention(s) | Procedure: Radiofrequency Ablation | | Study Population Size | 147 | | Ages Eligible for Study | 18 years and older | | Sponsor(s) | University of Pennsylvania | | Funded By | Other | | Study Type | Interventional | | Study Design | Treatment, Randomized, Open Label, Dose Comparison, Parallel Assignment, Efficacy Study | | Other IDs | UPenn805173 | | Start Date | October 2006 | | Expected Completion Date | November 2009 | | Last Updated | July 21, 2008 | References 1 www.ClinicalTrials.gov
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