Header Slide

1
(No Transcript)
2
FDA Advisory Panel MeetingMay 29, 2003

• Cardima, Inc.
• Linear Ablation REVELATION Tx Microcatheter RF
  Ablation System

3
Indications for Use

• Cardima, Inc., REVELATION Tx Microcatheter
  Ablation System is indicated for the treatment of
  atrial fibrillation in patients with drug
  refractory paroxysmal atrial fibrillation by
  mapping, pacing, and ablating with a set of
  continuous linear lesions in the right atrium.

4
Agenda

• Treatment Options for Atrial Fibrillation
• Corporate Profile
• Pre-clinical Studies
• Protocol Development/Validation
• Clinical Data Presentation
• Conclusions

5
Treatment Options for Atrial Fibrillation

• G. Neal Kay, M.D.
• Professor of Medicine
• Director of Electrophysiology
• University of Alabama at Birmingham
• Birmingham, AL

6
US and AF Age Distribution
U.S. populationx 1000
Population with AFx 1000
Population withatrial fibrillation
30,000 20,000 10,000 0
500 400 300 200 100 0
U.S. population
lt5
5-9
10-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
80-84
85-89
90-94
gt95
Age, yr
Feinberg WM. Arch Intern Med 1995155469-473.
7
Classification of Atrial FibrillationACC/AHA/ESC
Guidelines
AHA/ACC Guidelines J Am Coll Cardiol.
2001381231-1265.
8
d,l-Sotalol vs Placebo for AF/AFlTime to
Symptomatic Recurrence of AF/AFl
P values are vs placebo.Benditt Am J Cardiol
199984270-277.
9
Canadian Trial of Atrial Fibrillation (CTAF)
Excluded recurrence in first 21 days. Roy,
et al NEJM 2000342913-920.
10
Antiarrhythmic Drugs
CHF
Coronary Artery Disease
HTN
LVFW gt 1.4 cm
Sotalol
Amiodarone Dofetilide
Yes
No
Amiodarone Dofetilide
Amiodarone
Type 1C
Amiodarone Dofetilide Sotalol
Non-Pharmacologic Options
11
(No Transcript)
12
Circular Catheter in RSPV
Left Anterior Oblique
Right Anterior Oblique
13
Isolation of RSPV
14
PV Stenosis
15
Results of PV Isolation
Oral, et al. Circulation 20021051077.
16
Bi-atrial Surgery Better Outcome Than LA Alone
17
How does surgery work?
Cox JL, et al. Annals of Surg 1996224267
18
Comparative Results
Japan 2000
19
Cardima Profile
20
Cardima Background

• Since 1993 Cardima has been developing,
  manufacturing and marketing catheter based
  systems for the Electrophysiological field,
  exclusively.
• The devices include the PATHFINDER family of
  mapping devices, the VENAPORT, VUEPORT,
  NAVIPORT guiding catheters and the REVELATION
  family of mapping and ablation systems.

21

• Currently the company is marketing its diagnostic
  and guiding catheters in the USA, Canada, EU (CE
  Mark) and Japan.
• The REVELATION mapping and ablation family of
  devices is marketed in Canada and EU (CE Mark).

Cardima Background
22
Cardima FDA Product Approval History

• Diagnostic Microcatheters
• PATHFINDER (1997)
• REVELATION (1998)
• PATHFINDER mini (1998)
• TRACER (1999)
• Guide Catheters
• VENAPORT (1995)
• NAVIPORT (1998)
• VUEPORT (1998)
• Surgical Ablation System (2002)

23
PATHFINDER
24
Guide Catheters
25
REVELATION Series
26
Technology Comparison
FEATURES REVELATION TX CONVENTIONAL RF
Core Construction Angioplasty guidewire technology Plastic tube
Manufacturing From the outside-in From the inside-out
Flexibility Very flexible and torqueable Stiff, deflectable
Electrode Type Fine-wire coiled Sleeve
Ablation Electrode Number Eight One
Lesion Type Linear Focal
Power Reqd 7-35 W 50-70 W
27
Lesion Shape Comparison
Conventional Endocardial Hot Tip Catheter
Cardima Linear Coil Electrode
28
Linear Lesion Formation
Coil Ablation Electrode
Thermocouple
29
Pre-clinical Studies

• Hugh Calkins, M.D.
• Professor of Medicine
• Director of Electrophysiology
• The Johns Hopkins Medical Center
• Baltimore, MD

30
Pre-Clinical Studies

• Biocompatibility
• Compliant with applicable ISO 10993 requirements
• Reliability
• Compliant with Performance Testing requirements
  of Massi guidelines

31
Animal Studies

• David Keane, M.D. / Massachusetts General
  Hospital
• Performance of REVELATION Tx in Right Atrium of
  a Goat (n7)
• Mauricio Arruda, M.D.
• Performance of REVELATION Tx in the right atrium
  of a Canine (n6)
• RF Lesion Formation of REVELATION Tx in Canine
  Thigh Muscle (n2)
• RF Ablation Using the NavAblator in the Right
  Atrium (n6)
• Sam Asirvatham, M.D.
• Microcatheters Linear Lesion Transmurality (n
  14)
• Hugh Calkins, M.D.
• Prospective Comparison of Lesions (n10)

32
Lesion Comparison
Point-to-Point Technology
Cardima Linear Technology
33
Linear Lesions vs. Tip Ablator Lesions
MICRO System Standard RF Ablation P Value P Value
Length (mm) 29.6 ? 14.9 25 ? 11.2 25 ? 11.2 NS
Width (mm) 2.6 ? 0.9 4.9 ? 0.9 4.9 ? 0.9 0.0001
Depth (mm) 2.4 ? 0.8 2.1 ? 0.5 2.1 ? 0.5 NS
This slide will be revised to summarize my data
Hugh Calkins, M.D., The Johns Hopkins
34

Need data slide of results of this study
Can Microcatheters Produce Linear Lesions
without Sacrificing Transmurality in the Canine
Atrium? Circulation 1999 100(18)1-374 Sam
Asirvatham, M.D., Mayo Foundation
35
Protocol Development and Study Design

• Hugh Calkins, M.D.
• Professor of Medicine
• Director of Electrophysiology
• The Johns Hopkins Medical Center
• Baltimore, MD

36
Indications for Use

• The Cardima Inc., REVELATION Tx Microcatheter
  Ablation System is indicated for the treatment of
  atrial fibrillation in patients with drug
  refractory paroxysmal atrial fibrillation by
  mapping, pacing, and ablating with a set of
  continuous linear lesions in the right atrium.

37
Protocol Development Chronology

• Initial Study Design Collaboration with MGH,
  FDA, CARDIMA
• Phase Ia Mapping Study (PATHFINDER AF)
• Phase IIa Mapping and Ablation (REVELATION Tx)
• Circulatory Systems Recommendations for Clinical
  Trial Design
• Advisory Panel for AF Studies
• Phase IIb Mapping and Ablation (REVELATION Tx)
• Circulatory Systems Recommendations for Clinical
  Trial Design
• Advisory Panel for AF Studies
• Phase III Mapping and Ablation
• (REVELATION Tx and NAVABLATOR)

38
FDA Advisory Panel Recommendations
STUDY PARAMETER PANEL GUIDANCE CARDIMA STUDY
Trial Design Single Arm Non-Randomized ?
Control group Patient as control ?
Patient Population Failed 2 AADs or amiodarone ?
Baseline AF Two episodes over three months ?
39
FDA Advisory Panel Recommendations (contd)
PARAMETER PANEL GUIDANCE CARDIMA STUDY
Long-Term Success 50-75 reduction in frequency of symptomatic AF episodes Six months evaluation of therapy effectiveness ?
Safety Incidence of Major Complications ?
Quality of Life Improved quality of life may be a very important outcome. ?
40
Study Objective

• Right atrial ablation using the Cardima linear
  ablation system to achieve
• Reduction of symptomatic AF episodes
• Relief of symptoms
• Improvement in quality of life

41
Inclusion Criteria

• Three or more symptomatic AF episodes per month
  (documented by cardiac event monitor)
• Refractory to two or more (AADs) or to
  amiodarone alone
• Absence of significant structural heart disease,
  LA size lt 5 cm
• Absence of echocardiographic evidence (TEE) of
  intra-atrial thrombus, PFO, and/or ASD

42
Exclusion Criteria

• Acute ablation failure within 2 months
• MI within 6 weeks
• CVA or TIA within 6 months
• Pregnancy
• Coagulopathy or bleeding diathesis

43
Study Schema
44
Patient Follow-up
Assessment Study Interval
History, Physical Exam, 12-Lead EKG, Telephone interview Baseline, and office visits at 1, 3, 6 and 12 months post ablation 24 months
TEE Baseline
Echocardiogram and stress test Cardiac Event Monitor Baseline and 3 months Weekly and symptomatic transmissions _at_ baseline, months 1 to 3 and month 6
Quality of Life Questionnaires Baseline, Months 3 and 6
45
Study Endpoints

• Primary clinical endpoints
• Frequency of spontaneous symptomatic AF episodes
• Incidence of adverse effects

• Secondary clinical endpoint
• Quality of life based on the SF-36 and the AFSS

46
Success Criteria

• Primary Success
• ?50 reduction in AF episodes for patients with
  ? 5 AF episodes per month
• ?75 reduction in AF episodes for patients with
  ? 3-4 AF episodes per month

• Acute Procedural Success
• Reduction in amplitude, fragmentation or widening
  of local electrograms
• Appearance of split potentials
• Increase in pacing threshold

47
Success Criteria, contd

• Clinical Success
• 50 or more frequency reduction for subjects with
  5 or more episodes in 30-day baseline period
• 75 or more frequency reduction for subjects with
  3-4 episodes in 30-day baseline period.
• While maintained on the same anti-arrhythmic drug
  regimen or a reduced dosage

48
Sample Size

• N80 evaluable subjects at 6 months follow up
• Based on estimated patient success rate
• Statistical considerations with a clinical
  acceptable margin of error (SE0.056)
• This sample size was agreed to by the FDA

49
Summary

• Multiple animal studies have demonstrated safe
  creation of thin , transmural, linear ablation
  lesions.
• Clinical study was designed in collaboration with
  the FDA.
• Clinical study incorporates a large number of
  measures of safety and efficacy.
• As the first AF clinical trial this study is
  charting new waters.

50
Patient Population and Study Results

• Abraham G. Kocheril, M.D.
• Head of Cardiac Electrophysiology,
• Carle Heart Center.
• Associate Professor of Medicine,
• University of Illinois COM at U-C,
• Urbana, IL

51
Rationale for a Right Atrial Procedure

• Very likely lower risk than left atrial ablation
• May be more widely applicable
• If the risks are lower, physicians are likely to
  offer a right atrial ablation procedure to highly
  symptomatic patients even though the chances of
  success are lower
• May have application in combination with left
  atrial ablation

52
20 Clinical Sites
PRINCIPAL INVESTIGATOR CLINICAL INVESTIGATIONAL SITE
Ruey Sung, M.D. / Sung Chan, M.D. Stanford University Medical Center, Stanford, CA
Jeremy Ruskin, M.D. / David Keane, M.D. Massachusetts General Hospital, Boston, MA
Hugh Calkins, M.D. The Johns Hopkins Medical Center, Baltimore, MD
Douglas Packer, M.D. Mayo Clinic, Rochester, MN
Ted Friehling, M.D. Inova Inst. of Research Education, Falls Church, VA
Roger Marinchak, M.D./Douglas Esberg, M.D. Main Line Health Heart Center, Wynnewood, PA
David Wilber, M.D. University of Chicago, Chicago, IL
Bruce Hook, M.D. Catholic Medical Center, Manchester, NH
Seth Worley, M.D. Lancaster Heart Foundation, Lancaster, PA
Timothy Talbert, M.D. Diagnostic Center, Chattanooga, TN
Sanjeev Saksena, M.D. Cardiac Medicine Electrophysiology, Warren, NJ
Abraham Kocheril, M.D. Carle Heart Center, Urbana, IL
Larry Chinitz, M.D. NYU Medical Center, New York, NY
Imran Niazi, M.D. Wisconsin Center for Clinical Research, Milwaukee, WI
Jose Nazari, M.D. Cardiac Arrhythmia Consultants, Ltd., Chicago, IL
Randy Lieberman, M.D. Harper University Hospital, Detroit, MI
Roger Winkle, MD Sequoia Hospital, Redwood City, CA
Eli Gang, M.D. Access Clinical Trials, Beverly Hills, CA
Bruce Lerman, M.D. Cornell University Medical Center, New York, NY
Arjun Sharma, M.D. Regional Cardiology Associates, Sacramento, CA
53
Patient Accountability
Ablated n120
Withdrew n8
?6 Months Post Ablation n87
lt6 Months Post Ablation n18
Withdrew n7
54
Patients Withdrawn Prior to Six Months
Reason for Withdrawal pts
Unable/Unwilling to do follow-up 4
Not included in effectiveness analysis (4)
AVN ablation and/or PPM implantation 4
Included in effectiveness analysis as failure (3)
Included in effectiveness analysis (1)
55
Demographic and Baseline Characteristics
Age, mean SD, years 56.9 10.9
Male Gender 89 (77)
Cardiovascular Disease 84 (72)
Other Medical Conditions
Respiratory 30 (26)
Endocrine 30 (26)
Neurologic 22 (19)
Renal 21 (18)
56
Prior Cardiac Interventions
Type of Intervention Frequency ()
RF Ablation 33 (28)
CABG 9 (8)
DC Cardioversion 8 (7)
Pacemaker 7 (6)
PTCA/Stent 5 (4)
Angioplasty 2 (2)
57
Breakdown of Ablations(for 87 subjects with 6 mo
FU)
Prior RF Ablation Procedures Frequency ()
Subjects with Prior RFCA 22/87 (25)
Types
Atrial Flutter 22
Atrial Fibrillation 15
SVT/ Atrial Tachycardia 4
58
Baseline Arrhythmia Symptoms
Symptoms Presence, n ()
Palpitations 101 (87)
Fatigue 68 (59)
Shortness of Breath 58 (50)
Lightheadedness 43 (37)
Chest Pain 22 (19)
Other 34 (31)

59
Baseline Symptomatic AFEpisodes Per Month
Mean, SD 10.1 8.9
60
SF-36 Mean Scores at Baseline Study Group vs. US
Population
Adjusted for the age and gender distribution of
the study group
61
Study Results
62
Lesion Locations
63
Procedure Times
Total Time Mean SD (minutes)
Procedural Time 250 123
Fluoroscopy Time 47 46
64
Acute Procedural Success
Investigator assessment of acute procedural
success at the time of the procedure 110/118
(93) success
65
Long Term Results

• Primary Endpoint
• ?50 reduction for pts with ? 5 sAF episodes per
  month
• ?75 reduction for pts with 3-4 sAF episodes
  per month
• Results
• 69/81 (85) successful

66
Per-Subject Episode Reduction (n81)
67
Mean Episode Frequency Reduction (n81)
68
No symptomatic AF episodes at 6 months n
44/81 (54)
AF episode Reduction
69
Reduction in Common Arrhythmia Symptoms(Pre- vs.
Six Months Post-RFA)
70
Secondary Endpoint

• Improvement in Quality of Life Scores
• Atrial Fibrillation Severity Score (AFSS)
• SF-36

71
AFSS(Pre- vs. Six Months Post-RFA)
72
SF-36 Mean Scores Baseline vs. 6 Months
73
Effectiveness Cohorts
74
Effectiveness Evaluation
75
Primary Endpoint - Safety

• 2 Safety
• FDA guidelines and OPCs for VT studies state ?4
  major complications
• FDA Definitions of Complications in VT studies
  used as this protocols definition.
• Literature references of complications for other
  RFCA procedures cited for comparison range from
  8.3 to 22.2
• Cardimas complication rate in 120 treated
  patients 3.3 for Major Complications

76
Safety Results
Device or Procedure Related Major Complications Frequency () Upper 95 CI
Per Patient 4/120 (3) 8
Per Procedure (3 patients had a 2nd procedure) 4/123 (3) 8
includes uncertain relatedness
77
Major Complication Definition

• An adverse event that occurs within 7 days
  following investigational procedure and
• Is life-threatening
• Results in permanent impairment or damage to a
  body structure
• Requires significant intervention to prevent
  permanent impairment
• Requires hospitalization or an extended hospital
  stay
• Results in moderate transient impairment or
  damage to a body structure
• Requires intervention such as medication or
  cardioversion to prevent permanent impairment or
  damage to a body structure

FDA definition of acute major complications for
catheter ablation studies
78
Major Complications (Acute)

• Pericardial Effusion with Arrhythmia (n1)
• Sinus Node Injury Requiring Pacemaker
  Implantation (n1)
• Stroke (n1)
• AV Fistula (n1)

Not major complications 1 pacemaker within 7d,
but with documented preexisting sinus node
dysfunction. Patients with pacemakers
addressed later.
79
Late Adverse Events
AEs Reported by 31/120 (27) study subjects
Adverse Event Total
AVN Ablation/Permanent Pacemaker 6
Cardioversion 2
Infection (URI, UTI) 2
Sinus Node Dysfunction 1
Stroke (gt1yr FU) 1
Other 41
Total 53
80
Details of Other Adverse Events
81
Late Adverse Events Summary

• No reports of
• Mortality
• Bleeding
• Cardiac Perforation
• AV Fistula or arterial injury
• Thromboembolism
• 73 reported no complications

82
Summary Results
STUDY ENDPOINT DEFINITION PTs ()
Effectiveness
Primary Endpoint 50 Reduction in Frequency of sAF episodes at 6 Months 69/81 (85)
Clinical Success Reduction in sAF episodes While Maintained on Same AAD Regimen or Reduced Dosage 50/81 (62)
Quality of Life
Secondary Endpoint 1) SF-36 2) AFSS Statistically Significant QOL Improvements
Safety
Major Complications Serious Adverse Events 7 Days Post Procedure 4/120 (3.3)
83
Study Limitations

• Catheters/Lesion Sets
• Pacemakers
• Clinical Success
• Antiarrhythmic drugs
• TTM Compliance

84
Catheters/Lesion Sets

• REVELATION Tx used for all lateral and septal
  lines to create linear barriers to arrhythmias
• 4 mm Conventional RFA catheters used for Flutter
  Lines
• Cardima NAVABLATOR introduced in Phase III
• No significant difference in outcome
• Historical data do not support flutter line alone
  curing AF

85
Catheters/Lesion Sets

• Phase III FDA required that a conventional 4mm
  tip ablation catheter be specified.
• Cardima manufactured the NAVABLATOR to be
  specified as part of the system, solely for the
  creation of the flutter line at the isthmus
  when the anatomy was not compatible with the
  REVELATION Tx linear electrode array.

86
Primary Endpoint Success(Episode Reduction) by
Flutter Line Device
A, B D Lines REVELATION Tx (n73) REVELATION Tx (n73) REVELATION Tx (n73) REVELATION Tx (n73)
Isthmus line NAVABLATOR (n28) REVELATION Tx (n17) Other (n28) Total (n73)
Primary Success1 21/28 (75) 16/17 (94) 26/28 (93) 63/73 (86)
Episode Reduction2 6.0 10.8 8.6 6.1 10.0 10.6 8.2 9.8
Percent Episode Reduction2 76.6 33.5 91.4 16.6 89.1 18.5 84.5 26.1
1 Primary success, 50 reduction in episodes as per protocol, freq/n, 2 mean SD Includes 2 subjects treated with the REVELATION Tx and the NAVABLATOR Includes 20 subjects treated with REVELATION Tx or the NAVABLATOR and Other 1 Primary success, 50 reduction in episodes as per protocol, freq/n, 2 mean SD Includes 2 subjects treated with the REVELATION Tx and the NAVABLATOR Includes 20 subjects treated with REVELATION Tx or the NAVABLATOR and Other 1 Primary success, 50 reduction in episodes as per protocol, freq/n, 2 mean SD Includes 2 subjects treated with the REVELATION Tx and the NAVABLATOR Includes 20 subjects treated with REVELATION Tx or the NAVABLATOR and Other 1 Primary success, 50 reduction in episodes as per protocol, freq/n, 2 mean SD Includes 2 subjects treated with the REVELATION Tx and the NAVABLATOR Includes 20 subjects treated with REVELATION Tx or the NAVABLATOR and Other 1 Primary success, 50 reduction in episodes as per protocol, freq/n, 2 mean SD Includes 2 subjects treated with the REVELATION Tx and the NAVABLATOR Includes 20 subjects treated with REVELATION Tx or the NAVABLATOR and Other
87
Pacemakers Safety Relationship

• 3 Pacemakers Shortly After Procedure
• All 3 had known preexisting sinus node
  dysfunction
• II b 802 HR 49 when in SR
• II b 607 sinus pauses, 34 episodes to 1 at 6 mo
• III 1411 sinus brady, 3 sec pauses, 6 to 1
• Not major complications sinus node dysfunction
  unmasked by AF ablation
• Not likely to have damaged SA node by ablation

88
Pacemakers Effectiveness Relationship

• Per protocol Subjects electing to receive
  implantable ppms prior to 6 mo f/u will be
  considered failures.
• Intent subjects should not require adjunctive
  pacemaker therapy to address AF
• Not all pts receiving ppms fall into this
  category
• Patients with pacemakers not excluded from study

89
Pacemaker Outcomes
Total Post Procedure Device Implants 20
Post Procedure Device Implants lt6months 13
PPM for pre-existing SSS or brady 6 2 WD
ICD for Sinus Node injury at Tx (not WD) 1 Reported as AE
DDDR for AV block NSVT 1 Due to dofetilide from pre-study
AVN/PPM lt6 mo 5
Flutter ablation AVN/PPM (no sAF reported prior to Tx 1 WD (moved to another city)
Insurance coverage changed, new Dr. recommended AVN/PPM 1 WD lt6 mo
Treatment failures 3
90
Effectiveness Results
91
Percentage Of Patients Who Achieved Long Term
Success Including Failures"
Subject Groups Success (sAF ?) Success (sAF ?)
Subject Groups n
- 3 failures, - 5 patients with indeterminate baseline episodes 69/81 85
3 failures, 5 with indeterminate baseline episodes 73/89 82
92
Clinical Success at Six Months

• Reduction in sAF episodes while maintained on
  the same anti-arrhythmic drug regimen or a
  reduced dosage
• Result 50/81 study subjects (62) had a
  reduction in AF episodes with either no change or
  a decrease in AAD regimen.

93
Late Follow Up Status
Description 12 months n61 24 months n30
NSR
AEs
Mortality
AADs
94
AADs

• Primary endpoint was reduction in AF frequency
  independent of AAD use (69/81)
• Study population was drug refractory (avg. 3) and
  had concomitant medical conditions
• Clinical Success defined per protocol
  Reduction in sAF episodes while maintained on
  the same anti-arrhythmic drug regimen or a
  reduced dosage
• As determined by clinical site, 19/69 had
  increase in AADs
• Given current information on the efficacy of
  AADs, it is difficult to determine a true
  increase in an AAD regimen

95
Treatment Algorithm for AF
Sotalol or beta-blockers are the initial drugs
of choice for adrenergic AFIB. Consider
nonpharmacologic options to maintain sinus rhythm
if drug failure occurs. HF heart failure CAD
coronary artery disease LVH left ventricular
hypertrophy
96
Patients with Decrease/No Change in AADs(n60)

• 36 patients had decrease in AADs at 6 months
• 6 patients were off AADs at 6 months
• 18 patients had no change in AADs at 6 months

97
Patients with Increased AADs (n21)

• 19 had reduction in sAF episodes (success)
• 10/19 show a 100 reduction in sAF episodes at 6
  months with increases to an AAD regimen to
  which they were previously refractory
• The remaining 9/19 had gt 50 reduction in episodes

98
Changes in AADs
99
Patient Success by AAD Use at Six Months
100
Transtelephonic Event Monitoring

• Three redundant mechanisms for symptomatic
  episode monitoring
• Transtelephonic event monitoring
• Investigator interrogation at scheduled
  assessment intervals
• AFSS questionnaire

101
Transtelephonic Event Monitoring Protocol

• Record and transmit each symptomatic episode
• Transmit at least weekly (with or without
  symptoms)
• Perform as above at 1, 3 and 6 months post
  ablation

102
Baseline TTM

• Patients were blinded to required number of sAF
  episodes for study eligibility
• TTMs reviewed by independent cardiologist to
  verify sufficient sAF episodes for study
  eligibility

103
sAF Assessment at 6 Months

• TTM
• Capture both spontaneous and scheduled
  transmissions
• Arrhythmic events/CRF
• Documentation of AF frequency and severity
• EKG
• AFSS questionnaire
• Documentation of AF frequency and severity

104
TTM Compliance
Description Baseline (n86) Baseline (n86) 6 Months (n65) 6 Months (n65)
Description Mean, SD Range Mean, SD Range
Transmissions per Month 15.5 11.4 5-53 3.9 2.4 1-11
Symptomatic AF Episodes per Transmission 57.4 24.4 0-100 29.5 35.6 0-100
Symptomatic AF Episodes per Month 9.0 8.9 0-50 1.3 2.1 0-11
22 subjects did not transmit recordings at six
months. All had EKG/Office Visit at 6 month FU
One subject not included
105
TTM Compliance
106
TTM Compliance
Patient Compliance with 6-Month Assessments of
Arrhythmic Events
Assessment Pts Completed (n81)
TTM 60 (74)
Arrhythmia Symptoms 80 (99)
EKG 80 (99)
AFSS Questionnaire 74 (91)
21/81 pts did not transmit at all during
6-month post ablation
107
AFSS Mean Scores at Six Monthsby Six-Month
Transmission Compliance
108
Summary of Study Results

• This is the first multicenter clinical trial of
  catheter ablation for atrial fibrillation to be
  completed
• Right atrial linear ablation offers a level of
  success for control of paroxysmal atrial
  fibrillation
• Most patients continued on AADs at the same or
  lower dose
• This moderate level of success was accomplished
  with a very low risk of serious complications

109
Study Strengths

• Robust Study Design - Patients acted as their own
  control
• Study consistent with FDA Advisory Panel
  recommendations
• Use of TTM provided an objective measure of
  therapy success
• Use of subjective measures of therapy
  effectiveness (i.e., QOL) captured important
  patient parameters
• Study demonstrated excellent safety profile
• Study demonstrated clinically meaningful
  improvement in patient outcomes

110
Risk Benefit

• The lower risks of this relatively simple
  procedure are likely to allow it to be performed
  by a wider range of physicians than a complex
  left atrial ablation procedure
• It is likely that a simple right atrial ablation
  procedure will be offered to patients with highly
  symptomatic paroxysmal atrial fibrillation before
  more risky techniques

111
Conclusions

• Effectiveness
• Reduction in sAF episodes at 6 mo 69/81
  (85)
• No sAF at 6 months 44/81 (54)
• Off all AADs 6/81 (7 )
• Reduction in AADs 36/81 (86)
• Off amiodarone 9/81 (11 )
• Quality of Life
• Significant improvements
• Safety
• No Mortality 0/120
• Major Complications 4/120 (3)

112
Conclusions

• REVELATION Tx is a new RF catheter ablation
  technology specifically designed to create linear
  lesions in the right atrium
• Provides an important treatment option for many
  patients with drug refractory paroxysmal AF
• Addresses currently unmet public health need for
  safe and effective treatment of AF, a disease of
  great clinical significance to the medical
  community, both in terms of patient suffering and
  high medical costs of treating AF and its
  clinical sequelae
• This technology has been demonstrated to
  eliminate gt 50 of symptomatic AF episodes in
  treated patients

113
Closing Remarks

• G. Neal Kay, M.D.
• Professor of Medicine
• Director of Electrophysiology
• University of Alabama at Birmingham
• Birmingham, AL

114
Summation

• AF a significant clinical challenge
• Maze lesions
• Protocol development
• Clinical Results
• Future technology requirements

115
Current Clinical Need

• Catheter with Approved indication for AF
• Safe

116
REVELATION Tx