Summary of Safety and Effectiveness (Draft)

 

1.   General Information

Trade Name           REVELATION® Tx Microcatheter with NavAblator™ Ablation System

Generic Name:       Cardiovascular Ablation Catheter

Description             REVELATION® Tx Microcatheter / NavAblator Catheter Ablation system consists of:

·        REVELATION TxREVELATION®Tx Ablation Microcatheter

·        NavAblator Ablation Catheter

·        Naviport™ Guiding Catheter

·        REVELATION® Tx SELECT™elect Switch Box

·        REVELATION® Tx Cables

Applicant:  Cardima®, Inc.

47266 Benicia Street

Fremont, CA 94538 USA

Toll Free          888-354-0300

Phone: 510-354-0300

Fax                  510-657-4476

 

Modular PMA #M010005P020039

 

Date of Panel Recommendation:

 

Date of notice of approval to the applicant:

 

 

2.   Indications for Use

The Cardima Inc., REVELATION® Tx Microcatheter with NavAblator RF 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 compatible radiofrequency generator, creating a set of continuous linear lesions along the lateral and septal walls and along the isthmus in the right atrium. 

The REVLATION® Tx is intended for the creation of continuous linear lesions for the purpose of interrupting arrhythmia pathways.

The NavAblator is intended for the creation of linear lesions at the isthmus for the purpose of interrupting arrhythmia pathways when the REVELATION Tx is not used to complete the isthmus region.

The REVELATION Tx and the NavAblator connect to standard mapping/recording equipment and to compatible RF generators with accessory cables and a passive switchbox interface.

The Naviport guiding catheter (an approved device) is intended for access and delivery of the REVELATION Tx to the desired atrial site.

3.   Device Description

The Cardima REVELATION® Tx Microcatheter System consists of a single use, steerable, multi-electrode ablation microcatheter (3.7F) with an atraumatic, flexible, non-electrically active tip, and a single use, deflectable NavAblator "hot tip" ablation catheter (8F) with an electrically active tip.  Accessories to the system include the Cardima Naviport® (a cleared device under K974683), the Tx Select SELECT™ Switchbox and the associated connecting cables.  

The connecting cables and the passive switchbox (Tx SELECT Switchbox) are the interface between both ablation catheters and any commercially available electrocardiograph, pacing stimulator and any commercially available endocardial radio frequency generator that is thermocouple compatible. 

The REVELATION® Tx catheter has eight flexible electrodes and eight thermocouple temperature sensors in a linear array on the distal end of the catheter.  The most distal tip of the catheter is a highly flexible (floppy) non-electrically active platinum coil for fluoroscopic visualization and atraumatic placement.  The REVELATION® Tx is designed for the creation of thin linear lesions in the atrium for the treatment of atrial fibrillation by placing the linear array of electrodes along a desired trajectory in the atrium, conforming to the curvature of the wall.

The companion endocardial ablation catheter, the NavAblator, has four electrodes, one of which is the "hot tip" RF ablation electrode with a thermocouple embedded in its tip.  The NavAblator is intended for the creation of lesions (either linear or focal) from its tip when diverse myocardial anatomy requires the features of a "hot tip" ablation catheter to achieve effective lesions.

Both ablation catheters in this system are designed for mapping intracardiac potentials, pacing and ablating cardiac tissue with RF energy. 

4.   Contraindications, Warnings, and Precautions

Contraindications

·        This procedure is contraindicated in patients with active systemic infection.

·        The catheters in this system should not be used to create lesions in conditions where the catheter would be unsafe (e.g., intracardiac thrombus).

Warnings

·        This device is not intended for ablation from within the coronary vasculature.

·        Use of RF energy may interfere with proper function of pacemakers and implantable cardioverter/defibrillators.  Refer to PPM/ICD manufacturer’s instruction on use of RF energy with these devices mentioned.

·        Never advance or retract device against unknown resistance or damage to device or its components may occur.

·        Improper handling or use including reuse of this device may result in device failure and/or possible complications.

Precautions

·        Catheter placement should be accomplished under fluoroscopic imaging.

·        The long-term risks of fluoroscopic exposure have not been established.

·        The long-term risks of radiofrequency ablation have not been established.

·        Use in conjunction with the Tx SELECT switchbox and Tx Catheter Cable.  (See technical specification and requirements)

·        Excessive bending or kinking of the device may cause damage to the device or its components.

·        Always consult the RF-Generator Operating Manual and follow precautions prior to delivery of RF-Energy.

·        The safety and effectiveness of the use of this system in treating children or pregnant women have not been established.

·        This device should only be used by physicians thoroughly trained in the techniques of transvenous intracardiac studies and/or electrophysiology studies.

 

5.   Alternative Practices and Procedures

According to recent ACC/AHA/ESC guidelines, the recommended clinical course for the treatment of Atrial Fibrillation is medical therapy (drugs) intended to first minimize risk of stroke with anticoagulants and second, in more advanced arrhythmias, control heart rhythm by cardioverting (mechanically or pharmaceutically) followed by maintenance of normal sinus rhythm (NSR). 

Stroke risk management involves antiplatelet/anticoagulant medication.  Heart rhythm management progresses from the use of beta blockers to antiarrhythmic drugs (AADs) that range from Class 1C AADs including propafenone and flecainide, to Class III AADs, including sotalol and Amiodarone that can sometimes precipitate significant side effects, including arrhythmias.

Anticoagulation therapy for stroke risk management requires long-term commitment from the patient for recurring clotting time evaluations and has its own risks associated with increased bleeding.

The antiarrhythmic drugs (AADs) tend to become less effective over time and AF can return in spite of all medications, continuing the risk of stroke and decreasing the quality of life for the patient with AF.  In addition, in the presence of heart disease, hypertension or coronary artery disease, AAD therapy faces still further challenges. 

Thus, AAD therapy for the management of AF is, at best, palliative.  Their ability to maintain sinus rhythm ranges from 39% to 79%.  It has been reported for a particular Canadian patient population that 65% of the patients maintained NSR on Class III agent (Amiodarone) after a mean follow up of 16 months.  However, these drugs can be proarrhythmic and organ toxic, precipitating such conditions as Torsade de pointes, ventricular tachycardia, thyrotoxicosis, prostatism and pulmonary and renal toxicity and photosensitivity. 

6.   Marketing History

The REVELATION® Tx Microcatheter has been approved for commercial distribution in the European Union since November, 1998 and has been distributed in EU countries since that date.  This device is also registered for commercial distribution in those other countries that accept EU certification (CE Mark).

 

 

7.   Potential Adverse Effects

Risks to patients include all those risks currently associated with electrophysiology diagnostic procedures and radiofrequency catheter ablation procedures, such as: 

 

     Bleeding

     Cardiac or vessel wall injury or perforation

     Cerebrovascular accident

     Conduction system abnormalities

     Death

     Hematoma at entry site

     Local or systemic infection

     Pericardial effusion

     Permanent atrioventricular block

     Phrenic nerve damage

     Pneumothorax

     Thromboembolic events

 

7.   Summary of Preclinical Studies

Biocompatibility

The devices were evaluated consistent with the requirements of ISO 10993.  The testing demonstrated that the devices that are subject of this submission are biocompatible based upon testing at the Level 1 classification of blood-contacting medical devices. 

 


 

TEST

SUMMARY OF RESULTS

CONCLUSION

In-Vitro Cytotoxicity

No evidence of causing cell lysis or toxicity greater than mild reactivity

Acceptable

In-Vitro Hemolysis

Mean hemolysis = 0%, 1%, 2%
(non-hemolytic = 0-2%)

Acceptable

USP Acute Systemic Toxicity in Mice

No evidence of systemic toxic reaction

Acceptable

USP Intracutaneous Toxicity in Rabbits (Acute)

No evidence of significant irritation or reactivity

Acceptable

Delayed Contact Sensitization in the Guinea Pig (Maximization Method)

No evidence of causing delayed dermal contact sensitization

Acceptable

Thromboresistance in Dog

Minimal thrombus formation, no different than control.

Acceptable

Rabbit Pyrogen Study

No evidence of pyrogenicity

Acceptable

C3a Complement Activation

Lower than “Low biomaterial reference control”

Acceptable

 

Animal Studies

Cardima conducted four animal studies in support of the safety and performance of the REVELATION®  Tx and the NavAblator.  These studies provided evidence of preclinical safety and evidence of the most appropriate system settings to achieve optimal ablation lesions in the right atrium to create a “non-surgical MAZE” approach to treating atrial fibrillation. 

Three animal studies of the REVELATION® Tx indicated that the REVELATION® Tx was capable of creating continuous, linear transmural lesions, that a continuous lesion can be formed from sequential electrode ablations; that a set temperature of 50°C-55°C at 35W maximum power output were the best procedural parameters for minimal coagulum formation and optimal lesion formation.  These studies also demonstrated that a low pre-ablation pacing threshold was an indicator of good tissue contact and that a large increase in the pacing threshold was a good indicator that lesions had been formed.  There were no device-related complications in any of these studies.  Further, no correlation between RF energy delivery parameters and lesion size and location could be clearly identified. 

In support of the NavAblator a study with six dogs was conducted to evaluate the safety and performance of the device when used to create linear lesions in the isthmus of the right atrium, where anatomical challenges may require a "hot tip" device to reach certain areas of the isthmus.  The procedural parameter settings used primarily in this study temperature was 60°C for 60 seconds with power output between 25W and 50W.

Device

Study+Objectives

N

Outcome

REVELATION® Tx

Performance of Revelation TxREVELATION® Tx  in Right Atrium of Goat.  Assessment of device performance, lesion formation and depth with single placement in beating heart of 3 acute and 4 sub-chronic (1-4 weeks) goats. Includes measurement of pacing thresholds, electrogram signal quality and thrombus/coagulum formation.

7

·     No catheter-related complications occurred.

·     Contiguous, transmural lesions were obtained. 

·     Thrombus was generally absent on electrodes at 45° and 50°C.

·     An upper power limit of 25W in this study showed good control of thrombus formation.

Performance of REVELATION® TxRevelation Tx  in Right Atrium of Canine.  Assessment of deployment, lesion creation and device performance with single placement (no re-positioning) at predetermined locations and predefined control set temperatures in the beating heart of 2 acute and 4 sub-chronic (1 week) dogs.  Confirmation of above study in different cardiac morphology.

6

·     No significant catheter placement difficulties in the IVC, SVC, or sub-Eustacian isthmus

·     Contiguous, transmural lesions were obtained in the isthmus with a superior approach. 

·     Bipolar and unipolar electrograms were typically of good quality without significant noise.

·     Pacing data confirmed. 

·     Small thrombus observed on some electrodes

·     Recommended temp set range (based on this study) is 50°-55°C

REVELATION® TxRevelation Tx

RF Lesion Formation in Canine Thigh Muscle.  Assessment of lesion size and thrombus formation in 28 lesions created in 2 dogs

2

·     Continuous lesion was formed from sequential electrode ablations. 

·     Thrombus was not observed when 45°C was used, occasionally at50° and 55°C

NavAblatorNavAblator™

Radio Frequency Ablation Using the NavAblater for In Vivo Lesion Formation.  Assess ability of NavAblatorNavAblator™ to form transmural lesions in the isthmus region of the right atrium, ability to position and map, and a lack of coagulum formation

6

·     No coagulum was observed on the catheter tip following ablation.

·     Pathology reports no pericardial effusion, perforation, thrombus or valvular damage in any of the 6 animals.

·     Pathology confirmed transmural lesions were formed.

·     Unipolar and bipolar electrograms were of good quality, free of noise, and equivalent to those obtained with Cordis-Webster catheter.

·     Pacing threshold was low (<1mA @ 2.0 msec) and was comparable to the Cordis-Webster catheter.

 


Electro-mechanical Studies

Consistent with the 1995 draft guidance from CDRH, FDA for Cardiac Ablation catheters (Mark Massi, Barbara Zimmerman) performance testing was conducted to demonstrate the reliability and material properties of the REVELATION® Tx and the NavAblator.

The REVELATION® Tx is not a deflectable catheter nor does it have an open lumen, so joint seal and deflection fatigue testing was not performed.  The NavAblator does not have a lumen, so joint seal testing was not performed.  However, it is a deflectable catheter, so deflection fatigue testing was conducted.  The results demonstrate the design of both catheters is robust and consistent with similar devices for similar indications, where comparison can be made.  Unlike "conventional" endocardial RF ablation catheters, the REVELATION® Tx has been designed to provide a more flexible and less traumatic interface with endocardial tissue at its distal tip. 

The electrical characteristics of the devices were evaluated consistent with IEC 60601-1 and 601-2-2 and found to be compliant with the relevant standards.

The accessory cables and the passive switchbox interface for this system were also tested for reliability and compliance with relevant international standards and found to be compliant.  In the case of the switchbox, a third-party evaluation was performed by TÜV Product Services and a certification of compliance was issued. 

8.   Summary of Clinical Studies

Study Design

The study design is a multi-center, prospective, non-randomized, single-arm, controlled study in which the patients serve as their own control.  The “control” is the establishment of a baseline for each patient during a monitoring period in which patients record symptomatic episodes of atrial fibrillation (AF) with portable event monitor cards and transmit these recordings once per week during a 30-day period prior to final determination of eligibility and subsequent treatment.  This study design is consistent with the recommendation for ablation catheter study designs reported by the Circulatory Support Advisory Panel in its meeting of June/July, 1995.

The purpose of the study is to assess the safety and effectiveness of the REVELATION® Tx Ablation System in the treatment of patients with drug refractory paroxysmal AF by creating linear lesions with RF energy in the right atrium.

Patient Assessment

Drug refractory patients with diagnosed paroxysmal atrial fibrillation were assessed prior to treatment to establish a baseline episode frequency of symptomatic atrial fibrillation.  Follow up assessments were conducted at one month, three months and six months post ablation for changes in episode frequency, changes in antiarrhythmic medication requirements, general cardiac status and adverse events.

Demographics

Gender

Age in years Mean ± SD

Age Range in Years

Frequency

%

Female

62.060.7 ± 10.711.2

27.9-77.1

2327

24.223.3

Male

56.455.7 ± 10.210.6

35.327.6-75.978.3

7289

75.876.7

Total

57.856.9  ± 10.610.9

27.927.6-77.178.3

95116

100.0

 

Data Aanalysis and Result

The dataresults indicate significant reduction in the frequency of spontaneous symptomatic AF episodes experienced by the patients in this study, with an average reduction of 73.6% ± 5.2%82.9 + 3.0 and a median reduction of 93.8__% with a 4.01% 3.38% complication rate.

In addition, these patients reported a significant improvement in quality of life, based upon improvements in the scores of the SF-36 and AFSS questionnaires, demonstrating improvement in all eight SF-36 quality of life scales at both the three and six month follow up assessments.  There were quite substantial and clinically significant and highly statistically significant improvements for four of the eight domains (Role Physical, Role Emotional, Vitality, and Social Functioning) at both of these follow up assessments, clearly indicating overall substantial patient benefit.

Criteria

3 Month

(n=93) freq/n (%)

6 Month

(n=81) freq/n (%)

# of subjects with Episode Reduction compared to Baseline

76/93 (83.9)

79/81 (97.5)

³50% Reduction a, c

58/93 (64.5)

69/81 (85.2)

100% Reduction

33/93 (35.5)

44/81 (54.3)

<50% Reduction c

33/93 (35.5)c

12/81 (14.8)c

No Reduction

15/93 (16.1)

2/81 (2.5)

Withdrew

4/93 (4.3)

8/81 (9.9)

Non-Compliant (event monitor)

4

22

Patient not yet at 3, 6 months

12

19

Mean % reduction ± SE

53.1 b ± 6.6

82.9 b  ± 3.0

a     ³75% for 3-4 baseline episodes       b p<0.0001

b   Statistics do not include five subjects with disputed numbers of baseline episodes.

c     Includes those with “no reduction” as a subset of the <50% reduction group.  In the >50% reduction group, those with 100% reduction are included.

 




 

Device Failures and Replacements

There were no device failures or replacements in this study.

9.   Conclusions Drawn from the Studies

Risk/Benefit

Risks to include all those risks associated with all electrophysiology diagnostic procedures and radiofrequency catheter ablation procedures.  The risks of the procedure are related primarily to mechanical injury to the heart and vessels from catheter manipulation and thermal injury due to RF current delivery, including the risk of thromboembolism and myocardial infarction.  The standard risks of anesthesia also exist and include allergic reactions, medical complications and death. 

Benefits for drug refractory patients is are the potential for reduced symptoms of AF without the adverse effects of the drugs or with a reduced dependency on the medication, for an improved quality of life. 

Safety

The Major complication rate associated with this study waswere 4.013.4%.  A small number (53) of minor complications associated with this study occurred in 26% of the subjects (31/115) and were largely mild and transient in nature, related to the cardiac catheterization procedure and not the devices.  There were and no deaths associated with this study.

 

Effectiveness

The study demonstrated that the majority of the patients treated in this study reported a statistically and clinically significant reduction in the frequency of AF episodes and similar improvements in quality of life.

The results of these studies have demonstrated the safety and effectiveness of the Cardima REVELATION® Tx Ablation System.

 

 

10.  Panel Recommendations

 

11.  CDRH Decision

 

10.Approval Specifications
Table 2, Clinical Success

Criteria

3 Month

(n=84) freq/n (%)

6 Month

(n=79d) freq/n (%)

# of subjects with Episode Reduction compared to Baseline

74/84 (88.1)

72/79 (91.1)

³50% Reduction a

57/84 (67.9)

67/79 (84.8)

100% Reduction c

32/84 (38.1)

37/79 (46.8)

<50% Reduction c

27/84 (32.1)c

12/79 (15.2)c

No Reduction

10/84 (11.9)

7/79 (8.9)

Withdrew

2/84 (2.4%)

7

Non-Compliant (event monitor)

4

1

Patient not yet at 3, 6 months

9

12

Mean % reduction ± SE

59.5 b, d ± 6.4

74.7 b, d ± 4.9

 

Patients were evaluated for Quality of Life on two established scales:  SF-36 and AFSS.  The results for the SF-36 are illustrated in Figure 4, below.

 

 

Figure 4, SF-36 Results Over Six Months

 

 

The Atrial Fibrillation Severity Scale results are illustrated in Figure 5, below.

 


 

Figure 5, AFSS Mean Scores Over Six Months


Device Labeling (Draft)

 

REVELATION® Tx Cardiac Ablation System

  Contents sterile in unopened, undamaged package

 

 CAUTION:  This device is intended for one use only. Do not re-sterilize or re-use the device.

 

CAUTION:  Federal (U.S.A) Law restricts this device to sale by, or on the order of a physician.

 

Description

The Cardima® REVELATION® Tx Microcatheter System consists of a single use, steerable, eight-electrode ablation microcatheter (3.7F), the REVELATION® Tx, with an atraumatic, flexible, non-electrically active tip, and a single use, deflectable NavAblator™ "hot tip" (4mm) ablation catheter (8F) with an electrically active tip.  Both catheters incorporate thermocouple sensors for temperature feedback.

 

 

 

Figure 1, Cardima REVELATION® Tx Microcatheter

 

 

 

 

 

Figure 2, Cardima® NavAblator

Intended Use

The Cardima®Cardima Inc., REVELATION® Tx Microcatheter with NavAblator RF 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 compatible radiofrequency generator, creating a set of continuous linear lesions along the lateral and septal walls and along the isthmus in the right atrium. 

 

The REVLATION® Tx is intended for the creation of continuous linear lesions for the purpose of interrupting arrhythmia pathways.

 

The NavAblator is intended for the creation of linear lesions at the isthmus for the purpose of interrupting arrhythmia pathways.

 

Contraindications

This procedure is contraindicated in patients with active systemic infection.

The catheters in this system should not be used to create lesions in conditions where the catheter would be unsafe (e.g., intracardiac thrombus).

 

Warnings

                                                                                                                                                                                   This device is not intended for ablation from within the coronary vasculature.

                                                                                                                                                                                   Use of RF energy may interfere with proper function of pacemakers and implantable cardioverter/defibrillators.  Refer to PPM/ICD manufacturer’s instruction on use of RF energy with these devices mentioned.

                                                                                                                                                                                   Never advance or retract device against unknown resistance or damage to device or its components may occur.

                                                                                                                                                                                   Improper handling or use including reuse of this device may result in device failure and/or possible complications.

 

Precautions

                                                                                                                                                                                   Catheter placement should be accomplished under fluoroscopic imaging.

                                                                                                                                                                                   The long-term risks of fluoroscopic exposure have not been established.

                                                                                                                                                                                   The long-term risks of radiofrequency ablation have not been established.

                                                                                                                                                                                   Use in conjunction with the Tx SELECT switchbox and Tx Catheter Cable.  (See technical specification and requirements)

                                                                                                                                                                                   Excessive bending or kinking of the device may cause damage to the device or its components.

                                                                                                                                                                                   Always consult the RF-Generator Operating Manual and follow precautions prior to delivery of RF-Energy.

                                                                                                                                                                                   The safety and effectiveness of the use of this system in treating children or pregnant women have not been established.

                                                                                                                                                                                   This device should only be used by physicians thoroughly trained in the techniques of transvenous intracardiac studies and/or electrophysiology studies.

 

Technical Specifications And Requirements

Cardima REVELATION® Tx Dimensional Specifications

Description

REVELATION® Tx

NavAblatorNavAblator™

Nominal Electrode Region Diameter

3.7 F, .048”, 1.2 mm

8 F, 0.105", 2.7 mm

Nominal Proximal Shaft Diameter

3.5 F, .045”, 1.1 mm

8 F, 0.105", 2.7 mm

Nominal Curve Reach

n/a

30 mm (01-044001, 01-044007, 01-044013) 40 mm (01-044002, 01-044008, 01-044014)

Working Length

150 cm

90 cm (01-044001, 01-044002)                  
110 cm (01-044007, 01-044008)
125 cm (01-044013, 01-044014)

Tip Coil Length

1.0 cm

n/a

Number of Electrodes

8

4 (1 ablation, 3 mapping)

Electrode Material

Platinum

Platinum

Ablation Electrode Length

6 mm

4 mm

Mapping Electrode Length

6mm

1.5 mm

Interelectrode Spacing

2 mm

2 mm

Connectors: Quantity

1

1

Switchbox Requirements (not included)

Tx SELECT™ Switchbox

Connecting Cable (not included)

Tx Catheter Cable, Tx ECG Cable

 

Tx RFG Cables for these commercially available RF Generators:

 

 

 


Directions




A.                                                                                                                                                                                   REVELATION® Tx System Setup (see Figure 3)

 

 

 

Figure 3, REVELATION® Tx Ablation System Set-up

 

 

1.                                                                                                                                                                                   Attach the RF generator ground pad securely to the patient’s skin per manufacturers instructions.

2.                                                                                                                                                                                   Connect the Cardima Tx SELECT Switchbox to the electrocardiograph, pacing stimulator, and RF generator using the appropriate connecting cables as specified in the Cardima Tx SELECT Switchbox Instructions For Use.

 

NOTE: Adaptor cables are available for the Stockert 70, Medtronic Atakr and in Europe, the Osypka HAT 300 Smart generator. Please consult a Cardima representative.

 

a                                                                                                                                                                                   Select the appropriate NAVIPORT® French size, curve reach and length. 

b.                                                                                                                                                                                   Connect an RHV (Rotating Hemostatic Valve) adapter to the NAVIPORT® hub. 

c.                                                                                                                                                                                   Connect a pressurized, heparin/ saline flush bag to the RHV.  Maintain a continuous drip.

Introduce an appropriate size angiographic guidewire (e.g., .038”) into the NAVIPORT®.

 


4.                                                                                                                                                                                   Prepare the REVELATION® Tx catheter for use.

a.                                                                                                                                                                                   Flush catheter with a heparin/saline solution while it is still in its protective dispensing coil.

Remove catheter from dispensing coil and confirm electrode coil integrity.

 

B.                                                                                                                                                                                   Atrial Access

1.                                                                                                                                                                                   Place the NAVIPORT®/guidewire assembly through the introducer sheath and advance to the targeted area into the atrium under fluoroscopic guidance.

Remove the guidewire from the NAVIPORT®.

3.                                                                                                                                                                                   Place the introducer over distal tip of the REVELATION® Tx to cover electrodes, then insert into RHV.  Advance the REVELATION® Tx through the introducer into the NAVIPORT®.

4.                                                                                                                                                                                    Remove or pull back the introducer.

5.                                                                                                                                                                                   Place the REVELATION® Tx at the targeted area under fluoroscopic guidance and then connect it to the Cardima REVELATION® Tx Catheter Cable.

Hand off opposite end (male end) to be connected to switchbox.

 

C.                                                                                                                                                                                   Determination of Catheter/Tissue Contact

1.                                                                                                                                                                                   Observe the catheter on the fluoroscope to confirm correct positioning.

2.                                                                                                                                                                                   Record bipolar electrical signals from the REVELATION® Tx.

In general, sharp electrograms with high frequency components and large relative amplitudes are suggestive of good contact.

 

RF Energy Delivery

1.                                                                                                                                                                                   Consult the appropriate RF generator operating manual before starting, and configure using the following settings:

 

Control Mode:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         Constant Temperature

Set Temperature:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         Initially 50° C

Maximum Power:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         35 W

Differential Impedance

Setting:                                                                                                                                                                                   Switch on if available and adjust to 20Ω.

If not available, monitor impedance and stop RF energy delivery if impedance increases by more than 20Ω.

Timer Set:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            60 seconds

 

These settings will allow power to be delivered up to a maximum of 35 W during the course of the burn.  RF energy will shutoff automatically after 60 seconds unless the impedance rises to a user-determined level in which case the shutoff will occur immediately.

2.                                                                                                                                                                                   Determine which electrodes will receive RF energy based on the tissue contact assessment.  Energy will be delivered to each electrode individually.

3.                                                                                                                                                                                    Set the switchbox to correspond with the electrode receiving energy.

4.                                                                                                                                                                                   If RF energy delivery automatically terminates (due to sudden rise in impedance) before 60 seconds, remove the REVELATION® Tx at the completion of the burn line and inspect for coagulum on the electrodes.  Loosely adherent coagulum may be carefully cleaned off the catheter electrodes with a saline-soaked 4 x 4 gauze.  Do not apply force to the tip coil when wiping the electrodes.  If strongly adherent char is not easily wiped off, or if any damage is observed, use another REVELATION® Tx catheter.

 

NOTE: Following RF ablation electrogram amplitudes should decrease at least 25-50%.

 

Note: To avoid phrenic nerve damage, prior to ablation, pace with a stimulator setting of 10 mA at 2 ms.  Palpate the patient for a diaphragmatic stimulation.  Do not apply RF energy at any location where diaphragmatic stimulation is detected in this manner.

 

5.                                                                                                                                                                                   Repeat steps D2-D4 above for the remaining electrodes with sufficient tissue contact.

6.                                                                                                                                                                                   Repeat section C above to assess changes that have occurred as a result of the RF energy application. Repeat RF energy applications along a given trajectory as necessary.  The set temperatures may be increased to a maximum of 60° C at the physician’s discretion.

7.                                                                                                                                                                                   Reposition the catheter in the next desired location and repeat sections C and D above until RF lesions are created in all desired trajectories.

 

NOTE: If frequent impedance rises during RF delivery are noted and/or an  excessive amount of coagulum appears on the electrodes, it may be advisable to reduce the temperature setting or reposition the catheter prior to the next RF application.

NOTE:  If bi-directional block is not achieved at the isthmus, the NavAblatorNavAblator™ may be used for this lesion.

 

E.                                                                                                                                                                                   NavAblatorNavAblator™ Preparation

3.                                                                                                                                                                                   Prepare the NavAblator for use.

a.                                                                                                                                                                                   Remove the NavAblator from the sterile package under sterile conditions.  As with all medical devices, always inspect prior to use to ensure no damage has occurred during shipping.

b.                                                                                                                                                                                   Prior to use, activate the deflection mechanism of the catheter by pulling the control knob.  Then push the control knob distally to straighten the tip before inserting.

c.                                                                                                                                                                                   Place the NavAblator through the vascular introducer and advance to the atrium.

4.                                                                                                                                                                                   Set the switchbox to electrode position 1 only.

5.                                                                                                                                                                                   Follow the steps in B through D to create a line of block at the isthmus.  The duration of RF energy delivery may be increased from 20 to 120 seconds at the physician's discretion.

 

 

Potential Complications

Risks to patients include all those risks currently associated with electrophysiology diagnostic procedures and radiofrequency catheter ablation procedures, such as: 

 

                                                                                                                                                                                   Bleeding

                                                                                                                                                                                   Cardiac or vessel wall injury or perforation

                                                                                                                                                                                   Cerebrovascular accident

                                                                                                                                                                                   Conduction system abnormalities

                                                                                                                                                                                   Death

                                                                                                                                                                                   Hematoma at entry site

                                                                                                                                                                                   Local or systemic infection

                                                                                                                                                                                   Pericardial effusion

                                                                                                                                                                                   Permanent atrioventricular block

                                                                                                                                                                                   Phrenic nerve damage

                                                                                                                                                                                   Pneumothorax

                                                                                                                                                                                   Thromboembolic events

 

 

Reports Of Adverse Events

 

There have been 57 occurrences of adverse events reported.


REPORTS OF CLINICAL STUDIES

Clinical studies were conducted of more than 80 subjects treated with the investigational ablation system at approximately 20 investigational sites.  The Study Design was a prospective, non-randomized, single arm, controlled study in which the patients serve as their own control.  The "control" consisted of a baseline model for each patient based upon the number of symptomatic atrial fibrillation episodes documented by that patient in a 30-day period (before treatment). 

 

The study subjects were required by inclusion criteria to have documented paroxysmal atrial fibrillation that did not respond to antiarrhythmic drugs.  If the patient was taking Amiodarone, he or she need be unresponsive (refractory) to that one drug, otherwise, the patient was required to be unresponsive to two antiarrhythmic drugs.

 

The objective of the study was to determine the safety and effectiveness of the treatment system based upon a reduction in the number of symptomatic AF episodes each patient had during the follow up period compared to the number of episodes the patient had during the baseline period.  If the patient was found to have demonstrated a reduction of 50% or more from the reported number of baseline episodes, he was deemed to be a clinical success.

 

Eligible patients were treated and followed for 24 months, with assessments at 1, 3, and 6, month intervals for the number of symptomatic atrial fibrillation episodes they recorded and transmitted and for the number and type of complications reported during the follow up period. 

 

Table 1, Mean Episode Reduction

Number of Episodes

Baseline

3 months

6 months

freq

%

freq

%

freq

%

Total

11195

100.0

9384

100.0

8179

100.0

Mean, SDa

9.9 ± 8.79.9 ± 9.1

 

3.9 b  ± 5.93.5 a ± 5.4

 

1.2 b ± 2.01.9 a ± 2.9

 

a                                                                                                                                                                                                                                               p<0.0001, paired paired t-test

 

Table 2, Clinical Success

Criteria

3 Month

(n=8493) freq/n (%)

6 Month

(n=79d81) freq/n (%)

# of subjects with Episode Reduction compared to Baseline

76/93 (83.9)74/84 (88.1)

79/81 (97.5)72/79 (91.1)

³50% Reduction a, c

58/93 (64.5)57/84 (67.9)

69/81 (85.2)67/79 (84.8)

100% Reduction c

33/93 (35.5)32/84 (38.1)

44/81 (54.3)37/79 (46.8)

<50% Reduction c

33/93 (35.5 c)27/84 (32.1)c

12/81 (14.8 c)12/79 (15.2)c

No Reduction

15/93 (16.1)10/84 (11.9)

2/81 (2.5)7/79 (8.9)

Withdrew

4/93 (4.3)2/84 (2.4%)

8/81 (9.9)7

Non-Compliant (event monitor)

44

221

Patient not yet at 3, 6 months

129

1912

Mean % reduction ± SE

53.1 b ± 6.659.5 b, d ± 6.4

82.9 b  ± 3.074.7 b, d ± 4.9

a  ³75% for 3-4 baseline episodes  b p<0.0001

b  Statistics do not include five subjects with disputed numbers of baseline episodes.

c    Includes those with “no reduction” as a subset of the <50% reduction group.  In the >50% reduction group, those with 100% reduction are included.

 

 

Patients were evaluated for Quality of Life on two established scales:  SF-36 and AFSS.  The results for the SF-36 are illustrated in Figure 4, below.

 

 

Figure 4, SF-36 Results Over Six Months

 

 

The Atrial Fibrillation Severity Scale results are illustrated in Figure 5, below.

 

 

Figure 5, AFSS Mean Scores Over Six Months


 


Customer Service Information

If you have questions or comments regarding the use of this device, please address them to:

 

  CARDIMA, Inc.    MedLink Europe B.V.

  47266 Benicia St.    Ravenswade 86-88

  Fremont, CA 94538 USA  3439 LD Nieuwegein

  (800) 354-0102    The Netherlands

  (510) 354-0102    Voice + 31-30-2-870458

  Fax (510) 354-0103    Fax    + 31-30-2-800388

  http://www.Cardima.com 

 

 

DISCLAIMER AND EXCLUSION OF OTHER WARRANTIES

There are no warranties of any kind that extend beyond the description of the warranties above.  Cardima disclaims and excludes all warranties, whether expressed or implied, or merchantability or fitness for a particular use or purpose.

 

LIMITED WARRANTIES

Cardima®Cardima, Inc. warrants that this product is free from defects in original workmanship and materials.  Cardima warrants that sterile products will remain sterile for a period of two years as labeled as long as the original packaging remains intact.  Cardima®’s products are designed for single use only.  Cardima®’s products are not designed for reuse. If any Cardima® product is proved to be defective in original workmanship or original materials, Cardima®, in its absolute and sole discretion, will replace or repair any such product, less charges for transportation and labor costs incidental to inspection, removal or restocking of product.

 

This limited warranty applies only to original factory delivered products that have been used for their normal and intended uses.  Cardima®’s limited warranty shall NOT apply to Cardima® products which have been resterilized, repaired, altered, or modified in any way and shall NOT apply to Cardima® products which have been improperly stored or improperly installed, operated or maintained contrary to Cardima®’s instructions.

 

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In any claim or lawsuit for damages arising from alleged breach of warranty, breach of contract, negligence, product liability or any other legal or equitable theory, the buyer specifically agrees that Cardima® shall not be liable for damages for loss of profits or revenues, loss of use of the product, loss of facilities or services, any downtime costs, or for claims of buyer’s customers for any such damages.  Cardima®’s sole liability for damages shall be limited to the cost to buyer of the specified goods sold by Cardima® to buyer which give rise to the claim for liability.

The buyer’s use of the product shall be deemed acceptance of the terms and conditions of these limited warrantees, exclusions, disclaimers and limitations of liability for money damages.

 

PATENT NUMBERS

 

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