← Product Code [OAD](/productcode/OAD) · P030031S100

# THERMOCOOL SMARTTOUCH® SF Catheter (P030031S100)

_Biosense Webster, Inc. · OAD · Sep 30, 2020 · Cardiovascular · APPR_

**Canonical URL:** https://fda.innolitics.com/device/P030031S100

## Device Facts

- **Applicant:** Biosense Webster, Inc.
- **Product Code:** [OAD](/productcode/OAD.md)
- **Decision Date:** Sep 30, 2020
- **Decision:** APPR
- **Device Class:** Class 3
- **Review Panel:** Cardiovascular
- **Attributes:** Therapeutic, Real-World Evidence

## Real-World Evidence

| Submission | Device | Sponsor | RWD Sources | RWE Use Summary | Key Tags |
| --- | --- | --- | --- | --- | --- |
| P030031S100 · Sep 30, 2020 | THERMOCOOL SMARTTOUCH® SF Catheter | Biosense Webster, Inc. | Electronic Health Records (EHR) | A retrospective analysis of EHR data is required as a Post-Approval Study (PAS) to evaluate long-term effectiveness and safety of the device in a real-world setting through 36 months of follow-up. | Post-Approval Study; EHR; Retrospective Analysis; Persistent Atrial Fibrillation |

### Clinical Evidence

| Study Design | Population | Comparator | Key Endpoints |
| --- | --- | --- | --- |
| The Real-World Experience of Catheter Ablation of Persistent Atrial Fibrillation (PAS); Retrospective analysis of electronic health records (EHR); Follow-up/Duration: 36 months | 350 consecutive eligible persistent atrial fibrillation (PsAF) patients aged 18 years or older who underwent first-time catheter ablation with the THERMOCOOL SMARTTOUCH SF Catheter; Sample Size: 350 | Not applicable for this study | Primary effectiveness composite endpoint (direct current cardioversion, repeat ablation, or hospitalization for AF/atrial arrhythmia at 12-month follow-up); Primary safety measurements (primary adverse events within 7 days of ablation). |

## Indications for Use

The Biosense Webster THERMOCOOL SMARTTOUCH® SF Navigation Catheter and related accessory devices are indicated for catheter-based cardiac electrophysiological mapping (stimulating and recording) and, when used with a compatible RF generator, for the treatment of: - Type I atrial flutter in patients age 18 or older. - Drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with compatible three-dimensional electroanatomic mapping systems. - Drug refractory recurrent symptomatic persistent atrial fibrillation (defined as continuous atrial fibrillation that is sustained beyond 7 days but less than 1 year), refractory or intolerant to at least one Class I or III antiarrhythmic medicine, when used with compatible three-dimensional electroanatomic mapping systems.

## Device Story

Catheter-based cardiac electrophysiological mapping and RF ablation device; used in clinic/hospital settings by physicians. Inputs: electrical signals from heart tissue; contact force data from tip-mounted Nitinol spring/magnetic sensor assembly. Transforms inputs via CARTO® 3 Navigation System; displays real-time contact force (grams) and location. Output: RF energy delivered to endocardial tissue to create lesions. Benefits: real-time contact force feedback allows precise tissue contact, potentially reducing procedure time and fluid infusion. Affects clinical decision-making by guiding ablation location and force application to treat atrial arrhythmias. Used with compatible RF generators and irrigation pumps.

## Clinical Evidence

Evidence includes two prospective, multicenter, pivotal clinical trials. SMART SF study (IDE G140189, N=159) for paroxysmal AF met primary safety endpoint (2.5% AE rate). PRECEPT study (IDE G140102, N=348) for persistent AF met primary safety (4.7% AE rate, 97.5% UCB 7.4% < 16% goal) and effectiveness (59.3% success rate, 97.5% LCB 53.4% > 40% goal) endpoints. Primary endpoints assessed freedom from AF/AFL/AT recurrence and incidence of primary adverse events within 7 days. Quality of life improved significantly (AFEQT scores).

## Technological Characteristics

Percutaneous, deflectable (uni/bi-directional) irrigation catheter. Features Nitinol spring contact force sensor with magnetic coils (transmitting/receiving). Materials identical to predicate devices (biocompatible). Energy source: RF generator. Connectivity: wired to CARTO® 3 Navigation System. Sterilization: Ethylene Oxide (EtO) per ISO 11135. Software: SMARTTOUCH® module for real-time force/location visualization.

## Regulatory Identification

For the treatment of atrial flutter.

## Predicate Devices

- NAVISTAR® THERMOCOOL® Catheter ([P030031](/device/P030031.md))
- EZ STEER® THERMOCOOL® NAV Catheter ([P030031](/device/P030031.md)/S009)
- THERMOCOOL® SF NAV Catheter ([P030031](/device/P030031.md)/S025)
- THERMOCOOL SMARTTOUCH® Catheter ([P030031](/device/P030031.md)/S053)

## Reference Devices

- Lasso 2515 Nav eco Catheter

## Submission Summary (Full Text)

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# SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)

# I. General Information:

Device Generic Name: Electrode, percutaneous, conduction tissue ablation

Device Trade Names: THERMOCOOL SMARTTOUCH® SF Bi-Directional Navigation Catheter
THERMOCOOL SMARTTOUCH® SF Uni-Directional Navigation Catheter

Applicant's Name and Address: Biosense Webster, Inc.
31 Technology Drive, Suite 200
Irvine, CA 92618

Premarket Approval Numbers: P030031/S072 (for paroxysmal atrial fibrillation)
P030031/S100 (for persistent atrial fibrillation)

Date of Panel Recommendation: None

Date of FDA Notice of Approval to Applicant: P030031/S072 – August 11, 2016
P030031/S100 - September 30, 2020

The original PMA P030031 was approved on November 5, 2004. The ThermoCool SmartTouch SF Navigation Catheter was approved in PMA P030031/S072 on August 11, 2016 and is indicated for treatment of (1) Type I atrial flutter in patients age 18 or older, and (2) Drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with compatible three-dimensional electroanatomic mapping system. The current supplement P030031/S100 was submitted to expand the indication for the ThermoCool SmartTouch SF Navigation Catheter to treat symptomatic, drug refractory persistent atrial fibrillation.

# II. Indications for Use

# THERMOCOOL SMARTTOUCH® SF Catheter

The Biosense Webster THERMOCOOL SMARTTOUCH® SF Navigation Catheter and related accessory devices are indicated for catheter-based cardiac electrophysiological mapping (stimulating and recording) and, when used with a compatible RF generator, for the treatment of:

- Type I atrial flutter in patients age 18 or older.
- Drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with compatible three-dimensional electroanatomic mapping systems.

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- Drug refractory recurrent symptomatic persistent atrial fibrillation (defined as continuous atrial fibrillation that is sustained beyond 7 days but less than 1 year), refractory or intolerant to at least one Class I or III antiarrhythmic medicine, when used with compatible three-dimensional electroanatomic mapping systems.

The THERMOCOOL SMARTTOUCH® SF Navigation Catheter provides a real-time measurement of contact force between the catheter tip and heart wall, as well as location information when used with CARTO® 3 Navigation System.

### III. Contraindications

The THERMOCOOL SMARTTOUCH® SF Navigation Catheters are contraindicated for the following types of patients:

1. If the patient has had a ventriculotomy or atriotomy within the preceding eight weeks because the recent surgery may increase the risk of perforation.
2. In the patient with a myxoma or an intracardiac thrombus as the catheter could precipitate an embolus.
3. In patients with prosthetic valves as the catheter may damage the prosthesis.
4. In the coronary vasculature due to risk of damage to the coronary arteries.
5. In patients with an active systemic infection because this may increase the risk of cardiac infection.
6. Via the transseptal approach in a patient with an interatrial baffle or patch because the opening could persist and produce an iatrogenic atrial shunt.
7. Via the retrograde trans-aortic approach in patients who have had aortic valve replacement.
8. With a long sheath or short introducer < 8.5 French in order to avoid damage to the catheter shaft.

### IV. Warnings and Precautions

A list of Warnings and Precautions can be found in the THERMOCOOL SMARTTOUCH® SF Navigation Catheter labeling (Instructions for Use)

### V. Device Description

The THERMOCOOL SMARTTOUCH® SF Catheter utilizes a technology that measures the contact force between the catheter tip and endocardial tissue when connected to the CARTO® 3 System. The contact force sensing technology of the THERMOCOOL SMARTTOUCH® SF Catheter is equivalent to that of the standard THERMOCOOL SMARTTOUCH® Catheter. The THERMOCOOL SMARTTOUCH® SF Catheters are offered in both uni-directional and bi-directional deflectable platforms from product families D-1347-XX-S and D-1348-XX-S respectively as described in Table 1 below.

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Table 1: THERMOCOOL SMARTTOUCH® SF Catheters

|  Family | Curve Type | Part Numbers  |
| --- | --- | --- |
|  THERMOCOOL SMARTTOUCH® SF Bi-Directional Catheter | D-D | D-1348-01-S  |
|   |  F-F | D-1348-02-S  |
|   |  J-J | D-1348-03-S  |
|   |  F-J | D-1348-04-S  |
|   |  D-F | D-1348-05-S  |
|  THERMOCOOL SMARTTOUCH® SF Uni-Directional Catheter | D | D-1347-01-S  |
|   |  F | D-1347-02-S  |
|   |  J | D-1347-03-S  |

The uni-directional catheter is built on a similar platform and deflects with a similar deflection mechanism as the NAVISTAR® THERMOCOOL® Catheter, part number D-1197-XX-S. The bi-directional catheter is designed on a similar platform as the EZ STEER® THERMOCOOL® NAV Catheter, part number D-1292-XX-S. Both uni-directional and bi-directional catheters utilize a multi-hole tip electrode similar to the THERMOCOOL® SF NAV Catheter, part numbers D-1313-XX-S and D-1315-XX-S.

The catheter is compatible with the following devices: SMARTABLATE® Generator, Stockert 70 Generator, SMARTABLATE® Pump, nGEN™ Pump, COOLFLOW® Pump, SMARTABLATE® Tubing, and COOLFLOW® Tubing. For description of the operation of the compatible devices refer to the directions for use for the devices.

### Submission History

The submission history for the NAVISTAR® THERMOCOOL®, EZ STEER® THERMOCOOL® NAV, THERMOCOOL® SF NAV and THERMOCOOL SMARTTOUCH® Catheters is described in Table 2 below.

Table 2: Submission History for Precedent Devices

|  Submission | Description | Date of Approval  |
| --- | --- | --- |
|  P030031 | Approval of the NAVISTAR® THERMOCOOL® Catheter for the treatment of type I atrial flutter. | 11-11-2004  |
|  P030031/S009 | Approval of the EZ STEER® THERMOCOOL® NAV Catheter for the treatment of type I atrial flutter | 09-30-2008  |
|  P030031/S011 | Approval of the NAVISTAR® THERMOCOOL® Catheter and EZ STEER® THERMOCOOL® NAV Catheter for the treatment of drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with compatible three-dimensional electroanatomic mapping systems. | 02-06-2009  |
|  P030031/S025 | Approval of the THERMOCOOL® SF NAV Bi-Directional Catheter for the treatment of type I atrial flutter, and drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with compatible three-dimensional electroanatomic mapping systems. | 12-21-2011  |

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|  Submission | Description | Date of Approval  |
| --- | --- | --- |
|  P030031/S034 | Approval of the THERMOCOOL® SF NAV Uni-Directional Catheter for the treatment of type I atrial flutter, and drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with compatible three-dimensional electroanatomic mapping systems. | 12-21-2011  |
|  P030031/S053 | Approval of the THERMOCOOL SMARTTOUCH® Catheters (D-1327 and D-1336) for the treatment of type I atrial flutter, and drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with compatible three-dimensional electroanatomic mapping systems. | 2-11-2014  |
|  P030031/S072 | Approval for the THERMOCOOL SMARTTOUCH® SF Catheters, part numbers D-1347-XX-S and D-1348-XX-S, indicated for catheter-based cardiac electrophysiological mapping (stimulating and recording) and, when used with a compatible RF generator, for the treatment of: 1) Type I atrial flutter in patients age 18 or older; and 2) Drug refractory recurrent symptomatic paroxysmal atrial fibrillation, when used with compatible three dimensional electroanatomic mapping systems. The THERMOCOOL SMARTTOUCH® SF Navigation Catheter provides a real-time measurement of contact force between the catheter tip and heart wall, as well as location information when used with CARTO® 3 Navigation System. | 8-11-2016  |
|  P030031/S100 | Approval for the THERMOCOOL SMARTTOUCH® SF Catheters, part numbers D-1347-XX-S and D-1348-XX-S, for drug refractory recurrent symptomatic persistent atrial fibrillation (defined as continuous atrial fibrillation that is sustained beyond 7 days but less than 1 year), refractory or intolerant to at least one Class I or III antiarrhythmic medicine, when use electroanatomic mapping systems | -  |

## SMARTTOUCH™ Technology

Both the THERMOCOOL SMARTTOUCH® and THERMOCOOL SMARTTOUCH® SF Catheters utilize the same contact force sensing technology. The SMARTTOUCH® Catheters feature a sensor assembly embedded in the tip section that transmits both location and contact force information to the CARTO®3 Navigation System. The tip is illustrated in Figure 1. The contact force technology consists of a Nitinol spring located just proximal to the tip dome. A transmitting coil is located at the distal end of the spring and three receiving coils are located at the proximal end. The three receiving coils are positioned 120° apart and measure the signal strength from the transmitting coil. The catheter is calibrated so that the force versus displacement of the spring is calculated and written to an EEPROM located in the catheter handle. As a force is applied to the tip dome, the spring is displaced and the signals from each receiving coil are calculated into a force reading that is displayed to the user on the CARTO®3 Navigation System.

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![img-0.jpeg](img-0.jpeg)

Tip Electrode w/ Irrigation

Transmitter Coil

Nitinol Spring

Ring Electrodes (3)

Receiving Coils

Figure 1. SMARTTOUCH® Tip Section

The amplitude of the force signal emitted from the transmission coil is measured by the three vertical receiving coils proximal to the spring to determine the deflection of the spring. Those signals are used to calculate the force on the spring, and thus on the tip electrode, using the calibration information stored on the EEPROM related to each catheter's unique spring constant. The signal is processed by the CARTO®3 System. The CARTO® 3 System's SMARTTOUCH™ software module enables display of the actual force (in grams) applied to the tissue through the catheter tip, in real-time, using a dedicated graph. Both the force value is displayed (in grams) as well as the force direction as shown in Figure 2 below.

![img-1.jpeg](img-1.jpeg)

Figure 2: Dashboard Display of force magnitude (grams) and axial-lateral angle for force

The Real-Time Graph Viewer graph on the CARTO® 3 System displays force magnitude over time, as well as power, temperature and impedance graphs (Figure 3).

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![img-2.jpeg](img-2.jpeg)

Figure 3: Real-Time Viewer Graph

### VI. Alternative Practices and Procedures

Alternatives to ablation therapy with the THERMOCOOL SMARTTOUCH® SF Catheter include ablation therapy with a non-contact force sensing catheter, use of drug therapy for arrhythmia control, ablating the natural pacemaker of the heart and implanting an artificial pacemaker, or implantation of a device that paces or shocks the heart to stop the arrhythmia.

There are several other alternatives for the correction of drug refractory, recurrent, symptomatic persistent atrial fibrillation, including:

- Commercially available PMA-approved devices
- Pharmacological therapy for rate and/or rhythm control
- Electrical or pharmacologic cardioversion
- Surgical intervention to create atrial lesions
- Implantable devices to control heart rate

Each alternative has its own advantages and disadvantages. A patient should fully discuss these alternatives with his/her physician to select the method that best meets expectations and lifestyle.

### VII. Marketing History

THERMOCOOL SMARTTOUCH® SF Catheters (D-1347 and D-1348) are marketed worldwide, including in the United States and European Union. Other major regions where the product has been approved include Japan, China, Australia, Latin America, Canada, New Zealand, Israel and Turkey.

### VIII. Potential Adverse Events

Potential adverse events that could occur during cardiac ablation therapy to treat arrhythmias include the following:

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Table 3: Anticipated Adverse Events

|  1. | Acute Respiratory Distress Syndrome (ARDS)  |
| --- | --- |
|  2. | Air embolism  |
|  3. | Allergic reaction  |
|  4. | Anaphylactic shock  |
|  5. | Anemia  |
|  6. | Allergic reaction to Anesthesia (e.g., hair loss)  |
|  7. | Apnea - sedation induced  |
|  8. | Arrhythmia: bradycardia  |
|  9. | Arrhythmia: tachycardia  |
|  10. | Arrhythmia: pro-arrhythmias  |
|  11. | Arrhythmia: ventricular tachyarrhythmia / pro-arrhythmia  |
|  12. | Aspiration pneumonia  |
|  13. | Asthmatic attack  |
|  14. | Atelectasis  |
|  15. | Atrial fibrillation  |
|  16. | Exacerbation of pre-existing arrhythmia  |
|  17. | Atrio-Esophageal fistula  |
|  18. | Atypical left atrial flutter  |
|  19. | Arteriovenous (AV) fistula  |
|  20. | Bleeding complications  |
|  21. | Bleeding requiring transfusion  |
|  22. | Cardiac arrest  |
|  23. | Cardiac perforation  |
|  24. | Cardiac tamponade  |
|  25. | Cardiac thrombo-embolism  |
|  26. | Cerebro-vascular accident (CVA) / stroke  |
|  27. | Chest pain/discomfort  |
|  28. | Complete heart block, temporary or permanent  |
|  29. | Conduction block  |
|  30. | Congestive Heart Failure  |
|  31. | Coronary artery dissection  |
|  32. | Coronary artery occlusion  |
|  33. | Coronary artery spasm  |
|  34. | Coronary artery thrombosis  |
|  35. | Death  |
|  36. | Deep venous thrombosis  |
|  37. | Dislodgement of ICD (Implantable Cardioverter Defibrillator) lead  |
|  38. | Dislodgement of permanent pacing leads  |
|  39. | Disseminated Intravascular Coagulation  |
|  40. | Dyspnea  |
|  41. | Endocarditis  |
|  42. | Epistaxis  |

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|  43. | Expressive aphasia  |
| --- | --- |
|  44. | Fainting  |
|  45. | Fatigue  |
|  46. | Gastro-intestinal NOS  |
|  47. | Gastric reflux  |
|  48. | Nausea  |
|  49. | Gastrointestinal diverticulosis  |
|  50. | Heart Failure  |
|  51. | Hematoma (local) /ecchymosis  |
|  52. | Hemorrhage  |
|  53. | Hemothorax  |
|  54. | High / increased creatine phosphokinase (CPK)  |
|  55. | Hypotension  |
|  56. | Hypoxia  |
|  57. | Infection, localized  |
|  58. | Infection, systemic  |
|  59. | Laceration  |
|  60. | Leakage of air or blood into the lungs or other organs due to perforation  |
|  61. | Liver toxicity  |
|  62. | Mobile strands in Inferior Vena Cava  |
|  63. | Myocardial Infarction  |
|  64. | Neurological disorders (tremor)  |
|  65. | Neurological disorders (poor coordination)  |
|  66. | Neurological disorders (headache)  |
|  67. | Obstruction to the vascular system  |
|  68. | Perforation to the vascular system  |
|  69. | Damage to the vascular system  |
|  70. | Pericardial effusion resulting in tamponade  |
|  71. | Pericardial effusion without tamponade  |
|  72. | Pericarditis  |
|  73. | Peripheral embolus  |
|  74. | Peripheral nerve injury  |
|  75. | Peripheral thromboembolism  |
|  76. | Phlebitis  |
|  77. | Phrenic nerve damage  |
|  78. | Diaphragmatic paralysis  |
|  79. | Pleural effusion  |
|  80. | Pneumothorax  |
|  81. | Pseudoaneurysm  |
|  82. | Pulmonary edema  |
|  83. | Heart failure  |
|  84. | Pulmonary embolism  |
|  85. | Pulmonary hypertension  |

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|  86. | Pulmonary toxicity, like acute pulmonary syndrome  |
| --- | --- |
|  87. | Pulmonary vein dissection  |
|  88. | Pulmonary vein Stenosis  |
|  89. | Pulmonary vein thrombus  |
|  90. | Pump failure  |
|  91. | Renal failure  |
|  92. | Respiratory depression  |
|  93. | Respiratory failure  |
|  94. | Retroperitoneal hematoma  |
|  95. | Rhabdomyolysis, including produced by body position or propofol  |
|  96. | Sedation induced CO2 retention with lethargy and cholecystitis  |
|  97. | Seizure  |
|  98. | Sepsis  |
|  99. | Skin burns (due to cardioversion, tape, etc.)  |
|  100. | Skin discoloration  |
|  101. | Skin injury / muscle or connective tissue injury due to body position, electrical cardioversion  |
|  102. | Skin rash  |
|  103. | Thrombocytopenia  |
|  104. | Thromboembolism  |
|  105. | Thrombosis  |
|  106. | Thyroid disorders  |
|  107. | Transient extremity numbness  |
|  108. | Transient ischemic attack (TIA)  |
|  109. | Unintended complete or incomplete AV, Sinus node, or other heart block or damage  |
|  110. | Urinary retention  |
|  111. | Urinary tract infection  |
|  112. | Urinary tract injury or infection related to the urinary catheter  |
|  113. | Valvular damage/insufficiency  |
|  114. | Vasovagal reactions  |
|  115. | Vision change  |
|  116. | Volume overload  |
|  117. | Worsening obstructive, restrictive, or other form of pulmonary disease  |
|  118. | X-ray radiation injury of skin, muscle and/or organ  |

For a table of adverse events observed during paroxysmal atrial fibrillation clinical study, G140189, please refer to Section XI-C.4. For a table of adverse events observed during the persistent atrial fibrillation clinical study, G140102, please refer to Section XII-C.4.

### IX. Summary of Non-clinical Studies

For non-clinical testing, a risk assessment based testing program was used to validate the THERMOCOOL SMARTTOUCH® SF Catheters. Catheter designs were evaluated per guidance documents and recognized consensus standards to confirm the necessary verification / validation activities. Ablation in the canine model was determined to be the

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method of choice to validate the clinical equivalence of the THERMOCOOL SMARTTOUCH® SF Catheters to the commercially available and clinically tested devices. Thigh preparation studies in an animal evaluated lesion equivalence. Bench studies evaluated mechanical and electrical performance, and material safety (biocompatibility).

# a. Bench Testing

Design verification tests (DVT) were performed to evaluate the performance and integrity of the THERMOCOOL SMARTTOUCH® SF Catheters following three times ethylene oxide (EtO) sterilization, the equivalent of one (1) year of accelerated aging, thermal cycling and simulated transportation. Testing evaluated visual attributes; deflection characteristics such as curve profile and stability; electrical characteristics including DC resistance and isolation, RF impedance and leakage current; irrigation pressure and flow; thermocouple temperature accuracy; biosensor and force sensor integrity; mechanical integrity including tip stiffness and tip buckle force; integrity following simulated use conditioning; handle temperature; and finally, catheter strength and integrity following destructive tests. Results of DVT tests concluded that the THERMOCOOL SMARTTOUCH® SF Catheters met design requirements and are safe for use.

Proof of Design (POD) studies were performed to evaluate the contact force technology. Separate studies evaluated contact force magnetic sensor location accuracy; contact force accuracy using CARTO® 3; contact force influence on ECG signal quality; distortion in the magnetic field when paramagnetic material is placed in close proximity to the coils thus interfering with force readings and causing Shaft Proximity Interference (SPI); overall catheter testing including location-related (electromagnetic sensor) tests, force-related (contact force sensor) tests and system-level tests to ensure that the catheter met requirements when connected to a CARTO®3 system. Results of POD tests concluded that the THERMOCOOL SMARTTOUCH® SF Catheters met design requirements and are safe for use.

Electromagnetic compatibility testing was conducted on the complete system, including the THERMOCOOL SMARTTOUCH® Catheter which is designed with equivalent circuitry to the SF model, with satisfactory results.

# b. Animal Testing – Thigh Preparation Studies

A head to head ablation characteristics study was conducted in a canine thigh muscle preparation to compare lesions created by the THERMOCOOL SMARTTOUCH® SF Catheter to the currently approved NAVISTAR® THERMOCOOL® Catheter. Ablation procedures were conducted with the THERMOCOOL SMARTTOUCH® SF Catheter using the currently recommended flow rates of 8ml/min and 15ml/min, as outlined in the Instruction for Use (IFU). Lesions were compared to the control catheters. Recommended power settings between 30W-50W were used.

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Ablation characteristics evaluated included:

i) Quantification of lesion size (depth, width, volume)
ii) Quantification of coagulum, char, and pop incidence (percent incidence of coagulum, char, pop)

A statistical analysis was performed to support equivalency of the ablation characteristics. There was no statistical difference in maximum depth, maximum diameter, and volume of the lesions generated by the commercially available NAVISTAR® THERMOCOOL® Catheter in comparison to the THERMOCOOL SMARTTOUCH® SF Catheter for each orientation-power set. Occurrence of pop, thrombus, and char was equivalent or less for the THERMOCOOL SMARTTOUCH® SF Catheter compared to NAVISTAR® THERMOCOOL® Catheter for each orientation-power set.

# c. GLP Animal Studies

In-vivo testing in the canine model was determined to be the method of choice to validate the safety and overall functionality of the THERMOCOOL SMARTTOUCH® SF Catheters in simulated use. Acute and chronic testing was performed in animals using the catheter and complete system. Both acute and chronic studies complied with the guidelines for nonclinical laboratory studies as described in the Code of Federal Regulations, 21 Part 58 (GLP compliant).

The purpose of GLP animal studies was to demonstrate that the THERMOCOOL SMARTTOUCH® SF Catheters with contact force measurement capability (i.e. Test Catheters) could safely perform their intended function in an animal study without any unforeseen clinically adverse effects during the procedure when using standard practice percutaneous techniques. A comparison of performance was made to a Control Catheter (NAVISTAR® THERMOCOOL® Catheter), which is the commercially approved version of the same catheters but without contact force measurement capability. The studies evaluated the complete system including interface cables, Stockert Generator, COOLFLOW® Irrigation Pump, and CARTO® 3 System with contact force software.

Attributes evaluated included acute safety and any incidence of steam pops, perforation, thrombus, or char; mapping performance and the range of contact forces measured during mapping; ablation performance including the effectiveness of lesion creation; intracardiac signal recording; overall catheter performance.

All animals were electively euthanized at the study's conclusion for evaluation. All studies were successfully completed and verified the safe performance of the THERMOCOOL SMARTTOUCH® SF Catheters in an animal model without any clinically significant adverse events. Table 4 summarizes the results for both thigh preparation and GLP animal studies.

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**Table 4: Summary Table of Thigh Preparation and GLP Animal Studies**

|  Study Type | Number of Animals | Follow-up Duration | Relevant Findings  |
| --- | --- | --- | --- |
|  Canine Thigh Prep Study | 10 (48-80lb) | Acute | *A priori* acceptance criteria were pre-defined for lesion depth, width, volume for side-by-side comparison of the THERMOCOOL SMARTTOUCH® SF Catheter and NAVISTAR® THERMOCOOL® Catheter, respectively, to quantify lesion size (depth, width, volume) and adverse event (steampop, char, and thrombus). “Char” is referred to as blackened tissue surface without removable material and “thrombus” describes coagulated blood which is elevated red or brown material on the surface of the lesion or on the ablation electrode, which can be removed by wiping with gauze. - Lesion measurements, parallel tip orientation:     - At 30W, 7.8mm depth, 11.3mm width, 572mm³ volume vs. 7.8mm depth, 11.2mm width, 560mm³ volume     - At 50W, 9.5mm depth, 13.7mm width, 1,005 mm³ volume vs. 9.5mm depth, 13.3mm width, 939mm³ volume - Lesion measurements, perpendicular tip orientation:     - At 30W, 7.9mm depth, 10.8mm width, 521mm³ volume vs. 7.7mm depth, 10.3mm width, 474mm³ volume     - At 50W, 9.6mm depth, 13.2mm width, 949mm³ volume vs. 9.4mm depth, 13.0mm width, 886mm³ volume - Adverse Events, parallel tip orientation:     - At 30W, 0 pop, 0 thrombus, 0 char vs. 0 pop, 10 thrombus, 1 char     - At 50W, 2 pop, 5 thrombus, 0 char vs. 5 pop, 19 thrombus, 3 char - Adverse Events, perpendicular tip orientation:     - At 30W, 0 pop, 0 thrombus, 0 char vs. 0 pop, 0 thrombus, 0 char     - At 50W, 1 pop, 0 thrombus, 1 char vs. 1 pop, 1 thrombus, 0 char All acceptability criteria were met. There was no statistical difference in the lesions created by the two catheters. Adverse events were equivalent or less for THERMOCOOL SMARTTOUCH® SF compared to NAVISTAR® THERMOCOOL® for each orientation-power set  |
|  GLP Canine Study | 12 (24-34kg) | Acute and Chronic: 28 ± 2 days | *A priori* acceptance criteria were pre-defined for study objectives. - Catheters performed as intended: mapping the cardiac chambers, recording intracardiac signals, pacing/capturing electrical activity of the heart, and delivery of RF energy. - Maneuverability and Functionality tests were free of complications. - RF ablation lesions were created at all targeted locations without complications:     - THERMOCOOL SMARTTOUCH® SF Catheter -- 111 RF ablations, 22 in RA and 89 in LA  |

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|   |  |  | ○ NAVISTAR® THERMOCOOL® Catheter – 49 RF ablations, 11 in RA and 38 in LA • Of total RF ablations delivered using maximum settings of 50W power and 120sec duration, 22.5% THERMOCOOL SMARTTOUCH® SF Catheter and 10.2% NAVISTAR® THERMOCOOL® Catheter were stopped (< 30s duration) for various reasons including steampop, arrhythmia, catheter movement, achievement of PVI, etc. • All acute test animals passed post-ablation defibrillation withstand test at 360J without adverse events. • Up to three (3) PVI successfully achieved in all animals (a minimum of one pulmonary vein per animal was left untreated to serve as a vein diameter control). • Contact Force measurement during ablation averaged 8-16g with < 4g drift. • Adverse Events were minimal: ○ PV stenosis (acute or at 28d follow-up) was < 50% (20.8%-36.7%). ○ Rates of occurrence of steampop and char formation on catheter tip were statistically similar (Fisher's Exact p-Test). ○ Microscopic analysis revealed one perforation associated with steampop (Acute Control Animal) and one organized thrombus (Chronic Test Animal). All study objectives were met. The study did not raise questions of safety.  |
| --- | --- | --- | --- |

### d. Biocompatibility

The product design for the THERMOCOOL SMARTTOUCH® SF Catheters was evaluated to determine its biocompatibility based on similarity to currently approved/cleared products including the EZ STEER® THERMOCOOL® NAV, THERMOCOOL® SF, NAVISTAR® THERMOCOOL® Catheters, and Lasso 2515 Nav eco Catheters, and to confirm the applicability of the existing biocompatibility documentation. Device design, materials, construction and manufacturing environment were evaluated. All of the patient contacting materials for the THERMOCOOL SMARTTOUCH® SF Catheters (materials are identical for the uni-directional and bi-directional models) had been previously tested and are currently part of the design of one of the precedent devices. No new patient blood or fluid-contacting materials were used in the design of the THERMOCOOL SMARTTOUCH® SF Catheters. Based on the evaluation, it was determined that no additional biocompatibility testing was necessary.

### e. Sterilization

All Biosense Webster catheters are ethylene oxide (EtO) sterilized. The sterilization process incorporates all phases of sterilization (preconditioning, sterilization and aeration) within the sterilization chamber. Sterility assurance was verified to exceed a sterility assurance level (SAL) of 1 x 10⁻⁶. Sterilization validations met the

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requirements of ISO 11135. Residual results for EO and ECH are within allowable limits per ISO 10993-7.

Assessments were performed to determine if the THERMOCOOL SMARTTOUCH® SF Catheters could be adopted into the previously validated standard BWI sterilization cycle at the three FDA approved contract sterilizers. Assessment of device packaging, construction, manufacturing environment and lumen size for gas penetration were evaluated. Based on the similarities of the THERMOCOOL SMARTTOUCH® SF Catheters with the precedent devices, the THERMOCOOL SMARTTOUCH® SF Catheters do not provide a greater sterilization challenge when sterilized using the currently validated Biosense Webster EtO sterilization cycle when using the standard 10-pallet configuration.

# f. Shelf Life

The packaging for the THERMOCOOL SMARTTOUCH® SF Catheters is identical to that used with the NAVISTAR® THERMOCOOL® and EZ STEER® THERMOCOOL® NAV Catheters, and has been validated to maintain a sterile barrier for three years. Product shelf life for the THERMOCOOL SMARTTOUCH® Catheters has been validated for one year. The product will bear a one shelf life on its labeling.

# X. Summary of Clinical Studies

Sections XI and XII provide summaries of clinical investigations performed under IDEs G140189 and G140102 for the THERMOCOOL SMARTTOUCH® SF Catheter. All patients underwent informed consent per the study protocols, and in compliance with the Code of Federal Regulations, 21 §50. The protocols and informed consent materials were reviewed and approved by the appropriate IRBs prior to subject enrollment, and in compliance with the Code of Federal Regulations, 21 §56. Per the requirements of 21 CFR §812.20(b)(5), all participating investigators signed the Clinical Study Agreement prior to enrollment at their center, which included financial disclosure forms, current curricula vitae for the investigator and co-investigators, and written IRB approval for the investigational study. The clinical studies were monitored in a manner consistent with 21CFR, Part 812, Subpart C, Responsibilities of Sponsor. Monitoring visits included, but were not limited to, verification of all study logs, verification that informed consent was being obtained in accordance with requirements described in the study protocols for all subjects participating in the studies, verification of completeness of the Regulatory Binder, data source verification with the eCRFs, and identification and action to resolve any issues or problems with the studies. Data from these clinical studies were the basis for the PMA Supplement approval decisions.

# XI. SMART SF Study – IDE G140189

# A. OBJECTIVE

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The primary objective of this trial was to demonstrate the safety of the THERMOCOOL SMARTTOUCH® SF Catheter with Contact Force Sensing Capability in the treatment of drug refractory symptomatic paroxysmal AF during standard electrophysiology mapping and ablation procedures.

## B. STUDY DESIGN

The study was a prospective, single-arm, unblinded, multicenter, pivotal, clinical investigation conducted at 19 investigational sites in the US.

### B.1. – Study Endpoints:

The endpoints for the study were as follows:

*Primary Safety Endpoint* - incidence of any primary adverse event occurring within 7 days of any AF ablation procedure

Primary adverse events include the following conditions:

- Death
- Atrio-esophageal fistula*
- Cardiac Tamponade**/Atrial Perforation
- Myocardial infarction (MI)
- Stroke / Cerebrovascular accident (CVA)
- Thromboembolism
- Transient Ischemic Attack

- Diaphragmatic paralysis
- Pneumothorax
- Heart block
- PV stenosis*
- Pulmonary edema (Respiratory Insufficiency)
- Pericarditis
- Major vascular access complication / Bleeding

* Pulmonary vein (PV) stenosis and atrio-esophageal fistula that occurs greater than one week (7 days) post-procedure shall be deemed Primary AEs. Error! Reference source not found. Error! Reference source not found.

** Hemodynamic compromise or instability is defined as Systolic BP < 80 mm Hg.

### Secondary Endpoints

*Acute success* – confirmation of entrance block in all pulmonary veins

*Secondary Safety Endpoints* included:

- Occurrence of Early Onset (within 7 days of initial ablation) Serious Adverse Event
- Occurrence of Peri-Procedural (>7 to 30 days) Serious Adverse Event

### B.2. – Pre-specified Performance Goal:

The performance goal was prospectively established.

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- Safety: Performance Goal = 14.0% upper bound of the 95% CI around the primary AE rate

### B.3. – Subject Accountability:

Table 5: Subject Accountability and Disposition

|  Disposition | N | %*  |
| --- | --- | --- |
|  Enrolled Subjects** | 165 | 100.0  |
|  Excluded Subjects*** | 6 | 3.6  |
|  Safety Population†‡ | 159 | 96.4  |
|  Not Meeting Eligibility Criteria | 4 | 2.4  |
|  mITT Population§ | 155 | 93.9  |
|  Undergone RF Ablation | 155 | 93.9  |
|  Per-Protocol Population¶ | 155 | 93.9  |
|  Subjects Treated with Non-Study Catheter | 0 | 0  |
|  Subjects Treated for Non-Study Arrhythmia | 0 | 0  |

The following definitions were used to classify subjects:

Safety Population (n = 159) was comprised of enrolled subjects undergoing insertion of the THERMOCOOL SMARTTOUCH® SF catheter.

Modified Intent-To-Treat (mITT) Population (n = 155) consisted of enrolled subjects who met the eligibility criteria and had the study catheter inserted.

### B.4. – Subject Demographics and Baseline Characteristics:

Table 6: Subject Demographics (Enrolled Subjects, N=165; mITT Population, N = 155)

|  Demographics | Enrolled n/164 | mITT n/155  |
| --- | --- | --- |
|  Gender (%)  |   |   |
|  Male | 95 (57.9) | 93 (60.0)  |
|  Female | 69 (42.1) | 62 (40.0)  |
|  Ethnicity – Hispanic or Latino (%) | 2 (1.2) | 1 (0.6)  |
|  Race (%)  |   |   |
|  Asian | 1 (0.6) | 1 (0.6)  |
|  White | 159 (97.0) | 151 (97.4)  |
|  Pacific Islander | 1 (0.6) | 1 (0.6)  |

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|  Black | 2 (1.2) | 2 (1.3)  |
| --- | --- | --- |
|  Other | 1 (0.6) | 0  |
|  Age (Years) | 62.7 ± 10.44 | 62.7 ± 10.13  |
|  AF History (months) | 47.9 ± 67.45 (163) | 46.0 ± 63.82 (155)  |
|  LA Dimension (mm) | 38.8 ± 5.96 (154) | 38.9 ± 5.87 (150)  |
|  LVEF (%) | 60.1 ± 6.98 (155) | 59.9 ± 6.74 (150)  |

Table 7: Baseline Characteristics (Enrolled, N=165; mITT Population, n=155)

|  Medical History | Enrolled n/163 (%) | mITT n/155 (%)  |
| --- | --- | --- |
|  Hypertension | 93 (57.1%) | 90 (58.1%)  |
|  Diabetes | 23 (14.1%) | 22 (14.2%)  |
|  AAD Failed |  |   |
|  Class I & III | 116/161 (72.0) | 110/155 (71.0)  |
|  Class II & IV Only | 45/161 (28.0) | 45/155 (29.0)  |
|  Heart Disease | 44 (27.0%) | 43 (27.7%)  |
|  Coronary artery disease | 29 (17.8%) | 28 (18.1%)  |
|  Congestive heart failure | 6 (3.7%) | 5 (3.2%)  |
|  Prior Myocardial infarction | 6 (3.7%) | 6 (3.9%)  |
|  Cardiac surgical procedures | 12 (7.4%) | 12 (7.7%)  |
|  Thromboembolic Event | 10 (6.1%) | 10 (6.5%)  |
|  Transient ischemic attack | 3 (1.8%) | 3 (1.9%)  |
|  Stroke | 4 (2.5%) | 4 (2.6%)  |
|  Other Arrhythmia | 68 (41.7%) | 63 (40.6%)  |
|  Atrial Flutter | 51 (31.3%) | 47 (30.3%)  |
|  Atrial Tachycardia | 8 (4.9%) | 8 (5.2%)  |

## C. RESULTS

### C.1 - Procedural Data

Tables 8, 9 and 10 present the procedural data. There were 159 procedures in 159 subjects. All subjects underwent one (1) study ablation procedure.

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Table 8: Summary of Power, Temperature, and Impedance Data per Procedure (Safety Population, n =159)

|  Description | Mean ± SD (n)  |
| --- | --- |
|  Mean Maximum Power (W) | 31.3 ± 3.98 (151)  |
|  Mean Temperature (°C) | 27.8 ± 3.30 (151)  |
|  Mean Impedance (ohms) | 127.2 ± 15.13 (151)  |

On average, less power was used on the posterior wall during RF applications.

Table 9: Mean Max Power by Pulmonary Vein Anatomical Location (Safety Population, n = 159)

|  Location | Mean ± SD | Median | Min / Max  |
| --- | --- | --- | --- |
|  Anterior | 33.3 ± 4.24 | 35.0 | 12.0 / 45.8  |
|  Inferior | 31.1 ± 5.30 | 30.9 | 15.3 / 45.4  |
|  Posterior | 28.7 ± 5.84 | 30.0 | 10.0 / 45.5  |
|  Ridge | 34.5 ± 4.64 | 35.5 | 15.4 / 45.9  |
|  Roof Line | 32.2 ± 5.27 | 31.0 | 15.3 / 50.0  |

Table 10: Summary of Ablation Procedure Parameters (Safety Population, n =159)

|  Procedure Parameters | Mean ± SD (n)  |
| --- | --- |
|  Total Procedure Time (min) | 181.1 ± 74.75 (159)  |
|  Ablation Procedure Time (min) | 104.3 ± 51.48 (159)  |
|  Total Fluoroscopy Time (min) | 18.5 ± 13.93 (159)  |
|  Fluid Input (mL) | 2148.9 ± 1179.6 (158)  |
|  Fluid via Catheter (mL) | 898.4 ± 586.33 (156)  |
|  Fluid via IV (mL) | 1261.8 ± 901.76 (158)  |
|  Fluid Output (mL) | 937.2 ± 962.98 (95)  |
|  Balance (input - output) (mL) | 1443.0 ± 882.04 (95)  |

All AF ablation procedures began with circumferential lesions targeting all pulmonary veins, with additional atrial ablation lines created as clinically required. Table 11 and Table 12 summarizes the lesion sets applied to the subjects undergoing ablation during the index ablation procedures.

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**Table 11: Outcomes by Ablation Targets per Procedure (Safety Population, n = 159)**

|  Ablation Targets | n/159 (%)  |
| --- | --- |
|  PV Only | 60 (37.7)  |
|  PV + Atrial Linear Lesions | 78 (49.1)  |
|  PV + Foci | 5 (3.1)  |
|  PV + Atrial Linear Lesions + Foci | 16 (10.1)  |
|  **Total** | **159 (100.0)**  |

**Table 12: Atrial Linear Lesions per Procedure (Safety Population, n = 159)**

|  Linear Lesions | n/159 (%)  |
| --- | --- |
|  Left Inferior PV to Mitral | 3 (1.9)  |
|  SVC | 3 (1.9)  |
|  Cavo-Tricuspid Isthmus | 72 (45.3)  |
|  Roof line | 29 (18.2)  |
|  Other | 7 (4.4)  |

### **C.3 - Acute Procedural Success**

Acute success was defined as the confirmation of entrance block into all PVs. Any use of non-study catheters and >2 repeat ablations during the blanking period were considered acute procedural failures.

Acute procedural success results are presented in Table 13.

**Table 13: Acute Effectiveness Summary (Safety Population, n =159)**

|   | Safety  |
| --- | --- |
|  Number of Subjects with Success | 153 / 159  |
|  Percentage of Subjects with Success | 96.2%  |
|  95% Exact Binomial Confidence Interval | (92.0%, 98.6%)  |

### **C3 – Contact Force Data**

The THERMOCOOL SMARTTOUCH® SF Catheter for measuring the contact force (CF) applied to the endocardial wall of the heart is comprised of the THERMOCOOL SMARTTOUCH® SF catheter and CARTO® 3 EP navigation workstation with the SMARTTOUCH® module installed. The graphical user interface (GUI) of the CARTO® 3 workstation displays the pressure applied to the endocardial surface of the heart as gram forces that the investigator can visualize during the procedure.

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Table 14 presents the overall average contact force applied during procedure for all subjects who underwent a study ablation procedure. As shown, the overall average CF applied during ablation procedures was 16.7 ± 6.14 grams. Figure 4 presents a distribution of average contact force in 5 gram increments. In the majority of procedures (125/152), the average contact force applied was less than 20 grams.

Table 14: Average Contact Force Measurements Overall per Ablation Procedure (Safety Population, n=159)

|   | Average Contact Force (g)  |
| --- | --- |
|  n* | 152  |
|  Mean | 16.7  |
|  Standard Deviation | 6.14  |
|  Median | 15.7  |
|  Q1 / Q3 | 12.9 / 18.7  |
|  Min / Max | 7.4 / 38.3  |

* contact force data available for 152 of 159 subjects

![img-3.jpeg](img-3.jpeg)

Figure 4: Distribution of Average Contact Force Per Ablation Procedure (Safety Population, n =159)

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An integral part of the CARTO® 3 graph display includes a real-time rolling graph of applied CF which includes a user configurable working range that is displayed on the graph as horizontal lines for a low and high range. The real-time rolling graph display with the working ranges acts as a visual aid providing real-time feedback of the pressure being applied by the operator in relationship to their pre-selected CF values.

Table 15 presents the investigator selected working ranges used during the study ablation procedures with the THERMOCOOL SMARTTOUCH® SF Catheter.

**Table 15: Working Ranges (g) Configured by Investigators

|  Lower | Upper | n / 159 (%)  |
| --- | --- | --- |
|  0 | 38 | 1 (0.6%)  |
|  0 | 40 | 1 (0.6%)  |
|  2 | 23 | 1 (0.6%)  |
|  2 | 48 | 1 (0.6%)  |
|  3 | 50 | 5 (3.1%)  |
|  4 | 50 | 1 (0.6%)  |
|  5 | 20 | 6 (3.8%)  |
|  5 | 24 | 2 (1.3%)  |
|  5 | 25 | 8 (5.0%)  |
|  5 | 30 | 2 (1.3%)  |
|  5 | 35 | 16 (10.1%)  |
|  5 | 38 | 2 (1.3%)  |
|  5 | 40 | 70 (44.0%)  |
|  5 | 50 | 1 (0.6%)  |
|  5 | 60 | 1 (0.6%)  |
|  6 | 30 | 1 (0.6%)  |
|  6 | 40 | 1 (0.6%)  |
|  6 | 49 | 1 (0.6%)  |
|  7 | 46 | 1 (0.6%)  |
|  8 | 30 | 1 (0.6%)  |
|  9 | 58 | 1 (0.6%)  |
|  10 | 30 | 3 (1.9%)  |
|  10 | 40 | 28 (17.6%)  |

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|  Lower | Upper | n / 159 (%)  |
| --- | --- | --- |
|  10 | 70 | 1 (0.6%)  |
|  15 | 20 | 1 (0.6%)  |
|  20 | 35 | 1 (0.6%)  |
|  20 | 40 | 1 (0.6%)  |

* Contact force data available for 152 of 159 subjects

### C 3.1 – Average CF by Sex

Table 16 presents a comparison of average contact force by sex. There was no significant difference in the use of contact force between sexes.

Table 16: Average Contact Force Measurements (g) By Sex per Ablation Procedure (Safety Population, n=159)

|   | Male | Female | p-value  |
| --- | --- | --- | --- |
|  n* | 92 | 60 |   |
|  Mean ± SD | 16.6 ± 6.43 | 17.0 ± 5.73 | 0.3777  |
|  Median | 15.5 | 15.8 |   |
|  Min / Max | 7.4 / 35.1 | 9.9 / 38.3  |   |

* Contact force data available for 152 of 159 subjects

### C.4 - Adverse Events (AE)

The primary safety endpoint for this study was defined as the incidence of early-onset (within 7 days of ablation procedure) Primary AEs for subjects undergoing a study ablation procedure. The Safety Population (n=159) was comprised of all enrolled subjects who had the study catheter inserted.

### Primary Safety Endpoint – Primary Adverse Events

Table 17 presents the protocol-specified endpoint and safety results. There were 4 primary AEs reported for 4 subjects. One Primary AE was deemed related to the investigational catheter. Three (3) were deemed possibly device-related. The overall percentage of subjects in Safety Population who experienced a serious primary AE was 2.5% (4/159) with upper confidence at 6.3%. The safety endpoint specified in the protocol was 7.0% (upper confidence bound of 14.0%). Therefore, the results met the pre-specified performance goal for the safety endpoint.

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Table 17: Primary Safety Endpoint Outcome – Primary Adverse Events (Safety Population, n =159)

|   | Protocol Established Endpoint | n  |
| --- | --- | --- |
|  Number of Subjects in Safety Cohort |  | 159  |
|  Number of Subjects with Primary AEs |  | 4  |
|  % Primary AEs | 7.0 | 2.5  |
|  Upper bound pf 95% exact CI | 14.0 | 6.3  |

Table 18 summarizes the Primary AEs. Of the two subjects who experienced cardiac tamponade/perforation; one underwent emergent open chest surgical repair and the other was managed medically. All Primary AEs improved or resolved by the 30 day follow-up visit.

Table 18: Primary Safety Endpoint – Early-Onset (Within (≤) 7 Days) Primary Adverse Events (Safety Population, n =159)

|  Description | Number of Safety with Primary AEs n/159 (%)  |
| --- | --- |
|  Total Primary AEs | 4 (2.5)  |
|  Death | 0  |
|  Atrio-Esophageal Fistula | 0  |
|  Cardiac Tamponade/Perforation | 2 (1.3)  |
|  Myocardial Infarction | 0  |
|  Stroke | 0  |
|  Cerebrovascular Accident | 0  |
|  Thromboembolism (Ischemic colitis) | 1 (0.6)  |
|  Transient Ischemic Attack | 1 (0.6)  |
|  Diaphragmatic Paralysis | 0  |
|  Pneumothorax | 0  |
|  Heart Block | 0  |
|  Pulmonary Vein Stenosis | 0  |
|  Pulmonary Edema (Respiratory Insufficiency) | 0  |
|  Pericarditis | 0  |
|  Major Vascular Access Complication / Bleeding | 0  |

* The Cardiac Tamponades/Perforation for subject 106-002 was adjudicated as both definitely device and definitely procedure related; the second for subject 265-003 was adjudicated as possible device related and definitely procedure related.

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Table 15 summarizes the SAEs occurring within 30 days of a study ablation procedure that were not classified as Primary AEs by protocol definition.

**Table 19: SAEs Occurring Within 30 of the Ablation Procedure by Causality and Category (Safety Population, n=159)**

|  Description | Total Number of Subjects with SAEs | Total Number of SAEs  |
| --- | --- | --- |
|  **SAEs** | **6** | **6**  |
|  **Device-Related** | **0** | **0**  |
|  **Possibly Device-Related** | **0** | **0**  |
|  **Procedure-Related** | **2** | **2**  |
|  *Sepsis due to UTI* | 1 | 1  |
|  *Aspiration pneumonia* | 1 | 1  |
|  **Possibly Procedure-Related** | **3** | **3**  |
|  *Hospitalization due to transient neurological symptoms* | 1 | 1  |
|  *Gastrointestinal disorder* | 1 | 1  |
|  **Not Related to device or procedure** | **1** | **1**  |
|  *AF Recurrence with Rapid Ventricular Response* | 1 | 1  |

There were no deaths during the study.

#### **C 4.1 –Average CF and Primary AEs**

Table 20 compares the average CF during procedures in subjects experiencing Primary AEs with those who did not. Procedural average contact force used in subjects who experienced Primary AEs was similar to those that did not.

**Table 20: Average Contact Force by Primary Adverse Event (Safety Population, n =159)\***

|  Subject ID | Primary AE | Mean ± SD | Median | Min / Max  |
| --- | --- | --- | --- | --- |
|  106-001 | Thromboembolism | 19.4 ± 7.37 | 18.3 | 9.2 / 38.6  |
|  106-002 | Cardiac Tamponade | 15.7 ± 6.17 | 14.0 | 6.9 / 27.4  |
|  131-003 | TIA | 14.7 ± 4.79 | 15.0 | 8.2 / 25.4  |
|  Subjects who did not experience a Primary AE (n = 155) |   | 16.7 ± 6.14 | 15.7 | 7.4 / 38.3  |

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* Necessary procedural data for subject 265-003 (adjudicated as cardiac tamponade/perforation due to the size of the pericardial effusion [1.3cm]) was unavailable for analysis

### C.5 – Study Conclusion

The results demonstrate that the THERMOCOOL SMARTTOUCH® SF Catheter met pre-specified performance goal for safety.

### XII. PRECEPT Study – IDE G140102

### A. Objective

The purpose of this study was to demonstrate the safety and effectiveness of the THERMOCOOL SMARTTOUCH® SF catheter in the treatment of drug refractory symptomatic persistent atrial fibrillation (PsAF) following standard electrophysiology mapping and RF ablation procedures.

### B. Study Design

Patients were enrolled and treated between 7/27/2016 and 2/6/2018. The database for this Panel Track Supplement reflected data collected through October 10, 2019 and included 381 patients. There were 27 investigational sites (25 US sites and 2 Canadian sites).

The study was a prospective, non-randomized, uncontrolled, open-label, multicenter, pivotal clinical trial. The study enrolled subjects with symptomatic persistent atrial fibrillation refractory to at least one Class I or III antiarrhythmic drug (AAD). Enrolled subjects underwent catheter ablation with the investigational THERMOCOOL SMARTTOUCH SF ablation catheters and were followed for 15 months.

After the study ablation procedure, subjects entered a 3-Month Medication Adjustment Period (Day 0 – 90) followed by a 3-Month Therapy Consolidation Period (Day 91-180). Thereafter, subjects were followed for arrhythmia recurrence in the 9-Month Evaluation Period (Days 181-450).

The study success was assessed by freedom from documented atrial fibrillation, atrial flutter, and atrial tachycardia recurrence during the evaluation period (Day 181 – 450 following the index ablation procedure) and any Primary Adverse Event occurring within 7 days of the AF ablation procedure (PV stenosis and AE fistula occurring at any time). The study would be considered successful by meeting the predetermined performance goal for each primary endpoint.

The study utilized an independent Global Safety Monitoring Committee (GSMC) to oversee study progress, adjudicate adverse events and review clinical data and safety. An

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independent core laboratory provided interpretation of all electrocardiographic data (24-Hour Holter Monitors, ECGs, and TTMs).

# B.1- Clinical Inclusion and Exclusion Criteria

Enrollment in the PRECEPT study was limited to patients who met the following inclusion criteria:

1) Documented symptomatic persistent AF, which is defined as continuous AF sustains beyond 7 days and less than 1 year and is documented by the following:

i. Physician's note indicating continuous AF ≥ 7 days but no more than 1 year;

AND

ii. Two electrocardiograms (from any forms of rhythm monitoring) showing continuous AF, with electrocardiogram taken at least 7 days apart (electrograms cannot be >365 days prior to enrollment) OR

iii. 24-hour Holter within 90 days of the ablation procedure showing continuous AF

2) Failed at least one antiarrhythmic drug (AAD) (class I or III) as evidenced by recurrent symptomatic AF, or intolerable to the AAD.

3) Age 18 years or older.
4) Signed Patient Informed Consent Form (ICF).
5) Able and willing to comply with all pre-, post-, and follow-up testing and requirements.

Patients were not permitted to enroll in the PRECEPT study if they met any of the following exclusion criteria:

1) Continuous AF > 12 months (1-Year) (Longstanding Persistent AF)
2) Previous surgical or catheter ablation for atrial fibrillation
3) Any cardiac surgery within the past 2 months (60 days) (includes PCI)
4) CABG surgery within the past 6 months (180 days)
5) Valvular cardiac surgical/percutaneous procedure (i.e., ventriculotomy, atriotomy, and valve repair or replacement and presence of a prosthetic valve)
6) Any carotid stenting or endarterectomy
7) Documented LA thrombus on imaging
8) LA size > 50 mm (parasternal long axis view)
9) LVEF < 40%
10) Contraindication to anticoagulation (heparin or warfarin)
11) History of blood clotting or bleeding abnormalities
12) MI within the past 2 months (60 days)
13) Documented thromboembolic event (including TIA) within the past 12 months (365 days)

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14) Rheumatic Heart Disease
15) Uncontrolled heart failure or NYHA function class III or IV
16) Severe mitral regurgitation (Regurgitant volume ≥ 60 mL/beat, Regurgitant fraction ≥ 50%, and/or Effective regurgitant orifice area ≥ 0.40cm²)
17) Awaiting cardiac transplantation or other cardiac surgery within the next 12 months (365 days)
18) Unstable angina
19) Acute illness or active systemic infection or sepsis
20) AF secondary to electrolyte imbalance, thyroid disease, or reversible or noncardiac cause.
21) Diagnosed atrial myxoma.
22) Presence of implanted ICD/CRT-D.
23) Significant pulmonary disease, (e.g., restrictive pulmonary disease, constrictive or chronic obstructive pulmonary disease) or any other disease or malfunction of the lungs or respiratory system that produces chronic symptoms.
24) Gastroesophageal Reflux Disease (GERD; active requiring significant intervention not including OTC medication)
25) Significant congenital anomaly or medical problem that in the opinion of the investigator would preclude enrollment in this study.
26) Women who are pregnant (as evidenced by pregnancy test if pre-menopausal)
27) Enrollment in an investigational study evaluating another device, biologic, or drug.
28) Presence of intramural thrombus, tumor or other abnormality that precludes vascular access, or manipulation of the catheter.
29) Presence of any other condition that precludes appropriate vascular access.
30) Life expectancy less than 12 months

### B.2. - Follow-up Schedule

All patients were scheduled to return for follow-up examinations at baseline, operative/discharge, 7 days, 1, 3, 6, 9, 12, and 15 months following the index procedure. Preoperatively, all subjects were screened for left atrial thrombus. Post-ablation rhythm monitoring included symptomatic and monthly asymptomatic TTM transmissions during the evaluation period, 12-lead ECG at 6, 9, 12, and 15 months, and 24-hour Holter at 6, 12, and 15 months. Adverse events and complications were assessed and recorded at all visits.

The key timepoints are shown below in the table summarizing schedule of treatments and evaluations.

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**Table 21: Schedule of Treatments and Evaluations**

|  | Pre-Procedure | Ablation Procedure^{1} | Discharge | Phone Call | Phone/Office visit | Follow-Up Visits | Unscheduled Visit |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Screening / Baseline |  | 1 Month +/- 1 wks. | 3 Month +/- 1 wks. | 6 Month +/- 2 wks. | 9 Month +/- 4 wks. | 12 Month +/- 4 wks. | 15 Month +/- 4 wks. |
| Visit no. | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 |
| Informed consent^{1} | X |  |  |  |  |  |  |  |  |  |  |  |
| Inclusion & exclusion criteria | X |  |  |  |  |  |  |  |  |  |  |  |
| Demographics | X |  |  |  |  |  |  |  |  |  |  |  |
| Medical history / Hospitalization history | X |  |  |  | X | X | X | X | X | X | X | X |
| Arrhythmias | X [history] |  |  | X | X | X | X | X | X | X | X | X |
| NIH Stroke Scale^{13} |  | X |  | X^{13} |  |  |  |  |  |  |  |  |
| ECG |  | X |  | X |  |  |  | X | X | X | X | X |
| NYHA |  | X |  |  |  |  |  |  |  |  |  |  |
| CCS-SAF |  | X |  |  |  |  |  | X | X | X | X |  |
| QOL assessment^{2} |  | X |  |  |  |  |  | X | X | X | X |  |
| Pregnancy test^{3} |  | X |  |  |  |  |  |  |  |  |  |  |
| LA thrombus Imaging^{4} |  |  | X |  |  |  |  |  |  |  |  |  |
| TTE^{5} |  | X^{5} |  | X^{10} |  |  |  |  |  |  |  |  |
| Ablation assessments |  |  | X |  |  |  |  |  |  |  |  |  |
| Holter monitor (24 hr) |  | X optional |  |  |  |  |  | X |  | X | X |  |
| TTM monitoring^{11,14} |  |  |  |  |  |  |  | X^{11,14} | X^{11,14} | X^{11,14} | X^{11,14} |  |
| Device deficiency |  |  | X |  |  |  |  |  |  |  |  |  |
| Concomitant medications^{5} |  | X | X | X | X | X | X | X | X | X | X | X |
| Health Economic Data Collection^{5} |  |  |  | X^{7} | X^{7} | X^{7} | X^{7} | X^{7} | X^{7} | X^{7} | X^{7} | X^{7} |
| Adverse events^{5,6} | X | X | X | X | X^{10} | X^{10} | X | X | X | X | X | X |
| PV stenosis imaging assessment^{11} |  |  |  |  | X^{11} | X^{11} | X^{11} | X^{11} | X^{11} | X^{11} | X^{11} | X^{11} |
| AF recurrence |  |  |  |  |  |  |  | X | X | X | X | X |
| End-of study follow-up |  |  |  |  |  |  |  |  |  |  | X^{11} |  |

1 Initial ablation procedure should be done within 30 days of consent.

2 Quality of life tools (AFEQT and Symptom and Severity Checklist)

3 Pregnancy test must be done on pre-menopausal women only, within 24 hours of the procedure.

4 Imaging for the presence of LA thrombus (TEE, CT, ICE, MRI) on day prior or the day of the procedure.

5 Imaging TTE to determine the atrial size (if the subject has undergone an imaging procedure within the last 6 months where the atrial size was assessed, the pre-procedure imaging assessment is not required)

6 Concomitant medications: only cardiac related (anti-arrhythmia drugs, anticoagulation regimen, etc.)

7 Health Economic Data for hospitalizations (UB04), ER visits and outpatient visits, if any

8 AEs collected once consent has been signed

9 If AE results in Hospitalization health economic data collection is required

10 Collected via phone follow-up

11 PV imaging (CT/MRI) for subjects who have symptoms suggestive of PV stenosis

12 Performed prior to hospital discharge or 24 hours after the procedure, whichever is later or any time after the subject experiences a CVA/Stroke, perform Neuro consult as needed

13 Asymptomatic TTM: should be recorded monthly (i.e. at months 7, 8, 9, 10, 11, 12, 13, 14, 15) and transmitted to the Core Lab.

14 TTM: all symptomatic cardiac episodes should be recorded and transmitted at the time the event occurs.

15 15-month visit or last completed visit

16 Subjects who develop symptoms suggestive of pericardial effusion and/or pericarditis should undergo a transthoracic echocardiogram (TTE) to assess the pericardium

### B.3 – Study Endpoints

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The Endpoints for the study were as follows:

**Primary Effectiveness Endpoint** – freedom from documented atrial fibrillation, atrial flutter, and atrial tachycardia (AF/AFL/AT, atrial tachyarrhythmias) recurrence (episodes ≥ 30 sec on Holter recordings/TTM or continuously recorded on the standard 12-leads ECG) during the evaluation period (Day 181-450 following the index ablation procedure) and freedom from the following primary effectiveness failure modes:

- Acute procedural failure: entrance block not confirmed for all PVs post-procedure and subjects in whom a non-study catheter has been used to treat the study arrhythmia for the initial ablation procedure.
- Non-study catheter failure: use of a non-study catheter to treat the study arrhythmia for repeat ablation procedure during the 3-Month Medication Adjustment or 3-Month Therapy Consolidation Periods.
- Repeat ablation failure: > 2 repeat ablation procedures during Day 0 – 180 or any repeat ablation during the evaluation period.
- AAD failure: taking a new AAD or a previously failed AAD at a greater than the highest ineffective historical dose for AF during the evaluation period.
- Surgical failure: any surgical AF ablation or AF surgery

**Acute Success** – confirmation of entrance block in all pulmonary veins.

**Primary Safety Endpoint** – incidence primary adverse events (PAE) occurring within 7 days of the initial and repeat AF ablation procedures using the study catheter per protocol. Primary adverse events included the following conditions:

- Death
- Atrio-esophageal fistula¹
- Cardiac Tamponade / Perforation
- Myocardial Infarction (MI)
- Stroke / Cerebrovascular accident (CVA)
- Thromboembolism
- Transient Ischemic Attack (TIA)
- Diaphragmatic paralysis
- Pneumothorax
- Heart block
- Pulmonary Vein (PV) stenosis¹
- Pulmonary edema (Respiratory Insufficiency)
- Pericarditis
- Major vascular access complication / bleeding

¹ PV stenosis (PV) and atrio-esophageal fistula that occurs greater than one week (7 days) post-procedure shall be deemed Primary AEs.

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*Secondary safety endpoints* included:

- Occurrence of Early Onset (within 7 days of initial ablation) Serious Adverse Event
- Occurrence of Peri-Procedural (> 7 to 30 days) Serious Adverse Event
- Occurrence of Late Onset (> 30 days) Serious Adverse Event

# B.4 – Pre-determined Performance Goal

The performance goal was prospectively established.

- Effectiveness: Performance Goal = 40.0% lower bound of the of the 95% CI around the primary effectiveness success rate
- Safety: Performance Goal = 16.0% upper bound of the 95% CI around the primary AE rate

With regards to success/failure criteria, each primary endpoint was compared to a predetermined performance goal. The study would be considered a success when both of the following criteria are met:

- The primary safety endpoint event rate meets the prespecified performance goal of 0.16. The following primary safety hypotheses were evaluated using the exact test for a binomial proportion at a two-sided significance level of 5%:

$$\mathrm{H}_{\mathrm{o}}: \mathrm{P}_{\mathrm{s}} \geq 0.16$$

$$\mathrm{H}_{1}: \mathrm{P}_{\mathrm{s}} < 0.16$$

Where

Ps = proportion of subjects with the early onset (within seven days of the initial and repeat ablation procedure for AF*) primary AE.

The analysis cohort for the primary safety endpoint included all subjects in the Safety Population. Subjects with missing primary safety data were excluded from the primary analysis.

- The primary effectiveness endpoint rate meets the prespecified performance goal of 0.40. The following primary effectiveness hypotheses were evaluated using the exact test for a binomial proportion at a two-sided significance level of 5%.

$$\mathrm{H}_{\mathrm{o}}: \mathrm{P}_{\mathrm{E}} \leq 0.40$$

$$\mathrm{H}_{1}: \mathrm{P}_{\mathrm{E}} > 0.40$$

Where

PE = proportion of subjects who met the effectiveness success criteria at 15-months follow-up.

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The analysis cohort for the primary effectiveness endpoint included all Per Protocol subjects. Subjects with missing primary effectiveness outcomes were not included in the primary effectiveness endpoint calculation.

### B.5. – Subject Accountability

At the time of database lock, of 381 patients enrolled in the PMA study, 76.9% (N = 293) patients were available for analysis at the completion of the study, the 15-month post-operative visit. Table 22 shows an accounting of follow-up visit attendance during the study. Subjects who died or were withdrawn were not counted as having expected visits.

Table 22. Summary of Compliance of Follow-up Visits (Safety Population, N=348)

|  Follow-up Visit (Visit Window) | Total Subjects n/N (%)  |
| --- | --- |
|  Phone Call (7-9 days) | 344 / 348 (98.9%)  |
|  1-Month (23-37 days) | 346 / 348 (99.4%)  |
|  3-Month (83-97 days) | 341 / 345 (98.8%)  |
|  6-Month (166-194 days) | 322 / 338 (95.3%)  |
|  9-Month (242-298 days) | 306 / 330 (92.7%)  |
|  12-Month (332-388 days) | 295 / 323 (91.3%)  |
|  15-Month (422-478 days) | 293 / 313 (93.6%)  |

Of the 381 enrolled subjects, 33 subjects never underwent insertion of the study catheter and were excluded from the study. Of the remaining 348 subjects who had the study catheter inserted and underwent the study ablation procedure, 33 subjects withdrew or had early termination, 20 subjects were lost to follow up and 2 subjects died. As of the date of database lock (10/10/2019), 293 subjects completed the 15-month follow-up during the visit window.

The protocol specified analysis populations include:

- Safety Population (SP): The safety population consisted of 348 enrolled subjects who had undergone insertion of the study catheter.
- Modified Intent-To-Treat (mITT) Population: The mITT population consisted of 334 enrolled subjects who met all eligibility criteria and in whom the study catheter was inserted.

- Per Protocol (PP) Population: The PP population consisted of 333 subjects who met all eligibility criteria and had undergone RF ablation with the study catheter for study-related

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arrhythmia (1 subject in the mITT was treated with a non-investigational STSF catheter with commercial labeling).

## B.6 – Subject Demographics and Baseline Characteristics

The demographics of the study population were typical for a persistent atrial fibrillation catheter ablation study performed in the US. Table 23 summarizes demographics for all enrolled subjects, safety population, mITT population, and per-protocol population.

Table 23 – Subject Demographics
(Enrolled Subjects, N = 381; Safety, N = 348; Per-Protocol, N = 333)

|  Demographics | Enrolled n/381 (%) | Safety n/348 (%) | mITT n/334 (%) | Per- Protocol n/333 (%)  |
| --- | --- | --- | --- | --- |
|  **Gender (%)**  |   |   |   |   |
|  Male | 271 (71.1) | 246 (70.7) | 237 (71.0) | 237 (71.2)  |
|  Female | 110 (28.9) | 102 (29.3) | 97 (29.0) | 96 (28.8)  |
|  **Ethnicity – Hispanic or Latino (%)** | 7 (1.8) | 7 (2.0) | 7 (2.1) | 6 (1.8)  |
|  **Race (%)**  |   |   |   |   |
|  Asian | 3 (0.8) | 3 (0.9) | 3 (0.9) | 3 (0.9)  |
|  Black or African American | 6 (1.6) | 6 (1.7) | 6 (1.8) | 6 (1.8)  |
|  White | 349 (91.6) | 319 (91.7) | 307 (91.9) | 307 (92.2)  |
|  Not reported | 23 (6.0) | 20 (5.7) | 18 (5.4) | 17 (5.1)  |
|  **Age (years)** | 65.6 ± 8.72 | 65.4 ± 8.71 | 65.4 ±8.78 | 65.4 ± 8.79  |

Table 24 summarizes the baseline medical history of the enrolled, Safety, mITT and Per-Protocol populations. Most patients (68.2%, 260/381) had hypertension and 22.6% (86/381) had a history of atrial flutter. In the 6 months before enrollment, 70.1% (267/381) of enrolled subjects had at least one cardioversion. All enrolled subjects failed or were intolerant to at least a class I or III antiarrhythmic drug (AAD). On average, subjects (n=364) failed 1.3 ± 0.57 AADs prior to enrollment.

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Table 24 – Baseline Characteristics

|  Medical History | All Enrolled Subjects (N=381) n/N (%) | Safety Population (N=348) n/N (%) | mITT Population (N=334) n/N (%) | Per-Protocol Population (N=333) n/N (%)  |
| --- | --- | --- | --- | --- |
|  Known Cardiovascular Medical History | 296 (77.7%) | 270 (77.6%) | 259 (77.5%) | 258 (77.5%)  |
|  Congestive heart failure | 61 (16.0%) | 55 (15.8%) | 52 (15.6%) | 52 (15.6%)  |
|  NYHA Class I | 18 (4.7%) | 17 (4.9%) | 16 (4.8%) | 16 (4.8%)  |
|  NYHA Class II | 31 (8.1%) | 28 (8.0%) | 27 (8.1%) | 27 (8.1%)  |
|  NYHA Class III | 1 (0.3%) | 1 (0.3%) | 0 (0.0%) | 0 (0.0%)  |
|  Coronary artery disease | 86 (22.6%) | 77 (22.1%) | 74 (22.2%) | 74 (22.2%)  |
|  Vascular disease | 20 (5.2%) | 17 (4.9%) | 14 (4.2%) | 14 (4.2%)  |
|  Myocardial infarction | 23 (6.0%) | 19 (5.5%) | 19 (5.7%) | 19 (5.7%)  |
|  Hypertension (systemic) | 260 (68.2%) | 238 (68.4%) | 228 (68.3%) | 227 (68.2%)  |
|  Pulmonary hypertension | 8 (2.1%) | 7 (2.0%) | 7 (2.1%) | 7 (2.1%)  |
|  Cardiomyopathy | 43 (11.3%) | 42 (12.1%) | 39 (11.7%) | 39 (11.7%)  |
|  Hypertrophic | 5 (1.3%) | 5 (1.4%) | 4 (1.2%) | 4 (1.2%)  |
|  Ischemic | 7 (1.8%) | 7 (2.0%) | 6 (1.8%) | 6 (1.8%)  |
|  Non-Ischemic | 29 (7.6%) | 28 (8.0%) | 27 (8.1%) | 27 (8.1%)  |
|  Pacemaker | 21 (5.5%) | 18 (5.2%) | 18 (5.4%) | 18 (5.4%)  |
|  Other cardiovascular procedure (e.g. CABG, PCI, etc.) | 41 (10.8%) | 36 (10.3%) | 34 (10.2%) | 34 (10.2%)  |
|  Left ventricular hypertrophy | 11 (2.9%) | 11 (3.2%) | 11 (3.3%) | 11 (3.3%)  |
|  Documented Thromboembolic Event | 27 (7.1%) | 25 (7.2%) | 24 (7.2%) | 24 (7.2%)  |
|  Transient ischemic attacks (TIA) | 10 (2.6%) | 10 (2.9%) | 9 (2.7%) | 9 (2.7%)  |
|  Stroke | 8 (2.1%) | 6 (1.7%) | 6 (1.8%) | 6 (1.8%)  |
|  Pulmonary embolus | 5 (1.3%) | 5 (1.4%) | 5 (1.5%) | 5 (1.5%)  |
|  Any Arrhythmia Other Than Persistent AF | 113 (29.7%) | 107 (30.7%) | 102 (30.5%) | 101 (30.3%)  |
|  Left/right atrial tachycardia (AT) | 7 (1.8%) | 7 (2.0%) | 7 (2.1%) | 7 (2.1%)  |
|  AV node re-entry tachycardia (AVNRT) | 1 (0.3%) | 1 (0.3%) | 1 (0.3%) | 1 (0.3%)  |
|  Accessory pathway (WPW) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%)  |
|  Ventricular tachycardia (VT) | 7 (1.8%) | 6 (1.7%) | 6 (1.8%) | 6 (1.8%)  |
|  Atrial flutter (AFL) | 71 (18.6%) | 68 (19.5%) | 65 (19.5%) | 65 (19.5%)  |
|  Ventricular fibrillation (VF) | 2 (0.5%) | 2 (0.6%) | 2 (0.6%) | 2 (0.6%)  |
|  Other: arrhythmia | 36 (9.4%) | 34 (9.8%) | 32 (9.6%) | 31 (9.3%)  |
|  Diabetes | 69 (18.1%) | 62 (17.8%) | 61 (18.3%) | 61 (18.3%)  |
|  Obstructive sleep apnea (OSA) | 145 (38.1%) | 134 (38.5%) | 132 (39.5%) | 132 (39.6%)  |
|  CPAP use | 98/145 (67.6%) | 92/134 (68.7%) | 90/132 (68.2%) | 90/132 (68.2%)  |
|  CHADS₂ score | 1.3 ± 1.03 | 1.3 ± 1.03 | 1.3 ± 1.03 | 1.3 ± 1.03  |

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|  CHA₂DS₂-VASc score | 2.3 ± 1.48 | 2.3 ± 1.48 | 2.3 ± 1.48 | 2.3 ± 1.49  |
| --- | --- | --- | --- | --- |
|  AF History |  |  |  |   |
|  Length of time of Symptomatic PsAF (Month) | 15.2 ± 29.2 (n=378) | 15.5 ± 30.2 | 15.9 ± 30.8 | 15.9 ± 30.8  |
|  AAD Failed (Class I, III) | 1.3 ± 0.54 | 1.3 ± 0.55 | 1.3 ± 0.56 | 1.3 ± 0.56  |
|  Left Ventricular Ejection Fraction (%) | 56.0 ± 7.4 (n=361) | 56.2 ± 7.2 (n=346) | 56.2 ± 7.2 | 56.2 ± 7.2  |
|  Left Atrial Diameter (cm) | 42.6 ± 5.2 (n=357) | 42.4 ± 5.1 (n=345) | 42.6 ± 5.1 | 42.6 ± 5.1  |

### C. Results

#### C.1 – Index Ablation Procedure

Procedure Data

Table 25 and Table 26 present the index procedural data. There were 348 procedures in 348 subjects. All subjects underwent one (1) study ablation procedure.

Table 25 – Summary of Power, Temperature, and Impedance Data per Procedure (Safety Population, n = 348)

|  Description | Mean ± SD (n)  |
| --- | --- |
|  Mean Power (W) | 30.02 ± 7.83 (291)  |
|  Mean Temperature (°C) | 24.25 ± 2.49 (291)  |
|  Mean Impedance (ohms) | 117.72 ± 13.73 (277)  |

Table 26 – Summary of Ablation Procedure Parameters (Safety Population, n = 348)

|  Procedure Parameters | Mean ± SD (n)  |
| --- | --- |
|  Total Procedure Time (min) | 178.0 ± 70.97 (348)  |
|  Ablation Procedure Time (min) | 107.7 ± 48.64 (348)  |
|  Total Fluoroscopy Time (min) | 15.29 ± 16.61 (348)  |
|  Fluid Input (ml) | 2115.9 ± 1016.54 (343)  |
|  Fluid via Catheter (ml) | 886.3 ± 391.19 (339)  |
|  Fluid via IV (ml) | 1247.2 ± 857.14 (341)  |
|  Fluid Output (ml) | 1044.2 ± 835.18 (189)  |
|  Balance (input - output) (ml) | 1493.6 ± 914.34 (187)  |

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### Ablation Lesion Sets

All study AF ablation procedures were required to target and achieve electrical isolation of all pulmonary veins. Optional ablation targets were allowed based on clinical findings after PV isolation was completed.

Table 27 summarizes the lesion sets applied to the subjects undergoing ablation during the index ablation procedures. Table 28 presents a summary of non-PV targets in the 186 procedures in the SP and 179 procedures in the PP that involved ablation beyond PVI.

**Table 27 – Outcomes by Ablation Targets per Procedure**
(Safety Population, n = 348; Per-Protocol, n = 333)

|  Ablation Targets | Safety n/348 (%) | Per- Protocol n/333 (%)  |
| --- | --- | --- |
|  PVI only group | 193 (55.5) | 182 (54.7)  |
|  PVI+ CFAE group | 60 (17.2) | 59 (17.7)  |
|  PVI+ Non-CFAE group | 95 (27.3) | 92 (27.6)  |

**Table 28 – Ablation Targets per Procedure**
(Safety Population, n = 348; Per-Protocol, n = 333)

|  Ablation Target | Safety n/186 (%) | Per- Protocol n/179 (%)  |
| --- | --- | --- |
|  Left Inferior PV Mitral | 14 (7.5) | 14 (7.8)  |
|  Roof Line | 90 (48.4) | 87 (48.6)  |
|  Other: Linear Lesion | 16 (8.6) | 16 (8.9)  |
|  SVC | 10 (5.4) | 10 (5.6)  |
|  CFAE | 60 (32.3) | 59 (33.0)  |
|  Other: AF Foci | 75 (40.3) | 72 (40.2)  |
|  Cavo-Tricuspid Isthmus | 67 (36.0) | 63 (35.2)  |
|  RAGP | 1 (0.5) | 1 (0.6)  |

### Contact Force Data

The graphical user interface (GUI) of the CARTO® 3 workstation displays the pressure applied to the endocardial surface of the heart by the THERMOCOOL SMARTTOUCH® SF in gram forces that the investigator can visualize during the procedure.

Table 21 presents the overall average contact force applied during the procedure for all subjects who underwent a study ablation procedure. As shown, the overall average CF

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applied during ablation procedures was 15.23 ± 4.41 grams. Error! Reference source not found. presents a distribution of average contact force in 5-gram increments. In the majority of procedures (239/283), the average contact force applied was less than 20 grams.

Table 21 – Average Contact Force Measurements Overall per Ablation Procedure (Safety Population, n = 348)

|   | Average Contact Force (g)  |
| --- | --- |
|  n | 298  |
|  Mean | 15.23  |
|  Standard Deviation | 4.41  |
|  Median | 14.40  |
|  Q1 / Q3 | 12.10 / 18.13  |
|  Min / Max | 6.6 / 33.7  |

![img-4.jpeg](img-4.jpeg)

Figure 5 – Distribution of Average Contact Force per Ablation Procedure (Safety Population, n = 348)

The real-time rolling graph display with the working ranges acts as a visual aid providing real-time feedback of the pressure being applied by the operator in relationship to their pre-selected CF values. In this study, the most frequently selected working range of contact force was 5 to 40 g (37.5%, 130/347), which accounted for 37.5% of the procedures (130/347).

The CARTO® 3 System produces an auto tag (VISITAG) on the screen at the site of RF application that is dependent on the user's pre-defined settings. The auto tag appears

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when the RF application reaches a pre-determined time of application and the catheter has remained stable within a pre-determined range (mm) for the time. In this study the majority of operators chose a time to auto tag from 3-5 seconds with a stability of 1.5-3.0 mm.

![img-5.jpeg](img-5.jpeg)

Figure 6 – Operator-Configured VISITAG™ Stability Time per VISITAG™ Point (Safety Population, N = 348)

![img-6.jpeg](img-6.jpeg)

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Figure 7 – Operator-Configured VISITAG™ Stability Range per VISITAG™ Point (Safety Population, N = 348)

## C.2 - Rhythm Monitoring Compliance

In the 9-month evaluation period, rhythm monitoring included symptomatic and monthly asymptomatic TTM transmissions during the evaluation period, 12-lead ECG at 6, 9, 12, and 15 months, and 24-hour Holter at 6, 12, and 15 months. Figure 4 shows the TTM, 12-lead ECG, and Holter compliance rates at each evaluation time point in the Per-Protocol Population (n=333). The overall TTM, ECG, and Holter compliance rates were 65.9%, 93.9%, and 83.5%, respectively.

![img-7.jpeg](img-7.jpeg)

Figure 8. TTM/ECG/HM Compliance by Time Point (Per-Protocol Population, N=333)

## C.3 – Safety Results

The primary safety endpoint for this study was defined as the incidence of early onset (within 7 days of ablation procedure) Primary AEs for subjects undergoing a study ablation procedure. The Safety Population (N = 348) was comprised of all enrolled subjects who had the study catheter inserted.

### Primary Safety Endpoint – Primary Adverse Events

The primary safety analysis was based on the Safety Population cohort of 348 patients who were available for the 3-month evaluation. Table 30 presents the protocol-specified

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endpoint and safety results. Of 348 Safety Population subjects, 4 had missing outcomes (2 lost to follow up, 2 withdrawn). There were 17 primary AEs reported in 16 subjects. Among 17 primary AEs, sixteen (16) were considered definitely procedure-related, and one (1) was considered possibly procedure-related. One (1) was considered definitely device-related, thirteen (13) were considered possibly device-related, and three (3) were considered not device-related. The overall percentage of subjects in the Safety Population who experienced a serious primary AE was 4.7% (16/344) with upper confidence at 7.4%, which is significantly less than the specified performance goal of 16.0%. Therefore, the results met the pre-specified performance goal for the safety endpoint.

Table 30 – Primary Safety Endpoint Outcome – Primary Adverse Events

(Safety Population, n = 348)

|  Variable | Number of Subjects with Event | Number of Events | Event Rate n/N (%) | One-sided Exact 97.5% Upper Confidence Bound  |
| --- | --- | --- | --- | --- |
|  Primary Adverse Event | 16 | 17 | 16 / 344 (4.7) | 7.4%  |
|  Death | 0 | 0 | 0 / 344 (0.0) |   |
|  Atrio-esophageal Fistula | 0 | 0 | 0 / 344 (0.0) |   |
|  Cardiac Tamponade | 5 | 5 | 5 / 344 (1.5) |   |
|  Myocardial Infarction | 0 | 0 | 0 / 344 (0.0) |   |
|  Cerebrovascular Accident (CVA) / Stroke | 1 | 1 | 1 / 344 (0.3) |   |
|  Thromboembolism | 0 | 0 | 0 / 344 (0.0) |   |
|  Diaphragmatic Paralysis | 1 | 1 | 1 / 344 (0.3) |   |
|  Pneumothorax | 0 | 0 | 0 / 344 (0.0) |   |
|  Heart Block | 0 | 0 | 0 / 344 (0.0) |   |
|  Pulmonary Vein Stenosis | 0 | 0 | 0 / 344 (0.0) |   |
|  Pulmonary Edema (Respiratory Insufficiency) | 5 | 5 | 5 / 344 (1.5) |   |
|  Pericarditis | 2 | 2 | 2 / 344 (0.6) |   |
|  Major Vascular Access Complication / Bleeding | 3 | 3 | 3 / 344 (0.9) |   |

Table 31 summarizes the SAEs (by causality and body system) occurring within 30 days of a study ablation procedure that were not classified as Primary AEs by protocol

{39}

definition. GSMC adjudicated all serious adverse events of cardiac origin with 30 days of ablation procedure.

{40}

**Table 2 – Non-Primary SAEs Occurring within 30 Days of the Ablation Procedure by Causality and Body System (Safety Population, n = 348)**

|  Relationship to the Device/Procedure by Body System | Number of Subjects with Event | Number of Events  |
| --- | --- | --- |
|  Occurring 0-7 Days Post Ablation Procedure  |   |   |
|  Overall | 20 | 20  |
|  Definitely device related | 1 | 1  |
|  Esophageal ulcer | 1 | 1  |
|  Possibly device related | 1 | 1  |
|  Hypotension | 1 | 1  |
|  Not device related | 18 | 18  |
|  Atrial fibrillation | 2 | 2  |
|  Hypotension | 1 | 1  |
|  Complication associated with urinary catheter | 3 | 3  |
|  Diplopia | 1 | 1  |
|  Dyspnea | 1 | 1  |
|  Fluid overload | 2 | 2  |
|  Hypertensive crisis | 1 | 1  |
|  Hypoxia | 1 | 1  |
|  Pyrexia | 1 | 1  |
|  Renal failure | 1 | 1  |
|  Sepsis | 1 | 1  |
|  Tachycardia | 1 | 1  |
|  Torsade de pointes | 1 | 1  |
|  Urinary tract infection | 1 | 1  |
|  Definitely procedure related | 9 | 9  |
|  Complication associated with urinary catheter | 2 | 2  |
|  Fluid overload | 2 | 2  |
|  Esophageal ulcer | 1 | 1  |
|  Sepsis | 1 | 1  |
|  Hypotension | 2 | 2  |
|  Torsade de pointes | 1 | 1  |
|  Possibly procedure related | 6 | 6  |

{41}

|  Complication associated with urinary catheter | 1 | 1  |
| --- | --- | --- |
|  Diplopia | 1 | 1  |
|  Dyspnea | 1 | 1  |
|  Hypoxia | 1 | 1  |
|  Renal failure | 1 | 1  |
|  Urinary tract infection | 1 | 1  |
|  **Not procedure related** | 5 | 5  |
|  Atrial fibrillation | 2 | 2  |
|  Hypertensive crisis | 1 | 1  |
|  Pyrexia | 1 | 1  |
|  Tachycardia | 1 | 1  |
|  **Occurring 8-30 Days Post Ablation Procedure**  |   |   |
|  **Overall** | 6 | 7  |
|  **Not device related** | 6 | 7  |
|  Atrial flutter | 1 | 1  |
|  Complication associated with device | 1 | 1  |
|  Pleural effusion | 1 | 1  |
|  Presyncope | 1 | 1  |
|  Pulmonary embolism | 1 | 1  |
|  Tachycardia | 1 | 1  |
|  Tuberculosis | 1 | 1  |
|  **Definitely procedure related** | 1 | 1  |
|  Complication associated with urinary catheter | 1 | 1  |
|  **Possibly procedure related** | 2 | 2  |
|  Pleural effusion | 1 | 1  |
|  Pulmonary embolism | 1 | 1  |
|  **Not procedure related** | 4 | 4  |
|  Atrial flutter | 1 | 1  |
|  Presyncope | 1 | 1  |
|  Tachycardia | 1 | 1  |
|  Tuberculosis | 1 | 1  |

{42}

There were 2 deaths during the study. Two subjects died during the study. Neither death was adjudicated to be device or procedure-related by the GSMC. No deaths occurred within 3 months following the study procedure. An 80-year-old woman with known coronary artery disease, type II DM, and hypertension underwent uncomplicated study procedure for the treatment of persistent AF. The subject developed dyspnea and was hospitalized and treated for pneumonia and congestive heart failure at 452 days following the study procedure. She was discharged with home oxygen and died shortly after on day 464 following the index ablation. The second death occurred in an 83-year-old man who was hospitalized on day 164 for management of non-ST-elevation myocardial infarction, atrial fibrillation, and COPD exacerbation. The hospital course was complicated by respiratory decompensation and multifactorial neurologic dysfunction requiring intubation and mechanical ventilation support. The family subsequently withdrew care, and the patient died on day 166 following the index ablation.

### C.4 – Average CF and Primary AEs

Figure 9 compares the average CF during procedures in subjects experiencing Primary AEs with those who did not. Average contact force was recorded for three (3) subjects with tamponade. These are marked with black dots in the box plot of average contact force for all subjects in the safety population. Average contact force of these 3 subjects were above the Q3 (75th percentile) of overall average contact force.

![img-8.jpeg](img-8.jpeg)

Figure 9 – Comparison of Average Contact Force in Subjects with Tamponade vs Safety Population (Safety Population, n = 348)

### C.5 – Effectiveness Results

#### Primary Effectiveness Analysis

The primary effectiveness endpoint was defined as freedom from documented symptomatic and asymptomatic AF/AFL/AT (“atrial tachyarrhythmias”) based on

{43}

electrocardiographic data and freedom from failure modes during the effectiveness evaluation period (day 181-450).

The analysis of effectiveness was based on the 333 subjects in the Per-Protocol cohort. Of these, 36 subjects had missing outcomes (15 lost to follow-up, 1 death, and 20 withdrawals) and were not included in the primary effectiveness endpoint calculation. Approximately sixty percent (59.3%, 176/297) of the Per-Protocol population were free from documented atrial tachyarrhythmias and additional failure modes during their effectiveness evaluation period. The lower bound of the one-sided exact 97.5% lower confidence interval of the primary effectiveness rate was 53.4%, significantly higher than the pre-determined performance goal of 40%.

Primary effectiveness results are described in Table 32.

Table 3 – Primary…

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**Source:** [https://fda.innolitics.com/device/P030031S100](https://fda.innolitics.com/device/P030031S100)

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