FlexAbility™ Ablation Catheter, Sensor Enabled™

{0} # SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) ## I. GENERAL INFORMATION | Device Generic Name: | Irrigated RF Ablation Catheter | | --- | --- | | Device Trade Name: | FlexAbility™ Ablation Catheter, Sensor Enabled™ | | Device Procode: | LPB, OAD | | Applicant's Name and Address: | Abbott Medical 5050 Nathan Lane North Plymouth, MN 55442 | Date(s) of Panel Recommendation: None Premarket Approval Application (PMA) Number: P110016/S080 Date of FDA Notice of Approval: December 14, 2022 The original PMA (P110016) was approved on January 25th, 2012 where the ablation system, including the Therapy Cool Path Duo Ablation Catheter, Safire BLU Duo Ablation Catheter, IBI 1500T-9 v1.6 Cardiac Ablation Generator, and compatible irrigation pump, is indicated for endocardial mapping, stimulation, and ablation for the treatment of typical atrial flutter. The SSED to support the indication is available on the CDRH website (https://www.accessdata.fda.gov/cdrh_docs/pdf11/P110016B.pdf) and is incorporated by reference here. The next generation devices, FlexAbility Ablation Catheter and FlexAbility Ablation Catheter, Sensor Enabled (FlexAbility SE), were approved under PMA P110016/S013 on January 23rd, 2015 and P110016/S025 on February 17th, 2018, respectively for the same indication. The current supplement was submitted to expand the indication for the FlexAbility Ablation Catheter, Sensor Enabled to include treatment of recurrent, drug-refractory, sustained monomorphic ventricular tachycardia (MMVT) in patients with non-ischemic structural heart disease. ## II. INDICATIONS FOR USE The FlexAbility™ Ablation Catheter, Sensor Enabled™, when used in conjunction with a compatible irrigation pump and compatible RF cardiac ablation generator, is indicated for: - Endocardial mapping, stimulation, and ablation for the treatment of typical atrial flutter ---PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 2 of 39 {1} - Endocardial or epicardial mapping, stimulation, and ablation for the treatment of recurrent, drug-refractory, sustained monomorphic ventricular tachycardia in patients with non-ischemic structural heart disease, when used in conjunction with a compatible cardiac mapping system. ### III. CONTRAINDICATIONS The catheter is contraindicated for: - Patients with active systemic infection. - Patients with intracardiac thrombus or myxoma, or interatrial baffle or patch via transeptal approach. In addition, the following contraindications apply for treatment of ventricular tachycardia: - Patients who have had a ventriculotomy or atriotomy within the preceding four weeks as the recent surgery may increase the risk of perforation. - Patients with prosthetic valves as the catheter may damage the prosthesis. - The use in coronary arterial vasculature due to risk of damage to the coronary arterial vasculature. - The transseptal approach in a patient with an interatrial baffle or patch because the opening could persist and produce an iatrogenic atrial shunt. - The retrograde trans-aortic approach in patients who have had aortic valve replacement. - Patients unable to receive heparin or an acceptable alternative to achieve adequate anticoagulation ### IV. WARNINGS AND PRECAUTIONS The warnings and precautions can be found in the FlexAbility Ablation Catheter, Sensor Enabled labeling. ### V. DEVICE DESCRIPTION FlexAbility SE is a sterile, single use catheter with a 7.5 F shaft and an 8 F distal section. It is constructed of thermoplastic elastomer material and noble metal electrodes. The catheter has a flexible tip electrode and magnetic sensor (Figure 1). It has a fluid lumen connected to open conduits at the flexible tip electrode for saline irrigation during the ablation procedure. The FlexAbility SE catheter is available in bi-directional and uni-directional configurations (Figure 2). PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 3 of 39 {2} The tip curvature is manipulated by the control mechanism located on the handle at the catheter's proximal end. To adjust the curve of the distal tip on the uni-directional catheter, push or pull the thumb control located on the handle. To adjust the curve of the distal tip on the bi-directional catheter, use the actuator to deflect the catheter in either direction. The catheter is available in eight distal curve configurations identified on the catheter label. All curve configurations were acceptable for use during the clinical investigation. The catheter is compatible with EnSite Velocity, EnSite Precision, and Ensite X mapping systems.   Figure 1. FlexAbility SE, Catheter Tip PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 4 of 39 {3}  **Figure 2. FlexAbility SE, Bi-Directional (top) and Uni-Directional (bottom)** The catheters are available in eight distal curve configurations and the curve is identified on the catheter package label. The device and packaging are not made with natural rubber latex. | Device Name | Model Number | | --- | --- | | FlexAbility SE UniD-D | A-FASE-D | | FlexAbility SE BiD-DD | A-FASE-DD | | FlexAbility SE BiD-DF | A-FASE-DF | | FlexAbility SE BiD-FF | A-FASE-FF | | FlexAbility SE UniD-F | A-FASE-F | | FlexAbility SE BiD-FJ | A-FASE-FJ | PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 5 of 39 {4} | FlexAbility SE UniD-J | A-FASE-J | | --- | --- | | FlexAbility SE BiD-JJ | A-FASE-JJ | The following devices are required in addition to the FlexAbility SE catheters: - REF generator - Irrigation pump - Electrophysiology recording and mapping system In the LESS-VT IDE study, the following devices were used with the subject device to provide the treatment (Table 1). **Table 1. Associated Devices** | Devices | Model Number, SW Version | | --- | --- | | **Generator** | | | Ampere™ RF Ablation Generator | H700489 | | **Ancillary Device** | | | EnSite System (Amplifier and Display Workstation) | EE3000 | | EnSite Velocity Software | v5.0 or greater | | Ensite Precision Software | v2.0 or greater | | Ensite X EP System | v1.0 or greater | | Cool Point™ Irrigation Pump | IBI-89003, SW v24 or greater | | Cool Point Tubing Set | RO85785 | The PMA submission history for the FlexAbility SE catheters, and the previously approved FlexAbility™ Ablation Catheters, is described below in **Table 2**. **Table 2: PMA Submission History** | Submission | Description | Date of Approval | | --- | --- | --- | | P110016 | Original PMA Approval – Therapy™ Cool Path Duo, Safire™ BLU Duo, and IBI1500T-9 v1.6 Cardiac Ablation Generator | 25JAN2012 | | P110016/S013 | Approval of the FlexAbility™ Ablation Catheter | 23JAN2015 | | P110016/S025 | Approval of the FlexAbility™ Ablation Catheter, Sensor Enabled™ for the treatment of typical atrial flutter. | 17FEB2017 | | P110016/S080 | Approval of the FlexAbility™ Ablation Catheter, Sensor Enabled™ for the treatment of typical atrial flutter and recurrent, drug-refractory, sustained MMVT in patients with non-ischemic structural heart disease | *TBD* | PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 6 of 39 {5} ## **VI. ALTERNATIVE PRACTICES AND PROCEDURES** There are several other alternatives for the treatment of recurrent, drug-refractory, sustained monomorphic ventricular tachycardia in patients with non-ischemic structural heart disease, including: - Pharmacological therapy for arrhythmia control - Implantable cardiac defibrillator therapy - Antitachycardia pacing - Direct surgical ablation or removal of tissue 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** The FlexAbility SE catheters have been marketed in the United States for treatment of typical atrial flutter since February 2017 and is marketed in all major geographies including Argentina, Australia/New Zealand, Brazil, Canada, China, Colombia, Costa Rica, Ecuador, Egypt, EU Member Countries, Hong Kong, India, Israel, Japan, South Korea, Malaysia, Mexico, Russia, Saudi Arabia, Singapore, Taiwan, Thailand, Turkey, and UK, among others. These devices have not been withdrawn from market in any country for any reason related to safety or effectiveness. ## **VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH** Below is a list of the potential adverse effects (e.g., complications) associated with the use of the device. PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 7 of 39 {6} | Category | Adverse Event | | --- | --- | | Bleeding | Abdominal bleeding | | | Anemia | | | Blood loss requiring transfusion | | | Hemoperitoneum | | | Hemothorax | | Conduction System Complications | Abnormal electrocardiogram (ECG) | | | Arrhythmias resulting in clinically significant deterioration in subject medical condition | | | Atypical flutter | | | Exacerbation of pre-existing arrhythmia | | | Exacerbation of pre-existing atrial fibrillation | | | Inadvertent AV block | | | Temporary heart block | | | Unintended complete heart block requiring pacemaker insertion | | | Unintended sinus node dysfunction requiring pacemaker insertion | | | Ventricular arrhythmia requiring defibrillation | | Coronary Artery Injury or Vascular/Valvular Injury | Aortic dissection | | | Arterial spasm | | | Coronary artery dissection | | | Coronary artery injury/damage | | | Pulmonary vein dissection | | | Valvular damage | | | Valvular damage or insufficiency (i.e. new tricuspid regurgitation) | | | Vascular trauma | | Infection | Endocarditis | | | Infection | | | Sepsis | | Intra-procedure or post-procedure symptoms | Abnormal vision | | | Angina/chest pain | PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 8 of 39 {7} | Category | Adverse Event | | --- | --- | | | Component damage to implantable cardioverter defibrillator or pacemaker | | | Dislodgement of implantable cardioverter defibrillator or permanent pacing lead | | | Dizziness | | | Exacerbation of chronic obstructive pulmonary disease (COPD) | | | High creatinine phosphokinase | | | Laceration | | | Neck pain/back pain/groin pain related to the procedure | | | Palpitations | | | Radiation injury resulting in dermatitis (inflammation of the skin), erythema (redness), etc. | | | Respiratory failure | | | Seizure | | | Skin burns/ skin tears | | | Syncope | | | Vasovagal reaction | | Perforation/Tamponade | Arteriovenous fistula | | | Cardiac effusion/tamponade | | | Cardiac perforation | | | Left atrial/esophageal fistula | | | Pericardial bleeding | | | Pericardial effusion | | Procedure or Post-op Complications | Anaphylaxis | | | Anesthesia reaction | | | Hypotension | | | Hypoxia | | | Myocardial infarction (MI) | | | Pericarditis | | | Phrenic nerve damage | | | Pleural damage | | | Pleural effusion | | | Pneumonia | | | Pneumothorax | | | Pulmonary edema | | | Pulmonary embolism | | | Pulmonary hypertension | | | Pulmonary vein stenosis | | | Respiratory depression | | Thromboembolic Event | Air embolism | | | Arterial/venous thrombus | PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 9 of 39 {8} | Category | Adverse Event | | --- | --- | | Vascular Access Complication | Cardiac thromboembolism | | | Cerebrovascular accident/Stroke | | | Thromboembolic event | | | Transient ischemic attack (TIA) | | | Catheter insertion site hematoma | | | Groin hematoma | | | Obstruction/perforation/damage of the vascular system or vascular bleeding | | Worsened Heart Failure | Pseudoaneurysm | | | Congestive heart failure (CHF) exacerbation | | Death | Death | For the specific adverse events that occurred in the clinical study, please see Section X below. ## IX. SUMMARY OF NONCLINICAL STUDIES Pre-clinical testing of the FlexAbility SE catheter included verification and validation testing, biocompatibility of patient-contacting materials, sterilization, packaging and shelf-life testing, and animal studies. Performance testing was conducted to demonstrate design integrity. All tests performed which were identified in standards or guidance documents were based on the product specification requirements. A summary of previously reported preclinical studies can be found in the SSED for the original PMA at: https://www.accessdata.fda.gov/cdrh_docs/pdf11/P110016B.pdf All previously performed pre-clinical testing was conducted to support the initial PMA approval, approval of the FlexAbility Ablation Catheter (P110016/S013), and approval of the FlexAbility Ablation Catheter, Sensor Enabled (P110016/S025) of the FlexAbility SE catheter. No further pre-clinical testing was conducted for the current expanded indication submission. ## X. SUMMARY OF PRIMARY CLINICAL STUDY LESS-VT Trial – Non-ischemic Cardiomyopathy Cohort The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of RF ablation with the FlexAbility SE Catheter for the treatment of recurrent, drug-refractory, sustained monomorphic ventricular tachycardia in patients PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 10 of 39 {9} with non-ischemic structural heart disease in the US, Europe, and Australia under IDE # G170221. Data from this clinical study were the basis for the PMA approval decision. A summary of the clinical study is presented below. ### **A. Study Design** Patients were enrolled between 6/11/2018 and 6/9/2021. The database for this PMA reflected data collected through January 19, 2022 and included 182 patients at 24 investigational sites (US: 19 sites, Europe: 5 sites). The LESS-VT NICM Cohort is a prospective, open-label, non-randomized, single-arm multicenter pivotal trial. The study enrolled and treated subjects diagnosed with non-ischemic cardiomyopathy and drug refractory recurrent MMVT and was evaluated for success based on a composite of cardiovascular-related and procedure-related major complications through 7 days and freedom from recurrent sustained MMVT at 6 months. All subjects are followed for a total of 12 months. An independent Clinical Events Committee (CEC) provided blinded adjudication for all primary safety endpoint events. An independent ICD Event Review Committee reviewed all tachyarrhythmia events collected in the study and adjudicated the reported tachyarrhythmia for morphology (e.g. MMVT) and the appropriateness of any therapy delivered. An independent Data Safety Monitoring Board (DSMB) oversaw clinical data and safety. #### **1. Clinical Inclusion and Exclusion Criteria** Enrollment in the NICM Cohort of the LESS VT study was limited to patients who met the following inclusion criteria - Structural heart disease (non-ischemic) with one of the following: - Confirmed diagnosis via echocardiography and/or cardiac CT/MRI, or - Left ventricular ejection fraction (EF) <40% (documented within the last 6 months via echocardiography), or - Arrhythmogenic RV cardiomyopathy/dysplasia (per 2010 ARVC/D Task Force Criteria). - At least one documented episode of sustained MMVT by either EGM or ECG in the 6 months prior to enrollment - Implanted with a market released ICD or CRT-D for at least 30 days prior to index ablation procedure - Refractory (i.e. not effective, not tolerated or not desired) to at least one anti-arrhythmic medication (either amiodarone or sotalol) for treatment of MMVT PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 11 of 39 {10} - At least 18 years of age Informed of the nature of the study, agreed to its provisions and has provided written informed consent as approved by the Institutional Review Board/Ethics Committee (IRB/EC) of the respective clinical study site. - Able and willing to comply with all study requirements Patients were not permitted to enroll in the study if they met any of the following exclusion criteria: - Implanted with a subcutaneous ICD - Implanted with a ventricular assist device (VAD) (e.g. TandemHeart) - Currently receiving support, or anticipated to receive support prior to the index ablation procedure, via extracorporeal membrane oxygenation (ECMO) - Presence of intracardiac thrombus verified via computer tomography (CT), magnetic resonance imaging (MRI), transesophageal echocardiogram (TEE), or transthoracic echocardiogram (TTE) within 48 hours prior to the index ablation procedure or intra-procedure intracardiac echocardiography (ICE) - For subjects with a history of AF, this verification must be done via TEE or ICE - ST elevation myocardial infarction (MI) within 60 days prior to index ablation procedure - Previous cardiac surgery (e.g. ventriculotomy, atriotomy, coronary artery bypass graft), within 60 days prior to index ablation procedure - Percutaneous coronary intervention (PCI) within 30 days prior to index ablation procedure - Idiopathic VT - Incessant VT (continuous sustained VT that promptly recurs despite repeated intervention for termination over ≥3 hours) necessitating immediate treatment or requiring hemodynamic support prior to the ablation procedure - VT/VF thought to be from channelopathies - Reversible cause of VT - Severe aortic stenosis or flail mitral valve - Mechanical mitral and aortic valve - History of stroke with modified Rankin scale > 3 - Unstable angina - Chronic NYHA Class IV heart failure - Ejection fraction < 15% - Thrombocytopenia (defined as platelet count <80,000) or coagulopathy - Contraindication to systemic anticoagulation (i.e. heparin, warfarin, or a direct thrombin inhibitor) - Women who are pregnant or nursing - Active uncontrolled infection - Other anatomic or co morbid conditions or other medical, social, or psychological conditions that, in the investigator's opinion, could limit the patient's ability to PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 12 of 39 {11} participate in the study or to comply with follow up requirements, or impact the scientific soundness of the study results - Enrolled in an investigational study evaluating another device or drug that would confound the results of this study - Have a life expectancy of less than 12 months due to any condition. ## 2. Follow-up Schedule All patients were scheduled to return for follow-up examinations at 30 days, 6 and 12 months postoperatively. Preoperatively, all subjects underwent evaluation of LV ejection fraction, ICD interrogation, SF-12 QoL and HADS assessments, and thrombus screening. Postoperatively, the objective parameters measured during the study included ICD interrogation for VT occurrence and SF-12 QoL and HADS assessments. Adverse events and complications were screened and recorded at all visits. The key timepoints are shown below in the table summarizing safety and effectiveness. **Table 3: List of all clinical investigation specific tests and procedures** | Visit Study Activity | Enrollment & Baseline | Procedure (index and staged procedures) | Discharge | 30 days (± 7 days) | 6 and 12 Months (± 21 days ) | | --- | --- | --- | --- | --- | --- | | Informed Consent Process and Confirm enrollment criteria | X | | | | | | Demographics, Medical History incl. arrhythmias, MMVT | X | | | | | | Retrospective Health care utilization for 12 months prior to consent (US only) | X | | | | | | LVEF via echocardiography | X* | | | | | | Physical Examination | X | | X | X | | | 12-Lead ECG | X | | X | X | | | Modified Rankin Score assessment | X | | | | | | Device Programming, Interrogation, and session records | X | X | X | X | X | | Recurrence of VT | | | | X | X | PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 13 of 39 {12} | Cardiac and/or anti-arrhythmic medications | X | X | X | X | X | | --- | --- | --- | --- | --- | --- | | SF-12 QOL and HADS | X | | | | X | | Confirm absence of intracardiac thrombus | X^{a} | X^{a} | | | | | Procedure indication and ablation procedure strategy | | X | | | | | Ablation System details and future plans for additional procedures if any | | X | | | | | EnSite Precision Procedure Recording | | X | | | | | Repeat Ablation^{b} | | | (X) | (X) | (X) | | Adverse Event | | (X) | (X) | (X) | (X) | | Health Care Utilization | | | | (X) | (X) | | Deviation | (X) | (X) | (X) | (X) | (X) | | Withdrawal | (X) | (X) | (X) | (X) | (X) | | Death | (X) | (X) | (X) | (X) | (X) | (X) If applicable * Historical echocardiogram can be used if it was performed within the last 6 months prior to enrollment. a Thrombus assessment must be performed within 48 hrs of procedure which can take place at either baseline or procedure visit b Repeat ablation is to be reported for ventricular ablation procedures occurring >14 d after index procedure ### 3. Clinical Endpoints With regards to safety, the primary safety endpoint is a composite of cardiovascular-related and procedure-related major complications through 7 days post index ablation procedure. Major complication is defined as an adverse event that led to prolongation of hospital stay or to another hospitalization, required additional intervention for treatment, and/or resulted in significant injury or death. For this study, recurrence of a VT is not a reportable adverse event in the study, regardless of hospitalization or intervention, unless it results in new incessant VT/VT storm or significant deterioration of subject's medical condition, or death. With regards to effectiveness, the primary effectiveness endpoint is freedom from recurrent sustained MMVT at 6 months and a new or increased dose Class I or III AAD at 6 months following the index ablation procedure, where sustained MMVT is defined as a continuous MMVT for >30 seconds, or MMVT requiring intervention for termination regardless of its duration. With regard to success/failure criteria, each primary endpoint was compared to a predetermined performance goal. The study would be considered success when both of the following criteria are met: PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 14 of 39 {13} - The primary safety endpoint event rate meets the prespecified performance goal of 26.9%. The hypothesis for the primary safety endpoint is: $$\mathrm{H}_{0}: \mathrm{P}_{1} \geq 26.9\%$$ $$\mathrm{Ha}: \mathrm{P}_{1} < 26.9\%$$ Where P₁ is the 7-day rate (binomial proportion) of the primary safety endpoint. A sample size of 171 subjects was required to provide 85% power to reject null hypothesis at 5% significance level using the exact test for binomial proportion. The analysis population for the primary safety endpoint analysis included subjects enrolled in the NICM cohort who had the investigational catheter inserted in the EP lab for the VT ablation procedure (regardless of whether or not RF energy is delivered) and crossed the 7-day post index ablation time point. - The primary effectiveness endpoint event rate meets the prespecified performance goal of 40.2%. The hypothesis for the primary effectiveness endpoint is: $$\mathrm{H}_{0}: \mathrm{P}_{2} \leq 40.2\%$$ $$\mathrm{Ha}: \mathrm{P}_{2} > 40.2\%$$ Where P₂ is freedom from recurrent sustained MMVT and a new or increased dose of Class I or III AAD at 6 months following the index ablation procedure for the NICM cohort. A sample size of 138 subjects was required to provide at least 85% power to reject null hypothesis at the 5% significance level using the exact test for binomial proportion. The analysis population for the effectiveness endpoint analysis included subjects in the NICM cohort who had the catheter inserted and RF energy delivered in the EP lab for the VT ablation procedure, and who had their 6-month visit or crossed the 6-month visit window without the visit but with an effectiveness endpoint event. PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 15 of 39 {14} ## B. Accountability of PMA Cohort At the time of database lock, of 182 patients consented in the PMA study, 140 (76.8%) patients were available for analysis at the 6-month post-operative visit. Figure 3 presents the LESS-VT NICM Cohort subject disposition. Based on the subject accountability, Table 4 summarizes the protocol specified analysis populations. Figure 3: LESS-VT NICM Cohort Subject Disposition  ¹ Withdrawal due to study catheter not inserted was counted as pre-procedure withdrawal. Reasons for catheter not inserted include non-inducible or no arrhythmic substrate identified (5), transeptal access related cardiac perforation (1), and chronic aortic dissection (1). ² n is the number of visits observed at the time of this report that occurred within the visit window, excluding deaths and withdrawals. ³ Number of visits expected at the time of this report. A subject is considered expected at the given visit if they have not died or withdrawn by the end of the visit window, and the visit window has opened by the cutoff date. ⁴ A visit is considered missed if the visit window is closed at the time of this report and the visit has not occurred or has not been entered in the database, excluding deaths and withdrawals. PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 16 of 39 {15} 5 A visit is considered pending if the visit window is open at the time of this report but the visit has not occurred or has not been entered in the database, excluding deaths and withdrawals. 6 Withdrawal case report forms were submitted for three (3) NICM subjects after missing the 12-month visit and after the close of the 12-month visit window. For these subjects, the reason for withdrawal was documented as lost to follow-up (n=2) and subject and/or family request (n=1). These subjects are also counted as having missed visits for the 12-month follow-up. Table 4. Protocol Specified Analysis Populations | Population | Abbreviation for Analysis Population | Description | Subjects | | --- | --- | --- | --- | | Enrolled | ENR | Signed written informed consent | 182 | | Catheter-Inserted | CIN | Investigational catheter inserted into the vasculature | 166 | | Primary Safety Endpoint | SAF | Catheter inserted subjects who completed 7 days of follow-up or experienced a primary safety endpoint failure | 166 | | Treated | TRT | Investigational catheter inserted and RF energy delivered | 165 | | Primary Effectiveness Endpoint | EFF | Treated subjects who have completed a 6 or 12 Month visit with ICD interrogation or experienced a primary effectiveness endpoint failure | 146 | ### C. Study Population Demographics and Baseline Parameters The demographics of the study population are typical for patients with non-ischemic cardiomyopathy and recurrent MMVT referred for catheter ablation in the US. The mean age was 60.2 ± 13.8 years, and 16.3% were female. Tables 5 and 6 present the demographics and baseline cardiovascular history for the catheter-inserted (CIN) population, respectively. Approximately half of subjects (84/166) had NYHA II-III functional class at baseline, and the mean left ventricular ejection fraction was 38.1 ± 12.9%. Amiodarone or sotalol had not been effective or tolerated in 88% subjects. Prior catheter ablation for the treatment of ventricular tachycardia had been performed in 55 (33.1%) subjects. Table 5. Baseline Demographics (CIN Population) | Demographic Variable | CIN Population (N=166) | | --- | --- | | Age (year) | | | Mean ± SD (n) | 60.2 ± 13.8 (166) | | Range (Min, Max) | (22.0, 88.0) | | Sex, n (%) | | | Female | 16.3% (27/166) | | Male | 83.7% (139/166) | | Ethnicity, n (%) | | | Hispanic or Latino | 2.0% (3/152) | | Not Hispanic or Latino | 98.0% (149/152) | | Race, n (%) | | | American Indian or Alaskan Native | 0.7% (1/152) | PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 17 of 39 {16} | Asian | 2.0% (3/152) | | --- | --- | | Black or African American | 13.2% (20/152) | | Native Hawaiian or Other Pacific Islander | 0.0% (0/152) | | White | 84.2% (128/152) | | Height (cm) | | | Mean ± SD (n) | 175.4 ± 9.6 (165) | | Range (Min, Max) | (150.0, 198.0) | | Weight (kg) | | | Mean ± SD (n) | 89.4 ± 22.4 (165) | | Range (Min, Max) | (45.0, 155.6) | Table 6. Baseline Cardiovascular History (CIN Population) | Demographic Variable | CIN Population (N=166) | | --- | --- | | Cardiovascular History, n (%) | | | Structural Heart Disease | 100.0% (166/166) | | Ischemic Cardiomyopathy | 0.0% (0/166) | | Non-ischemic Cardiomyopathy | 100.0% (166/166) | | Coronary Artery Disease | 16.3% (27/166) | | Diastolic Dysfunction | 27.7% (46/166) | | Heart Failure | 61.4% (102/166) | | NYHA Class I | 17.6% (18/102) | | NYHA Class II | 52.0% (53/102) | | NYHA Class III | 30.4% (31/102) | | NYHA Class IV | 0.0% (0/102) | | Not Specified | 0.0% (0/102) | | Hypercholesterolemia | 27.7% (46/166) | | Hyperlipidemia | 45.8% (76/166) | | Hypertension | 48.2% (80/166) | | Infective Endocarditis | 1.2% (2/166) | | Myocardial Infarction | 5.4% (9/166) | | Percutaneous Coronary Intervention | 7.2% (12/166) | | Valvular Heart Disease | 19.9% (33/166) | | Class I/III AAD Use at Study Enrollment | 58.4% (97/166) | | Amiodarone or Sotalol not Effective | 78.9% (131/166) | | Amiodarone or Sotalol not Tolerated | 37.3% (62/166) | | LV Ejection Fraction (%) | 38.1 ± 12.9 (163) | | | (15.0, 70.0) | All enrolled subjects had non-ischemic cardiomyopathy and none had been diagnosed with ischemic cardiomyopathy. Table 7 presents the reported etiologies of non-ischemic heart disease in the study population. The distribution of NICM subtypes in the pivotal study aligns with other large published series.¹ Table 7. Types of Non-Ischemic Heart Disease (CIN Population) | Types of Non-Ischemic Heart Disease | (N=166) | | --- | --- | PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 18 of 39 {17} | Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia | 21.7% (36/166) | | --- | --- | | Cardiac Sarcoidosis | 10.2% (17/166) | | Congenital Heart Disease | 3.6% (6/166) | | Hypertrophic Cardiomyopathy | 6.6% (11/166) | | Non-Ischemic Left Ventricular Cardiomyopathy and/or Dilated Cardiomyopathy | 54.2% (90/166) | | Other | 14.5% (24/166) | | Genetic Cardiomyopathy | 1.2% (2/166) | | Other Cardiomyopathy* | 3.0% (5/166) | | Myocarditis | 2.4% (4/166) | | Scar Associated with Previous Cardiac Surgery | 0.6% (1/166) | | Unknown | 1.8% (3/166) | *Site-provided descriptions of Other Cardiomyopathy include focal LV ventricular scar/fibrosis, LV dysfunction, ESRD related cardiomyopathy, focal basal septum fibrosis, acute on chronic systolic HF. ## Procedural Data ### Repeat procedures: The study allows for staged ablation procedures based on physician discretion and would be considered a continuation of the index ablation procedure if performed within 14 days of the index ablation procedure. Overall, 9 of 165 TRT subjects underwent a staged procedure within 14 days. Of these, 5 staged procedures were performed due to early recurrence of ventricular arrhythmia. ### Cardiac Access The basis of mapping and ablation in this study is scar-based late potential ablation. The study protocol encourages mapping of both ventricular chambers and epicardium. Table 8 summarizes the cardiac access utilized in the study. Subxiphoid epicardial access was performed in 48.8% of the index procedures. Including the staged procedures, epicardial mapping was performed in 53% with epicardial ablation performed in 43%. Table 8. Cardiac Access (CIN Population) | Access* | Index Procedure (N=166) | Staged Procedure (N=9) | | --- | --- | --- | | LV Endocardial Access | 77.1% (128/166) | 66.7% (6/9) | | Transseptal | 59.4% (76/128) | 66.7% (4/6) | | Retrograde Aortic | 60.9% (78/128) | 33.3% (2/6) | | Epicardial Access | 51.2% (85/166) | 55.6% (5/9) | | Subxiphoid | 95.3% (81/85) | 100.0% (5/5) | | Other: coronary sinus mapping | 4.7% (4/85) | 0.0% (0/5) | ### Programmed Electrical Stimulation PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 19 of 39 {18} The study protocol recommends programmed electrical stimulation (PES) at a minimum of two sites (including one LV site) using two cycle lengths (600 ms and 400 ms typically) with at least double extra-stimuli (up to four extra-stimuli may be used) to induce VT at the beginning of the study unless there is a clinical reason not to do so. At the end of the study, the same PES protocol used at baseline is encouraged unless the patient is felt to be unable to tolerate it. Table 9 presents the PES results. Overall, a median of 2.0 (mean: 2.3 ± 2.0) MMVTs were identified for each subject at the index procedure. Table 9. MMVT inducibility pre- and post-ablation (TRT population, Index Procedure) | | Number of Subjects (n= 165) | | --- | --- | | Pre-procedure programmed electrical stimulation conducted | 92.1% (152/165) | | MMVT inducible pre-procedure | 79.6% (121/152) | | Post-ablation induction attempted | 91.7% (111/121) | | Post-ablation induction attempted and MMVT not inducible | 88.2% (97/110) | ### Mapping Strategies The basis of mapping and ablation in this study was ventricular tachycardia substrate mapping and scar-based late potential ablation guided by electroanatomic mapping. Investigators used the assigned catheter or another market cleared multipolar mapping catheter to create voltage maps and identify ablation targets. Table 10 summarizes the additional mapping strategies utilized for subjects with spontaneous or induced MMVT. Table 10. Mapping During MMVT (TRT Population, Index Procedure) | Mapping Done In MMVT | Index Procedure (N=165) | | --- | --- | | Entrainment | 17.6% (29/165) | | Timing/Activation | 52.7% (87/165) | | Voltage | 13.3% (22/165) | | Other | 4.2% (7/165) | | Not Done | 41.2% (68/165) | | Unsustainable | 20.6% (14/68) | | Untolerated by Subject | 39.7% (27/68) | | Not Inducible | 32.4% (22/68) | | Physician Discretion | 8.8% (6/68) | ### Ablation Locations Ablation locations included the endocardial surface in 80.6% (133/165) of subjects and the epicardial surface in 43.0% (71/165) of subjects. The left ventricle was most frequently PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 20 of 39 {19} targeted (120/165, 72.7%), followed by right ventricle (54/165, 32.7%) and interventricular septum (15/165, 9.1%). Table 11. Ablation Locations (TRT Population) | Ablation Target Location | Index Procedure (N=165) | Staged Procedure (N=9) | | --- | --- | --- | | Surface | | | | Endocardial | 80.6% (133/165) | 77.8% (7/9) | | Epicardial | 40.0% (66/165) | 55.6% (5/9) | | Chamber or Component | | | | Right Ventricle | 32.1% (53/165) | 11.1% (1/9) | | Left Ventricle | 72.7% (120/165) | 100.0% (9/9) | | Septal | 8.5% (14/165) | 11.1% (1/9) | # Procedure Parameters Table 12 presents the procedural results. Table 12. Procedure and Ablation Parameters | Procedure Metric | Index Procedure (N=165) | Staged Procedure (N=9) | | --- | --- | --- | | Anesthesia | | | | Conscious Sedation | 7.9% (13/165) | 22.2% (2/9) | | General | 83.6% (138/165) | 66.7% (6/9) | | Monitor Anesthesia Care | 8.5% (14/165) | 11.1% (1/9) | | Hemodynamic Support | | | | Balloon Pump | 0.6% (1/165) | 11.1% (1/9) | | Impella | 0.6% (1/165) | 22.2% (2/9) | | Other | 0.6% (1/165) | 0.0% (0/9) | | Not used | 98.2% (162/165) | 66.7% (6/9) | | Irrigation Fluid Input from Pump (ml) | | | | Mean ± StdDev (n) | 746.3 ± 433.4 (160) | 1056.4 ± 545.4 (9) | | Median (Q1, Q3) | 676.0 (402.5, 1000.0) | 1000.0 (853.0, 1358.0) | | (Min, Max) | (0, 2222) | (100, 2000) | | Cardioversion Performed | 66.1% (109/165) | 88.9% (8/9) | | Number Performed | | | | Mean ± StdDev (n) | 3.1 ± 2.5 (109) | 3.5 ± 2.1 (8) | | Median (Q1, Q3) | 2.0 (1.0, 4.0) | 3.0 (2.0, 5.0) | | (Min, Max) | (1, 13) | (1, 7) | | Ventricular Ablation Abandoned | 4.8% (8/165) | 22.2% (2/9) | | Procedure Time (min) | | | | Mean ± StdDev (n) | 231.8 ± 96.6 (165) | 294.4 ± 106.0 (9) | | Median (Q1, Q3) | 207.0 (170.0, 267.0) | 311.0 (235.0, 369.0) | | (Min, Max) | (82, 710) | (113, 440) | | Fluoroscopy Time (min) | | | | Mean ± StdDev (n) | 33.2 ± 19.6 (164) | 43.0 ± 24.6 (9) | PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 21 of 39 {20} Median (Q1, Q3) (Min, Max) 29.5 (19.0, 42.0) (3, 112) 46.0 (24.0, 56.0) (6, 88) ## D. Safety and Effectiveness Results ### 1. Safety Results #### a. Primary Safety Endpoint The analysis of safety was based on the cohort of 166 catheter inserted subjects who completed 7 days of follow-up or experienced a primary safety endpoint event within the 7-day window. Overall, 27 of 166 subjects (16.3%) experienced a primary safety endpoint event. The upper bound of the 95% one-sided confidence interval of 21.7% was lower than the pre-specified performance goal, and the primary safety endpoint was met. | Primary Safety Endpoint | | | | | --- | --- | --- | --- | | Population | Number of Subjects | 95% One-Sided Confidence Interval Upper Bound | Performance Goal | | Safety Population | 16.3% (27/166) | 21.7% | < 26.9% | The key safety outcomes for this study are presented below in Table 13 by pre-specified categories and by CEC adjudication. Nine subjects had a staged procedure performed within 14 days. Including major complications that occurred after the staged procedures, a total of 29 (17.5%) subjects experienced cardiovascular-related and procedure-related major complications through 7 days post index ablation procedure or staged procedure. **Table 13. Primary Safety Endpoint Events (SAF Population)** | Primary Safety Endpoint Event Criteria (pre-specified categories and by CEC adjudication) | PSAE within 7 days of index procedure (N=166) | | | --- | --- | --- | | | Number of Events | Number of Subjects | | Acute Myocardial Infarction | 0 | 0.0% (0/166) | | Acute Pulmonary edema requiring reintubation | 1 | 0.6% (1/166) | | Cardiac perforation/tamponade | 6 | 3.0% (5/166) | | Cardiogenic shock | 2 | 1.2% (2/166) | | Chordae entrapment requiring surgical intervention | 0 | 0.0% (0/166) | | Complete heart block | 0 | 0.0% (0/166) | | Damage or movement of ICD leads requiring revisions | 0 | 0.0% (0/166) | | Death from any cause | 2 | 1.2% (2/166) | | New incessant VT/VF | 2 | 1.2% (2/166) | | Phrenic nerve injury which does not resolve in 7 days | 0 | 0.0% (0/166) | PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 22 of 39 {21} | Pulmonary embolism documented by imaging and requiring intervention | 0 | 0.0% (0/166) | | --- | --- | --- | | Stroke | 1 | 0.6% (1/166) | | TIA | 0 | 0.0% (0/166) | | Valve injury requiring surgical intervention | 1 | 0.6% (1/166) | | Vascular access complications requiring surgical intervention or >2 units of blood transfusion | 2 | 1.2% (2/166) | | Other | 20 | 9.0% (15/166) | | Arrhythmia New | 1 | 0.6% (1/166) | | Bleeding/Anemia | 1 | 0.6% (1/166) | | Hypotension | 5 | 3.0% (5/166) | | Infection | 2 | 1.2% (2/166) | | Myocardial Infarction | 1 | 0.6% (1/166) | | Pericardial Bleed | 1 | 0.6% (1/166) | | Pericardial Effusion | 1 | 0.6% (1/166) | | Pericarditis | 3 | 1.8% (3/166) | | Respiratory Failure/Depression/Compromise | 1 | 0.6% (1/166) | | Vascular Access Site Complications | 2 | 1.2% (2/166) | | Ventricular Arrhythmia With Significant Deterioration | 1 | 0.6% (1/166) | | Visceral Structure Or Organ Damage Including Bleed/Hematoma | 1 | 0.6% (1/166) | | **Total** | **37** | **16.3% (27/166)** | Note: Some subjects may have experienced more than one type of event. Therefore, the total number of subjects may be less than the sum of the numbers of subjects who experienced each type of event. PSAE denotes primary safety adverse event, VT/VF ventricular tachycardia/ventricular fibrillation, TIA transient ischemic attack, and ICD implantable cardioverter-defibrillator or cardiac resynchronization therapy-defibrillator. ## b. Summary of Adverse Device Effects ### *Serious Adverse Device Effects* Table 14 presents all device or procedure related serious adverse events reported at the time of data lock as adjudicated by the CEC. There were no unanticipated serious adverse device effects. **Table 14. Serious Adverse Events Related to the Procedure or Device (CIN Population)** | Adverse Event | Events | Subject % (n/N) | CEC Assessment | | | --- | --- | --- | --- | --- | | | | | Device Related | Procedure Related | | Abnormal Labs (E.G. Cpk, Creatinine, Troponin) | 1 | 0.6% (1/166) | 0 | 1 | | Arrhythmia New (atrial arrhythmia) | 1 | 0.6% (1/166) | 0 | 1 | | Bleeding/Anemia | 2 | 1.2% (2/166) | 0 | 2 | | Cardiac Arrest | 2 | 1.2% (2/166) | 0 | 2 | | Cardiac Perforation | 3 | 1.8% (3/166) | 0 | 3 | | Cardiac Tamponade | 2 | 1.2% (2/166) | 2 | 2 | | Chest Pain/Angina (Cardiac) | 1 | 0.6% (1/166) | 0 | 1 | | Heart Failure | 4 | 2.4% (4/166) | 4 | 4 | | Hemothorax | 1 | 0.6% (1/166) | 0 | 1 | | Hypotension | 4 | 2.4% (4/166) | 0 | 4 | | Infection | 3 | 1.8% (3/166) | 0 | 3 | | Myocardial Infarction | 1 | 0.6% (1/166) | 0 | 1 | | Pericardial Bleed | 1 | 0.6% (1/166) | 0 | 1 | | Pericardial Effusion | 3 | 1.8% (3/166) | 1 | 3 | PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 23 of 39 {22} | Pericarditis | 4 | 2.4% (4/166) | 3 | 4 | | --- | --- | --- | --- | --- | | Peripheral Thrombus | 2 | 0.6% (1/166) | 0 | 2 | | Pleural Effusion | 1 | 0.6% (1/166) | 0 | 1 | | Pulmonary Embolism | 1 | 0.6% (1/166) | 0 | 1 | | Respiratory Failure/Depression/Compromise | 1 | 0.6% (1/166) | 0 | 1 | | Shock | 2 | 0.6% (1/166) | 0 | 2 | | Stroke/CVA/Embolic Event | 1 | 0.6% (1/166) | 0 | 1 | | Valve Damage/Insufficiency/Regurgitation | 2 | 1.2% (2/166) | 2 | 2 | | Vascular Access Site Complications | 4 | 2.4% (4/166) | 0 | 4 | | Ventricular Arrhythmia With Significant Deterioration | 4 | 2.4% (4/166) | 1 | 4 | | Visceral Structure Or Organ Damage (NG tube related gastric ulcer) | 1 | 0.6% (1/166) | 0 | 1 | | Total | 52 | 21.1% (35/166) | 13 | 52 | ## Cardiac Perforation and Pericardial Complications In the pivotal study, cardiac perforation and pericardial complications (including tamponade, pericardial effusion, and excessive pericardial bleeding) occurred in 9 (5.4%) subjects. Of these, 6 (3.6%) subjects required surgical drainage or pericardiocentesis for treatment. Cardiac perforation/tamponade occurred in 5 subjects (5/166, 3.0%). One of three adjudicated cardiac perforation events occurred during mapping and prior to application of any radiofrequency ablation. Another cardiac perforation event resulted from inadvertent LV puncture during chest tube placement to treat hemothorax that had developed after epicardial access. The subject could not be resuscitated despite emergent surgical repair. Three (1.8%) subjects had procedure-related pericardial effusion. Two subjects were treated conservatively for small pericardial effusion. In the third subject, delayed pericardial effusion was drained 20 days following an index procedure that included epicardial access. Lastly, a subject whose ablation procedure included epicardial access developed excessive pericardial bleeding requiring prolonged pericardial drainage from the pericardial drain that had been left in place post procedure. ## Hypotension/Cardiogenic shock A total of 5 (3.0%) subjects developed persistent hemodynamic instability during the procedure. Of these, one subject (0.6%) with cardiogenic shock required unplanned IABP placement for continued hemodynamic support after the procedure. The other 4 subject with hypotension and/or cerebral hypoperfusion were treated pharmacologically and only required transient inotrope/pressor support post-operatively. PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 24 of 39 {23} ## Coronary Artery Injury or Myocardial Infarction/Ischemia Epicardial ablation was performed in 40% of index procedures. There were no reported adverse events of direct injury to the coronary arteries. A subject (0.6%) with elevated troponin and T wave changes on ECG in the setting of infection was adjudicated to have procedure-related non-ST elevated myocardial infarction. ## Heart Failure CEC adjudicated 4 (2.4%) subjects to have experienced significant procedure-related heart failure/acute pulmonary edema requiring intubation or hospitalization for IV diuresis. Of these, one subject was re-intubated peri-operatively due to significant pulmonary edema. The other 3 subjects experienced heart failure decompensation during the 30 days following the index procedure. ## Valvular Injury There were no cases of chordae entrapment by a mapping and/or ablation catheter requiring immediate open surgical removal. Two (1.2%) subjects with significant procedure-related valvular regurgitation (one AR, one MR) underwent corrective valve intervention on POD 16 and 189, respectively. ## New Incessant VT/VF or Ventricular Arrhythmia with Significant Deterioration Within the 30 days following the index procedure, 9 (5.4%) subjects experienced worsened ventricular arrhythmias. Of these, 3 (1.8%) subjects had procedure related new incessant VT/VF, defined as VF or VT of a new morphology compared with pre-ablation that is now unresponsive to ICD therapies, external defibrillation or antiarrhythmic medication, or quickly recurs after a brief termination, as adjudicated by the CEC. Of the other remaining 6 subjects with significant ventricular arrhythmia recurrence, one was adjudicated as procedure related. ## Neurological Complication One subject (0.6%) suffered right MCA stroke that's diagnosed immediately after the procedure. ## Vascular Access Complications Vascular access complications requiring intervention (including ultrasound guided compression) occurred in 4 subjects (2.4%). Another subject had retroperitoneal hemorrhage. In total, 5 of 166 subjects (3.0%) experienced PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 25 of 39 {24} vascular access complications requiring intervention or >2 units of blood transfusion. ### Pericarditis There were 4 procedure-related SAEs occurred in 4 subjects (2.4%). Of these, 3 of 4 subjects underwent subxiphoid epicardial access and mapping. At the time of database lock, there were no procedure-related serious adverse events of complete heart block, damage or dislodgement of ICD leads requiring revisions, or phrenic nerve injury. ### *Non-serious adverse device effects* Nineteen (19) non-serious adverse events that occurred in 17 subjects were adjudicated as being related to the procedure and/or the device. Table 15 presents all non-serious adverse device effects as adjudicated by the CEC. **Table 15. Summary of Non-Serious Adverse Events Related to the Procedure or Device** | Adverse Event | Events | Subject % (n/N) | CEC Assessment | | | --- | --- | --- | --- | --- | | | | | Device Related | Procedure Related | | Abnormal Labs (E.G. Cpk, Creatinine, Troponin) | 1 | 0.6% (1/166) | 0 | 1 | | Arrhythmia New | 4 | 2.4% (4/166) | 1 | 4 | | Chest Pain/Angina (Cardiac) | 2 | 1.2% (2/166) | 0 | 2 | | Heart Failure | 1 | 0.6% (1/166) | 0 | 1 | | Hypotension | 1 | 0.6% (1/166) | 0 | 1 | | Hypoxia | 1 | 0.6% (1/166) | 0 | 1 | | Pain (Non-Cardiac) | 1 | 0.6% (1/166) | 0 | 1 | | Pericarditis | 2 | 1.2% (2/166) | 0 | 2 | | Vascular Access Site Complications | 2 | 1.2% (2/166) | 0 | 2 | | Vascular Bleeding/Local Hematomas/Ecchymosis | 2 | 1.2% (2/166) | 0 | 2 | | Other | 2 | 1.2% (2/166) | 1 | 2 | | Left Bundle Branch Block | 1 | 0.6% (1/166) | 1 | 1 | | Urinary Retention | 1 | 0.6% (1/166) | 0 | 1 | | **Total** | **19** | **10.2% (17/166)** | **2** | **19** | ### c. Mortality As of the database cut-off date, there were 18 subject deaths (18/166, 10.8%) in the CIN population. In addition, 5 patients (3.0%) underwent cardiac transplant. The Kaplan Meier estimate of survival at 12 months based on the available data is 88.6%. **Figure 4: Kaplan Meier Estimate of Survival at 12 Months** PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 26 of 39 {25}  The table below summarizes the adverse events that led to death. The primary cause of death was classified by the CEC as cardiovascular in all 18 subjects. Two (2) events leading to death were adjudicated as procedure related, and none (0) were adjudicated as device related. One subject (1/166, 0.6%) died within 7 days of the index procedure. Another subject had an adverse event within 7 days of the index procedure that led to death on day 15. Table 16: Summary of Causes of Deaths PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 27 of 39 {26} | Adjudicated AE event leading to death | Days from procedure to Death | CEC adjudication | | | --- | --- | --- | --- | | | | Procedure related | Device related | | 0 - 7 days | | | | | Cardiac perforation | During staged procedure | Yes | No | | 8 – 30 days | | | | | Ischemic leg, septic shock | 15 | Yes | No | | Respiratory failure | 23 | No | No | | Ventricular arrhythmia with significant deterioration | 26 | No | No | | 1 – 3 months | | | | | Shock | 78 | No | No | | 3 – 6 months | | | | | Unknown (sudden death) | 95 | No | No | | Unknown (loss to follow-up) | 102 | No | No | | Ventricular arrhythmia with significant deterioration | 120 | No | No | | Unknown | 126 | No | No | | Shock | 150 | No | No | | Heart failure | 170 | No | No | | Ventricular arrhythmia with significant deterioration | 176 | No | No | | Heart failure | 239 | No | No | | Heart failure | 240 | No | No | | Ventricular arrhythmia with significant deterioration | 256 | No | No | | Ventricular arrhythmia with significant deterioration | 259 | No | No | | Cancer | 297 | No | No | | Shock (after repeat VT ablation procedure) | 324 | No | No | ## 2. Effectiveness Results ### a. Primary Effectiveness Endpoint The primary effectiveness endpoint was freedom from recurrent sustained MMVT at 6 months and a new or increased dose of Class I or III AAD at 6 months following the index ablation procedure, where sustained MMVT was defined as a continuous MMVT for >30 seconds, or MMVT requiring intervention for termination regardless of its duration. The analysis of effectiveness was based on the 146 evaluable patients at the 6-month time point. Evaluable patients include subjects who missed the 6-month visit but completed 12-month visit with ICD interrogation or experienced a primary effectiveness endpoint failure through 6 months. PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 28 of 39 {27} A total of 85 of 146 subjects (58.2%) were free from a primary effectiveness endpoint event. The lower bound of the 95% one-sided confidence interval is 51.1% and greater than the predetermined performance goal, and the primary effectiveness endpoint is met. **Primary Effectiveness Endpoint Analysis (EFF Population\*)** | Population | Primary Effectiveness Endpoint | | | | --- | --- | --- | --- | | | Number of Subjects | 95% One-Sided Confidence Interval Lower Bound | Performance Goal | | Effectiveness Population* | 58.2% (85/146) | 51.1% | > 40.2% | \*The analysis population for the primary effectiveness endpoint includes treated subjects who have completed a 6- or 12-Month visit with ICD interrogation or experienced a primary effectiveness endpoint failure Most subjects were free from repeat ablation through 6 months (139/146, 95.2%). Table 17 summarizes the specific primary effectiveness endpoint failure modes. **Table 17. Primary Effectiveness Endpoint Failure Modes (EFF Population\*)** | Endpoint Failure Mode | Number of Subjects | | --- | --- | | Repeat Ablation | 4.8% (7/146) | | Recurrent Sustained MMVT | 19.9% (29/146) | | New or Increased Class I/III AAD | 30.8% (45/146) | \*The analysis population for the primary effectiveness endpoint includes treated subjects who have completed a 6- or 12-Month visit with ICD interrogation or experienced a primary effectiveness endpoint failure ### Sensitivity analysis Of 165 treated subjects (TRT population), 19 had unknown 6-month rhythm status due to study exit, lost to follow-up, or did not complete a 6-month or 12-month visit with ICD interrogation, and did not experience a primary effectiveness endpoint failure. In the worst-case analysis, subjects with missing primary effectiveness endpoint data were treated as failures, and the primary effectiveness endpoint rate was 51.5% (85/165) with the 95% one-sided confidence interval lower bound of 44.8%. With the worst-case analysis, the lower bound of the primary endpoint remains higher than the predetermined performance goal of 40.2%. ### Worst Case Analysis for the Primary Effectiveness Endpoint (TRT Population) PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 29 of 39 {28} | Population | Primary Effectiveness Endpoint: Worst Case | | | | --- | --- | --- | --- | | | Number of Subjects | 95% One-Sided Confidence Interval Lower Bound | Performance Goal | | Treated Subjects | 51.5% (85/165) | 44.8% | > 40.2% | # b. Acute procedural success In the LESS-VT NICM Cohort, the acute procedural endpoint is defined as - For subjects with no inducible ventricular tachycardia (VT) at the beginning of the ablation procedure, the acute procedural endpoint was defined as elimination of all late potentials (greater than approximately 70% reduction in amplitude) in the scar and scar border; and - For subjects with inducible VT at the beginning of the ablation procedure, the acute procedural endpoint was defined as elimination of all late potentials (greater than approximately 70% reduction in amplitude) in the scar and scar border and elimination of all inducible sustained monomorphic ventricular tachycardias (MMVTs) slower than 200 bpm (CL 300ms). Overall, 92.7% (153/165) of treated subjects achieved acute procedure success as defined in the protocol. # c. Descriptive Effectiveness Endpoint Results Table. 18 Protocol Specified Descriptive Effectiveness Endpoints | 1. Changes in SF-12 Quality of Life (TRT Population) | | | | --- | --- | --- | | | NICM Cohort^{1} | Paired Change from Baseline^{2} | | Aggregated Physical Health Score | | | | Baseline | 39.46 ± 10.39 (163) | | | Month 6 | 41.59 ± 10.10 (136) | 1.9 ± 10.8 (135) [0.0, 3.7] | | Aggregated Mental Health Score | | | | Baseline | 45.43 ± 12.29 (163) | | | Month 6 | 49.84 ± 10.56 (136) | 3.7 ± 12.3 (135) [1.6, 5.8] | | 2. Changes in HADS Score at 6 Months (TRT Population) | | | | | NICM Cohort^{1} | Paired Change from Baseline^{2} | | Anxiety Score | | | | Baseline | 7.4 ± 4.6 (163) | | | Month 6 | 5.2 ± 3.8 (136) | -2.1 ± 4.0 (135) [-2.7, -1.4] | | Depression Score | | | PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 30 of 39 {29} Baseline 5.6 ± 4.1 (163) Month 6 4.3 ± 3.8 (136) -1.1 ± 3.9 (135) [-1.8, -0.4] # 3. Freedom from appropriate ICD shocks at 6 months (183 days) post index procedure, adjudicated by the ICD Event Review Committee The Kaplan Meier estimate of freedom from appropriate ICD shock at 6 months was 92.0% ± 2.3%. # 4. Freedom from Spontaneous Recurrence of Any Sustained VT During the Follow-Up Period of 6 months Of 139 treated subjects who have completed a 6- or 12-Month visit with ICD interrogation or experienced sustained VT recurrence, 109 (78.4%) subjects were free from recurrence of sustained VT through 6 months. # 5. Number of VT Recurrences During the Follow-Up Period Of 6 Months From 30 TRT subjects with documented VT recurrence through 6 months, a total of 176 VT events were recorded in all subjects. ¹Mean ± Standard Deviation (n) ²Mean ± Standard Deviation (n) [95% CI] # 3. Subgroup Analyses The following preoperative characteristics were evaluated for potential association with outcomes: gender, age (< 65 vs. ≥ 65 years), and race (Tables 19 – 20). The treatment-by-subgroup interaction was statistically significant at the alpha = 0.15 level for age in both primary safety and effectiveness analyses. Elderly patients were more likely to experience acute procedural complications and recurrence of MMVT than patients younger than 65 years of age. Further analysis of the baseline characteristics and procedural parameters between the two age groups showed that elderly subjects (age ≥ 65 years) on average had more comorbidities (coronary artery disease, diastolic dysfunction, heart failure, hyperlipidemia, hypertension, and valvular heart disease), as well as lower mean left ventricular ejection fraction (32.7% ± 10% vs. 42.4% ± 13.4%). In terms of procedural parameters, the age ≥ 65 years group had higher number of MMVTs during procedure (2.9 ± 2.3 vs. 2.2 ± 2.3) with a higher proportion of subjects receiving cardioversion (75.7% vs. 59.2%) and hemodynamic support (2.7% vs. 0.0%). Table 19. Primary Safety Endpoint: Subgroup Analysis (SAF Population) | | Primary Safety Endpoint | | | | --- | --- | --- | --- | | | Subjects % (n/N) | Difference [95% CI]¹ | P-value² | | Females | 14.8% (4/27) | -1.73% [-13.09%, 16.70%] | 1.0000³ | | Males | 16.5% (23/139) | | | | Age < 65 Years | 12.0% (11/92) | -9.67% [-21.50%, 1.69%] | 0.0935² | PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 31 of 39 {30} | Age ≥ 65 Years | 21.6% (16/74) | | | | --- | --- | --- | --- | | Race Subgroup: White | 18.8% (24/128) | 14.58% [-2.51%, 22.95%] | 0.1289^{3} | | Race Subgroup: Races other than White | 4.2% (1/24) | | | $^{1}$ By Newcombe score confidence interval $^{2}$ By Chi-Square Test $^{3}$ By Fisher Exact Test **Table 20. Primary Effectiveness Endpoint: Subgroup Analysis (EFF Population)** | | Subjects % (n/N) | Primary Effectiveness Endpoint | | | --- | --- | --- | --- | | | | Difference [95% CI]^{1} | P-value^{2} | | Females | 14.8% (4/27) | -1.01% [-12.32%, 17.38%] | 1.0000^{3} | | Males | 15.8% (22/139) | | | | Age < 65 Years | 65.1% (54/83) | 15.83% [-0.26%, 31.04%] | 0.0544^{2} | | Age ≥ 65 Years | 49.2% (31/63) | | | | Race Subgroup: White | 58.0% (65/112) | -6.96% [-26.22%, 16.44%] | 0.5596^{3} | | Race Subgroup: Races other than White | 65.0% (13/20) | | | $^{1}$ By Newcombe score confidence interval $^{2}$ By Chi-Square Test $^{3}$ By Fisher Exact Test The study was not powered for subgroup analyses, and these results should be considered to be exploratory. ### Additional analyses Post-hoc stepwise logistic regression analyses were used to evaluate the association between a wide range of clinically relevant variables (including primary NICM subtype) and procedure-related SAEs through 30 days and the primary effectiveness endpoint. Variables with a P-value of <0.15 in univariable analyses were included in the multivariable models. Multivariable logistic regression analyses revealed that none of the primary NICM subtypes displayed a significant effect on the outcome of procedure-related SAEs through 30 days post index procedure. The model revealed a potential association between presence of New York Heart Association (NYHA) Class III heart failure and procedure-related SAEs through 30 days (odds ratio 3.42). The multivariable logistic regression analysis of freedom from primary effectiveness endpoint events (including MMVT recurrence) also included primary NICM subtypes. Multivariable logistic regression analyses revealed that none of the primary NICM subtypes displayed a significant effect on the outcome PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 32 of 39 {31} of freedom from primary effectiveness endpoint events. The model revealed a potential correlation with medical history of diastolic dysfunction (odds ratio 2.19). 4. Pediatric Extrapolation In this premarket application, existing clinical data was not leveraged to support approval of a pediatric patient population. E. Financial Disclosure The Financial Disclosure by Clinical Investigators regulation (21 CFR 54) requires applicants who submit a marketing application to include certain information concerning the compensation to, and financial interests and arrangement of, any clinical investigator conducting clinical studies covered by the regulation. The pivotal clinical study included 92 investigators of which none were full-time or part-time employees of the sponsor and 3 had disclosable financial interests/arrangements as defined in 21 CFR 54.2(a), (b), (c) and (f) and described below: - Compensation to the investigator for conducting the study where the value could be influenced by the outcome of the study: none - Significant payment of other sorts: 3 - Proprietary interest in the product tested held by the investigator: none - Significant equity interest held by investigator in sponsor of covered study: none The applicant has adequately disclosed the financial interest/arrangements with clinical investigators. Statistical analyses were conducted by FDA to determine whether the financial interests/arrangements had any impact on the clinical study outcome. The information provided does not raise any questions about the reliability of the data. XI. PANEL MEETING RECOMMENDATION AND FDA'S POST-PANEL ACTION In accordance with the provisions of section 515(c)(3) of the act as amended by the Safe Medical Devices Act of 1990, this PMA was not referred to the an FDA advisory committee, for review and recommendation because the information in the PMA substantially duplicates information previously reviewed by this panel. PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 33 of 39 {32} # **XII. CONCLUSIONS DRAWN FROM PRECLINICAL AND CLINICAL STUDIES** # **A. Effectiveness Conclusions** The benefits of the device are based on data collected in the clinical study conducted to support PMA approval as described above. The effectiveness results of the LESS-VT study support that the FlexAbility™ Ablation Catheter, Sensor Enabled™ is effective for treatment of recurrent, drug-refractory, sustained monomorphic ventricular tachycardia in patients with non-ischemic structural heart disease. The LESS-VT study met its primary effectiveness endpoint for the NICM Cohort. The proportion of subjects with primary effectiveness endpoint success, defined as freedom from recurrence of sustained MMVT or repeat ablation at 6 months without any escalation in antiarrhythmic drug (AAD) therapy, was 58.2%. The 95% one-sided confidence interval lower bound of 51.1% was higher than the predetermined performance goal of 40.2%, thereby passing the endpoint. The goal of VT treatment is to eliminate VT circuit and prevent recurrence of sustained episodes, and freedom from any sustained MMVT is a well accepted objective measure of clinical benefit of VT ablation. Freedom from VT recurrence was 80.1% at 6 months following ablation regardless of the AAD therapy, and the outcome is clinically meaningful. The following limitations of the pivotal study resulted in uncertainties in the treatment benefits: - The pivotal study has a non-randomized single arm study design. Without including an active control arm, it is uncertain from the study results how catheter ablation using the subject catheter compares with other therapeutic options. Nonetheless, currently there isn't an approved device that's indicated to treat NICM VT patients. - The primary analysis was based on treated patients with known effectiveness status at 6 months. There were some missing data due to early study exits or loss-to-follow-up. The favorable results of the worst case analysis support that the outcomes are robust for meeting the predetermined primary effectiveness endpoint success criteria. - The results of subgroup analyses show elderly ≥ 65 years) patients might not have gained the same degree of clinical benefit, in terms of freedom from recurrent sustained MMVT, from the study treatment when compared to their younger counterparts. The disparity may not be unexpected given that advancing PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 34 of 39 {33} age has been linked to disease progression and severity of structural damage in some subtypes of NICM, including ARVC/D$^{2}$ and cardiac sarcoidosis$^{3}$. Overall, the totality of evidence from the pivotal study supports that catheter ablation using the FlexAbility Ablation Catheter, SE is effective for the treatment of recurrent, drug-refractory, monomorphic VT in patients with non-ischemic cardiomyopathy. ## **B. Safety Conclusions** The risks of the device are based on nonclinical laboratory and animal studies as well as data collected in a clinical study conducted to support PMA approval as described above. The results from the nonclinical laboratory and animal studies performed on the FlexAbility ablation catheter demonstrate that the device is suitable for endocardial and epicardial mapping and ablation. The potential risks associated with the device for the intended use include percutaneous endocardial ablation-related complications such as cardiac tamponade/perforation, valvular injury, cardiogenic shock, heart failure, thromboembolism, and procedure-related major bleeding complications. As nonischemic cardiomyopathy encompasses a heterogenous group of diseases with diverse arrhythmic substrates, VT ablation targets in this population also frequently include the right ventricle and epicardium. As the result, the risks for pericardial complications and epicardial access related major complications may be higher when compared to catheter ablation of ischemic VT. The pivotal clinical study met the primary safety endpoint for the NICM cohort. A primary safety endpoint event was experienced by 16.3% (27/166) of subjects, and the 95% one-sided confidence interval upper bound of 21.7% was lower than the pre-defined performance goal of 26.9%. There were no unanticipated adverse device effects. The overall rate of major complications is in line with those reported in similar premarket IDE studies of catheter ablation for the treatment of ischemic ventricular tachycardia. The observed severity, types, and rates of adverse events associated with using the study device to treat recurrent, drug-refractory, sustained monomorphic ventricular tachycardia in patients with non-ischemic cardiomyopathy align with published literature. These results support the safety of the FlexAbility™ Ablation Catheter, Sensor Enabled™ for the intended use. ---PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 35 of 39 {34} Results of subgroup analyses show elderly ≥ 65 years) might be more likely to experience acute procedural complications than younger patients. Advanced age is known as a risk factor for procedural major complications and a component of the PAINESD score described by Musser and colleagues to calculate the risk of periprocedural acute hemodynamic decompensation.⁴ Elderly patients with non-ischemic VT are likely to have multiple co-morbidities and advanced cardiomyopathic disease, which may further account for the observed elevated risks of complications. ### C. Benefit-Risk Determination The probable benefits of the device are also based on data collected in a clinical study conducted to support PMA approval as described above. For patients with non-ischemic structural heart disease and recurrent, drug-refractory, sustained monomorphic ventricular tachycardia, ablation treatment with the FlexAbility™ Ablation Catheter, Sensor Enabled™ resulted in freedom from recurrence of MMVT for the majority of patients. The probable risks of the device are also based on data collected in a clinical study conducted to support PMA approval as described above. The probable risks of the FlexAbility™ Ablation Catheter, Sensor Enabled™ for treating recurrent sustained monomorphic ventricular tachycardia in patients with non-ischemic structural heart disease include ablation procedure-related serious adverse events (such as cardiac perforation, cardiac tamponade, hemodynamic instability, heart failure, valvular injury, and procedure-related major bleeding complications). The safety data from the LESS-VT study (NICM cohort) demonstrates that the safety profile of the device remains clinically acceptable for the intended use. # Patient Perspectives This submission did not include specific information on patient perspectives, and patient perspectives did not serve as part of the basis of the decision to approve the PMA for this device. Based on a subgroup analysis, the benefit/risk balance for the subject device to treat NICM VT might be less favorable in elderly (age > 65) than in younger patients with higher observed incidences of major complications and arrhythmia recurrence in the 6 months following ablation. A Post-Approval Study is planned to ascertain the magnitude of the treatment effect and to assure that a consistent risk/benefit profile will be maintained with broad clinical use of the device. PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 36 of 39 {35} #### **D. Overall Conclusions** The data in this application support the reasonable assurance of safety and effectiveness of the FlexAbility™ Ablation Catheter, Sensor Enabled™ when used in accordance with the indications for use. Given all of the available data, it is reasonable to conclude that the benefits of the use of the device for the target population outweigh the risk of illness or injury when used as indicated in accordance with the labeling and Instructions for Use. ### **XIII. CDRH DECISION** CDRH issued an approval order on December 14, 2022. The final clinical conditions of approval cited in the approval order are described below. **LESS VT Continued Follow-up of IDE Non-Ischemic Cardiomyopathy Cohort:** The study objective is to characterize the safety and effectiveness of the FlexAbility, SE Ablation Catheter for the treatment of monomorphic ventricular tachycardia in patients with non-ischemic structural heart disease through 12 months post-procedure. This study should be conducted per version H of the LESS VT protocol. The study will consist of all IDE patients who are currently enrolled and alive and will evaluate the protocol specified descriptive 12-month endpoints. **LESS VT NICM Post-Approval Study** is a prospective, single-arm, open-label, multi-center study to evaluate the long-term effectiveness and safety of the FlexAbility, Sensor Enable Ablation Catheter for the treatment of ventricular tachycardia in patients with non-ischemic structural heart disease in the post-market space. A total of up to 150 patients will be enrolled at sites in the United States, and at least 50% will be ≥ 65 years of age. The primary objectives will be: (1) Estimate the 12-month freedom from ventricular tachycardia (VT) recurrence, death, and cardiac transplantation; (2) Estimate the rate of device- or procedure-related serious adverse events through 12 months. From the time of study protocol approval, the sponsor must meet the following timelines for the LESS VT NICM PAS: - First subject enrolled within 6 months of post approval study protocol approval - 20% of subjects enrolled within 18 months - 50% of subjects enrolled within 30 months - 100% of subjects enrolled within 48 months - Submission of Final study report: 3 months from study completion (i.e., last subject, last follow-up date) The applicant's manufacturing facilities have been inspected and found to be in compliance with the device Quality System (QS) regulation (21 CFR 820). PMA P110016 S080: FDA Summary of Safety and Effectiveness Data 37 of 39 {36} # XIV. APPROVAL SPECIFICATIONS Directions for use: See device labeling. Hazards to Health from Use of the Device: See Indications, Contraindications, Warnings, Precautions, and Adverse Events in the device labeling. Post-approval Requirements and Restrictions: See approval order. # XV. REFERENCES ¹ Vaseghi M, Hu TY, Tung R, et al. Outcomes of Catheter Ablation of Ventricular Tachycardia Based on Etiology in Nonischemic Heart Disease: An International Ventricular Tachycardia Ablation Center Collaborative Study. J Am Coll Cardiol EP. 2018, 4(9): 1141-1150 ² Sen-Chowdhry, S., et al., Clinical and genetic characterization of families with arrhythmogenic right ventricular dysplasia/cardiomyopathy provides novel insights into patterns of disease expression. Circulation, 2007. 115(13): p. 1710-20. ³ Zhou, Y., et al., Cardiac Sarcoidosis: The Impact of Age and Implanted Devices on Survival. Chest, 2017. 151(1): p. 139-148. ⁴ Muser, D., et al., Outcomes with prophylactic use of percutaneous left ventricular assist devices in high-risk patients undergoing catheter ablation of scar-related ventricular tachycardia: A propensity-score matched analysis. Heart Rhythm, 2018. 15(10): p. 1500-1506. 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