Aurora EV-ICD System

{0} SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) I. GENERAL INFORMATION Device Generic Name: Extravascular Implantable Cardioverter Defibrillator (EV-ICD) and Extravascular Lead Device Trade Name: Aurora EV-ICD™ System This system is comprised of the following: - Aurora EV-ICD™ MRI SureScan™ DVEA3E4 Extravascular Implantable Cardioverter Defibrillator (EV-ICD) - Aurora EV-ICD Application Software SW041 v8.4 - Epsila EV™ MRI SureScan™ EV2401 Extravascular lead - Epsila EV™ EAZ101 Sternal Tunneling Tool - Epsila EV™ EAZ201 Transverse Tunneling Tool Device Procode: LWS, NVY Applicant’s Name and Address: Medtronic, Inc. Cardiac Rhythm Management 8200 Coral Sea Street NE MV MVS11 Mounds View, MN 55112 Date(s) of Panel Recommendation: None Premarket Approval Application (PMA) Number: P220012 Date of FDA Notice of Approval: October 20, 2023 {1} II. INDICATIONS FOR USE The Aurora EV-ICD MRI SureScan Model DVEA3E4 device is indicated for the automated treatment of patients who have experienced, or are at significant risk of developing, life-threatening ventricular tachyarrhythmias through the delivery of antitachycardia pacing, cardioversion, and defibrillation therapies. Medical conditions that may indicate a patient for an EV-ICD for primary or secondary prevention of sudden cardiac death due to life-threatening ventricular tachyarrhythmias include: - Previous ventricular tachyarrhythmias - Coronary disease with left ventricular dysfunction - Cardiomyopathy - Inherited primary arrhythmia syndromes - Congenital heart disease Note: For patient-specific recommendations regarding indications for primary and secondary prevention of sudden cardiac death, refer to current clinical guidelines from the European Society of Cardiology (ESC), American Heart Association (AHA), American College of Cardiology (ACC), and Heart Rhythm Society (HRS). The Epsila EV™ MRI SureScan™ Model EV2401 extravascular lead is indicated for use in the anterior mediastinum for pacing therapies, cardioversion, and defibrillation when an extravascular implantable cardioverter defibrillator is indicated to treat patients who have experienced, or are at significant risk of developing, life-threatening ventricular tachyarrhythmias. The Epsila EV EAZ101 Sternal Tunneling Tool is indicated for use in the implant of a compatible anterior mediastinum defibrillation lead. The Epsila EV EAZ201 Transverse Tunneling Tool is indicated for use in the implant of a compatible anterior mediastinum defibrillation lead. III. CONTRAINDICATIONS The Aurora EV-ICD MRI SureScan Model DVEA3E4 device is contraindicated for use in the following situations: - If implanted with a unipolar pacemaker - If implanted with a device delivering dual-chamber or triple-chamber pacing - If implanted with a device delivering antitachyarrhythmia therapies - If incessant ventricular tachyarrhythmia (VT) or ventricular fibrillation (VF) exists - If the patient’s primary disorder is chronic atrial tachyarrhythmia with no concurrent VT or VF - If symptomatic bradycardia exists - If tachyarrhythmias with transient or reversible causes exist. The Epsila EV MRI SureScan Model EV2401 lead is contraindicated for any application that is not specified in the Indications. {2} The Epsila EV Model EAZ101 Sternal Tunneling Tool is contraindicated for use in patients with a prior sternotomy. The Epsila EV Model EAZ201 Transverse Tunneling Tools is contraindicated for any application that is not specified in the Indications. ## IV. WARNINGS AND PRECAUTIONS Warnings and precautions for the Aurora EV-ICD System are provided in the product labeling. ## V. DEVICE DESCRIPTION The Aurora EV-ICD System is comprised of the implantable Aurora EV-ICD™ MRI SureScan™ DVEA3E4 extravascular implantable cardioverter defibrillator (EV-ICD), the Aurora EV-ICD Application Software SW041, and the implantable Epsila EV™ MRI SureScan™ EV2401 extravascular lead. The single use Epsila EV™ EAZ101 Sternal Tunneling Tool and the Epsila EV™ EAZ201 Transverse Tunneling Tool are used as part of the implantation of the System. ## Aurora EV-ICD DVEA3E4 Device The Medtronic Aurora EV-ICD MRI SureScan Model DVEA3E4 single chamber, extravascular implantable cardioverter defibrillator (ICD) is a multiprogrammable cardiac device that monitors and regulates the patient's heart rate. It provides ventricular tachyarrhythmia detection and therapy, post-shock pacing, and prolonged pause detection and therapy (Pause Prevention pacing). The device also provides diagnostic and monitoring features to assist with system evaluation and patient care.  Figure 1. Aurora EV-ICD DVEA3E4 ## EV-ICD SW041 Application Software The EV-ICD SW041 application software is intended to provide diagnostic information for the patient which is used by the healthcare professional to make treatment decisions and determine appropriate therapeutic program settings. The EV-ICD SW041 application software package includes all the executable files and data files needed to support programming of the Aurora EV-ICD device on the 2090 and 29901 CareLink Programmer Systems. {3} # Epsila EV2401 Lead The Medtronic Epsila EV Model EV2401 lead is an extravascular quadripolar lead with shaped passive fixation, designed for sensing, cardioversion, defibrillation, and pacing therapies. The lead has been tested for use in the magnetic resonance imaging (MRI) environment. All lead lengths for this lead model are MR Conditional. The lead has the ability to pace and sense between the ring and coil electrodes. In addition, the Coil 1 and Coil 2 electrodes deliver cardioversion and defibrillation therapy. The EV4-LLHH1 four-pole inline connector enables connection to an EV4 device during implant. The lead body has a multi-lumen construction, and the lead is free of any pharmacological agents, e.g., steroids.  Figure 2. Epsila EV2401 Lead # Epsila EV EAZ101 Sternal Tunneling Tool The Epsila EV EAZ101 Sternal Tunneling Tool is designed to deliver an introducer and an extravascular lead into the anterior mediastinum during implant of an extravascular implantable device system. The Epsila EV EAZ101 Sternal Tunneling Tool creates a tunnel in the mediastinal space and delivers an introducer to the posterior of the sternum. It has a positive bias intended to allow the tool to maintain contact with the posterior of the sternum. The tunneling rod is malleable to accommodate patient anatomy. The guide rod remains above the skin during tunneling, indicating the path of the tunneling rod and the overall distance the rod has moved within the mediastinal space. The external guide rod is hinged and removable to accommodate user preferences and patient anatomy during tunneling. The thumb tab on the guide rod is used to raise and lower the external guide.  Figure 3: Epsila EV EAZ101 Sternal Tunneling Tool {4} # Epsila EV EAZ201 Transverse Tunneling Tool The Epsila EV EAZ201 Transverse Tunneling Tool is a tool designed to deliver the proximal portion of an extravascular lead to the device pocket during implant of an extravascular implantable device system. The Epsila EV EAZ201 Transverse Tunneling Tool consists of a handle and a tunneling rod. The tunneling rod has a bullet-shaped tip and the rod can be removed from the handle to expose a channel into which the Epsila EV2401 lead can be secured during tunneling. The flexible polymer tunneling rod and a removable handle are used to gain access from the xiphoid incision to the device pocket. It has a channel that is capable of interfacing with the EV4 connector and allows the lead to be drawn through the tunnel to the device pocket.  Figure 4: Epsila EV EAZ201 Transverse Tunneling Tool ## VI. ALTERNATIVE PRACTICES AND PROCEDURES Alternative therapies include the use of antiarrhythmic medication, ablation and cardiac surgery, and other commercially available implantable cardioverter defibrillators. These alternatives have advantages and disadvantages. A patient should fully discuss alternatives with his/her physician to select the method that best meets expectations and lifestyle. ## VII. MARKETING HISTORY The Aurora EV-ICD System has been distributed commercially outside the United States since September, 2023. Specifically, the Aurora EV-ICD system has been commercially distributed in the following countries: Netherlands, Denmark, Switzerland, Austria, Hungary, Germany, Italy, Spain, New Zealand, and Hong Kong. The device has not been withdrawn from marketing in these markets for any reason related to its safety or effectiveness. ## VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH Below is a list of potential adverse effects associated with the use of the Aurora EV-ICD System: - Acute tissue trauma - Allergic reaction - Bradyarrhythmia - Cardiac arrest - Cardiac inflammation - Cardiac perforation - Cardiac tamponade - Death - Device migration - Discomfort - Dizziness - Dyspnea - Erosion - Extracardiac stimulation - Fever - Hematoma - Hemorrhage - Hemothorax - Hiccups - Hospitalization - Inappropriate shock - Infection - Lethargy - Mental anguish {5} - Organ damage (liver, mammary arteries, diaphragmatic arteries) - Palpitations - Pericardial effusion - Pericarditis - Pneumothorax - Seroma - Syncope - Tachyarrhythmia - Toxic reaction - Wound dehiscence For the specific adverse events that occurred in the clinical study, please see Section X below. ## IX. SUMMARY OF NONCLINICAL STUDIES ### A. In Vitro Studies The EV-ICD System has been evaluated through in-vitro (non-clinical) testing to assure suitability and reliability for its intended use. Design verification testing, and system validation testing demonstrated that the devices meet their design specifications. #### 1. System Validation System validation testing is defined as testing against user/stakeholder requirements and intended use scenarios. This testing was performed by evaluating the compatibility, interaction, and functional operation of the system (device, lead, implant tools, programmer, and manuals) using actual and simulated use scenarios covering the functions defined by the project scope. Also included in this testing was product manual validation which validated that the technical statements as written are true and reflect the actual operation of the system. Based on the results of this testing, the Aurora EV-ICD System is considered validated for its intended use. #### 2. MRI Validation of the Aurora EV-ICD DVEA3E4 device and the Epsila EV2401 lead for use within an MR environment was completed to support the ability to diagnose patients implanted with the Aurora EV-ICD System using medical imaging. The MRI environment includes a strong static magnetic field as well as a gradient electromagnetic (time-varying) field and Radiofrequency (RF) electromagnetic (time-varying) field, all of which could potentially interact with the Aurora EV-ICD System. During the development of the Aurora EV-ICD System, potentially hazardous interactions between the Aurora EV-ICD System and the MRI environment were identified and a strategy was developed to evaluate the risks associated with each interaction. When appropriate, design requirements for device performance in the MRI environment were established. The potentially hazardous interactions for the Aurora EV-ICD System are similar to other commercially available MR conditional transvenous systems. The primary differences are related to the new implant location and lead position in the body, which required new use conditions for the MR exposure to be evaluated at those implant conditions. Additionally, some requirements were updated to reflect the different tissues that are in contact with the Epsila EV2401 lead. MRI-induced hazards for the Aurora EV-ICD System were comprehensively evaluated, and the results of those assessments verify {6} the Aurora EV-ICD System functions as intended during and following exposure to the MRI environment. # 3. Cybersecurity Medtronic has established cybersecurity design inputs for the Aurora EV-ICD System and has also established a cybersecurity vulnerability and management approach as part of the software validation and risk analysis that is required by 21 CFR 820.30(g). This approach addresses the following elements: - Identification of assets, threats, and vulnerabilities. - Assessment of the impact of threats and vulnerabilities on device functionality and end users/patients. - Assessment of the likelihood of a threat and of a vulnerability being exploited. - Determination of risk levels and suitable mitigation strategies. - Assessment of residual risk and risk acceptance criteria. In addition to minimizing cybersecurity and patient safety risks, usability is a key performance indicator for the Aurora EV-ICD System. Thus, efforts have been made to ensure an appropriate risk-based approach to security while maintaining ease of use in the Aurora EV-ICD System. # 4. Design Verification Activities Nonclinical testing for each device was conducted to ensure that the components and the finished devices perform in accordance with their design specifications. | Aurora EV-ICD Device | | | --- | --- | | Mechanical – Mechanical design verification by review was performed to verify conformance to specification requirements for the Aurora EV-ICD device. The review report concludes that requirements were verified via specification review and/or using computer-aided design software analysis. This provides direct evidence that design specifications met design requirements. | | | Component and Sub-Assembly Testing – Specific components and subassemblies of the Aurora EV-ICD were evaluated against their specific requirements. All of the components and subassemblies of the Aurora EV-ICD device were verified for use in their intended applications. | | | Feedthrough | The 11-pin feedthrough used on the Aurora EV-ICD device is the same as used on many other market-released ICD devices, and its acceptability for use was documented. | | Connector | Most aspects of the connector design are identical between the Aurora EV-ICD and the other Medtronic market-released connectors. The Aurora EV-ICD meets all the requirements for connector mechanical requirements. The Aurora EV-ICD connector is identical to the existing market-released single chamber connector that is already in commercial production, therefore, the connectors are considered equivalent. | | High-Voltage Capacitor | The mechanical configuration of Aurora EV-ICD and capacitors are identical to those used in commercially available Medtronic ICDs. Therefore, verification of mechanically related tests such as shock and vibration were done by similarity to other Medtronic MRI capacitor designs. Testing was conducted to qualify the 40J high voltage capacitor for use in the Aurora EV-ICD device. | {7} | Battery | The battery used in the Aurora EV-ICD device is the same battery that is used in other market-released ICDs. This was documented via verification review. | | --- | --- | | Electrical – The electrical design verification activities performed that support the Aurora EV-ICD DVEA3E4 device demonstrate the device meets the electrical requirements. The report concludes that all electrical design requirements were satisfied. | | | Environmental | Electromagnetic Compatibility (EMC) – EMC verification testing was completed for EV-ICD devices in accordance with ISO 14708-2 and ISO 11117. All EMC device requirements and compliance with standards, where applicable, were met. | | | Mechanical Environmental – Mechanical environmental verification activities were performed which supported that the Aurora EV-ICD device meets the mechanical requirements. An analysis report documented that analysis was performed and the Pilot device meets its design requirements. | | Firmware – The device firmware documentation provided is consistent with FDA’s Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices (issued May 11, 2005). The process used for the design and design verification of the EV-ICD firmware is compliant with IEC 62304:2006 AMDI:2015 (Medical device software – Software life-cycle processes). Aurora EV-ICD firmware verification testing verified the functionality and performance of the firmware against its firmware requirements, as well as regression testing to demonstrate that all firmware requirements have been correctly implemented. | | | Software – The SW041 software includes all the executable and non-executable files and data files needed to support programming the Aurora EV-ICD device on the 2090 and Encore 29901 programmer systems. This software allows the clinician to interrogate and program the device, navigate through the user interface to interact with the implantable device, run tests, set up therapies, perform data analysis, and print reports. Based on the results of the system design validation testing, the Aurora EV-ICD software is validated for its intended use. | | | Shelf Life – Packaged and sterilized Aurora EV-ICD devices are labeled with an 18-month shelf life. The purpose of the packaging test was to verify that the packaging protects the device and media during transportation and storage. Verification test results from predicate products and packaging indicate that no further testing is necessary; previous test conclusions remain valid for the Aurora EV-ICD device. | | | Packaging – The purpose of the packaging analysis was to verify that the packaging protects the Aurora EV-ICD DVEA3E4 device and media during transportation and storage use conditions. Verification test results from predicate products and packaging indicate that no further testing is necessary; previous test conclusions remain valid for the Aurora EV-ICD device. | | | Biocompatibility – Biocompatibility for the EV-ICD device was determined in accordance with EN ISO 10993-1: 2018, Biological Evaluation of Medical Devices Part 1: Evaluation and Testing within a Risk Management Process. The requirements were based on the nature of body contact and contact duration with respect to the device and lead during normal use. Per ISO 10993-1: 2018, the combination of materials, chemicals and processes for the final, finished device was evaluated. Biocompatibility and full compliance with ISO 10993-1:2018 have been demonstrated for the EV-ICD device. | | | Sterilization - The Aurora EV-ICD device is sterilized utilizing the 30-minute 100% EO sterilization process. The Aurora EV-ICD device has been successfully qualified into the 30-minute 100% EO sterilization process. A Sterility Assurance Level (SAL) in excess of 10^{-6} is achieved when the Aurora EV-ICD device is sterilized. | | | Epsila EV2401 Lead | | {8} | **Design Verification** – The Epsila EV2401 lead has been verified through a combination of test, analysis, and review methods. The reviews conclude that design specifications met design requirements and is considered verified. | | --- | | **Shelf Life** – Packaged and sterilized Epsila EV2401 leads are labeled with a 2-year shelf life. Accelerated aging verification was conducted. Following completion of the accelerated aging testing, it was determined that the Epsila EV2401 lead met all requirements. | | **Packaging** – The purpose of the packaging test was to verify that the packaging protects the device and media during transportation and storage use conditions. The test report provides evidence that all requirements for the Epsila EV2401 lead packaging have been met, including both functional and package integrity. | | **Biocompatibility** – A biocompatibility design verification analysis of the Medtronic Model EV2401 lead and its compliance to ISO 10993-1: 2018 was conducted. Analysis determined that the EV2401 lead and the combination of all materials, chemicals, and processes have an acceptable biological risk in their intended use and meets the requirements of ISO 10993-1: 2018. | | **Sterilization** - The Epsila EV2401 lead product family is sterilized utilizing the 30-minute 100% EO sterilization process. The Epsila EV2401 lead product family was successfully sterilized into the 30-minute 100% EO sterilization process. A SAL better than 10^{-6} is achieved when the Epsila EV2401 lead product family is sterilized. | | **Epsila EV EAZ101 Sternal Tunneling Tool** | | **Design Verification** – The Epsila EV EAZ101 Sternal Tunneling Tool has been verified through a combination of test, analysis, and review methods. The outcomes of these verification activities were that the Epsila EV EAZ101 Sternal Tunneling Tool meets its design requirements and is considered verified. | | **Packaging**–The purpose of the packaging test was to verify that the packaging protects the device and media during transportation and storage. The testing concludes that the Epsila EV EAZ101 Sternal Tunneling Tool meets all the requirements and is considered verified. | | **Sterilization** – The Epsila EV EAZ101 Sternal Tunneling Tool is qualified to demonstrate a Sterility Assurance Level (SAL) of 1.0x10^{-6} following terminal sterilization via gamma radiation. | | **Shelf-Life** – Shelf-life verification was conducted using verification by analysis leveraging design equivalency to market-released packaging. All materials used in the Epsila EV EAZ101 Sternal Tunneling Tool are the same or similar to other devices which have had acceptable field performance and testing demonstrating a shelf life of 2 years. | | **Biocompatibility** – Biocompatibility for the Epsila EV EAZ101 Sternal Tunneling Tool was determined in accordance with EN ISO 10993-1, *Biological Evaluation of Medical Devices Part 1: Evaluation and Testing within a Risk Management Process*. All materials were demonstrated to be biocompatible per ISO 10993-1. | | **Epsila EV EAZ201 Transverse Tunneling Tool** | | **Design Verification** – The Epsila EV EAZ201 Transverse Tunneling Tool has been verified through a combination of test, analysis, and review methods. The outcomes of these verification activities were that the Epsila EV EAZ201 Transverse Tunneling Tool meets its design requirements and is considered verified. | | **Packaging**– Packaged and sterile Epsila EV EAZ201 Transverse Tunneling Tools are labeled with a shelf life of 2 years The testing concludes that the Epsila EV EAZ201 Transverse Tunneling Tool meets all requirements identified in the plan and is considered verified. | | **Sterilization** – The Epsila EV EAZ201 Transverse Tunneling Tool is qualified to demonstrate a Sterility Assurance Level (SAL) of 1.0x10^{-6} following terminal sterilization via gamma radiation. | {9} # B. Animal and Additional In Vivo Studies The safety of substernal pacing, sensing and defibrillation has been demonstrated through pre-clinical animal safety and cadaver evaluations. Further, animal safety studies have demonstrated the safety of substernal tunneling and acute catheter or lead implantation within the substernal tissues. As observed in Good Laboratory Practice (GLP) animal safety testing, substernal defibrillation is comparable to other forms of defibrillation, including defibrillation from epicardial patch electrodes and leads placed within the pericardial sac. According to comparisons with historical animal studies and published literature, substernal defibrillation is also comparable to transvenous defibrillation, the accepted standard of care for treating arrhythmias with an implantable device. Across all GLP animal safety studies, no cardiac lesion, test or control, measured greater than two cubic centimeters (cc). MRI characterization of cardiac lesions in human patients has demonstrated that lesions of less than two cubic centimeters are regarded as subclinical in nature and not indicative of long-term sequelae. Across all animal safety studies, no damage was observed to the lungs, kidneys, spleen or liver, and any observed changes to the substernal tissues were minor and expected to heal in time. Table 1. Additional In Vivo Testing | Study Name / Identifier | Study Purpose | Results | | --- | --- | --- | | EV ICD Lead Shape and Tip Displacement Measurements in Canines | Assess lead bend in vivo to inform reliability testing | All electrode regions experience similar conditions for a given implant. Implant locations closest to the heart cause highest displacement and curvature. These measurements, along with fatigue test data, were used to estimate long-term reliability to verify the lead design meets requirements | | EVALUATION OF THE EPISAL AND THE EPISAL PROTECTION OF THE EPISAL AND THE EPISAL PROTECTION OF THE EPISAL AND THE EPISAL PROTECTION OF THE EPISAL AND THE EPISAL PROTECTION OF THE EPISAL AND THE EPISAL PROTECTION OF THE EPISAL | Assess the EPISAL and EPISAL performance of the EPISAL and EPISAL and the EPISAL and EPISAL performance of the EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL | EVALUATION OF EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL | | EVALUATION OF EPISAL AND EPISAL PROTECTION OF EPISAL AND EPISAL | Evaluate the EPISAL and EPISAL performance of EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL | EVALUATION OF EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL and EPISAL | {10} | Study Name / Identifier | Study Purpose | Results | | --- | --- | --- | | Thompson AE, Marshall M, Lentz L, Mazzetti H. Three-year extraction experience of a novel substernal extravascular defibrillation lead in sheep. Pacing Clin Electrophysiol. 2022; 45: 314–322. https://doi.org/10.1111/pace.14451 | 5-year lead extraction study. (Three-year extraction data are available as a published manuscript) | Chronic extraction of EV ICD leads from the substernal space was successfully performed using traction and simple tools through 3 years in sheep | | EV ICD Chronic Lead Study (S3922) | Characterize chronic tissue encapsulation | Histopathological comparisons of chronically implanted EV ICD and transvenous ICD control leads in 5 swine revealed tissue capsules of similar thickness, maturity, and inflammatory response at 12 weeks | | EV ICD Lead Axial Force Measurement due to Posturing in Human Cadavers Extravascular ICD Lead Use Conditions due to Postures Simulated in Human Cadavers | Use of cadavers for lead stability testing and lead fatigue inputs | All encountered tissue changes (pockets, subcutaneous lead portions, distal lead portions) were found to be within an expected range of responses for procedures of similar type and duration | X. SUMMARY OF PRIMARY CLINICAL STUDY EV-ICD Pivotal Study The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of substernal implant with the EV-ICD System for substernal pacing in the United States (US)/Canada, Asia Pacific (APAC), and Europe, Middle, East and Africa (EMEA) regions under IDE #G190186. The EV-ICD Pivotal study is a prospective, multi-center, single-arm, pre-market clinical study, designed to demonstrate the safety and efficacy of the EV-ICD System. The study enrolled 356 subjects. A total of 299 subjects were successfully implanted with the full system by 55 physicians at 46 centers across 17 countries. 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 This study was a prospective, multi-center, single-arm, pre-market clinical study. The purpose of this clinical study was to demonstrate the safety and efficacy of the EV-ICD System. The study design allowed for up to 400 enrollments at up to 60 sites worldwide, to allow at least 292 subjects to, in the case of the safety objective, undergo an implant attempt of the EV-ICD System, and in the case of the efficacy objective, complete the pre-specified defibrillation testing protocol. {11} The first worldwide subject was enrolled in the EV-ICD Pivotal Clinical Study on 16 September 2019 and underwent an EV-ICD implant the same day. On 15 October 2021, the last subject underwent an implant attempt, completing the enrollment and implant phase of the study. On 28 April 2022, the final 6-month follow-up visit was completed, triggering the visit cutoff date for the PMA report analysis. Case report form data analyzed for this PMA report was collected on or before 28 April 2022 and was received at Medtronic on or before 13 May 2022. The study database was frozen for analysis on 7 June 2022. As of the 28 April 2022 visit cutoff date, 356 subjects were enrolled in the study, of which 316 underwent an implant attempt with the EV-ICD System. Of the 316 subjects who underwent an implant attempt, the substernal lead was positioned in 315. A total of 299 subjects were successfully implanted with the full system by 55 physicians at 46 centers across 17 countries. Maximum number of subjects enrolled at each site was capped at 35, which is approximately 10% of the total number of subjects enrolled. Subjects indicated for single-chamber ICD therapy were recruited and implanted with the Medtronic EV-ICD System. Once enrolled, subjects were assessed at the following visits: - Baseline - Implant - Pre-Hospital Discharge (PHD) - 2 Weeks (2WK) - 3 Months (3M) - 6 Months (6M) - Long-term: Every 6 months thereafter until study closure (12, 18, 24... Months) - Unscheduled (as they occur) - System Modifications (as they occur) - Exit The primary safety objective was to demonstrate the freedom from major complications related to the EV-ICD System and/or procedure at 6 months post-implant exceeds 79% performance goal (PG). The endpoint was defined as a subject’s first occurrence of a major complication related to the EV-ICD System and/or procedure, as determined by an independent Clinical Events Committee (CEC), that occurs on or prior to 6 months (182 days) post-implant. To evaluate the safety primary objective, a 95% confidence interval for the Kaplan-Meier estimate of 6-month system/procedure related major complication-free rate was generated using the log-log transformation and its lower bound compared against the pre-specified threshold of 79%. A Kaplan-Meier curve was also generated to provide incidence of EV-ICD System/procedure-related major complications over time. The primary efficacy objective was to demonstrate the defibrillation efficacy at implant of the EV-ICD System exceeds 88% (PG). The endpoint, defibrillation testing success, was defined as: - Single sustained shockable ventricular arrhythmia (SSVA) conversion at 20J, or - Conversion of two consecutive episodes of SSVA at 30J in final system configuration. {12} The efficacy primary objective was evaluated using an exact binomial 95% confidence interval and comparing the lower bound against the pre-specified threshold of 88%. The sponsor consulted with the Steering Committee before and during the course of the study. 1. Clinical Events Committee A Clinical Events Committee (CEC) consisted of physicians independent of the study was used to review and adjudicate adverse events (AEs) for their relationship to the EV-ICD Pivotal system and/or procedure. 2. Data Monitoring Committee A Data Monitoring Committee (DMC) consisted of members independent of the study is used to periodically review the total incidence of AEs and follow trends of these events in the study, and to make recommendations to Medtronic and/or the Steering Committee regarding study conduct and subject safety. An Episode Review Committee (ERC) consisted of independent physicians and Medtronic experts was used to evaluate device-treated ventricular episodes according to an ERC Charter. 3. Clinical Inclusion and Exclusion Criteria Enrollment in the EV-ICD Pivotal study was limited to patients who met the following inclusion criteria: | | Inclusion Criteria | | --- | --- | | 1. | Patient has a Class I or IIa indication for implantation of an ICD according to the ACC/AHA/HRS Guidelines^{a}, or ESC guidelines^{b}. | | 2. | Patient is at least 18 years of age and meets age requirements per local law. | | 3. | Patient is geographically stable and willing and able to complete the study procedures and visits for the duration of the follow-up. | Patients were not permitted to enroll in the EV-ICD Pivotal study if they met any of the following exclusion criteria: | | Exclusion Criteria | | --- | --- | | 1. | Patient is unwilling or unable to personally provide Informed Consent. | | 2. | Patient has indications for bradycardia pacing^{c} or Cardiac Resynchronization Therapy (CRT)^{d} (Class I, IIa, or IIb indication). | a Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias. b Priori SG, Blomstrom-Lundqvist C, Mazzanti A, et al. 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. European Heart Journal 2015 36:41 (2793-2867). https://doi.org/10.1093/eurheartj/ehv316 c 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing). d ACC/AHA/HRS guidelines for Cardiac Resynchronization Therapy {13} | | Exclusion Criteria | | --- | --- | | 3. | Patients with an existing pacemaker, ICD, or CRT device or leads. | | 4. | Patients with these medical interventions are excluded from participation in the study: 1. Prior sternotomy 2. Any prior medical condition or procedure that leads to adhesions in the anterior mediastinal space (i.e., prior mediastinal instrumentation, mediastinitis) 3. Prior abdominal surgery in the epigastric region 4. Planned sternotomy 5. Prior chest radiotherapy Or any other prior/planned medical intervention not listed that precludes their participation in the opinion of the Investigator. | | 5. | Patient has previous pericarditis that: • Was chronic and recurrent, or • Resulted in pericardial effusion^{e}, or Resulted in pericardial thickening or calcification.^{f} | | 6. | Patients with these medical conditions or anatomies are excluded from participation in the study: - Hiatal hernia that distorts mediastinal anatomy - Marked sternal abnormality (e.g., pectus excavatum) - Decompensated heart failure - COPD with oxygen dependence - Gross hepatosplenomegaly Or any other known medical condition or anatomy type not listed that precludes their participation in the opinion of the Investigator. | e As documented on echo or MRI f As documented on CT scan or MRI {14} | | Exclusion Criteria | | --- | --- | | 7. | Patients with a medical condition that precludes them from undergoing defibrillation testing: — Severe aortic stenosis — Current Intracardiac Left Atrium (LA) or Left Ventricular (LV) thrombus — Severe proximal three-vessel or left main coronary artery disease without revascularization — Hemodynamic instability — Unstable angina — Recent stroke or transient ischemic attack (within the last 6 months) — Known inadequate external defibrillation — Left Ventricular Ejection Fraction (LVEF) < 20% — Left Ventricular End Diastolic Diameter (LVEDD) >70 mm Or any other known medical condition not listed that precludes their participation in the opinion of the Investigator. | | 8. | Patient with any evidence of active infection or undergoing treatment for an infection. | | 9. | Patient is contraindicated from temporary suspension of oral/systemic anticoagulation | | 10. | Patient with current implantation of neurostimulator or any other chronically implanted device that delivers current in the body. | | 11. | Patient meets ACC/AHA/HRS or ESC clinical guideline Class III criteria for an ICD (e.g., life expectancy of less than 12 months). | | 12. | Patient is enrolled or planning to enroll in a concurrent clinical study that may confound the results of this study, without documented pre-approval from a Medtronic study | | 13. | Patient with any exclusion criteria as required by local law (e.g., age or other). | | 14. | Pregnant women or breastfeeding women, or women of child bearing potential and who are not on a reliable form of birth regulation method or abstinence. ^{8} | ## 4. Follow-up Schedule This is a single-arm study. After subjects signed the informed consent form, they were enrolled in the study. Extensive inclusion/exclusion criteria have been chosen in this study to restrict the target population to those thought to be best served by this EV-ICD system and mitigate the risk of selection bias as well as to exclude subjects who may be more vulnerable to potential increased risk during the evaluation of the clinical study defibrillation protocol. Enrollment could be a stand-alone visit or could occur on the same day as the baseline visit. After that, subjects underwent implant of the EV-ICD system, with required defibrillation, sensing, impedance and pacing g If required by local law, women of child-bearing potential must undergo a pregnancy test within seven days prior to EV-ICD Pivotal Study procedures {15} testing. Subjects then returned for follow-up visits at 2 Weeks, 3 Months, 6 Months, and every 6 months thereafter. Refer to Table 2 for the schedule of events for the Pivotal study visit. {16} Table 2. EV-ICD Pivotal Study schedule of events | Study procedure | Baseline | Implant | PHD | 2 Weeks | 3 Months | 6 Months | Long-Term (12, 18, 24... months) | Unsched. | Sys. Mod. | Exit | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Informed Consent | X | | | | | | | | | | | Inclusion/Exclusion Assessment | X | | | | | | | | | | | Physical Exam, Demographics, Cardiovascular Medical History, Surgical History | X | | | | | | | | | | | SF-12 quality of life survey | X | | | | | X | | | | | | Florida Patient Acceptance Survey (FPAS)1 | | | | | | X | | | | | | System and procedure information | | X | | | | | | | X | | | Pre-procedure Transesophageal Echocardiogram (TEE)7 | | X3 | | | | | | | | | | CT or MRI scan | X3 | | | | | | | | | | | Fluoroscopy recordings during tunneling procedure | | X | | | | | | | X6 | | | Fluoroscopy (AP and Lateral cine) of final ICD generator and lead position | | X | | | | | | | X6 | | | Sensing, Impedance & Pacing Tests | | X | X | X | X | X | X | X5 | X6 | | | Defibrillation Testing | | X | | | | Subset4 | | | X6 | | | Chest Radiographs – (PA/Lateral) | X | | X | | | X | | | | | | Echocardiographic data within the last 6 months | X | | | | | | | | | | | Save-to-media files | | X | X | X | X | X | X | X | X | X | | Medications (for subjects implanted with any device) | X | X | X | X | X | X | X | X | X | X | | Adverse Events7 (including AEs with fatal outcome), Device Deficiencies, HCUs, Study Deviations, and Other Cardiac Imaging | As they occur | | | | | | | | | | 1 Only for subjects who complete their Informed Consent Form (ICF) in English. 2 Required for subjects presenting in persistent atrial fibrillation to confirm the absence of Left Atrium (LA) or Left Ventricular (LV) thrombus. 3 Taken within the last year. Recommended for first 3 subjects at minimum, for each implanter. If collected/reviewed, send CT-scan and/or MRI to Medtronic. 4 Only for subjects participating in chronic defibrillation testing, see CIP Addendum for 6-Month Defibrillation Testing. 5 Optional. If electrical testing conducted, print the Testing Reports to PDF or paper and send a copy of the reports to Medtronic System modification where a subject leaves the procedure with an EV-ICD System. Recommended to collect incision photographs if an infection related to the EV ICDEV-ICD System is suspected. {17} 5. Clinical Endpoints With regards to safety, the primary safety objective was to demonstrate the freedom from major complications related to the EV-ICD System and/or procedure at 6 months post-implant exceeds 79% performance goal (PG). The endpoint was defined as a subject’s first occurrence of a major complication related to the EV-ICD System and/or procedure, as determined by an independent Clinical Events Committee (CEC), that occurred on or prior to 6 months (182 days) post-implant. For an adverse event to meet the endpoint, the event must have occurred within 182 days (inclusive) of the EV-ICD System implant and been adjudicated by the CEC as being a major complication related (causal relationship) to the EV-ICD System and/or procedure. Major complications were those complications resulting in: - Death - Permanent loss of defibrillation function (specifically shock) due to mechanical or electrical dysfunction of the device - Hospitalization - Prolongation of an existing hospitalization by at least 48 hours - System revision (reposition, replacement, explant) With regards to effectiveness, the primary efficacy objective was to demonstrate the defibrillation efficacy at implant of the EV-ICD System exceeds 88% (PG). The endpoint, defibrillation testing success, was defined as: - Single sustained shockable ventricular arrhythmia (SSVA) conversion at 20J, or - Conversion of two consecutive episodes of SSVA at 30J in final system configuration. C. Accountability of PMA Cohort Among 356 enrolled subjects, 40 exited the study without having an implant attempt and 316 underwent an implant attempt of the EV-ICD System. Of the 316 subjects who underwent an implant attempt, 315 subjects had the lead positioned and proceeded to electrical testing during the implant procedure. In total, 299 (94.6%) had the EV-ICD System fully implanted and 17 did not. Reasons for not having a successful implant included: - Failed defibrillation testing (4) - Inadequate R-wave sensing (7) - Incomplete defibrillation testing protocol (4) - Other reasons (2) - Tunneling stopped due to resistance - Oversensing of atrial fibrillation in all lead positions attempted All 17 subjects with an unsuccessful implant exited the study following the instructions in the Clinical Investigational Protocol (CIP). Of them, 15 subjects exited between 28-36 days post implant attempt and two subjects exited 54 and 70 days post implant attempt, respectively. {18} Subject disposition is presented using a flow diagram (refer to Figure 5) where completed visits, missed visits, and attrition due to exit and death are indicated.  {19}  Figure 5: Subject Disposition Diagram # D. Study Population Demographics and Baseline Parameters The demographics of the study population are younger than typical ICD recipients, with a high frequency of hypertrophic cardiomyopathy. Baseline characteristics are summarized in Table 3 - Table 13. Among 356 subjects enrolled, 343 had baseline forms completed at the time of this report, and all subjects without a baseline form have been exited. There were 316 subjects with an implant attempt; of these, $74.7\%$ were male, the average age $(\pm$ standard deviation) was $53.8 \pm 13.1$ years, the average BMI $(\pm$ standard deviation) was $28.0 \pm 5.6$ , $23.7\%$ were known to be NYHA Class I and $65.5\%$ were known to be NYHA Class II/III. Of those with an implant attempt, 258 (81.6%) were indicated for primary prevention as defined in Table 6, 57 (18.0%) were indicated for secondary prevention and 1 (0.3%) did not provide enough information to classify as primary or secondary. Of the 18 subjects with an explanted device indicated in cardiovascular surgical history (Table 11), ten had their explant within two weeks prior to enrollment, seven had their explant more than two weeks prior to enrollment with a maximum of 258 days, and one had their explant 33 days after enrollment but seven days prior to EV-ICD implant. {20} Table 3: Subject Demographics | | Subjects with EV-ICD Implant Attempted (N = 316) | Subjects without EV-ICD Implant Attempted (N = 27) | Total Subjects with Baseline Form (N = 343) | | --- | --- | --- | --- | | Sex (N,%) | | | | | Male | 236 (74.7%) | 22 (81.5%) | 258 (75.2%) | | Female | 80 (25.3%) | 5 (18.5%) | 85 (24.8%) | | Age (years) | | | | | Mean ± Standard Deviation | 53.8 ± 13.1 | 53.3 ± 14.7 | 53.8 ± 13.2 | | Median | 55.0 | 55.0 | 55.0 | | 25thPercentile - 75thPercentile | 46 - 64 | 43 - 68 | 46 - 64 | | Minimum - Maximum | 18 - 84 | 19 - 76 | 18 - 84 | | Number Of Subjects With Measure Available (N, %) | 316 (100.0%) | 27 (100.0%) | 343 (100.0%) | | Number of Subjects 90 Years or Older | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | Ethnicity (N,%) | | | | | Not Reported due to local requirements (Non-US) | 197 (62.3%) | 10 (37.0%) | 207 (60.3%) | | Not Reported for other reasons | 2 (0.6%) | 0 (0.0%) | 2 (0.6%) | | Not Hispanic or Latino | 110 (34.8%) | 17 (63.0%) | 127 (37.0%) | | Hispanic or Latino | 7 (2.2%) | 0 (0.0%) | 7 (2.0%) | | Unknown | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | Race (N,%) | | | | | Not Reported due to local requirements (Non-US) | 197 (62.3%) | 10 (37.0%) | 207 (60.3%) | | Not Reported for other reasons | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | American Indian or Alaska Native | 2 (0.6%) | 0 (0.0%) | 2 (0.6%) | | Asian | 7 (2.2%) | 1 (3.7%) | 8 (2.3%) | | Black or African American | 16 (5.1%) | 1 (3.7%) | 17 (5.0%) | | Native Hawaiian or Other Pacific Islander | 1 (0.3%) | 0 (0.0%) | 1 (0.3%) | {21} | | Subjects with EV-ICD Implant Attempted (N = 316) | Subjects without EV-ICD Implant Attempted (N = 27) | Total Subjects with Baseline Form (N = 343) | | --- | --- | --- | --- | | White | 87 (27.5%) | 15 (55.6%) | 102 (29.7%) | | Other | 6 (1.9%) | 0 (0.0%) | 6 (1.7%) | Table 4: Physical Exam Results | Status | Subjects with EV-ICD Implant Attempted (N = 316) | Subjects without EV-ICD Implant Attempted (N = 27) | Total Subjects with Baseline Form (N = 343) | | --- | --- | --- | --- | | Height (cm) | | | | | Mean ± Standard Deviation | 173.8 ± 9.4 | 172.9 ± 10.0 | 173.8 ± 9.4 | | Median | 174.0 | 172.7 | 174.0 | | 25th Percentile – 75th Percentile | 167 - 180 | 165 - 182 | 167 - 180 | | Minimum – Maximum | 145 - 203 | 147 - 188 | 145 - 203 | | Number of Subjects With Measure Available (N,%) | 316 (100.0%) | 27 (100.0%) | 343 (100.0%) | | Weight (kg) | | | | | Mean ± Standard Deviation | 85.1 ± 19.7 | 83.8 ± 20.7 | 85.0 ± 19.8 | | Median | 83.0 | 85.3 | 83.0 | | 25th Percentile – 75th Percentile | 70 - 96 | 69 - 93 | 70 - 96 | | Minimum – Maximum | 48 - 148 | 49 - 137 | 48 - 148 | | Number of Subjects With Measure Available (N,%) | 316 (100.0%) | 27 (100.0%) | 343 (100.0%) | | BMI (kg/m2) | | | | | Mean ± Standard Deviation | 28.0 ± 5.6 | 27.9 ± 5.7 | 28.0 ± 5.6 | | Median | 27.7 | 27.5 | 27.7 | | 25th Percentile – 75th Percentile | 24 - 31 | 24 - 33 | 24 - 32 | | Minimum – Maximum | 18 - 46 | 17 - 41 | 17 - 46 | | Number of Subjects With Measure Available (N,%) | 316 (100.0%) | 27 (100.0%) | 343 (100.0%) | {22} Table 5: Cardiac Disease Classification Characteristics | Status | Subjects with EV-ICD Implant Attempted (N = 316) | Subjects without EV-ICD Implant Attempted (N = 27) | Total Subjects with Baseline Form (N = 343) | | --- | --- | --- | --- | | New York Heart Association (N,%) | | | | | Class I | 75 (23.7%) | 5 (18.5%) | 80 (23.3%) | | Class II | 184 (58.2%) | 17 (63.0%) | 201 (58.6%) | | Class III | 23 (7.3%) | 4 (14.8%) | 27 (7.9%) | | Class IV | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | NYHA classification not available | 34 (10.8%) | 1 (3.7%) | 35 (10.2%) | Table 6: Summary of ICD Indication | | Subjects with EV-ICD Implant Attempted (N = 316) | Subjects without EV-ICD Implant Attempted (N = 27) | Total Subjects with Baseline Form (N = 343) | | --- | --- | --- | --- | | Primary prevention | 258 (81.6%) | 25 (92.6%) | 283 (82.5%) | | LVEF<=35% due to prior MI, NYHA Class II or III | 94 (29.7%) | 9 (33.3%) | 103 (30.0%) | | Nonischemic dilated cardiomyopathy, LVEF<=35%, NYHA Class II/III | 76 (24.1%) | 8 (29.6%) | 84 (24.5%) | | LV dysfunction due to prior MI, LVEF<=30%, NYHA Class I | 14 (4.4%) | 2 (7.4%) | 16 (4.7%) | | NSVT due to prior MI, LVEF<40%, inducible VT/VF | 1 (0.3%) | 1 (3.7%) | 2 (0.6%) | | Hypertrophic cardiomyopathy, 1 or more major risk factors for SCD | 33 (10.4%) | 2 (7.4%) | 35 (10.2%) | | Arrhythmogenic RV dysplasia/cardiomyopathy, 1 or more risk factor for SCD | 5 (1.6%) | 0 (0.0%) | 5 (1.5%) | | Brugada syndrome and has had syncope | 1 (0.3%) | 0 (0.0%) | 1 (0.3%) | {23} | | Subjects with EV-ICD Implant Attempted (N = 316) | Subjects without EV-ICD Implant Attempted (N = 27) | Total Subjects with Baseline Form (N = 343) | | --- | --- | --- | --- | | Brugada syndrome and has documented VT that has not resulted in cardiac arrest | 1 (0.3%) | 0 (0.0%) | 1 (0.3%) | | Cardiac sarcoidosis, giant cell myocarditis, or Chagas disease | 3 (0.9%) | 0 (0.0%) | 3 (0.9%) | | Nonischemic heart disease, LVEF <=35%, NYHA functional Class I | 9 (2.8%) | 0 (0.0%) | 9 (2.6%) | | Long-QT Syndrome and risk factors for SCD | 1 (0.3%) | 0 (0.0%) | 1 (0.3%) | | Familial cardiomyopathy associated with sudden death | 13 (4.1%) | 1 (3.7%) | 14 (4.1%) | | LV noncompaction | 0 (0.0%) | 2 (7.4%) | 2 (0.6%) | | Other primary prevention* | 7 (2.2%) | 0 (0.0%) | 7 (2.0%) | | Secondary prevention | 57 (18.0%) | 2 (7.4%) | 59 (17.2%) | | Cardiac arrest due to VF/hemodynamically unstable sustained VT | 40 (12.7%) | 1 (3.7%) | 41 (12.0%) | | Structural heart disease and spontaneous sustained VT | 6 (1.9%) | 1 (3.7%) | 7 (2.0%) | | Syncope with induced sustained VT/VF | 1 (0.3%) | 0 (0.0%) | 1 (0.3%) | | Unstable VT and/or VT with syncope and LVEF<=40% | 4 (1.3%) | 0 (0.0%) | 4 (1.2%) | | Sustained VT and normal ventricular function | 6 (1.9%) | 0 (0.0%) | 6 (1.7%) | | Other** | 1 (0.3%) | 0 (0.0%) | 1 (0.3%) | * Other primary prevention indications for subjects with an Implant Attempt included “FAMILIAL IDIOPATHIC VF (DPP6 GENE)” (2), “ISCHAEMIC CARDIOMYOPATHY, LVEF 30%, NYHA II” (1), “ISCHEMIC CARDIOMYOPATHY AND HAS AN LVEF LESS THAN OR EQUAL TO 35% AND IS IN NYHA FUNCTIONAL CLASS II OR III” (1), “ISCHEMIC CARDIOMYOPATHY, HAS AN LVEF LESS THAN OR EQUAL TO 30% AND IS IN NYHA FUNCTIONAL CLASS I(WITHOUT MYOCARDIAL INFRACTION DOCUMENTED” (1), “ISCHEMIC CARDIOPATHY, ELF 35%, NYHA II” (1), and “ISCHEMIC HEART DISEASE, LVEF LESS THAN 35%, NYHA II”(1). ** Other unclassified indication included "STRUCTURAL HEART DISEASE WITH NON-SUSTAINED VT" (1). {24} Table 7: EP Testing and ECG Characteristics | Status | Subjects with EV-ICD Implant Attempted (N = 316) | Subjects without EV-ICD Implant Attempted (N = 27) | Total Subjects with Baseline Form (N = 343) | | --- | --- | --- | --- | | EP Testing Within Last 180 Days (N,%) | | | | | Not done | 308 (97.5%) | 26 (96.3%) | 334 (97.4%) | | Non-inducible ventricular arrhythmias | 2 (0.6%) | 0 (0.0%) | 2 (0.6%) | | Inducible, specify | 6 (1.9%) | 1 (3.7%) | 7 (2.0%) | | Sustained VF | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | Non-sustained VF | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | Ventricular flutter | 1 (0.3%) | 0 (0.0%) | 1 (0.3%) | | Ventricular fibrillation | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | Sustained monomorphic VT | 2 (0.6%) | 1 (3.7%) | 3 (0.9%) | | Sustained polymorphic VT | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | Sustained VT, morphology unknown | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | Non-sustained VT (5 beats or less) | 1 (0.3%) | 0 (0.0%) | 1 (0.3%) | | Torsades de Pointes | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | Other* | 2 (0.6%) | 0 (0.0%) | 2 (0.6%) | * Other indications included "NON DIAGNOSTIC STUDY – NO ARRHYTHMIAS INDUCED" (1) and "NON INDUCIBLE SVT ON MONITOR &gt; 3 MIN" (1). Table 8: Imaging Testing Results | Status | Subjects with EV-ICD Implant Attempted (N = 316) | Subjects without EV-ICD Implant Attempted (N = 27) | Total Subjects with Baseline Form (N = 343) | | --- | --- | --- | --- | | Methods Used for LVEF Measurement (%) | | | | | Transthoracic Echocardiography | 303 (95.9%) | 27 (100.0%) | 330 (96.2%) | | Stress Echocardiography | 1 (0.3%) | 0 (0.0%) | 1 (0.3%) | | Transesophageal Echocardiography | 11 (3.5%) | 0 (0.0%) | 11 (3.2%) | | Other | 1 (0.3%) | 0 (0.0%) | 1 (0.3%) | | Echo Not Done | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | LV Election Fraction (%) | | | | | Mean ± Standard Deviation | 38.9 ± 15.4 | 36.0 ± 12.5 | 38.7 ± 15.2 | | Median | 33.0 | 35.0 | 33.0 | {25} | Status | Subjects with EV-ICD Implant Attempted (N = 316) | Subjects without EV-ICD Implant Attempted (N = 27) | Total Subjects with Baseline Form (N = 343) | | --- | --- | --- | --- | | 25^{th} Percentile – 75^{th} Percentile | 27 - 53 | 28 - 45 | 27 - 51 | | Minimum – Maximum | 20 - 85 | 15 - 70 | 15 - 85 | | Number of Subjects With Measure Available | 316 (100.0%) | 27 (100.0%) | 343 (100.0%) | | **LV End Diastolic Volume (mL)** | | | | | Mean ± Standard Deviation | 158.7 ± 69.9 | 146.4 ± 57.0 | 157.7 ± 69.0 | | Median | 150.0 | 136.2 | 150.0 | | 25^{th} Percentile – 75^{th} Percentile | 110 - 197 | 116 - 194 | 110 - 196 | | Minimum – Maximum | 5 - 503 | 38 - 255 | 5 - 503 | | Number of Subjects With Measure Available | 244 (77.2%) | 20 (74.1%) | 264 (77.0%) | | **LV End Diastolic Diameter (mm)** | | | | | Mean ± Standard Deviation | 55.8 ± 9.2 | 56.1 ± 10.3 | 55.8 ± 9.2 | | Median | 57.0 | 58.0 | 57.0 | | 25^{th} Percentile – 75^{th} Percentile | 50 - 62 | 50 - 61 | 50 - 62 | | Minimum – Maximum* | 22 - 72 | 31 - 75 | 22 - 75 | | Number of Subjects With Measure Available | 314 (99.4%) | 27 (100.0%) | 341 (99.4%) | | **LA Systolic Diameter (mm)** | | | | | Mean ± Standard Deviation | 40.4 ± 11.8 | 44.2 ± 10.9 | 40.7 ± 11.8 | | Median | 41.0 | 44.0 | 41.0 | | 25^{th} Percentile – 75^{th} Percentile | 35 - 46 | 38 - 50 | 35 - 46 | | Minimum – Maximum | 3 - 93 | 21 - 72 | 3 - 93 | | Number of Subjects With Measure Available | 260 (82.3%) | 23 (85.2%) | 283 (82.5%) | | **RA Size (N.%)** | | | | | Normal | 223 (70.6%) | 14 (51.9%) | 237 (69.1%) | | Enlarged | 69 (21.8%) | 9 (33.3%) | 78 (22.7%) | | Measure not available | 24 (7.6%) | 3 (11.1%) | 27 (7.9%) | * LVEDD &gt; 70 is an exclusion criterion for this study. Two deviations have been completed for the two patients with an implant attempt and an LVEDD of 71 and 72. {26} Table 9: Spontaneous Arrhythmia History | Status* | Subjects with EV-ICD Implant Attempted (N = 316) | Subjects without EV-ICD Implant Attempted (N = 27) | Total Subjects with Baseline Form (N = 343) | | --- | --- | --- | --- | | None | 127 (40.2%) | 7 (25.9%) | 134 (39.1%) | | Supraventricular tachycardia | | | | | Atrial fibrillation | 44 (13.9%) | 8 (29.6%) | 52 (15.2%) | | Paroxysmal | 28 (8.9%) | 2 (7.4%) | 30 (8.7%) | | Persistent | 8 (2.5%) | 6 (22.2%) | 14 (4.1%) | | Long-standing persistent | 4 (1.3%) | 1 (3.7%) | 5 (1.5%) | | Permanent | 5 (1.6%) | 1 (3.7%) | 6 (1.7%) | | Atrial flutter | 7 (2.2%) | 4 (14.8%) | 11 (3.2%) | | Atrial tachycardia | 7 (2.2%) | 1 (3.7%) | 8 (2.3%) | | Sinus node dysfunction (any of the following) | 34 (10.8%) | 5 (18.5%) | 39 (11.4%) | | Bradycardia-tachycardia syndrome | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | Chronotropic incompetence | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | Sinus arrest/pause/exit block | 1 (0.3%) | 0 (0.0%) | 1 (0.3%) | | Sinus bradycardia | 19 (6.0%) | 3 (11.1%) | 22 (6.4%) | | Sinus tachycardia | 16 (5.1%) | 2 (7.4%) | 18 (5.2%) | | Ventricular arrhythmias | 135 (42.7%) | 9 (33.3%) | 144 (42.0%) | | Premature ventricular complexes | 41 (13.0%) | 1 (3.7%) | 42 (12.2%) | | Torsades de pointes | 2 (0.6%) | 0 (0.0%) | 2 (0.6%) | | Ventricular fibrillation | 32 (10.1%) | 1 (3.7%) | 33 (9.6%) | | Ventricular flutter | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | Ventricular tachycardia non-sustained | 70 (22.2%) | 7 (25.9%) | 77 (22.4%) | | Ventricular tachycardia, sustained monomorphic | 14 (4.4%) | 0 (0.0%) | 14 (4.1%) | | Ventricular tachycardia, sustained polymorphic | 4 (1.3%) | 1 (3.7%) | 5 (1.5%) | | Ventricular tachycardia, sustained unknown | 10 (3.2%) | 0 (0.0%) | 10 (2.9%) | | AV block | 12 (3.8%) | 2 (7.4%) | 14 (4.1%) | | 1st degree AV block | 12 (3.8%) | 2 (7.4%) | 14 (4.1%) | | 2nd degree AV block | 3 (0.9%) | 0 (0.0%) | 3 (0.9%) | | 3rd degree AV block | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | Bundle branch blocks | 22 (7.0%) | 2 (7.4%) | 24 (7.0%) | | Left bundle branch block | 5 (1.6%) | 0 (0.0%) | 5 (1.5%) | | Intraventricular conduction delay | 9 (2.8%) | 1 (3.7%) | 10 (2.9%) | | Right bundle branch block | 11 (3.5%) | 1 (3.7%) | 12 (3.5%) | * Categories in medical history tables may not be mutually exclusive. {27} Table 10: Cardiovascular History | Status* | Subjects with EV-ICD Implant Attempted (N = 316) | Subjects without EV-ICD Implant Attempted (N = 27) | Total Subjects with Baseline Form (N = 343) | | --- | --- | --- | --- | | None of the following | 4 (1.3%) | 0 (0.0%) | 4 (1.2%) | | Cardiac arrest | 45 (14.2%) | 2 (7.4%) | 47 (13.7%) | | Cardiomyopathy | 265 (83.9%) | 25 (92.6%) | 290 (84.5%) | | Ischemic | 128 (40.5%) | 12 (44.4%) | 140 (40.8%) | | Non-ischemic | 102 (32.3%) | 12 (44.4%) | 114 (33.2%) | | Hypertrophic | 41 (13.0%) | 2 (7.4%) | 43 (12.5%) | | Coronary artery disease | 147 (46.5%) | 16 (59.3%) | 163 (47.5%) | | Hypertension | 155 (49.1%) | 12 (44.4%) | 167 (48.7%) | | Hypotension | 8 (2.5%) | 0 (0.0%) | 8 (2.3%) | | Idiopathic structural heart disease | 9 (2.8%) | 2 (7.4%) | 11 (3.2%) | | Left ventricular hypertrophy | 52 (16.5%) | 4 (14.8%) | 56 (16.3%) | | Myocardial infarction | 132 (41.8%) | 13 (48.1%) | 145 (42.3%) | | Primary/idiopathic electrical disease (of the following) | 24 (7.6%) | 2 (7.4%) | 26 (7.6%) | | Arrhythmogenic RV dysplasia | 6 (1.9%) | 0 (0.0%) | 6 (1.7%) | | Brugada syndrome | 2 (0.6%) | 0 (0.0%) | 2 (0.6%) | | Long O/T syndrome | 5 (1.6%) | 0 (0.0%) | 5 (1.5%) | | Unknown type | 2 (0.6%) | 1 (3.7%) | 3 (0.9%) | | Other | 9 (2.8%) | 1 (3.7%) | 10 (2.9%) | | Stroke and stroke-related events | 24 (7.6%) | 3 (11.1%) | 27 (7.9%) | | Stroke, ischemic | 14 (4.4%) | 1 (3.7%) | 15 (4.4%) | | Stroke, hemorrhagic | 1 (0.3%) | 0 (0.0%) | 1 (0.3%) | | Thromboembolism | 6 (1.9%) | 1 (3.7%) | 7 (2.0%) | | Transient ischemic attack | 8 (2.5%) | 1 (3.7%) | 9 (2.6%) | | Syncope | 32 (10.1%) | 4 (14.8%) | 36 (10.5%) | | Due to arrhythmia | 13 (4.1%) | 3 (11.1%) | 16 (4.7%) | | Due to no arrhythmia causes | 3 (0.9%) | 1 (3.7%) | 4 (1.2%) | | Unexplained/unknown | 17 (5.4%) | 0 (0.0%) | 17 (5.0%) | | Vascular disease | 28 (8.9%) | 2 (7.4%) | 30 (8.7%) | * Categories in medical history tables may not be mutually exclusive. {28} Table 11: Cardiovascular Surgical History | Status* | Subjects with EV-ICD Implant Attempted (N = 316) | Subjects without EV-ICD Implant Attempted (N = 27) | Total Subjects with Baseline Form (N = 343) | | --- | --- | --- | --- | | None of the following | 190 (60.1%) | 14 (51.9%) | 204 (59.5%) | | Ablation (of the following) | 4 (1.3%) | 1 (3.7%) | 5 (1.5%) | | AV node | 0 (0.0%) | 1 (3.7%) | 1 (0.3%) | | HIS bundle | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | VT | 4 (1.3%) | 0 (0.0%) | 4 (1.2%) | | Coronary artery bypass graft(CABG) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | Coronary artery intervention | 110 (34.8%) | 12 (44.4%) | 122 (35.6%) | | Balloon angioplasty | 46 (14.6%) | 4 (14.8%) | 50 (14.6%) | | Stent | 102 (32.3%) | 12 (44.4%) | 114 (33.2%) | | Other | 7 (2.2%) | 1 (3.7%) | 8 (2.3%) | | Previous CIED System Implanted | 18 (5.7%) | 2 (7.4%) | 20 (5.8%) | | Pacemaker | 1 (0.3%) | 0 (0.0%) | 1 (0.3%) | | S-ICD | 9 (2.8%) | 0 (0.0%) | 9 (2.6%) | | TV ICD | 10 (3.2%) | 2 (7.4%) | 12 (3.5%) | | CRT-P | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | CRT-D | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | Days Since Most Recent Explant Procedure | | | | | Mean ± Standard Deviation | 42.22 ± 69.06 | 87.00 ± 2.83 | 46.70 ± 66.77 | | Median | 13.00 | 87.00 | 13.50 | | 25thPercentile - 75thPercentile | 7.0 - 56.0 | 85.0 - 89.0 | 7.0 - 77.5 | | Minimum - Maximum | -33.0† - 258.0 | 85.0 - 89.0 | -33.0 - 258.0 | | Number Of Subjects With Measure Available (N, %) | 18 (5.70%) | 2 (7.41%) | 20 (5.83%) | * Categories in medical history tables may not be mutually exclusive. † One subject had their previous CIED system explanted 33 days after enrollment but seven days prior to the EV-ICD implant attempt. {29} Table 12: Other Medical History | Status | Subjects with EV-ICD Implant Attempted (N = 316) | Subjects without EV-ICD Implant Attempted (N = 27) | Total Subjects with Baseline Form (N = 343) | | --- | --- | --- | --- | | None | 204 (64.6%) | 13 (48.1%) | 217 (63.3%) | | Asthma | 21 (6.6%) | 2 (7.4%) | 23 (6.7%) | | Chronic obstructive pulmonary disease | 13 (4.1%) | 3 (11.1%) | 16 (4.7%) | | Chronic bronchitis | 3 (0.9%) | 0 (0.0%) | 3 (0.9%) | | Diabetes | 66 (20.9%) | 8 (29.6%) | 74 (21.6%) | | Emphysema | 0 (0.0%) | 2 (7.4%) | 2 (0.6%) | | Pleural effusion | 13 (4.1%) | 2 (7.4%) | 15 (4.4%) | | Renal dysfunction | 30 (9.5%) | 4 (14.8%) | 34 (9.9%) | Table 13: Baseline Medications | Anatomical Group | Medication Type | Subjects with EV-ICD Implant Attempt (N=316) | Subjects without EV-ICD Implant Attempt (N=27) | Total Subjects with Baseline Form (N=343) | | --- | --- | --- | --- | --- | | Alimentary Tract And Metabolism | Antacids | 3 (3, 0.9%) | 0 (0, 0%) | 3 (3, 0.9%) | | | Antiemetics And Antinauseants | 3 (2, 0.6%) | 0 (0, 0%) | 3 (2, 0.6%) | | | Ascorbic Acid (Vitamin C), Incl. Combinations | 2 (2, 0.6%) | 0 (0, 0%) | 2 (2, 0.6%) | | | Blood Glucose Lowering Drugs, Excl. Insulins | 78 (55, 17.4%) | 8 (4, 14.8%) | 86 (59, 17.2%) | | | Calcium | 7 (7, 2.2%) | 1 (1, 3.7%) | 8 (8, 2.3%) | | | Drugs For Constipation | 6 (6, 1.9%) | 0 (0, 0%) | 6 (6, 1.7%) | | | Drugs For Functional Gastrointestinal Disorders | 0 (0, 0%) | 0 (0, 0%) | 1 (1, 0.3%) | {30} | Anatomical Group | Medication Type | Subjects with EV-ICD Implant Attempt (N=316) | Subjects without EV-ICD Implant Attempt (N=27) | Total Subjects with Baseline Form (N=343) | | --- | --- | --- | --- | --- | | Anti-infectives For Systemic Use | Drugs For Peptic Ulcer And Gastro-Oesophageal Reflux Disease (GORD) | 97 (96, 30.4%) | 4 (4, 14.8%) | 102 (101, 29.4%) | | Insulins And Analogues | 20 (16, 5.1%) | 1 (1, 3.7%) | 21 (17, 5.0%) | | Intestinal Anti-inflammatory Agents | 2 (2, 0.6%) | 0 (0, 0%) | 2 (2, 0.6%) | | Multivitamins, Combinations | 4 (4, 1.3%) | 1 (1, 3.7%) | 5 (5, 1.5%) | | Other Alimentary Tract And Metabolism Products | 1 (1, 0.3%) | 0 (0, 0%) | 1 (1, 0.3%) | | Other Drugs For Acid Related Disorders | 5 (5, 1.6%) | 0 (0, 0%) | 5 (5, 1.5%) | | Other Mineral Supplements | 7 (7, 2.2%) | 0 (0, 0%) | 7 (7, 2.0%) | | Other Plain Vitamin Preparations | 4 (4, 1.3%) | 0 (0, 0%) | 4 (4, 1.2%) | | Other Vitamin Products, Combinations | 14 (12, 3.8%) | 3 (3, 11.1%) | 17 (15, 4.4%) | | Potassium | 27 (27, 8.5%) | 1 (1, 3.7%) | 28 (28, 8.2%) | | Propulsives | 2 (2, 0.6%) | 0 (0, 0%) | 2 (2, 0.6%) | | Vitamin A And D, Incl. Combinations Of The Two | 19 (19, 6.0%) | 1 (1, 3.7%) | 20 (20, 5.8%) | | Vitamin B1, Plain And In Combination With Vitamin B6 And B12 | 4 (4, 1.3%) | 0 (0, 0%) | 4 (4, 1.2%) | | Anti-infectives For Systemic Use | Direct Acting Antivirals | 4 (4, 1.3%) | 0 (0, 0%) | 4 (4, 1.2%) | | Other Antibacterials | 2 (2, 0.6%) | 0 (0, 0%) | 2 (2, 0.6%) | | Other Beta-Lactam Antibacterials | 1 (1, 0.3%) | 0 (0, 0%) | 1 (1, 0.3%) | | Sulfonamides And Trimethoprim | 2 (2, 0.6%) | 0 (0, 0%) | 2 (2, 0.6%) | | Antineoplastic And Immunomodulating Agents | Hormone Antagonists And Related Agents | 0 (0, 0%) | 1 (1, 3.7%) | 1 (1, 0.3%) | {31} | Anatomical Group | Medication Type | Subjects with EV-ICD Implant Attempt (N=316) | Subjects without EV-ICD Implant Attempt (N=27) | Total Subjects with Baseline Form (N=343) | | --- | --- | --- | --- | --- | | Blood And Blood Forming Organs | Immunosuppressants | 13 (9, 2.8%) | 0 (0, 0%) | 13 (9, 2.6%) | | | Antithrombotic Agents | 259 (183, 57.9%) | 20 (14, 51.9%) | 280 (198, 57.7%) | | | I.V. Solution Additives | 0 (0, 0%) | 1 (1, 3.7%) | 2 (2, 0.6%) | | | Iron Preparations | 9 (9, 2.8%) | 0 (0, 0%) | 10 (10, 2.9%) | | | Vitamin B12 And Folic Acid | 12 (11, 3.5%) | 0 (0, 0%) | 12 (11, 3.2%) | | Cardiovascular System | ACE Inhibitors, Combinations | 3 (3, 0.9%) | 0 (0, 0%) | 3 (3, 0.9%) | | | ACE Inhibitors, Plain | 95 (95, 30.1%) | 7 (7, 25.9%) | 102 (102, 29.7%) | | | Angiotensin II Receptor Blockers (ARBs), Combinations | 68 (67, 21.2%) | 4 (4, 14.8%) | 73 (72, 21.0%) | | | Angiotensin II Receptor Blockers (ARBs), Plain | 37 (37, 11.7%) | 0 (0, 0%) | 37 (37, 10.8%) | | | Antiadrenergic Agents, Centrally Acting | 1 (1, 0.3%) | 0 (0, 0%) | 1 (1, 0.3%) | | | Antiadrenergic Agents, Peripherally Acting | 4 (4, 1.3%) | 0 (0, 0%) | 4 (4, 1.2%) | | | Antiarrhythmics, Class I And III | 16 (16, 5.1%) | 3 (3, 11.1%) | 19 (19, 5.5%) | | | Arteriolar Smooth Muscle, Agents Acting On | 7 (7, 2.2%) | 0 (0, 0%) | 8 (8, 2.3%) | | | Beta Blocking Agents | 239 (236, 74.7%) | 14 (14, 51.9%) | 254 (251, 73.2%) | | | Beta Blocking Agents And Thiazides | 4 (4, 1.3%) | 0 (0, 0%) | 4 (4, 1.2%) | | | Beta Blocking Agents, Other Combinations | 1 (1, 0.3%) | 0 (0, 0%) | 1 (1, 0.3%) | | | Cardiac Glycosides | 6 (6, 1.9%) | 1 (1, 3.7%) | 7 (7, 2.0%) | | | Diuretics And Potassium-Sparing Agents In Combination | 2 (2, 0.6%) | 0 (0, 0%) | 2 (2, 0.6%) | {32} | Anatomical Group | Medication Type | Subjects with EV-ICD Implant Attempt (N=316) | Subjects without EV-ICD Implant Attempt (N=27) | Total Subjects with Baseline Form (N=343) | | --- | --- | --- | --- | --- | | Dermatologicals | High-Ceiling Diuretics | 113 (110, 34.8%) | 8 (8, 29.6%) | 123 (120, 35.0%) | | | Lipid Modifying Agents, Combinations | 6 (6, 1.9%) | 2 (2, 7.4%) | 8 (8, 2.3%) | | | Lipid Modifying Agents, Plain | 182 (163, 51.6%) | 6 (6, 22.2%) | 188 (169, 49.3%) | | | Low-Ceiling Diuretics, Excl. Thiazides | 3 (3, 0.9%) | 0 (0, 0%) | 4 (4, 1.2%) | | | Low-Ceiling Diuretics, Thiazides | 3 (3, 0.9%) | 0 (0, 0%) | 3 (3, 0.9%) | | | Other Antihypertensives | 3 (3, 0.9%) | 0 (0, 0%) | 3 (3, 0.9%) | | | Other Cardiac Preparations | 18 (14, 4.4%) | 0 (0, 0%) | 18 (14, 4.1%) | | | Other Diuretics | 1 (1, 0.3%) | 0 (0, 0%) | 1 (1, 0.3%) | | | Potassium-Sparing Agents | 125 (124, 39.2%) | 3 (3, 11.1%) | 129 (128, 37.3%) | | | Selective Calcium Channel Blockers With Direct Cardiac Effects | 5 (5, 1.6%) | 0 (0, 0%) | 5 (5, 1.5%) | | | Selective Calcium Channel Blockers With Mainly Vascular Effects | 17 (16, 5.1%) | 0 (0, 0%) | 17 (16, 4.7%) | | | Vasodilators Used In Cardiac Diseases | 26 (24, 7.6%) | 2 (1, 3.7%) | 29 (26, 7.6%) | | | Anti-Acne Preparations For Topical Use | 1 (1, 0.3%) | 0 (0, 0%) | 1 (1, 0.3%) | | | Antipruritics, Incl. Antihistamines, Anesthetics, Etc. | 1 (1, 0.3%) | 0 (0, 0%) | 1 (1, 0.3%) | | | Corticosteroids, Plain | 1 (1, 0.3%) | 0 (0, 0%) | 1 (1, 0.3%) | | Other Dermatological Preparations | 2 (2, 0.6%) | 0 (0, 0%) | 2 (2, 0.6%) | | {33} | Anatomical Group | Medication Type | Subjects with EV-ICD Implant Attempt (N=316) | Subjects without EV-ICD Implant Attempt (N=27) | Total Subjects with Baseline Form (N=343) | | --- | --- | --- | --- | --- | | Genito Urinary System And Sex Hormones | Androgens | 1 (1, 0.3%) | 1 (1, 3.7%) | 2 (2, 0.6%) | | | Drugs Used In Benign Prostatic Hypertrophy | 13 (12, 3.8%) | 0 (0, 0%) | 13 (12, 3.5%) | | | Estrogens | 1 (1, 0.3%) | 0 (0, 0%) | 1 (1, 0.3%) | | | Hormonal Contraceptives For Systemic Use | 2 (2, 0.6%) | 0 (0, 0%) | 2 (2, 0.6%) | | | Progestogens And Estrogens In Combination | 1 (1, 0.3%) | 0 (0, 0%) | 1 (1, 0.3%) | | | Urologicals | 3 (3, 0.9%) | 0 (0, 0%) | 3 (3, 0.9%) | | Musculo-Skeletal System | Antigout Preparations | 26 (23, 7.3%) | 2 (1, 3.7%) | 28 (24, 7.0%) | | | Antiinflammatory And Antirheumatic Products, Non-Steroids | 7 (7, 2.2%) | 1 (1, 3.7%) | 8 (8, 2.3%) | | | Muscle Relaxants, Centrally Acting Agents | 4 (4, 1.3%) | 1 (1, 3.7%) | 7 (6, 1.7%) | | Nervous System | Anesthetics, General | 1 (1, 0.3%) | 0 (0, 0%) | 1 (1, 0.3%) | | | Anesthetics, Local | 1 (1, 0.3%) | 0 (0, 0%) | 1 (1, 0.3%) | | | Antidepressants | 30 (27, 8.5%) | 1 (1, 3.7%) | 32 (29, 8.5%) | | | Antiepileptics | 3 (2, 0.6%) | 0 (0, 0%) | 3 (2, 0.6%) | | | Antimigraine Preparations | 7 (7, 2.2%) | 0 (0, 0%) | 7 (7, 2.0%) | | | Antipsychotics | 3 (3, 0.9%) | 0 (0, 0%) | 3 (3, 0.9%) | | | Antivertigo Preparations | 1 (1, 0.3%) | 0 (0, 0%) | 1 (1, 0.3%) | | | Anxiolytics | 11 (11, 3.5%) | 1 (1, 3.7%) | 12 (12, 3.5%) | | | Drugs Used In Addictive Disorders | 4 (3, 0.9%) | 2 (2, 7.4%) | 6 (5, 1.5%) | | | Hypnotics And Sedatives | 13 (13, 4.1%) | 0 (0, 0%) | 14 (14, 4.1%) | | | Opioids | 13 (11, 3.5%) | 0 (0, 0%) | 13 (11, 3.2%) | {34} | Anatomical Group | Medication Type | Subjects with EV-ICD Implant Attempt (N=316) | Subjects without EV-ICD Implant Attempt (N=27) | Total Subjects with Baseline Form (N=343) | | --- | --- | --- | --- | --- | | Respiratory System | Other Analgesics And Antipyretics | 27 (25, 7.9%) | 0 (0, 0%) | 27 (25, 7.3%) | | | Psychostimulants, Agents Used For ADHD And Nootropics | 1 (1, 0.3%) | 0 (0, 0%) | 1 (1, 0.3%) | | | Adrenergics For Systemic Use | 2 (2, 0.6%) | 0 (0, 0%) | 2 (2, 0.6%) | | | Adrenergics, Inhalants | 22 (15, 4.7%) | 0 (0, 0%) | 24 (17, 5.0%) | | | Antihistamines For Systemic Use | 15 (13, 4.1%) | 0 (0, 0%) | 15 (13, 3.8%) | | | Cough Suppressants, Excl. Combinations With Expectorants | 1 (1, 0.3%) | 0 (0, 0%) | 1 (1, 0.3%) | | | Expectorants, Excl. Combinations With Cough Suppressants | 2 (2, 0.6%) | 0 (0, 0%) | 2 (2, 0.6%) | | | Other Drugs For Obstructive Airway Diseases, Inhalants | 9 (9, 2.8%) | 0 (0, 0%) | 9 (9, 2.6%) | | | Other Systemic Drugs For Obstructive Airway Diseases | 4 (4, 1.3%) | 0 (0, 0%) | 4 (4, 1.2%) | | | Antiglaucoma Preparations And Miotics | 2 (2, 0.6%) | 0 (0, 0%) | 2 (2, 0.6%) | | Sensory Organs | Systemic Hormonal Preparations, Excl. Sex Hormones And Insulins | 1 (1, 0.3%) | 0 (0, 0%) | 1 (1, 0.3%) | | | Anti-Parathyroid Agents | 6 (6, 1.9%) | 0 (0, 0%) | 6 (6, 1.7%) | | | Corticosteroids For Systemic Use, Plain | 16 (16, 5.1%) | 0 (0, 0%) | 16 (16, 4.7%) | | | Thyroid Preparations | 1 (1, 0.3%) | 0 (0, 0%) | 1 (1, 0.3%) | | Various | All Other Therapeutic Products | 5 (5, 1.6%) | 0 (0, 0%) | 5 (5, 1.5%) | | | Homeopathic Preparation | 1 (1, 0.3%) | 0 (0, 0%) | 1 (1, 0.3%) | | | Magnetic Resonance Imaging Contrast Media | 0 (0, 0%) | 1 (1, 3.7%) | 1 (1, 0.3%) | | | Other Nutrients | 1 (1, 0.3%) | 0 (0, 0%) | 1 (1, 0.3%) | {35} | Anatomical Group | Medication Type | Subjects with EV-ICD Implant Attempt (N=316) | Subjects without EV-ICD Implant Attempt (N=27) | Total Subjects with Baseline Form (N=343) | | --- | --- | --- | --- | --- | | | Unspecified Herbal And Traditional Medicine | 3 (2, 0.6%) | 0 (0, 0%) | 3 (2, 0.6%) | | Total | | 1860 (278, 88.0%) | 102 (17, 63.0%) | 1981 (297, 86.6%) | # E. Safety and Effectiveness Results # 1. Safety Results Of the 316 subjects that underwent an implant attempt, 23 subjects had a total of 25 major EV-ICD System and/or procedure-related complications through 182 days post-implant. The freedom from any major EV-ICD System/procedure-related complication through 182 days post implant was estimated using the Kaplan-Meier method. Table 14 shows that the Kaplan-Meier estimated major EV-ICD System/procedure-related complication free rate through 182 days post implant was $92.6\%$ , with a lower confidence bound of two-sided $95\%$ confidence interval of $89.0\%$ . This was greater than the PG of $79\%$ , hence the primary safety objective was met $(p &lt; 0.0001)$ . Table 14: Results of Primary Safety Objective | Number of subjects with an implant attempt | Number of subjects with major EV-ICD System/procedure-related complications through 182 days post implant attempt | Kaplan-Meier estimate of major EV-ICD System/procedure-related complication free rate through 182 days post implant attempt | Lower confidence bound of two-sided 95% confidence interval | p-Value | | --- | --- | --- | --- | --- | | 316 | 23 | 92.6% | 89.0% | <0.0001 | Figure 6 is the Kaplan-Meier plot for the freedom from EV-ICD System and/or procedure-related major complications through 182 days post implant. Among the 23 subjects that experienced at least one major EV-ICD System and/or procedure-related complication within 182 days post implant, 15 subjects experienced it within 30 days post implant attempt. {36}  Figure 6: Kaplan-Meier Plot of EV-ICD System/procedure-related Major Complication Free Rate Through 182 Days Post Implant Figure 7 is the Kaplan-Meier plot for the freedom from EV-ICD System and/or procedure-related major complications through 360 days post implant. The longest follow-up duration among the 299 subjects who underwent an implant attempt without having a major EV-ICD System and/or procedure-related complication was 924 days from implant attempt to the last documented contact. {37}  Figure 7: Kaplan-Meier Plot of EV-ICD System/procedure-related Major Complication Free Rate Through 360 Days Post Implant The cumulative number of subjects with major EV-ICD System and/or procedure-related complications over time are listed in Table 15. The EV-ICD System and/or procedure-related major complication free rate estimated by the Kaplan-Meier method was $98.4\%$ at the day of implant attempt, $95.2\%$ at 30 days post implant attempt, and $92.6\%$ from 180 days through 210 days post implant attempt. {38} Table 15. Major EV-ICD System/procedure-related Complications Free Rate | Days since implant attempt | Cumulative number of subjects with major EV-ICD System/procedure-related complications | Major EV-ICD System/procedure-related complication free rate | | --- | --- | --- | | 0 | 5 | 98.4% | | 30 | 15 | 95.2% | | 60 | 19 | 93.9% | | 90 | 19 | 93.9% | | 120 | 21 | 93.2% | | 150 | 22 | 92.9% | | 180 | 23 | 92.6% | | 210 | 23 | 92.6% | | 240 | 24 | 92.0% | | 270 | 24 | 92.0% | | 300 | 24 | 92.0% | | 330 | 25 | 91.4% | | 360 | 25 | 91.4% | A poolability analysis was performed to compare the results of the primary safety endpoint between different geographic regions using a log-rank test. Table 16 shows that there were no statistical differences in the major EV-ICD System and/or procedure-related complication free rate through 182 days post implant attempt among APAC, EMEA and US/Canada regions $(p = 0.3330)$ . Figure 8 is the Kaplan-Meier plot by region. {39} Table 16: Poolability Analysis of Primary Safety Endpoint on Region | Region | Number of subjects with an implant attempt | Number of subjects with major EV-ICD System/procedure-related complications through 182 days post implant attempt | Kaplan-Meier estimate of major EV-ICD System/procedure-related complication free rate through 182 days post implant attempt (95% CI) | Log-Rank Test p-Value | | --- | --- | --- | --- | --- | | APAC | 37 | 4 | 88.9% (73.1%, 95.7%) | 0.3330 | | EMEA | 159 | 9 | 94.2% (89.2%, 97.0%) | | | US/CAN | 120 | 10 | 91.5% (84.7%, 95.3%) | |  Figure 8: Kaplan-Meier Plot of EV-ICD System/procedure-related Major Complication Free Rate Through 182 Days Post Implant by Region {40} # 2. Adverse effects that occurred in the Pivotal clinical study: In the EV-ICD Pivotal study, the CEC adjudicates Adverse Event (AE) relatedness into Causal Relationship, Possible and Not Related. The CEC also classifies system- or procedure-related AEs into complication (major, minor) or observation. Seriousness of AE and whether an AE is an Unanticipated (Serious) Adverse Device Effect (U(S)ADE) are determined by Medtronic. Adverse events are coded using the MedDRA, Medical Dictionary for Regulatory Activities, which is organized with a five-level hierarchy, The highest or broadest level is System Organ Class (SOC), further divided into High-Level Group Terms (HLGT), High-Level Terms (HLT), Preferred Terms (PT), and finally into the most granular Lowest Level Terms (LLT). Preferred Terms (i.e., AE Key Terms) are used in this report. Table 18 provides a high-level summary of AE seriousness, U(S)ADE, AE relatedness, and complication/observation. All AEs in this report have been evaluated by Medtronic and fully adjudicated by the CEC. Adverse events that were adjudicated by the CEC as Causal Relationship or Possible to the EV-ICD system, to a procedure or to an accessory were regarded as system-, procedure- or accessory-related, respectively. Note that the categories of AE relatedness were not mutually exclusive as an AE could be related to more than one category (e.g., an AE could be system-, procedure- and accessory-related). There were 756 AEs from 243 enrolled subjects, including 731 AEs from 231 subjects who underwent an EV-ICD implant attempt and 25 AEs from 12 subjects who did not undergo an EV-ICD implant attempt. Among all the adverse events, 331 were serious, three were U(S)ADE, 144 were system- and/or procedure-related (90 procedure-related and 92 EV-ICD System-related), and 31 were accessory-related. Of the 144 system- and/or procedure-related AEs, 50 were complications (27 major and 23 minor complications) and 94 were observations. Table 17: Overall Summary of Adverse Events | | Number of Events (Number of Subjects, % of Subjects) | | | | --- | --- | --- | --- | | Adverse Event Classification | Subjects with EV-ICD Implant Attempt (N = 316) | Subjects without EV-ICD Implant Attempt (N = 40) | Total Subjects (N = 356) | | Serious* | | | | | Yes | 318 (164, 51.9%) | 13 (8, 20.0%) | 331 (172, 48.3%) | | No | 413 (162, 51.3%) | 12 (6, 15.0%) | 425 (168, 47.2%) | | U(S)ADE** | 3 (3, 0.9%) | 0 (0, 0.0%) | 3 (3, 0.8%) | {41} | | Number of Events (Number of Subjects, % of Subjects) | | | | --- | --- | --- | --- | | Adverse Event Classification | Subjects with EV-ICD Implant Attempt (N = 316) | Subjects without EV-ICD Implant Attempt (N = 40) | Total Subjects (N = 356) | | Complications/Observations*** | 144 (108, 34.2%) | 0 (0, 0.0%) | 144 (108, 30.3%) | | Complication | 50 (45, 14.2%) | 0 (0, 0.0%) | 50 (45, 12.6%) | | Major Complication | 27 (25, 7.9%) | 0 (0, 0.0%) | 27 (25, 7.0%) | | Minor Complication | 23 (22, 7.0%) | 0 (0, 0.0%) | 23 (22, 6.2%) | | Observation | 94 (76, 24.1%) | 0 (0, 0.0%) | 94 (76, 21.3%) | | Relatedness*** | | | | | System and/or Procedure Relatedness | | | | | Causal Relationship | 140 (106, 33.5%) | 0 (0, 0.0%) | 140 (106, 29.8%) | | Probable | 0 (0, 0.0%) | 0 (0, 0.0%) | 0 (0, 0.0%) | | Possible | 4 (4, 1.3%) | 0 (0, 0.0%) | 4 (4, 1.1%) | | Unlikely | 0 (0, 0.0%) | 0 (0, 0.0%) | 0 (0, 0.0%) | | Not Related | 587…