Biffi, Mauro

BACKGROUND: Substernal lead placement of the extravascular implantable cardioverter defibrillator (EV ICD) permits both defibrillation at thresholds similar to those seen with transvenous implantable cardioverter defibrillators and effective anti-tachycardia pacing (ATP) while avoiding the vasculature and associated complications. The global Pivotal study has shown the EV ICD system to be safe and effective through 6 months, but long-term experience has yet to be published. Our aim was to report the performance and safety of the EV ICD system throughout the study. METHODS: The EV ICD Pivotal study was a prospective, global, single-arm, premarket clinical study. Individuals with a Class I or IIa indication for a single-chamber implantable cardioverter defibrillator per guidelines were enrolled. Freedom from major system- or procedure-related complications and appropriate and inappropriate therapy rates were assessed through 3 years with the Kaplan-Meier method. ATP success was calculated from simple proportions. RESULTS: An implantation was attempted in 316 patients (25.3% female; 53.8±13.1 years of age; 81.6% primary prevention; left ventricular ejection fraction, 38.9±15.4%). Of 299 patients with a successful implantation, 24 experienced 82 spontaneous arrhythmic episodes that were appropriately treated with ATP only (38, 46.3%), shock only (34, 41.5%), or both (10, 12.2%) for a Kaplan-Meier–estimated rate of first any appropriate therapy of 9.2% at 3 years. ATP was successful in 77.1% (37/48) of episodes, and ATP use significantly increased from discharge to last follow-up visit ( P <0.0001). Shock therapy was successful in 100% (27/27) of discrete, spontaneous ventricular arrhythmias. The inappropriate shock rates at 1 and 3 years were 9.8% and 17.5%, respectively, with P-wave oversensing the predominant cause. No major intraprocedural complications were reported, and the estimated freedom from system- or procedure-related major complications was 91.9% at 1 year and 89.0% at 3 years. The most common major complications were lead dislodgement (10 events; n=9 patients, 2.8%), postoperative wound or device pocket infection (n=8, 2.5%), and device inappropriate shock delivery (n=4, 1.3%). Twenty-four system revisions were performed as a result of major complications related to the EV ICD system or procedure. CONCLUSIONS: From implantation to study completion, the EV ICD Pivotal study demonstrated that a single integrated system with an extravascular lead placed in the substernal space maintains high ATP success, effective defibrillation, and a consistent safety profile. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04060680.

Abstract Aims The extravascular implantable cardioverter-defibrillator (EV ICD) has been shown to be safe and effective for patients at risk of sudden cardiac death, but little is known about EV ICD lead removal in humans. This analysis aimed to characterize the EV ICD lead removal experience thus far. Methods and results This was a retrospective analysis of lead removals from the EV ICD Pilot, Pivotal, and Continued Access Studies. Patients with a successful EV ICD implant who underwent lead removal were included. The main objective was lead removal success. Ancillary objectives included characterizing technique used, procedure complications, and reimplantation status. An EV ICD system was successfully implanted in 347 patients across the 3 studies (25.9% female; 53.4 ± 13.3 years; left ventricular ejection fraction: 39.7 ± 15.9). Of these patients, 29 (8.4%) underwent lead removal with a mean lead dwell time of 12.6 ± 14.3 months (0.2–58.4). The main reason for lead removal was lead dislodgement (n = 9, 31.0%). Lead removal was successful in 27/29 (93.1%) cases [100% (19/19) success rate &lt;1 year and 80% (8/10) success rate &gt;1 year post-implant]. Simple traction was used in 22/26 (84.6%) and extraction tools in 4/26 (15.4%) successful cases where technique was known. No complications were reported for any of the removal procedures. All 11 EV ICD reimplant attempts were successful. Conclusion Complete removal of the EV ICD lead was successful in 93.1% of cases, and simple traction was sufficient in most instances. Based on these results, lead removal from the substernal space was safe and achievable up to 3 years post-implant.

Abstract Background Implantable cardioverter defibrillators (ICDs) prevent sudden cardiac death in patients at high risk for ventricular arrhythmias, but conventional systems carry a risk of transvenous (TV) lead-related complications. The novel extravascular ICD (EV ICD) may reduce some of these complications, while offering anti-tachycardia pacing (ATP), pause prevention pacing, and a device of similar size and projected battery longevity as a TV ICD, by placing a lead substernally. The EV ICD Pivotal study demonstrated EV ICD safety and performance for termination of ventricular arrythmias at 6 months. Longer-term performance is unknown. Purpose To report the chronic safety and performance of the EV ICD system. Methods The extravascular implantable cardioverter defibrillator (EV ICD) Pivotal study was a prospective, international, single-arm, premarket clinical study. Patients with a class I or IIa indication for a single-chamber ICD per ESC or ACC/AHA/HRS guidelines were enrolled. Freedom from major system- and/or procedure-related complications at 18 mo was evaluated, as well as conversion of arrhythmias by anti-tachycardia pacing (ATP) or shock through all available follow up. Rates of ATP success were evaluated using the generalized estimating equation (GEE) and simple proportions. Results Implantation was attempted in 316 patients: 74.7% male, age 53.8±13.1 years, 82% primary prevention, left ventricular ejection fraction of 38.9%±15.4%, and New York Heart Association Class I (23.4%) or II/III (65.5%). Of 299 implanted patients (average follow up 16.2±7.2 mo), 19 experienced 80 spontaneous, appropriately treated arrhythmic episodes: 37 treated by ATP, 15 by ATP and shock, and 28 by shock alone with a Kaplan-Meier (KM) estimated 6.8% of patients experiencing appropriate therapy by 18 mo (Figure). Of discrete episodes treated with shock, 21/21 (100%) were successfully terminated. ATP was delivered in 12 patients, successfully treating 35/52 episodes (67.3%; GEE adjusted 59.0%). Inappropriate shocks occurred in 35 patients through all follow up, with a rate of 10.2% at 1 year. The KM estimate of freedom from major EV ICD system-or procedure-related complications rate through 18 mo was 91.9% (95% CI: 88.2% to 94.4%). The most common event was lead dislodgment (10 events in 9 patients) identified 0 to 120 days post-implant, predominantly due to anchoring technique. Conclusion The safety and effectiveness of a novel EV ICD system with a substernal lead extends through chronic follow up. Shocks were avoided in nearly half of all spontaneous episodes because of the availability of ATP.Figure

AbstractAimsIntraoperative defibrillation testing (DT) during implant or replacement of implantable cardioverter-defibrillators (ICDs) has been a matter of debate for many years. This debate was put to rest by the Simple and Nordic ICD trials, and the practice of testing during new implantations has essentially been almost abandoned. Old registries demonstrated an increased incidence of significant findings in DT during replacements. The aim of the present study was to evaluate frequency of significant findings and safety of DT in subjects undergoing device replacement.Methods and resultsA prospective observational multi-centre study included consecutive patients undergoing ICD generator replacement. The primary outcome was a failure to terminate induced ventricular fibrillation (VF) with a single shock 10 J below the maximal capacity of the device. Secondary outcomes included complications of DT. Patients were followed-up at 1- and 6-months post-procedure. A total of 92 patients were eligible, and consented to the study, of which 84 underwent DT during battery replacement. The median age was 68 years and 79.8% were males. Induction of VF was successful in 84 patients as was a successful conversion on the first attempt in all. There were no procedure-related complications. During follow up one patient had two appropriate ICD shock events. In four patients, ICD programming was changed. None suffered inappropriate shock. There was no evidence of lead malfunction. Two deaths occurred, none of which was related to arrhythmia.ConclusionThe present study found DT was not associated with complications in patients undergoing ICD generator replacement but produced no clinically important information.

AbstractBackgroundInfection remains a major complication of cardiac implantable electronic devices and can lead to significant morbidity and mortality. Implantable devices that avoid transvenous leads, such as the subcutaneous implantable cardioverter‐defibrillator (S‐ICD), can reduce the risk of serious infection‐related complications, such as bloodstream infection and infective endocarditis. While the 2017 AHA/ACC/HRS guidelines include recommendations for S‐ICD use for patients at high risk of infection, currently, there are no clinical trial data that address best practices for the prevention of S‐ICD infections. Therefore, an expert panel was convened to develop a consensus on these topics.MethodsAn expert process mapping methodology was used to achieve consensus on the appropriate steps to minimize or prevent S‐ICD infections. Two face‐to‐face meetings of high‐volume S‐ICD implanters and an infectious diseases specialist, with expertise in cardiovascular implantable electronic device infections, were conducted to develop consensus on useful strategies pre‐, peri‐, and postimplant to reduce S‐ICD infection risk.ResultsExpert panel consensus on recommended steps for patient preparation, S‐ICD implantation, and postoperative management was developed to provide guidance in individual patient management.ConclusionAchieving expert panel consensus by process mapping methodology for S‐ICD infection prevention was attainable, and the results should be helpful to clinicians in adopting interventions to minimize risks of S‐ICD infection.

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Maurice Kahn Foundation via the Mayo- Sheba Collaboration Fund. Background The need for intraoperative defibrillation testing (DFT) during implant and/or replacement of implantable cardioverter-defibrillators (ICDs) has been a matter of debate for many years. This debate was put to rest by the Simple and the Nordic ICD trials, and the practice of testing during new implantations has practically been nearly abandoned. Nevertheless, induction of VF for testing purposes (VFT) may still have an important role in selective populations at risk for defibrillation failure, who were not included in the SIMPLE and Nordic trials. One such population includes those who undergo device replacements. Old registries demonstrated an increased incidence of significant findings in VFT during replacements. In the present study, we sought to test this observation. Objectives Evaluate frequency of significant findings and the safety of VFT in subjects undergoing device replacement. Methods A prospective observational multi-center study of VFT included consecutive patients undergoing ICD generator replacement in 5 centers in Israel, Europe, and the US. All centers followed the same VFT protocol. The primary outcome was defined as failure to terminate induced VF with a single shock at 10 Joules below the maximal capacity of the device. Secondary outcomes included complications of VFT. Patients were followed-up at 1 month and 6 months post-procedure. Data collection included documentation of any peri-operative complications and clinical endpoints (occurrence of appropriate shock, inappropriate shocks, lead failure, need for re-intervention, and infection). Results A total of 92 patients were eligible, and consented for the study, of which 84 underwent DFT during battery replacement. The median age was 68 years and 79.8% were male subjects. Induction of VF was successful in all 84 patients as well as VFT with a successful conversion on first attempt. During follow up one patient had two appropriate ICD shock events. In four patients, the ICD programming was changed. None suffered an inappropriate shock. There was no evidence of lead malfunction. A total of two deaths occurred, none of which were related to the device. Conclusion The present study found VFT was not associated with complications in patients undergoing ICD/CRTD generator replacement but produced no clinically important information.

Introduction: Device-related infection is estimated to occur in 1.9% of the Medicare patients with de novo transvenous (TV) implantable cardioverter-defibrillators (ICD) within 2 years post-implant. TV-ICD infection is a serious complication that frequently requires complete device removal for attempted cure, which can be associated with patient morbidity and mortality. The objective of this study is to expand on limited published data and assess mortality risk associated with TV-ICD infection in a large Medicare population with de novo TV-ICD implants. Methods: A survival analysis was conducted using 100% fee-for-service Medicare facility-level claims data to identify patients who underwent de novo TV-ICD implantation between 7/2016 and 1/2018. TV-ICD infection within 2 years of implantation was identified using ICD-10 and CPT codes. Baseline patient risk factors associated with mortality were identified using the Charlson Comorbidity Index categories. Infection was treated as a time-dependent variable in a multivariate Cox proportional hazards model to account for immortal time bias. Results: Among 26,742 Medicare patients with de novo TV-ICD, 518 (1.9%) had a device-related infection. The overall number of decedents was 4,721 (17.7%) over 2 years, with 4,555 (17%) in the non-infection group and 166 (32%) in the infection group. After adjusting for baseline patient demographic characteristics and various comorbidities, the presence of TV-ICD infection was associated with an increase of 2.4 [95% CI: 2.08-2.85] times in the mortality hazard ratio (see attached Figure). Most of the baseline patient risk factors were also associated with higher risk of mortality in the Cox model. Conclusion: The rate of de novo TV-ICD infection and associated mortality in a large, real-world Medicare population is noteworthy. The positive association between device-related infection and risk of mortality further highlights the need to reduce infections.

AbstractIntroductionTransvenous implantable cardioverter‐defibrillators (TV‐ICD) infection is a serious complication that frequently requires complete device removal for attempted cure, which can be associated with patient morbidity and mortality. The objective of this study is to assess mortality risk associated with TV‐ICD infection in a large Medicare population with de novo TV‐ICD implants.MethodsA survival analysis was conducted using 100% fee‐for‐service Medicare facility‐level claims data to identify patients who underwent de novo TV‐ICD implantation between 7/2016 and 1/2018. TV‐ICD infection within 2 years of implantation was identified using International Classification of Disease, 10th Edition and current procedural terminology codes. Baseline patient risk factors associated with mortality were identified using the Charlson Comorbidity Index categories. Infection was treated as a time‐dependent variable in a multivariate Cox proportional hazards model to account for immortal time bias.ResultsAmong 26,742 Medicare patients with de novo TV‐ICD, 518 (1.9%) had a device‐related infection. The overall number of decedents was 4721 (17.7%) over 2 years, with 4555 (17%) in the noninfection group and 166 (32%) in the infection group. After adjusting for baseline patient demographic characteristics and various comorbidities, the presence of TV‐ICD infection was associated with an increase of 2.4 (95% CI: 2.08–2.85) times in the mortality hazard ratio.ConclusionThe rate of TV‐ICD infection and associated mortality in a large, real‐world Medicare population is noteworthy. The positive association between device‐related infection and risk of mortality further highlights the need to reduce infections

Background: Infection remains a major complication of cardiac implantable electronic devices (CIEDs) and can lead to significant morbidity and mortality. Extrathoracic devices that avoid epicardial or transvenous leads, such as the subcutaneous implantable cardioverter-defibrillator (S-ICD), can reduce the risk of serious infection-related complications, such as bloodstream infection and infective endocarditis. While the 2017 AHA/ACC/HRS guidelines include recommendations for S-ICD use for patients at high risk of infection, currently, there are no clinical trial data that address best practices for the prevention of S-ICD infections. Therefore, an expert panel was convened to develop consensus on these topics. Methods: An expert process mapping methodology was used to achieve consensus on the appropriate steps to minimize or prevent S-ICD infections. Two face-to-face meetings of high-volume S-ICD implanters and an infectious diseases specialist, with expertise on cardiovascular implantable electronic device infections, were conducted to develop consensus on useful strategies pre-, peri-, and post-implant to reduce S-ICD infection risk. Results: Expert panel consensus of recommended steps for patient preparation, S-ICD implantation, and post-operative management were developed to provide guidance in individual patient management. Conclusion: Achieving expert panel consensus by process mapping methodology for S-ICD infection prevention was attainable, and the results should be helpful to clinicians in adopting interventions to minimize risks of S-ICD infection.