Antibiotic Envelope Research Articles

Do Antibiotic-Impregnated Envelopes Prevent Deep Brain Stimulation Implantable Pulse Generator Infections? A Prospective Cohort Study

Introduction: Infection after deep brain stimulation (DBS) implanted pulse generator (IPG) replacement is uncommon but when it occurs can cause significant clinical morbidity, often resulting in partial or complete DBS system removal. An antibiotic absorbable envelope developed for cardiac implantable electronic devices (IEDs), which releases minocycline and rifampicin for a minimum of 7 days, was shown in the WRAP-IT study to reduce cardiac IED infections for high-risk cardiac patients. We aimed to assess whether placing an IPG in the same antibiotic envelope at the time of IPG replacement reduced the IPG infection rate. Methods: Following institutional ethics approval (UnitingCare HREC), patients scheduled for IPG change due to impending battery depletion were prospectively randomised to receive IPG replacement with or without an antibiotic envelope. Patients with a past history of DBS system infection were excluded. Patients underwent surgery with standard aseptic neurosurgical technique [J Neurol Sci. 2017;383:135–41]. Subsequent infection requiring antibiotic therapy and/or IPG removal or revision was recorded. Results: A total of 427 consecutive patients were randomised from 2018 to 2021 and followed for a minimum of 12 months. No patients were lost to follow-up. At the time of IPG replacement, 200 patients received antibiotic envelope (54 female, 146 male, mean age 72 years), and 227 did not (43 female, 184 male, mean age 71 years). The two groups were homogenous for risk factors of infection. The IPG replacement infection rate was 2.1% (9/427). There were six infections, which required antibiotic therapy and/or IPG removal, in the antibiotic envelope group (6/200) and three in the non-envelope group (3/227) (p = 0.66). Conclusion: This prospective randomised study did not find that an antibiotic envelope reduced the IPG infection rate in our 427 patients undergoing routine DBS IPG replacement. Further research to reduce IPG revisions and infections in a cost-effective manner is required.

PO-02-059 INFLAMMATORY REACTION TO ANTIBIOTIC ELUTING POUCH MASQUERADING AS RECURRENT CARDIAC IMPLANTABLE ELECTRONIC DEVICE INFECTION

Absorbable antibacterial envelopes mitigate risk of pocket infections during repeat cardiac implantable electronic device (CIED) procedures. Despite use of antibacterial envelopes, risk of CIED infection persists. However, hallmark signs of CIED infection including incisional erythema, drainage, and wound dehiscence overlap with a less common clinical entity – allergic reaction. To present a case of recurrent CIED wound dehiscence secondary to an inflammatory response to the antibacterial envelope proven with histological evaluation. N/A A 52-year-old male with remote aortic valve replacement complicated by complete heart block and a dual chamber pacemaker (DC PPM) underwent generator change with use of a Tyrx antibacterial pouch. One week later, he developed partial wound dehiscence and cloudy incisional drainage. The patient was started on antibiotic therapy and underwent percutaneous system extraction with placement of an externalized right ventricular lead. Pocket cultures were negative. A contralateral DC PPM was inserted with a Tyrx pouch. The patient completed a course of antibiotics. Within two weeks of placement, he presented with recurrent wound dehiscence. The new device was removed with a pathologic specimen obtained from the presumably infected pocket and an externalized pacing lead was placed. Cultures were again negative. The pathologic specimen demonstrated foreign body response with lymphoplasmacytic and focal neutrophilic inflammation most consistent with allergic reaction. The patient underwent implantation of a low-lateral left-sided DC PPM distant from the prior site without the use of a Tyrx antibacterial envelope. The patient was discharged without antibiotics with no evidence of infection or inflammation at the new site over a follow up period of 6-months. Allergic reaction to Tyrx antibiotic envelope should be considered with wound dehiscence, particularly if recurrent. Tissue biopsy with foreign body response can elucidate an allergic mechanism.

PO-03-075 RISK OF CARDIOVASCULAR IMPLANTABLE ELECTRONIC DEVICE INFECTION IN PATIENTS WITH CARDIAC SARCOIDOSIS

Immunosuppression is an essential aspect of managing cardiac sarcoidosis (CS). The decision to implant a cardiovascular implantable electronic device (CIED) is often made in conjunction with starting immunosuppression. It is unclear if immunosuppression at the time of implantation increases the risk of CIED infections. Since both are potentially life-saving therapies for CS, it is vital to understand if there is a need to adjust immunosuppressive regimen before implanting CIEDs to reduce infection risk. To evaluate the rate of CIED infections in cardiac sarcoidosis patients at a tertiary hospital. We performed a retrospective analysis of patients with biopsy-proven CS and a history of a CIED implant who had received care at the Johns Hopkins Hospital. For each patient, we compiled information on the type of CIED, number of procedures and leads, presence of an antibiotic envelope, and immunosuppressive regimen at the time of each procedure. The primary outcome was a CIED pocket or bloodstream infection (BSI). Of the 175 patients included, average age was 60.1 years (SD=11.4), 111/175 (63.4%) were male, 93/175 (53.1%) were White and 72/175 (41.1%) Black. Most CIEDs were implantable cardioverter-defibrillators (ICD) (162/175, 92.5%). The average follow-up time post-CIED implant was 8.6 years. At the time of CIED implantation, 70/175 were on immunosuppression: 36 on corticosteroid monotherapy, 8 on a steroid-sparing agent alone, and 26 on a combination of both. During the study period, 12/175 patients had documented BSIs, occurring at an average of 5 years post-implant. Five of the 12 patients were on immunosuppression at time of CIED implantation. All 12 patients were treated with antibiotics and 9/12 had device extractions. There was no significant difference in CIED infection rate among those on vs off immunosuppression at the time of CIED implant (5/70 vs 7/105 p=0.90). Two patients with BSIs also had a CIED pocket infection, both occurring in the context of multiple prior CIED procedures. One patient had a dual chamber ICD for 5 years before developing an S. aureus pocket infection, 4 years after a revision performed on immunosuppression. A second patient had a single chamber ICD for 3 years before developing a P. acnes pocket infection, 4 months after a revision performed off immunosuppression. Among patients with CS undergoing a CIED implant, we found no significantly increased risk of CIED infection among patients on immunosuppression at time of implant.

An antibiotic envelope to reduce infections in deep brain stimulation surgery

The therapeutic benefits of Deep Brain Stimulation (DBS) surgery in patients with movement disorderssuch as Parkinson’s Diseaseare life-altering. Surgical site infections (SSI), however, can result in increasedhospitalisations, prolonged antibiotics and neurological sequelae. We performed aretrospective review to evaluate the effectiveness of an antibiotic envelope to reduce SSI in DBS surgeries.This study includedall DBS surgeries performed between August 2020 to May 2022 using a single-use, multifilament, antibiotic-coated mesh envelope wrapped around the DBS implantable pulse generator (IPG)(TYRX™ Absorbable Antibacterial Envelope,Medtronic Fridley, MN, USA). Standardised infection-prevention measures were applied and various patient-specific and surgery-specific factors were analysed.44 patients were analysed with 26 (59.1 %) primary implantations and 18 (40.9 %) revision surgeries.The median age was 65 years old with an average follow-up of 13.5 months (range 3–24 months). The mean Body Mass Indexwas 24.0 (range 16.7–35.6). 8 (18.2 %) patients had underlying diabetes mellitus. There were only 2 (4.5 %) SSIs reported with neither involvingthe subcutaneous IPG and antibiotic envelope. 1 superficial-incisional SSI (2.3 %) was from a prior retro-auricular abscess around a lead-wirerequiring antibiotics and subcutaneous implanttransposition. The other was a deep-incisional SSI (2.3 %) from repetitive trauma causingdelayed scalp wound dehiscence and lead-wire extrusion, requiring antibiotics and wound revision. Both subjects were discharged well with no implants removed. Theantibioticenvelope therefore appears to be a safe and well-tolerated adjunct that may reduce SSIs in DBS surgery. Further prospective work withlarger sample sizes in a multi-institution setting is required.

Risk factors of mortality after secondary procedures during the world-wide randomized antibiotic envelope infection prevention trial (WRAP-IT)

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Medtronic Background Previous analysis of WRAP-IT (World-wide Randomized Antibiotic Envelope Infection Prevention trial) data identified both patient and procedural characteristics as risk factors for cardiac implantable electronic device (CIED) infection. In the current analysis, we sought to similarly use prospectively collected WRAP-IT data to assess risk factors of all-cause mortality. Understanding if mortality risk can be modified and identifying baseline characteristics associated with high risk can help guide physician decision making. Purpose To identify modifiable and non-modifiable risk factors for 1-year all-cause mortality after a secondary (replacement, revision, or upgrade) CIED procedure. Methods This analysis included 5,461 secondary procedure patients from the WRAP-IT study. Included as candidate factors were patient and procedural characteristics. Patients with more than one year follow-up were censored at one year. A multivariate Cox Proportional Hazards model was reached by stepwise selection to minimize Akaike Information Criterion. Results The overall one-year mortality rate was 5.2% after secondary procedures. Of the 26 patient and 18 procedural characteristics analyzed, the following variables best predicted risk of a 1-year all-cause mortality: age, NYHA class, renal dysfunction, anticoagulant use, ischemic cardiomyopathy, diabetes, BMI, procedure time, myocardial infarction, valve surgery, and hypertrophic cardiomyopathy (Table). Conclusion In WRAP-IT patients undergoing secondary procedures, the only procedure characteristics that had any association with all-cause 1-year mortality risk was procedure time suggesting that most of the risk factors of mortality are non-modifiable. Baseline patient characteristics and co-morbidities were the principal risk factors of all-cause 1-year mortality. Specifically, increasing age, NYHA class, and a history of renal dysfunction were strongly associated with mortality.

Clinical performance of implantable cardioverter-defibrillator lead monitoring diagnostics.

Implantable cardioverter-defibrillator (ICD) lead monitoring diagnostic alerts facilitate the diagnosis of structural lead failure. The purpose of this study was to prospectively study the performance of Medtronic ICD lead monitoring alerts. A prespecified ancillary substudy, World-Wide Randomized Antibiotic Envelope Infection Prevention Trial, was conducted in patients with an ICD with all available alerts enabled. The investigators reported possible lead system events (LSEs), with or without an alert. An independent committee reviewed all data and classified events as lead failure, other LSE, or nonlead system events (NLEs). In 4942 patients who were followed for 19.4 ± 8.7 months, there were 124 alerts (65 LSEs, 59 NLEs) and 19 LSEs without an alert. Lead monitoring alerts had 100% sensitivity for the 48 adjudicated lead failures (95% confidence interval 92.6%-100%) and for 10 events adjudicated as either lead failure or connection issue. The positive predictive value of alerts forlead failure was 38.7% (48 of 124). For 34 pace-sense lead failures,an alert that incorporated oversensing was more sensitivethan thepacing impedance threshold alert (33 patients [97.1%] vs 9 patients[26.5%]; P < .0001). However, the sensitivity was only 13.6% for lead dislodgments or perforations. Inappropriate shocksoccurred in 2 patients with pace-sense lead failure (5.9%). No patient had unnecessary lead replacement for any of the NLEs. In this first real-world prospective study, lead monitoring alerts had 100% sensitivity for identifying lead failures. Although their positive predictive value was modest, no false-positive alerts resulted in an unnecessary lead replacement. For the diagnosis of pace-sense lead failure, an alert for oversensing was more sensitive than a pacing impedance threshold alert. ClinicalTrials.gov identifier: NCT02277990.

Cost-Effectiveness of Antibiotic-Eluting Envelope for Prevention of Cardiac Implantable Electronic Device Infections in Heart Failure.

Use of an antibiotic-eluting envelope (AEE) during cardiac implantable electronic device procedures reduces infection risk but increases procedural costs. We aim to estimate the cost-effectiveness of AEE use during cardiac implantable electronic device procedures among patients with heart failure. A state-transition cohort model of heart failure patients undergoing cardiac implantable electronic device implantation or generator replacement was developed with input parameters estimated from randomized trials, registries, surveys, and claims data. Effectiveness was estimated from the World-Wide Randomized Antibiotic Envelope Infection Prevention Trial. AEE was assumed to cost $953 per unit. The model projected mortality, quality-adjusted life-years, costs, and the incremental cost-effectiveness ratio of AEE use compared with usual care from a US healthcare sector perspective over a lifetime horizon. We assumed a cost-effectiveness threshold of $100 000 per quality-adjusted life-year gained. Compared with usual care, AEE use in initial implantations produced an incremental cost-effectiveness ratio of $112 000 per quality-adjusted life-year gained (39% probability of being cost-effective). In generator replacement procedures, AEE use produced an incremental cost-effectiveness ratio of $54 000 per quality-adjusted life-year gained (84% probability of being cost-effective). Results were sensitive to the underlying rate of infection, cost of the AEE, and durability of AEE effectiveness. Universal AEE use for cardiac implantable electronic device procedures in patients with heart failure with reduced ejection fraction is unlikely to be cost-effective, reinforcing the need for individualized risk assessment to guide uptake of the AEE in clinical practice. Selective use in patients at increased risk of infection, such as those undergoing generator replacement procedures, is more likely to meet health system value benchmarks.

Risk Factors for CIED Infection After Secondary Procedures: Insights From the WRAP-IT Trial.

This study aimed to identify risk factors for infection after secondary cardiac implantable electronic device (CIED) procedures. Risk factors for CIED infection are not well defined and techniques to minimize infection lack supportive evidence. WRAP-IT (World-wide Randomized Antibiotic Envelope Infection Prevention trial), a large study that assessed the safety and efficacy of an antibacterial envelope for CIED infection reduction, offers insight into procedural details and infection prevention strategies. This analysis included 2,803 control patients from the WRAP-IT trial who received standard preoperative antibiotics but not the envelope (44 patients with major infections through all follow-up). A multivariate least absolute shrinkage and selection operator machine learning model, controlling for patient characteristics and procedural variables, was used for risk factor selection and identification. Risk factors consistently retaining predictive value in the model (appeared >10 times) across 100 iterations of imputed data were deemed significant. Of the 81 variables screened, 17 were identified as risk factors with 6 being patient/device-related (nonmodifiable) and 11 begin procedure-related (potentially modifiable). Patient/device-related factors included higher number of previous CIED procedures, history of atrial arrhythmia, geography (outside North America and Europe), device type, and lower body mass index. Procedural factors associated with increased risk included longer procedure time, implant location (non-left pectoral subcutaneous), perioperative glycopeptide antibiotic versus nonglycopeptide, anticoagulant, and/or antiplatelet use, and capsulectomy. Factors associated with decreased risk of infection included chlorhexidine skin preparation and antibiotic pocket wash. In WRAP-IT patients, we observed that several procedural risk factors correlated with infection risk. These results can help guide infection prevention strategies to minimize infections associated with secondary CIEDprocedures.

Infectious consequences of hematoma from cardiac implantable electronic device procedures and the role of the antibiotic envelope: A WRAP-IT trial analysis

Hematoma is a complication of cardiac implantable electronic device (CIED) procedures and may lead to device infection. The TYRX antibacterial envelope reduced major CIED infection by 40% in the randomized WRAP-IT (World-wide Randomized Antibiotic Envelope Infection Prevention Trial) study, but its effectiveness in the presence of hematoma is not well understood. The purpose of this study was to evaluate the incidence and infectious consequences of hematoma and the association between envelope use, hematomas, and major CIED infection among WRAP-IT patients. All 6800 study patients were included in this analysis (control 3429; envelope 3371). Hematomas occurring within 30 days postprocedure (acute) were characterized and grouped by study treatment and evaluated for subsequent infection risk. Data were analyzed using Cox proportional hazard regression modeling. Acute hematoma incidence was 2.2% at 30 days, with no significant difference between treatment groups (envelope vs control hazard ratio [HR] 1.15; 95% confidence interval [CI] 0.84-1.58; P = .39). Through all follow-up, the risk of major infection was significantly higher among control patients with hematoma vs those without (13.1% vs 1.6%; HR 11.3; 95% CI 5.5-23.2; P <.001). The risk of major infection was significantly lower in the envelope vs control patients with hematoma (2.5% vs 13.1%; HR 0.18; 95% CI 0.04-0.85; P = .03). The risk of hematoma was 2.2% among WRAP-IT patients. Among control patients, hematoma carried a >11-fold risk of developing a major CIED infection. This risk was significantly mitigated with antibacterial envelope use, with an 82% reduction in major CIED infection among envelope patients who developed hematoma compared to control.

Antibiotic eluting envelopes: evidence, technology, and defining high-risk populations.

Cardiovascular implantable electronic devices (CIED) are effective and important components of modern cardiovascular care. Despite the dramatic improvements in the functionality and reliability of these devices, over time patients are at risk for developing several morbidities, the most feared of which are local and systemic infections. Despite significant financial investment and aggressive therapy with hospitalization, intravenous antibiotics, and transvenous lead extraction, the outcomes include a 1-year mortality rate as high as 25%. This risk of infection has increased over time, likely due to the increased complexity of the surgical interventions required to insert and replace these devices. The only way to reduce this morbidity and mortality is to prevent these infections, and other than preoperative antibiotics, there were little data supporting effective therapy until the WRAP-IT trial provided randomized data showing that pocket infections can be reduced by 60% at 12 months and major CIED infections reduced by 40% at 1 year with the use of the absorbable antibiotic eluting envelope in patient CIED procedures at high risk of infection. Not all CIED procedures are at high risk of infection and justify the use of the envelope, but cost-effectiveness data support the use of the antibiotic envelope particularly in patients with defibrillator replacements, revisions, and upgrades, such as to a resynchronization device and in patients with prior CIED infection, history of immunocompromise, two or more prior procedures, or a history of renal dysfunction.

Cost-Effectiveness Analyses of an Absorbable Antibacterial Envelope for Use in Patients at Increased Risk of Cardiac Implantable Electronic Device Infection in Germany, Italy, and England

ObjectivesTo model the cost-effectiveness of the TYRX Absorbable Antibacterial Envelope when used in patients at increased risk of cardiac implantable electronic device (CIED) infection in the context of 3 European healthcare systems: Germany, Italy, and England. MethodsA decision tree model with a lifetime horizon was populated using data from the Worldwide Randomized Antibiotic Envelope Infection Prevention Trial, a large multicenter randomized controlled trial. Use of the antibacterial envelope adjunctive to standard of care was compared to standard of care infection prevention alone. Patients in the model were divided into subgroups based on presence of factors known to increase infection risk. ResultsThe antibacterial envelope had the most favorable cost-effectiveness profile when patients had previously experienced CIED infection, had a history of immunosuppressive therapy, or had a Prevention of Arrhythmia Device Infection Trial (PADIT) score indicating high risk of infection (scores ≥6) at cost-effectiveness thresholds of €50 000 in Germany (assumed in the absence of an official threshold), €40 000 in Italy, and £30 000 in England. Probabilistic sensitivity analysis indicated that the antibacterial envelope was likely to be cost-effective in patients with other risk factors (including replacement of high power CIEDs, generator replacement with lead modification, and PADIT scores indicating intermediate risk of infection) when used with some device types and in some countries. ConclusionsThe absorbable antibacterial envelope was associated with cost-effectiveness ratios below European benchmarks in selected patients at increased risk of infection, suggesting the envelope provides value for European healthcare systems by reducing CIED infections.

Low-temperature electrocautery reduces adverse effects from secondary cardiac implantable electronic device procedures: Insights from the WRAP-IT trial

Cardiac device procedures require tissue dissection to free existing device lead(s). Common techniques include blunt dissection, standard electrocautery, and low-temperature electrocautery (PlasmaBlade, Medtronic); however, data on the type of electrosurgical tool used and the development of procedure- or lead-related adverse events are limited. The purpose of this study was to determine whether standard or low-temperature electrocautery impacts the development of an adverse event. We evaluated patients enrolled in WRAP-IT (Worldwide Randomized Antibiotic EnveloPe Infection PrevenTion Trial) undergoing cardiac implantable electronic device (CIED) revision, upgrade, or replacement. All adverse events were adjudicated by an independent physician committee. Data were analyzed using Cox proportional hazard regression modeling. In total, 5641 patients underwent device revision/upgrade/replacement. Electrocautery was used in 5205 patients (92.3%) (mean age 70.6 ± 12.7 years; 28.8% female), and low-temperature electrocautery was used in 1866 patients (35.9%). Compared to standard electrocautery, low-temperature electrocautery was associated with a 23% reduction in the incidence of a procedure- or lead-related adverse event through 3 years of follow up (hazard ratio [HR] 0.77; 95% confidence interval [CI] 0.65-0.91; P = .002). After controlling for the number of active leads, degree of capsulectomy, degree of lead dissection, and renal dysfunction, low-temperature electrocautery was associated with a 32% lower risk of lead-related adverse events (HR 0.68; 95% CI 0.52-0.89; P= .004). These effects were consistent across a spectrum of lead-related adverse event types. This study represents one of the largest assessments of electrocautery use in patients undergoing CIED revision, upgrade, or replacement procedures. Compared to standard electrocautery, low-temperature electrocautery significantly reduces adverse effects from these procedures.

Clinical Presentation, Timing, and Microbiology of CIED Infections: An Analysis of the WRAP-IT Trial.

This study characterized the microbiology of major cardiac implantable electronic device (CIED) infections that occurred during the WRAP-IT (Worldwide Randomized Antibiotic Envelope Infection Prevention Trial) study. The WRAP-IT study offers a unique opportunity for further understanding of the pathogens involved in major CIED infections in a prospective dataset, with implications for clinical practice and infection management. A total of 6,800 patients randomized 1:1 to receive an antibacterial envelope or not (control subjects) were included in this analysis. Patient characteristics, infection manifestation (pocket vs. systemic), and infection microbiology were evaluated through all follow-up (36months). Data were analyzed using Cox proportional hazards regression. A total of 3,371 patients received an envelope, and 3,429 patients were control subjects. Major CIED infection occurred in 32 patients who received an envelope and 51 control subjects (36-month Kaplan-Meier estimated event rate, 1.3% and 1.9%, respectively; p=0.046). A 61% reduction in major pocket infection was observed within 12months of the procedure in the envelope group (hazard ratio: 0.39, 95% confidence interval: 0.21 to 0.73; p=0.003). Among 76 patients with major infections who had a sample taken, causative pathogens were identified in 47 patients. Staphylococcus species were the predominate pathogen (n=31) and envelope use resulted in a 76% reduction in Staphylococcus-related pocket infections (n=4 vs. 17; p=0.010). Envelope use was not associated with delayed onset of pocket infections and did not affect the presentation of infections. Antibacterial envelope use resulted in a significant reduction of major CIED pocket infections and was particularly effective against Staphylococcus species, the predominant cause of pocket infections. (Worldwide Randomized Antibiotic Envelope Infection Prevention Trial [WRAP-IT]; NCT02277990).

Economic evaluation of an absorbable antibiotic envelope for prevention of cardiac implantable electronic device infection

Recent evidence suggests that an antibiotic impregnated envelope inserted at time of cardiac implantable electronic device (CIED) implantation may reduce risk of subsequent CIED infection compared with standard of care (SoC). The objective of the current work was to perform a cost-effectiveness analysis comparing an antibiotic impregnated envelope with SoC at time of CIED insertion. Decision analytic models were used to project healthcare costs and benefits of two strategies, an antibiotic impregnated envelope plus SoC (Env+SoC) vs. SoC alone, in a cohort of patients undergoing CIED implantation over a 1-year time horizon. Evidence from published literature informed the model inputs. Probabilistic and deterministic sensitivity analyses were performed. The primary outcome was the incremental cost per infection prevented, assessed from the Canadian healthcare system perspective. Envelope plus SoC was associated with fewer CIED infection (7 CIED infections/1000 patients) at higher total costs ($29 033 000/1000 patients) compared with SoC (11 CIED infections and $27 926 000/1000 patients). The incremental cost per infection prevented over 1 year was $274 416. Use of Env+SoC was cost saving only when baseline CIED infection risk was increased to 6% (vs. base case of 1.2%). A strategy of Env+SoC was not economically favourable compared with SoC alone, and the opportunity cost of widescale implementation should be considered. Future work is required to develop validated risk stratification tools to identify patients at greatest risk of CIED infection. The value proposition of Env+SoC improves when applying this intervention to patients at greatest infection risk.

Abstract 16842: Cost-Effectiveness of Antibiotic-Eluting Envelopes for Prevention of Infections Associated With Cardiac Implantable Electronic Devices

Introduction: Infections of cardiac implantable electronic devices result in substantial morbidity and healthcare costs. Using an antibiotic-eluting envelope (AEE) during implantation may reduce the incidence of device-related infection. We examined the cost-effectiveness of an AEE in patients receiving CRT-D devices. Methods: This analysis was conducted independent of the trial sponsor. We developed a state-transition Markov model to compare the use of an AEE with usual care during CRT-D initial implantation or reimplantation. Effectiveness of the AEE (unit cost $1000) was estimated from the Worldwide Randomized Antibiotic Envelope Infection Prevention Trial. Other inputs were derived from prior trials, registries, vital statistics, and nationally representative datasets. Long-term survival was projected using a non-parametric approach. The model reported incidence of infections, mortality, quality-adjusted life years (QALYs), and direct healthcare costs. Future costs and QALYs were discounted by 3% annually. The primary outcome was the incremental cost-effectiveness ratio (ICER) of AEE use from the US healthcare sector perspective over a lifetime analytic horizon. We assumed a cost-effectiveness threshold of $100,000 per QALY gained. Results: Use of an AEE at initial CRT-D implantation added 0.008 QALYs per patient at an incremental cost of $918 (ICER $118,000/QALY). Due to higher infection rates, the use of AEE in reimplantation procedures was more economically attractive (ICER $55,900/QALY). One-way sensitivity analyses showed an inverse relationship between ICER and rate of infection. The ICER was less than $100,000/QALY with infection rate greater than 2.42% in the first year after new CRT-D (Figure 1). Conclusions: At current prices, use of AEE is cost-effective for CRT-D reimplantation procedures but not for initial CRT-D implants. Cost-effectiveness of AEEs may be improved by restricting use to patients at increased risk of infection.

New frontiers in cardiac devices.

This article provides an overview of current cardiac device management, complications, and future areas for development. The last 70 years have seen huge advances in the field of implantable cardiac devices, from diagnostic tools to electrical therapies for bradycardia, ventricular arrhythmia and cardiac resynchronisation. While out-of-hours specialist cardiology cover and regional arrhythmia pathways are increasingly established, they are not universal, and the management of arrhythmia remains an important facet of clinical medicine for the general physician. This article discusses core recommendations from international guidelines with respect to heart rhythm diagnostics, pacing for bradycardia, cardiac resynchronisation and implantable cardioverter defibrillators, along with common complications. Finally, future innovations such as the diagnostic potential of portable technologies, antibiotic envelopes for cardiac devices and the increasing use of leadless pacemakers are described.

The role of an antibiotic envelope in the prevention of major cardiac implantable electronic device infections: A systematic review and meta-analysis.

Background:Over the past decade, rates of cardiac implantable electronic device (CIED) related infections have increased and been associated with increased morbidity, mortality and financial burden on healthcare systems.Methods:To examine the effect of an antibacterial envelope in reducing major CIED related infections, we performed a systematic review and meta-analysis by searching PubMed/MEDLINE, CENTRAL, Google scholar and Clinicaltrials.gov for studies that examined the effect of an antibiotic envelope in reducing major related CIED infections, comprising of device-related endocarditis, systemic infection requiring systemic antibiotics and or device extraction, compared to control up till February 15th, 2020. A random-effects meta-analysis was conducted by calculating risk ratios (RR) and respective 95% confidence intervals (CI).Results:We include 6 studies that comprise of 11,897 patients, of which 5844 received an antibiotic envelope and 6053 did not. Compared with control, utilization of an antibiotic envelope at the time of procedure was associated with a significant 74% relative risk reduction in major CIED related infections among patients at high risk for infection (RR: 0.26 [95% CI, 0.08–0.85]; P = .03), while no significant reduction was observed among patients enrolled from studies with any risk for infection (RR: 0.53 [95% CI, 0.06–4.52]; P = .56). Additionally, no reduction in mortality among patients that received an envelope compared to control was observed (RR: 1.15 [95% CI, 0.53–2.50]; P = .72).Conclusion:The utilization of an antibiotic envelope at the time of device implantation or upgrade reduces major CIED infections, especially if used in patients perceived to be at higher risk for infection.

1261Geographical variations in the incidence of CIED infection and infection prevention strategies: Update from the global WRAP-IT study

Abstract Funding Acknowledgements Medtronic, Inc. Introduction Cardiac Implantable Electronic Device (CIED) infections lead to significant morbidity, mortality, and use of health care resources. There is variation in infection prevention strategies among centers, and it is not clear whether there is also variation in infection rates across different geographies. Recently, WRAP-IT, the largest global randomized trial to evaluate an infection reduction strategy, randomized 6,983 patients to receive an antibacterial envelope (treatment) vs. no envelope (control). The results demonstrated a significant reduction in major CIED infection with the TYRX antibiotic envelope (12-mo infection rate for envelope vs. control 0.7% and 1.2%, respectively; HR, 0.60; 95% [CI], 0.36 to 0.98; P = 0.04). The purpose of this analysis is to assess geographical variations in patient characteristics, procedural routines, and infection rates. Methods The WRAP-IT study enrolled patients undergoing a CIED pocket revision, generator replacement, or system upgrade or an initial implantation of a cardiac resynchronization therapy defibrillator and randomized them to receive the envelope or not, in addition to mandated pre-procedure intravenous antibiotic prophylaxis. To assess geographical variations in infection rates, the control group (per protocol) baseline demographics and procedural characteristics were identified. Major infection was defined as CIED infections resulting in system extraction or revision, long-term antibiotic therapy with infection recurrence, or death. Results A total of 3429 control patients were evaluated and followed for a mean of 20.9 ± 8.3 months; 2530 patients from 123 centers in North America, 777 patients from 46 centers in Europe, and 122 patients from 11 centers in Asia/South America. The 24-month Kaplan-Meier major infection rates were 1.2% in North America (30 pts), 2.5% in Europe (16 pts), and 4.3% Asia/South America (5 pts) (see Figure). These geographical variations in the incidence of major CIED infections were significant (overall P = 0.008, univariate). There were differences in baseline patient characteristics, including age, sex, medication use, NYHA Class, and number of previous devices across geographies. Differences also included procedural characteristics, such as device type, use of pocket wash, skin preparation, pre-operative antibiotic drug use, and procedure time. Conclusion Major CIED infection rates vary significantly across geographies. The effect of patient demographics and procedural characteristics on these findings will be assessed and presented at EHRA. Insights into geographical variability of CIED infections is important to mitigate infection risk, reduce morbidity and cost. Abstract Figure. Major CIED Infection Rate by Geography

Abstract 103: A Meta Analysis of Antibiotic Envelope Use to Prevent Cardiac Implantable Electronic Device Infections

Introduction: Cardiac Implantable Electronic Device (CIED) infections are a major source of morbidity, mortality and increased healthcare cost. There are several well established risk factors associated with increased infection. An antibiotic coated envelope has been developed as an infection prevention intervention. Hypothesis: Whether antibiotic coated envelope is an effective preventive strategy against Cardiac Implantable Electronic Device Infections. Methods: 6 trials comparing use of antibiotic envelope to control, including 1 randomized trial and 5 cohort studies were selected using PubMed and Embase data bases through May 2019. The efficacy end point was prevention of CIED Infection. Outcomes were combined using random effects model and estimated by odds ratio with 95% confidence intervals (CI). Results: In our analysis of total 12,024 patients undergoing CIED implantation, 5,844 patients received antibiotic envelope while 6,180 patients were included in the control group. Antibiotic envelope was superior to control in reducing the risk of device infection (OR 0.40 CI [0.17-0.95], p=0.04). Conclusions: The use of antibiotic envelope in Cardiac Implantable Electronic Devices (CIED) is associated with reduced incidence of CIED infection.

Impact of Cardiac Implantable Electronic Device Infection: A Clinical and Economic Analysis of the WRAP-IT Trial.

Current understanding of the impact of cardiac implantable electronic device (CIED) infection is based on retrospective analyses from medical records or administrative claims data. The WRAP-IT (Worldwide Randomized Antibiotic Envelope Infection Prevention Trial) offers an opportunity to evaluate the clinical and economic impacts of CIED infection from the hospital, payer, and patient perspectives in the US healthcare system. This was a prespecified, as-treated analysis evaluating outcomes related to major CIED infections: mortality, quality of life, disruption of CIED therapy, healthcare utilization, and costs. Payer costs were assigned using medicare fee for service national payments, while medicare advantage, hospital, and patient costs were derived from similar hospital admissions in administrative datasets. Major CIED infection was associated with increased all-cause mortality (12-month risk-adjusted hazard ratio, 3.41 [95% CI, 1.81-6.41]; P<0.001), an effect that sustained beyond 12 months (hazard ratio through all follow-up, 2.30 [95% CI, 1.29-4.07]; P=0.004). Quality of life was reduced (P=0.004) and did not normalize for 6 months. Disruptions in CIED therapy were experienced in 36% of infections for a median duration of 184 days. Mean costs were $55 547±$45 802 for the hospital, $26 867±$14 893, for medicare fee for service and $57 978±$29 431 for Medicare Advantage (mean hospital margin of -$30 828±$39 757 for medicare fee for service and -$6055±$45 033 for medicare advantage). Mean out-of-pocket costs for patients were $2156±$1999 for medicare fee for service, and $1658±$1250 for medicare advantage. This large, prospective analysis corroborates and extends understanding of the impact of CIED infections as seen in real-world datasets. CIED infections severely impact mortality, quality of life, healthcare utilization, and cost in the US healthcare system. Registration: URL: https://www.clinicaltrials.gov Unique Identifier: NCT02277990.