Risk factors for hematoma in patients undergoing cardiac device procedures: A WRAP-IT trial analysis.

Background: Implant site hematoma is a known complication of cardiac device procedures and can lead to major consequences. Objectives: To evaluate risk factors for hematoma and further understand the relationship between anticoagulant (AC), antiplatelet (AP) use, and hematoma development. Methods: We included 6800 patients from the WRAP-IT trial. To assess baseline and procedural characteristics associated with hematoma within the first 30 days postprocedure, a stepwise Cox regression model was implemented with minimal Akaike information criterion. Cox regressions were also used to evaluate AC/AP use and hematoma risk. Results: The overall rate of hematoma was 2.2%. The model identified 11 baseline and procedural characteristics associated with hematoma risk. AC use (hazard ratio [HR]: 2.44, P < .001), lower body mass index (HR: 1.06, P < .001), and history of valve surgery (HR: 2.11, P < .001) were associated with the highest risk. AP use, male sex, history of coronary artery disease, existing pocket, history of nonischemic cardiomyopathy, number of previous cardiac implantable electronic device (CIED) procedures, procedure time, and lead revision were associated with moderate risk. Antithrombotic use was high overall (86%) and AC+AP use was highly predictive of hematoma risk. Regardless of AC status, AP use was associated with an almost doubling of risk vs no AP (HR = 1.85, P = .0006) in the general cohort. Interruption of AC was associated with the lowest hematoma risk (HR = 2.35) while heparin bridging (HR = 4.98) and AP use vs no AP use (HR = 1.85) was associated with the highest hematoma risk. Conclusion: The results of this analysis highlight risk factors associated with the development of hematoma in patients undergoing CIED procedures and can inform antithrombotic management.

Machine learning-derived major adverse event prediction of patients undergoing transvenous lead extraction: Using the ESC EHRA EORP European lead extraction ConTRolled ELECTRa registry.

BACKGROUND: Transvenous lead extraction (TLE) remains a high-risk procedure. OBJECTIVE: The purpose of this study was to develop a machine learning (ML)-based risk stratification system to predict the risk of major adverse events (MAEs) after TLE. A MAE was defined as procedure-related major complication and procedure-related death. METHODS: We designed and evaluated an ML-based risk stratification system trained using the European Lead Extraction ConTRolled (ELECTRa) registry to predict the risk of MAEs in 3555 patients undergoing TLE and tested this on an independent registry of 1171 patients. ML models were developed, including a self-normalizing neural network (SNN), stepwise logistic regression model ("stepwise model"), support vector machines, and random forest model. These were compared with the ELECTRa Registry Outcome Score (EROS) for MAEs. RESULTS: There were 53 MAEs (1.7%) in the training cohort and 24 (2.4%) in the test cohort. Thirty-two clinically important features were used to train the models. ML techniques were similar to EROS by balanced accuracy (stepwise model: 0.74 vs EROS: 0.70) and superior by area under the curve (support vector machines: 0.764 vs EROS: 0.677). The SNN provided a finite risk for MAE and accurately identified MAE in 14 of 169 "high (>80%) risk" patients (8.3%) and no MAEs in all 198 "low (<20%) risk" patients (100%). CONCLUSION: ML models incrementally improved risk prediction for identifying those at risk of MAEs. The SNN has the additional advantage of providing a personalized finite risk assessment for patients. This may aid patient decision making and allow better preoperative risk assessment and resource allocation.

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

OBJECTIVES: This study aimed to identify risk factors for infection after secondary cardiac implantable electronic device (CIED) procedures. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 CIED procedures.

Lead fixation mechanism impacts outcome of transvenous lead extraction: data from the European Lead Extraction ConTRolled Registry.

AIMS: The aims of this study is to characterize the transvenous lead extraction (TLE) population with active (A) compared with passive fixation (PFix) leads and to compare the safety, efficacy, and ease of extracting active fixation (AFix) compared with PFix right atrial (RA) and right ventricular (RV) leads. METHODS AND RESULTS: The European Lead Extraction ConTRolled Registry (ELECTRa) was analysed. Patients were divided into three groups; those with only AFix, only PFix, and combined Fix leads. Three outcomes were defined. Difficult extraction, complete radiological, and clinical success. Multivariate model was used to analyse the independent effect of Fix mechanism on these outcomes. The study included 2815 patients, 1456 (51.7%) with only AFix leads, 982 (34.9%) with only PFix leads, and 377 (13.4%) with combined Fix leads. Patients with AFix leads were younger with shorter lead dwelling time. Infection was the leading cause for TLE among the combined Fix group with lowest rates among AFix group. No difference in complications rates was noted between patients with only AFix vs. PFix leads. Overall, there were 1689 RA (1046 AFix and 643 PFix) and 2617 RV leads (1441 AFix and 1176 PFix). Multivariate model demonstrated that PFix is independently associated with more difficult extraction for both RA and RV leads, lower radiological success in the RA but has no effect on clinical success. CONCLUSION: Mechanism of Fix impact the ease of TLE of RA and RV leads and rates of complete radiological success in the RA but not clinical success. These findings should be considered during implantation and TLE procedures.

Location of Superior Vena Cava Tears in Transvenous Lead Extraction.

BACKGROUND: Superior vena cava (SVC) tears are rare but potentially lethal complications associated with transvenous lead extraction. When lacerations occur, surgeons need to be prepared for an emergent response. Nonetheless, little is known about the precise whereabouts of these lesions. Understanding the location and injury patterns enables a more anticipated and targeted surgical response. METHODS: We collected data via physician interviews after an SVC laceration occurred. These physicians were identified through the US Food and Drug Administration's Manufacturer and User Facility Device Experience database and independent physician reports of adverse events. We identified 116 reports of SVC tears between July 1, 2016, and July 31, 2018. For an SVC tear to be included in our registry, a cardiothoracic surgeon had to be physically present to confirm the injury via emergent sternotomy. In each case, the surgeon recorded the SVC injury's exact location after a repair was attempted. RESULTS: During the study period, 116 SVC tears were confirmed by sternotomy. Tears occurred in any combination of the following locations: SVC-innominate vein, body of the SVC, and SVC-right atrial junction. The majority of tears (n = 72; 62%) were located in the isolated body of the SVC, followed by the SVC-right atrial junction (n = 23;19.8%) and the SVC-innominate junction (n = 17;14.6%). Combined tears were rare, accounting for only 3.6% (n = 4) of the adverse events recorded. CONCLUSIONS: Most SVC tears occurred in the isolated body of the SVC. The second most common location was the SVC-right atrial junction. The SVC-innominate junction was the third most common location for these injuries. Combined tears were uncommon.

Clinical performance of implantable cardioverter-defibrillator lead monitoring diagnostics.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) lead monitoring diagnostic alerts facilitate the diagnosis of structural lead failure. OBJECTIVE: The purpose of this study was to prospectively study the performance of Medtronic ICD lead monitoring alerts. METHODS: 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). RESULTS: 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 for lead failure was 38.7% (48 of 124). For 34 pace-sense lead failures, an alert that incorporated oversensing was more sensitive than the pacing 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 shocks occurred in 2 patients with pace-sense lead failure (5.9%). No patient had unnecessary lead replacement for any of the NLEs. CONCLUSION: 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. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02277990.

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.

OBJECTIVES: To 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. METHODS: A 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. RESULTS: The 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. CONCLUSIONS: The 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.

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

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

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

BACKGROUND: 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. OBJECTIVE: The purpose of this study was to determine whether standard or low-temperature electrocautery impacts the development of an adverse event. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Risk stratification of patients undergoing transvenous lead extraction with the ELECTRa Registry Outcome Score (EROS): an ESC EHRA EORP European lead extraction ConTRolled ELECTRa registry analysis.

AIMS: Transvenous lead extraction is associated with a significant risk of complications and identifying patients at highest risk pre-procedurally will enable interventions to be planned accordingly. We developed the ELECTRa Registry Outcome Score (EROS) and applied it to the ELECTRa registry to determine if it could appropriately risk-stratify patients. METHODS AND RESULTS: EROS was devised to risk-stratify patients into low risk (EROS 1), intermediate risk (EROS 2), and high risk (EROS 3). This was applied to the ESC EORP European Lead Extraction ConTRolled ELECTRa registry; 57.5% EROS 1, 31.8% EROS 2, and 10.7% EROS 3. Patients with EROS 3 or 2 were significantly more likely to require powered sheaths and a femoral approach to complete procedures. Patients with EROS 3 were more likely to suffer procedure-related major complications including deaths (5.1 vs. 1.3%; P < 0.0001), both intra-procedural (3.5 vs. 0.8%; P = 0.0001) and post-procedural (1.6 vs. 0.5%; P = 0.0192). They were more likely to suffer post-procedural deaths (0.8 vs. 0.2%; P 0.0449), cardiac avulsion or tear (3.8 vs. 0.5%; P < 0.0001), and cardiovascular lesions requiring pericardiocentesis, chest tube, or surgical repair (4.6 vs. 1.0%; P < 0.0001). EROS 3 was associated with procedure-related major complications including deaths [odds ratio (OR) 3.333, 95% confidence interval (CI) 1.879-5.914; P < 0.0001] and all-cause in-hospital major complications including deaths (OR 2.339, 95% CI 1.439-3.803; P = 0.0006). CONCLUSION: EROS successfully identified patients who were at increased risk of significant procedural complications that require urgent surgical intervention.

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

OBJECTIVES: 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. BACKGROUND: 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. METHODS: 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 (36 months). Data were analyzed using Cox proportional hazards regression. RESULTS: 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 12 months 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. CONCLUSIONS: 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).

Mechanical extraction of cardiac implantable electronic devices leads with long dwell time: Efficacy and safety of the step up approach.

The aim of this study was to evaluate the efficacy and safety of the stepwise mechanical transvenous lead extraction approach in a patient population with chronically implanted transvenous leads with a long dwell time. From January 2014 till December 2018, all lead extractions with lead dwell time ≥5 years performed at our tertiary centre were retrospectively analysed. A total of 173 leads, from 78 patients (median age 68 years; 81% male) with a median dwell time of 9 years (interquartile range [IQR] 5) were extracted, with three or more leads in 42% of the patients. Right atrial leads: 41%; right ventricular pacing leads: 16%; implantable cardioverter-defibrillator (ICD) leads: 31% (72% dual coil); coronary sinus leads: 12%. The majority (75%) of the leads had an active fixation. Most frequent indication for extraction was pocket infection/erosion (76%). Overall clinical success was 97%, and complete procedural success was 93%. Venous patency, assessed with venous angiography, was well preserved in 93% of the cases. The overall procedural complication rate was 3.8% (2.6% major and 1.3% minor). Despite the complexity of the population and a very long dwell time (median 9 years), a clinical success rate of 97% was achieved with the stepwise mechanical approach. Analysis of impeding progression of pectoral extraction suggests that dense fibrosis and sharp lead curvature in the transvenous trajectory pose a challenge. Complication rate was low, and acute venous patency was generally well preserved.

Cost-Effectiveness of an Antibacterial Envelope for Cardiac Implantable Electronic Device Infection Prevention in the US Healthcare System From the WRAP-IT Trial.

BACKGROUND: In the WRAP-IT trial (Worldwide Randomized Antibiotic Envelope Infection Prevention), adjunctive use of an absorbable antibacterial envelope resulted in a 40% reduction of major cardiac implantable electronic device infection without increased risk of complication in 6983 patients undergoing cardiac implantable electronic device revision, replacement, upgrade, or initial cardiac resynchronization therapy defibrillator implant. There is limited information on the cost-effectiveness of this strategy. As a prespecified objective, we evaluated antibacterial envelope cost-effectiveness compared with standard-of-care infection prevention strategies in the US healthcare system. METHODS: A decision tree model was used to compare costs and outcomes of antibacterial envelope (TYRX) use adjunctive to standard-of-care infection prevention versus standard-of-care alone over a lifelong time horizon. The analysis was performed from an integrated payer-provider network perspective. Infection rates, antibacterial envelope effectiveness, infection treatment costs and patterns, infection-related mortality, and utility estimates were obtained from the WRAP-IT trial. Life expectancy and long-term costs associated with device replacement, follow-up, and healthcare utilization were sourced from the literature. Costs and quality-adjusted life years were discounted at 3%. An upper willingness-to-pay threshold of $150 000 per quality-adjusted life year was used to determine cost-effectiveness, in alignment with the American College of Cardiology/American Heart Association practice guidelines and as supported by the World Health Organization and contemporary literature. RESULTS: The base case incremental cost-effectiveness ratio of the antibacterial envelope compared with standard-of-care was $112 603/quality-adjusted life year. The incremental cost-effectiveness ratio remained lower than the willingness-to-pay threshold in 74% of iterations in the probabilistic sensitivity analysis and was most sensitive to the following model inputs: infection-related mortality, life expectancy, and infection cost. CONCLUSIONS: The absorbable antibacterial envelope was associated with a cost-effectiveness ratio below contemporary benchmarks in the WRAP-IT patient population, suggesting that the envelope provides value for the US healthcare system by reducing the incidence of cardiac implantable electronic device infection. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02277990.

The effect of centre volume and procedure location on major complications and mortality from transvenous lead extraction: an ESC EHRA EORP European Lead Extraction ConTRolled ELECTRa registry subanalysis.

AIMS: Transvenous lead extraction (TLE) should ideally be undertaken by experienced operators in a setting that allows urgent surgical intervention. In this analysis of the ELECTRa registry, we sought to determine whether there was a significant difference in procedure complications and mortality depending on centre volume and extraction location. METHODS AND RESULTS: Analysis of the ESC EORP European Lead Extraction ConTRolled ELECTRa registry was conducted. Low-volume (LoV) centres were defined as <30 procedures/year, and high-volume (HiV) centres as ≥30 procedures/year. Three thousand, two hundred, and forty-nine patients underwent TLE by a primary operator cardiologist; 17.1% in LoV centres and 82.9% in HiV centres. Procedures performed by primary operator cardiologists in LoV centres were less likely to be successful (93.5% vs. 97.1%; P < 0.0001) and more likely to be complicated by procedure-related deaths (1.1% vs. 0.4%; P = 0.0417). Transvenous lead extraction undertaken by primary operator cardiologists in LoV centres were associated with increased procedure-related major complications including death (odds ratio 1.858, 95% confidence interval 1.007-3.427; P = 0.0475). Transvenous lead extraction locations varied; 52.0% operating room, 9.5% hybrid theatre and 38.5% catheterization laboratory. Rates of procedure-related major complications, including death occurring in a high-risk environment (combining operating room and hybrid theatre), were similar to those undertaken in the catheterization laboratory (1.7% vs. 1.6%; P = 0.9297). CONCLUSION: Primary operator cardiologists in LoV centres are more likely to have extractions complicated by procedure-related deaths. There was no significant difference in procedure complications between different extraction settings. These findings support the need for TLE to be performed in experienced centres with appropriate personnel present.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The World-wide Randomized Antibiotic Envelope Infection Prevention (WRAP-IT) trial: Long-term follow-up.

BACKGROUND: The World-wide Randomized Antibiotic Envelope Infection Prevention trial reported a 40% reduction in major cardiac implantable electronic device (CIED) infections within 12 months of the procedure with the use of an antibacterial-eluting envelope (TYRX Absorbable Antibacterial Envelope, Medtronic, Mounds View, MN). OBJECTIVE: The purpose of this report was to describe the longer-term (>12 months) envelope effects on infection reduction and complications. METHODS: All trial patients who underwent CIED replacement, upgrade, revision, or initial cardiac resynchronization therapy - defibrillator implantation received standard-of-care infection prophylaxis and were randomized in a 1:1 ratio to receive the envelope or not. CIED infection incidence and procedure and system-related complications were characterized through all follow-up (36 months) by using Cox proportional hazards regression modeling. RESULTS: In total, 6800 patients received their intended randomized treatment (3371 envelope; 3429 control; mean follow-up period 21.0 ± 8.3 months). Major CIED-related infections occurred in 32 envelope patients and 51 control patients (Kaplan-Meier [KM] estimate 1.3% vs 1.9%; hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.41-0.99; P = .046). Any CIED-related infection occurred in 57 envelope patients and 84 control patients (KM estimate 2.1% vs 2.8%; HR 0.69; 95% CI 0.49-0.97; P = .030). System- or procedure-related complications occurred in 235 envelope patients and 252 control patients (KM estimate 8.0% vs 8.2%; HR 0.95; 95% CI 0.79-1.13; P < .001 for noninferiority); the most common were lead dislodgment (1.1%), device lead damage (0.5%), and implant site hematoma (0.4%). Implant site pain occurred less frequently in the envelope group (0.1% vs 0.4%; P = .067). There were no (0.0%) reports of allergic reactions to the components of the envelope (mesh, polymer, or antibiotics). CONCLUSION: The effects of the TYRX envelope on the reduction of the risk of CIED infection are sustained beyond the first year postprocedure, without an increased risk of complications.

Transvenous lead extraction procedures in women based on ESC-EHRA EORP European Lead Extraction ConTRolled ELECTRa registry: is female sex a predictor of complications?

AIMS: Female sex is considered an independent risk factor of transvenous leads extraction (TLE) procedure. The aim of the study was to evaluate the effectiveness of TLE in women compared with men. METHODS AND RESULTS: A post hoc analysis of risk factors and effectiveness of TLE in women and men included in the ESC-EHRA EORP ELECTRa registry was conducted. The rate of major complications was 1.96% in women vs. 0.71% in men; P = 0.0025. The number of leads was higher in men (mean 1.89 vs. 1.71; P < 0.0001) with higher number of abandoned leads in women (46.04% vs. 34.82%; P < 0.0001). Risk factors of TLE differed between the sexes, of which the major were: signs and symptoms of venous occlusion [odds ratio (OR) 3.730, confidence interval (CI) 1.401-9.934; P = 0.0084], cumulative leads dwell time (OR 1.044, CI 1.024-1.065; P < 0.001), number of generator replacements (OR 1.029, CI 1.005-1.054; P = 0.0184) in females and the number of leads (OR 6.053, CI 2.422-15.129; P = 0.0001), use of powered sheaths (OR 2.742, CI 1.404-5.355; P = 0.0031), and white blood cell count (OR 1.138, CI 1.069-1.212; P < 0.001) in males. Individual radiological and clinical success of TLE was 96.29% and 98.14% in women compared with 98.03% and 99.21% in men (P = 0.0046 and 0.0098). CONCLUSION: The efficacy of TLE was lower in females than males, with a higher rate of periprocedural major complications. The reasons for this difference are probably related to disparities in risk factors in women, including more pronounced leads adherence to the walls of the veins and myocardium. Lead management may be key to the effectiveness of TLE in females.