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.

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.

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.

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 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.

Antibacterial Envelope to Prevent Cardiac Implantable Device Infection.

BACKGROUND: Infections after placement of cardiac implantable electronic devices (CIEDs) are associated with substantial morbidity and mortality. There is limited evidence on prophylactic strategies, other than the use of preoperative antibiotics, to prevent such infections. METHODS: We conducted a randomized, controlled clinical trial to assess the safety and efficacy of an absorbable, antibiotic-eluting envelope in reducing the incidence of infection associated with CIED implantations. Patients who were undergoing a CIED pocket revision, generator replacement, or system upgrade or an initial implantation of a cardiac resynchronization therapy defibrillator were randomly assigned, in a 1:1 ratio, to receive the envelope or not. Standard-of-care strategies to prevent infection were used in all patients. The primary end point was infection resulting in system extraction or revision, long-term antibiotic therapy with infection recurrence, or death, within 12 months after the CIED implantation procedure. The secondary end point for safety was procedure-related or system-related complications within 12 months. RESULTS: A total of 6983 patients underwent randomization: 3495 to the envelope group and 3488 to the control group. The primary end point occurred in 25 patients in the envelope group and 42 patients in the control group (12-month Kaplan-Meier estimated event rate, 0.7% and 1.2%, respectively; hazard ratio, 0.60; 95% confidence interval [CI], 0.36 to 0.98; P = 0.04). The safety end point occurred in 201 patients in the envelope group and 236 patients in the control group (12-month Kaplan-Meier estimated event rate, 6.0% and 6.9%, respectively; hazard ratio, 0.87; 95% CI, 0.72 to 1.06; P<0.001 for noninferiority). The mean (±SD) duration of follow-up was 20.7±8.5 months. Major CIED-related infections through the entire follow-up period occurred in 32 patients in the envelope group and 51 patients in the control group (hazard ratio, 0.63; 95% CI, 0.40 to 0.98). CONCLUSIONS: Adjunctive use of an antibacterial envelope resulted in a significantly lower incidence of major CIED infections than standard-of-care infection-prevention strategies alone, without a higher incidence of complications. (Funded by Medtronic; WRAP-IT ClinicalTrials.gov number, NCT02277990.).