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

Implant site haematoma is a potential complication of cardiac implantable electronic device (CIED) procedures and may lead to device infection. The risk of device infection is 1% to 4% and is increased more than 7-fold in patients who develop a haematoma, resulting in significant impacts on mortality, quality of life, healthcare utilisation and expense. The World-wide Randomized Antibiotic Envelope Infection Prevention (WRAP-IT) trial found that use of the TYRXTM absorbable antibacterial envelope (Medtronic, Inc., Minneapolis, MN) was effective in reducing Staphylococcus-related pocket infections.

The aim of this study was to analyse data from the WRAP-IT study to evaluate the association between envelope use, haematomas and CIED infections.

Use of the antibacterial envelope was associated with an 82% reduction in major CIED infection among patients who developed haematoma compared with the control group.

Haematomas after CIED procedures can have serious consequences. This analysis suggests that these consequences can be significantly mitigated with the use of an antibacterial envelope.

The WRAP-IT study (NCT02277990) was a randomised, prospective, multi-centre, single blinded, post-market, interventional clinical study evaluating the ability of the TYRX™ envelope to reduce CIED infections for 12 months post-procedure following CIED generator replacement, upgrade, revision, or de novo cardiac resynchronisation therapy defibrillator (CRT-D) implant, and involved 3,429 patients in control group, and 3,371 patients in the envelope group). This analysis evaluated the incidence of haematomas occurring in patients within 30 days post procedure. The subsequent incidence of major CIED infection was evaluated through the study follow-up.

• Overall haematoma incidence (within 30 days post procedure).
• Major CIED infections, defined as infections that resulted in CIED system removal, an invasive CIED procedure (e.g. pocket revision without removal), treatment with long-term antibiotic therapy (if the patient was not a candidate for device removal) with infection recurrence after discontinuation of antibiotic therapy, or death.

• Age at least 18 years
• At least one of the following:
  • Existing CIED and undergoing implantable pulse generator (IPG) (including cardiac resynchronisation therapy pacemaker [CRT-P]), implantable cardioverter-defibrillator (ICD) or CRT-D replacement or upgrade
  • Undergoing a de novo Medtronic CRT-D system implant according to approved indications
  • Existing Medtronic CIED in which the pocket was not accessed within the last 365 days, and undergoing pocket or lead revision

• Known contraindications to use of a TYRX envelope
• Current therapy with chronic oral immunosuppressive agents
• Prior history of a CIED infection, other prosthetic device infection, or endovascular infection, including endocarditis, in the past 12 months.

• Acute haematoma incidence was 2.2% at 30 days, and did not differ between treatment groups (envelope vs control hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.84–1.58; p = 0.39)
• Approximately 15% of patients underwent pocket intervention to manage the haematoma, whereas 72.7% of the major CIED infections occurred in haematoma patients who had no pocket intervention
• Throughout follow-up, the risk of major infection was more that 11-fold greater in the control group among patients with haematoma vs. those without haematoma (13.1% vs. 1.6%; p<0.001)
• The use of the envelope reduced the risk of major infection among patients with haematoma by 82% compared to control patients with haematoma (2.5% vs. 13.1%; p=0.03)

These findings suggest that the use of an antibacterial envelope significantly mitigates the risk of CIED infection among patients who developed haematoma within 30 days of the procedure. These data reflect real-world physician experiences in high-volume centres.

• Haematoma incidence was not a prespecified endpoint of the WRAP-IT trial, and was assessed according to site-specific practices
• Inter-assay variability was seen in the different platelet function tests