ABSTRACT
Background
The TYRX absorbable antibacterial envelope has been shown to stabilize implantable
cardiac devices and reduce infection. A third-generation envelope was developed to
reduce surface roughness with a redesigned multifilament mesh and enhanced form-factor
but identical polymer coating and antibiotic concentrations as the currently available
second-generation envelope.
Objective
To compare drug elution, bacterial challenge efficacy, stabilization, and absorption
of second- vs. third-generation envelopes.
Methods
Antibiotic elution was assessed in vitro and in vivo. For efficacy against gram+/gram- bacteria, 40 rabbits underwent device insertions
with or without third-generation envelopes. For stabilization (migration, rotation),
5 sheep were implanted with 6 devices each in second- or third-generation envelopes.
Pre-specified acceptance criteria were <83 mm migration and <90 degrees rotation.
Absorption was assessed via gross pathology.
Results
Elution curves were equivalent (similarity factors ≥50 per FDA guidance). Third-generation
envelopes eluted antibiotics above minimal inhibitory concentration (MIC) in vivo at 2hr post-implant through 7d, consistent with second-generation envelopes. Bacterial
challenge showed reductions (p<0.05) in infection with second- and third-generation
envelopes. Device migration was 5.5±3.5 (third-generation) vs. 9.9±7.9 mm (second-generation)
(p<0.05). Device rotation was 18.9±11.4 (third-generation) vs. 17.6±15.1 degrees (second-generation)
and did not differ (p=0.79). Gross pathology confirmed absence of luminal mesh remainders
and no differences in peri-device fibrosis at 9 or 12wks.
Conclusion
The third-generation TYRX absorbable antibacterial envelope demonstrated equivalent
pre-clinical performance to the second-generation envelope: antibiotic elution curves
were similar, elution was above MIC for 7d, infections were reduced compared to no
envelope, and acceptance criteria for migration, rotation, and absorption were met.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Accepted:
January 12,
2023
Received in revised form:
January 3,
2023
Received:
September 27,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
1
In vivo results do not cover all 4 strains.2Non-inferiority is for migration alone. Non-inferiority criteria were not applicable to rotation or erosion, but no rotation exceeded 90° and no erosion was observed.
Conflicts of interest/disclosure:
Charles J. Love: Consulting fees from Abbott, Cook Medical, Medtronic, Philips; Research support from Boston Scientific
Ibrahim Hanna: No conflicts of interest to disclose.
George Thomas: Consulting Fee from Medtronic, Biotronik and Acutus Medical.
Arnold J. Greenspon: Honoraria, Consulting Fees and Research Support from Medtronic.
Melissa Christie: Employment by Medtronic.
Matt Sanders: Employment by Medtronic.
Carrie Bauer: Employment by Medtronic.
Jonathan Goodman: Employment by Medtronic.
Matt Christopherson: Employment by Medtronic.
Vasanthi Balaji: Employment by Medtronic.
Shira Skulsky: Employment by Medtronic.
Bill Schindeldecker: Employment by Medtronic.
Nicole Kirchhof: Employment by Medtronic.
M. Rizwan Sohail: Honoraria/consulting fees from Medtronic, Philips, and Aziyo Biologics, Inc.
Advisory Board: Philips.
Funding: This work was supported by Medtronic, Inc.
Identification
Copyright
© 2023 Published by Elsevier Inc. on behalf of Heart Rhythm Society.
