Effects of envelopes on CIED pocket healing: a head-to-head preclinical evaluation

Abstract

Abstract Background The body's natural immune response to cardiac implantable electronic device (CIED) implantation results in capsule formation with healthy surrounding tissue. Alternatively, chronic inflammation and infection can disrupt healing, cause pocket instability, and increase morbidity and cost, while complicating future interventions. Two envelopes are currently available to provide CIED stabilization: the TYRX absorbable antibacterial envelope and the CanGaroo envelope derived from porcine extracellular matrix (ECM). Effects of these envelopes on CIED pocket healing are not well known. Purpose To compare TYRX, ECM, and no envelope on CIED pocket healing. Methods An ovine model was used for time-course evaluation of pocket healing. CIEDs were implanted with TYRX or ECM per manufacturer's instructions or with negative control (no envelope) to allow for direct comparison. Envelope type was rotated across animals to minimize localized effects associated with implant location. At least one control was implanted in each animal. Across 18 sheep, a total of 50 CIED pockets were evaluated (TYRX=16, control=20, ECM=14). Morphometric and histopathologic analyses were completed for pockets at 3 days, 7 days, 4 wks, and 12 wks post-implant. An independent pathologist completed blinded histopathology assessment of all tissue blocks using ISO 10993–6:2016 scoring standards. For capsule thickness comparisons, a mixed effects model with a random subject (sheep) effect and fixed time and treatment effects was used. Results The TYRX inflammatory response was low, as indicated by scoring measurements of neutrophils, fibrin, and macrophages (Figure 1). Neutrophil infiltration scores with TYRX and control declined from moderate (≤2) at 3 days to absent (score = 0) at 4 and 12 wks, whereas ECM scoring showed an elevated response at 3 days (3.2) and 7 days (2.2). A lower rate of fibrin deposition was observed with TYRX at 3 days compared to control and ECM (0.8 vs 1.6 vs 2.0). Macrophage scoring was lower at 7 days for TYRX compared to control and ECM (2.2 vs 2.8 vs 3.0). Rapid tissue repair with TYRX was evidenced by increased fibrosis at 7 days compared to control (1.8 vs 1.0), with substantial resolution by 12 wks. Tissue granulation and neovascularization progressed similarly for pockets with TYRX and control over time. Capsule thickness peaked at 4 wks for all groups (TYRX 1.3±0.4, control 0.9±0.4, ECM 2.3±0.1), was reduced at 12 wks (TYRX 0.7±0.2, control 0.7±0.2, ECM 1.2±0.2), and ECM was significantly different compared to TYRX and control (p<0.01, Figure 2). There was no evidence of fat infiltration or calcification in any sample. Conclusion The TYRX absorbable antibacterial envelope was associated with a more rapid natural healing response with less inflammation and thin uniform capsule formation compared to ECM. These healing conditions can foster development of a well-healed pocket that may ease secondary procedures when required. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Medtronic, Inc.