End of Life Biocompatibility Assessment for Chronically Implanted Cardiac Leads

Abstract

Medical devices should be biocompatible throughout the entire lifecycle, but the evaluation for biocompatibility is typically performed on a new, fully finished device. While long-term implantable devices such as cardiac leads maintain function for more than a decade, studies have not addressed changes in extractable species throughout the implant life cycle. In this study, we performed extractables analysis on cardiac leads that were implanted in humans for times ranging from 3 to 130 months. The exhaustive extracts were analyzed using liquid chromatography coupled to mass spectrometry to identify and relatively quantify extractable species. Over implant times exceeding a decade, no new species were formed, and the quantity of each class of mobile species remained constant or decreased over time. Polyurethane oligomers, a byproduct of the polymerization route, generally remained at constant levels, suggesting that there is little to no driving force for them to enter the surrounding tissue. Small molecule additives, such as the antioxidant Irganox 1076, contained within the polyurethane outer coating, decreased at a rate that was consistent with diffusional release rather than reactive consumption. These results support two important conclusions. First, the chemical profile of the mobile species does not change over the implanted lifecycle, indicating the biocompatibility of durable cardiac leads does not change over time. Second, the toxicological assumption that all mobile species identified in exhaustive extractions of a new device are released upon implant is extremely conservative when contrasted with the diffusional release rates measured in the human explanted leads studied herein.

Keywords: cardiac leads; chronic biocompatibility; human explant analysis.