Substernal Extravascular Implantable Cardioverter-Defibrillator System Infections in Large Animals

The extravascular implantable cardioverter-defibrillator (EV ICD) with lead implantation in the substernal space may provide clinical advantages over transvenous and subcutaneous systems. This is the first reported examination of substernal infection in large animals implanted with the EV ICD system. The system was implanted in 13 large animals (canine, porcine, and ovine). The porcine were co-implanted with a transvenous cardiac resynchronization therapy with defibrillator (CRT-D) system. Infection was promoted through a cadence of immunosuppressive monitors and study interventions. The animals were monitored for clinical presentation of infection over 12-18 weeks, and cultures were collected to confirm infection. Treatment was bifurcated: 1) some infections were treated only with antibiotics ("antibiotics only"), whereas 2) some infections were treated with system removal and antibiotics ("antibiotics + explant"). Histopathology was conducted at the study closure. Five infections were confirmed over the course of the study, four of which involved infection of the EV ICD system and one infection of only the concomitantly implanted transvenous CRT-D system without EV ICD-related infection. Among the four EV ICD infections, two of two infections treated with antibiotics only did not resolve whereas two of two infections treated with antibiotics + explant resolved, as shown by histology. The transvenous CRT-D system infection progressed to septicemia and endocarditis, requiring early study discontinuation. No EV ICD-related infection progressed to blood stream infection, and the sternal bone did not become infected when infection was present in the substernal tissues. The study findings suggest that EV ICD-related infections are treatable with system removal and antibiotic therapy.