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.

Preclinical evaluation of a third-generation absorbable antibacterial envelope.

BACKGROUND: The TYRX (Medtronic) 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: The purpose of this study was 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-positive/gram-negative 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. Prespecified acceptance criteria were <83-mm migration and <90° rotation. Absorption was assessed via gross pathology. RESULTS: Elution curves were equivalent (similarity factors ≥50 per Food and Drug Administration guidance). Third-generation envelopes eluted antibiotics above minimal inhibitory concentration (MIC) in vivo at 2 hours postimplant through 7 days, consistent with second-generation envelopes. Bacterial challenge showed reductions (P <.05) in infection with second- and third-generation envelopes. Device migration was 5.5 ± 3.5 mm (third-generation) vs 9. 9 ±7.9 mm (second-generation) (P <.05). Device rotation was 18.9° ± 11.4° (third-generation) vs 17.6° ± 15.1° (second-generation) and did not differ (P = .79). Gross pathology confirmed the absence of luminal mesh remainders and no differences in peridevice fibrosis at 9 or 12 weeks. CONCLUSION: The third-generation TYRX absorbable antibacterial envelope demonstrated equivalent preclinical performance to the second-generation envelope. Antibiotic elution curves were similar, elution was above MIC for 7 days, infections were reduced compared to no envelope, and acceptance criteria for migration, rotation, and absorption were met.

Parental Perceptions of Adolescent Connectedness and the Role of the Primary Care Provider.

INTRODUCTION: Adolescent connectedness to adults, schools, and peers is a protective factor for development. This study aimed to describe parental perceptions of opportunities for youth connectedness and the potential role of the primary care provider in supporting these opportunities. METHOD: Eleven parents or caregivers of youth aged 11-18 years participated in semistructured interviews for a prospective qualitative descriptive study. Interview transcripts were analyzed using constant comparison and deductive and inductive coding. RESULTS: Findings suggest that parents and caregivers view adolescent participation in activities as positive, and nonparental adults play a large role in influencing adolescent involvement in activities. Parents and caregivers did not recall discussing connectedness with their adolescent's primary care provider but would find this helpful. DISCUSSION: Conversations about connectedness are missing from the well adolescent visit, and more research is needed to explore the most effective ways to have these discussions with adolescents and their parents or caregivers.

Conversion of L-dopa to Extended Release L-dopa (Rytary®) in Patients with Fluctuating Parkinson's Disease: Predictors of Dose.

BACKGROUND: A new extended release levodopa capsule (C/L ERC), Rytary®, has demonstrated improved "on" time in fluctuating Parkinson's disease patients, compared to optimally dosed immediate release levodopa. The milligram dosing, however, differs markedly and no empiric ratio or formula for dose conversion currently exists. OBJECTIVE: To determine the most effective conversion strategy from C/L to C/L ERC. METHODS: We reviewed fluctuating PD patients with problematic "off" time who were converted to C/L ERC using a semi-structured dose titration schedule, and collected data regarding basic efficacy, tolerability, and dosing, in order to determine an empirically based dose conversion formula. We collected demographics, PD historic data, and other medication use. RESULTS: Eighty fluctuating PD patients were given C/L ERC samples, 68 took at least one dose [46 male (67.6%), age 66.6±10.3 y], and 62 had adequate data for dose convergence calculations. At a mean follow-up of 119±101 days, [Range: 24-355 days], 43/68 (63.3%) remained on C/L ERC. CGI-I of "much improved" or "very much improved" was reported by 27/62 (43.5%) and dyskinesia scores from the Movement Disorder Society Unified Parkinson's Disease Rating Scale item 4.1, (0-4 range)) tended to improve from 0.9±1.1 to 0.5±0.6, P = 0.08. The mean individual daily ratio was 2.0±0.6 : 1, [range 1.0-3.5]. A lower number of baseline daily L-dopa doses predicted a higher conversion ratio, but pre-conversion dyskinesia did not. CONCLUSIONS: This retrospective study found that C/L ERC was generally well tolerated and preferred by many patients. The mean total daily conversion ratio is 2 : 1.

Feasibility of extravascular pacing with a novel substernal electrode configuration: The Substernal Pacing Acute Clinical Evaluation study.

BACKGROUND: Subcutaneous implantable cardioverter-defibrillators provide an alternative to transvenous defibrillation but require higher shock outputs and offer no antitachycardia pacing. The Substernal Pacing Acute Clinical Evaluation (SPACE) study evaluated the feasibility of pacing from an extravascular substernal location. OBJECTIVES: The primary purpose of the SPACE study was to characterize pacing from the substernal space. Secondary objectives included evaluating extracardiac stimulation and recording electrograms. METHODS: The SPACE study prospectively evaluated the feasibility of pacing with a commercially available electrophysiology catheter acutely implanted in the substernal space via minimally invasive subxiphoid access. Pacing data were collected in ≥7 vectors using constant current stimulation up to 20 mA and pulse width up to 10 ms. RESULTS: Catheter placement was successful in all 26 patients who underwent the procedure, with a mean placement time of 11.7 ± 10.1 minutes. Eighteen patients (69%) had successful ventricular capture in ≥1 tested vector. The mean pacing threshold at a pulse width of 10 ms was 7.3 ± 4.2 mA across all vectors (5.8 ± 4.4 V). Failed capture was generally associated with suboptimal catheter placement or presumed air ingression. A low level of extracardiac stimulation was observed in 1 patient. The mean R-wave amplitude ranged from 2.98 to 4.11 mV in the unipolar configuration and from 0.83 to 3.95 mV in the bipolar configuration. CONCLUSION: The data from the SPACE study demonstrate that pacing is feasible from the extravascular substernal location. A substernal electrode configuration has the potential to provide pacing in a future extravascular device without need for intracardiac hardware placement.