Global LEADR pivotal trial results.

BACKGROUND: Implantable cardioverter-defibrillators last longer, and interest in reliable leads with targeted lead placement is growing. The OmniaSecure™ defibrillation lead is a novel small-diameter, catheter-delivered lead designed for targeted placement, based on the established SelectSecure SureScan MRI Model 3830 lumenless pacing lead platform. OBJECTIVE: This trial assessed safety and efficacy of the OmniaSecure defibrillation lead. METHODS: The worldwide LEADR pivotal clinical trial enrolled patients indicated for de novo implantation of a primary or secondary prevention implantable cardioverter-defibrillator/cardiac resynchronization therapy defibrillator, all of whom received the study lead. The primary efficacy end point was successful defibrillation at implantation per protocol. The primary safety end point was freedom from study lead-related major complications at 6 months. The primary efficacy and safety objectives were met if the lower bound of the 2-sided 95% credible interval was >88% and >90%, respectively. RESULTS: In total, 643 patients successfully received the study lead, and 505 patients have completed 12-month follow-up. The lead was placed in the desired right ventricular location in 99.5% of patients. Defibrillation testing at implantation was completed in 119 patients, with success in 97.5%. The Kaplan-Meier estimated freedom from study lead-related major complications was 97.1% at 6 and 12 months. The trial exceeded the primary efficacy and safety objective thresholds. There were zero study lead fractures and electrical performance was stable throughout the mean follow-up of 12.7 ± 4.8 months (mean ± SD). CONCLUSION: The OmniaSecure lead exceeded prespecified primary end point performance goals for safety and efficacy, demonstrating high defibrillation success and a low occurrence of lead-related major complications with zero lead fractures.

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.

Ancient Lowland Maya neighborhoods: Average Nearest Neighbor analysis and kernel density models, environments, and urban scale.

Many humans live in large, complex political centers, composed of multi-scalar communities including neighborhoods and districts. Both today and in the past, neighborhoods form a fundamental part of cities and are defined by their spatial, architectural, and material elements. Neighborhoods existed in ancient centers of various scales, and multiple methods have been employed to identify ancient neighborhoods in archaeological contexts. However, the use of different methods for neighborhood identification within the same spatiotemporal setting results in challenges for comparisons within and between ancient societies. Here, we focus on using a single method-combining Average Nearest Neighbor (ANN) and Kernel Density (KD) analyses of household groups-to identify potential neighborhoods based on clusters of households at 23 ancient centers across the Maya Lowlands. While a one-size-fits all model does not work for neighborhood identification everywhere, the ANN/KD method provides quantifiable data on the clustering of ancient households, which can be linked to environmental zones and urban scale. We found that centers in river valleys exhibited greater household clustering compared to centers in upland and escarpment environments. Settlement patterns on flat plains were more dispersed, with little discrete spatial clustering of households. Furthermore, we categorized the ancient Maya centers into discrete urban scales, finding that larger centers had greater variation in household spacing compared to medium-sized and smaller centers. Many larger political centers possess heterogeneity in household clustering between their civic-ceremonial cores, immediate hinterlands, and far peripheries. Smaller centers exhibit greater household clustering compared to larger ones. This paper quantitatively assesses household clustering among nearly two dozen centers across the Maya Lowlands, linking environment and urban scale to settlement patterns. The findings are applicable to ancient societies and modern cities alike; understanding how humans form multi-scalar social groupings, such as neighborhoods, is fundamental to human experience and social organization.

Efficacy and Safety of an Extravascular Implantable Cardioverter-Defibrillator.

BACKGROUND: The extravascular implantable cardioverter-defibrillator (ICD) has a single lead implanted substernally to enable pause-prevention pacing, antitachycardia pacing, and defibrillation energy similar to that of transvenous ICDs. The safety and efficacy of extravascular ICDs are not yet known. METHODS: We conducted a prospective, single-group, nonrandomized, premarket global clinical study involving patients with a class I or IIa indication for an ICD, all of whom received an extravascular ICD system. The primary efficacy end point was successful defibrillation at implantation. The efficacy objective would be met if the lower boundary of the one-sided 97.5% confidence interval for the percentage of patients with successful defibrillation was greater than 88%. The primary safety end point was freedom from major system- or procedure-related complications at 6 months. The safety objective would be met if the lower boundary of the one-sided 97.5% confidence interval for the percentage of patients free from such complications was greater than 79%. RESULTS: A total of 356 patients were enrolled, 316 of whom had an implantation attempt. Among the 302 patients in whom ventricular arrhythmia could be induced and who completed the defibrillation testing protocol, the percentage of patients with successful defibrillation was 98.7% (lower boundary of the one-sided 97.5% confidence interval [CI], 96.6%; P<0.001 for the comparison with the performance goal of 88%); 299 of 316 patients (94.6%) were discharged with a working ICD system. The Kaplan-Meier estimate of the percentage of patients free from major system- or procedure-related complications at 6 months was 92.6% (lower boundary of the one-sided 97.5% CI, 89.0%; P<0.001 for the comparison with the performance goal of 79%). No major intraprocedural complications were reported. At 6 months, 25 major complications were observed, in 23 of 316 patients (7.3%). The success rate of antitachycardia pacing, as assessed with generalized estimating equations, was 50.8% (95% CI, 23.3 to 77.8). A total of 29 patients received 118 inappropriate shocks for 81 arrhythmic episodes. Eight systems were explanted without extravascular ICD replacement over the 10.6-month mean follow-up period. CONCLUSIONS: In this prospective global study, we found that extravascular ICDs were implanted safely and were able to detect and terminate induced ventricular arrhythmias at the time of implantation. (Funded by Medtronic; ClinicalTrials.gov number, NCT04060680.).

The development of the extravascular defibrillator with substernal lead placement: A new Frontier for device-based treatment of sudden cardiac arrest.

INTRODUCTION: The extravascular implantable cardioverter-defibrillato (EV ICD) system with substernal lead placement is a novel nontransvenous alternative to current commercially available ICD systems. The EV ICD provides defibrillation and pacing therapies without the potential long-term complications of endovascular lead placement but requires a new procedure for implantation with a safety profile under evaluation. METHODS: This paper summarizes the development of the EV ICD, including the preclinical and clinical evaluations that have contributed to the system and procedural refinements to date. RESULTS: Extensive preclinical research evaluations and four human clinical studies with >140 combined acute and chronic implants have enabled the development and refinement of the EV ICD system, currently in worldwide pivotal study. CONCLUSION: The EV ICD may represent a clinically valuable solution in protecting patients from sudden cardiac death while avoiding the long-term consequences of transvenous hardware. The EV ICD offers advantages over transvenous and subcutaneous systems by avoiding placement in the heart and vasculature; relative to subcutaneous systems, EV ICD requires less energy for defibrillation, enabling a smaller device, and provides pacing features such as antitachycardia and asystole pacing in a single system.

Three-year extraction experience of a novel substernal extravascular defibrillation lead in sheep.

BACKGROUND: The extravascular implantable cardioverter-defibrillator (EV ICD) with lead implantation in the substernal space may provide an alternative to transvenous and subcutaneous systems. This is the first-reported chronic extraction experience for EV ICD leads. The aim of the study is to evaluate the chronic encapsulation and extractability of EV ICD leads. METHODS: Two EV ICD leads and one transvenous lead were implanted in each of 24 mature sheep. A subset of animals was evaluated yearly for histology and lead extractability. Extractions were performed using simple traction or extraction tools. Histology evaluated the encapsulating tissue. RESULTS: At 1 year, extraction was performed successfully for two of five EV ICD leads with traction alone using ≤3.1 kg-force (kgf) and the remainder extracted successfully with extraction tools; no transvenous leads were removed with traction alone. At 2 years, no EV ICD or transvenous leads were extracted with traction alone, while at 3 years, one of eight EV ICD leads and two of four transvenous leads were extracted with traction (0.8 and ≤2.3 kgf, respectively). There was one observation of hemopericardium resulting in tamponade with EV ICD extraction but without injury to cardiovascular structures and related to the unique implant tract. Among transvenous leads, inversion of the ventricle with loss of cardiac output resulted in abandonment of traction for two animals. CONCLUSIONS: Chronic extraction of EV ICD leads from the substernal space was successfully performed using traction and simple tools through 3 years in sheep with one observation of hemopericardium that did not originate from cardiovascular injury.

The extravascular implantable cardioverter-defibrillator: characterization of anatomical parameters impacting substernal implantation and defibrillation efficacy.

AIMS: The aim of this study is to provide a thorough, quantified assessment of the substernal space as the site of extravascular implantable cardioverter-defibrillator (ICD) lead placement using computed tomography (CT) scans and summarizing adverse events and defibrillation efficacy across anatomical findings. Subcutaneous ICDs are an alternative to transvenous defibrillators but have limitations related to ICD lead distance from the heart. An alternative extravascular system with substernal lead placement has the potential to provide defibrillation at lower energy and pacing therapies from a single device. METHODS AND RESULTS: A multi-centre, non-randomized, retrospective analysis of 45 patient CT scans quantitatively and qualitatively assessing bony, cardiac, vascular, and other organ structures from two human clinical studies with substernal lead placement. Univariate logistic regression was used to evaluate 15 anatomical parameters for impact on defibrillation outcome and adjusted for multiple comparisons. Adverse events were summarized. Substernal implantation was attempted or completed in 45 patients. Defibrillation testing was successful in 37 of 41 subjects (90%) using ≥10 J safety margin. There were two intra-procedural adverse events in one patient, including reaction to anaesthesia and an episode of transient atrial fibrillation during ventricular fibrillation induction. Anatomical factors associated with defibrillation failure included large rib cage width, myocardium extending very posteriorly, and a low heart position in the chest (P-values <0.05), though not significant adjusting for multiple comparisons. CONCLUSION: Retrospective analysis demonstrates the ability to implant within the substernal space with low intra-procedural adverse events and high defibrillation efficacy despite a wide range of anatomical variability.

Assessing Classic Maya multi-scalar household inequality in southern Belize.

Inequality is present to varying degrees in all human societies, pre-modern and contemporary. For archaeological contexts, variation in house size reflects differences in labor investments and serves as a robust means to assess wealth across populations small and large. The Gini coefficient, which measures the degree of concentration in the distribution of units within a population, has been employed as a standardized metric to evaluate the extent of inequality. Here, we employ Gini coefficients to assess wealth inequality at four nested socio-spatial scales-the micro-region, the polity, the district, and the neighborhood-at two medium size, peripheral Classic Maya polities located in southern Belize. We then compare our findings to Gini coefficients for other Classic Maya polities in the Maya heartland and to contemporaneous polities across Mesoamerica. We see the patterning of wealth inequality across the polities as a consequence of variable access to networks of exchange. Different forms of governance played a role in the degree of wealth inequality in Mesoamerica. More autocratic Classic Maya polities, where principals exercised degrees of control over exclusionary exchange networks, maintained high degrees of wealth inequality compared to most other Mesoamerican states, which generally are characterized by more collective forms of governance. We examine how household wealth inequality was reproduced at peripheral Classic Maya polities, and illustrate that economic inequity trickled down to local socio-spatial units in this prehispanic context.

Therapy From a Novel Substernal Lead: The ASD2 Study.

OBJECTIVES: The ASD2 (Acute Extravascular Defibrillation, Pacing, and Electrogram) study evaluated the ability to adequately sense, pace, and defibrillate patients with a novel implantable cardioverter-defibrillator (ICD) lead implanted in the substernal space. BACKGROUND: Subcutaneous ICDs are an alternative to a transvenous defibrillator system when transvenous implantation is not possible or desired. An alternative extravascular system placing a lead under the sternum has the potential to reduce defibrillation energy and the ability to deliver pacing therapies. METHODS: An investigational lead was inserted into the substernal space via a minimally invasive subxiphoid access, and a cutaneous defibrillation patch or subcutaneous active can emulator was placed on the left mid-axillary line. Pacing thresholds and extracardiac stimulation were evaluated. Up to 2 episodes of ventricular fibrillation were induced to test defibrillation efficacy. RESULTS: The substernal lead was implanted in 79 patients, with a median implantation time of 12.0 ± 9.0 min. Ventricular pacing was successful in at least 1 vector in 76 of 78 patients (97.4%), and 72 of 78 (92.3%) patients had capture in ≥1 vector with no extracardiac stimulation. A 30-J shock successfully terminated 104 of 128 episodes (81.3%) of ventricular fibrillation in 69 patients. There were 7 adverse events in 6 patients causally (n = 5) or possibly (n = 2) related to the ASD2 procedure. CONCLUSIONS: The ASD2 study demonstrated the ability to pace, sense, and defibrillate using a lead designed specifically for the substernal space.

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.

Two-year extractability of novel left ventricular, active fixation leads in the sheep model.

BACKGROUND: A cardiac lead with a side helix for active fixation to the coronary vein wall (Attain Stability® , Model 20066, Medtronic, Minneapolis, MN, USA) recently received CE Mark. The lead is designed to improve left ventricular (LV) placement and reduce dislodgement rates. The extractability of this active fixation LV lead has not been studied extensively. METHODS: Seventeen sheep were implanted with either an LV lead with a side helix (Model 20066, Model 20096, Medtronic) or a unipolar LV lead (Model 4193, Medtronic) as a control. Leads were extracted at approximately 26, 52, or 118 weeks. Standard extraction methodology was employed with quantitative traction up to 907 g (2 lbs.) using a locking stylet. Gross pathology and histology of the heart with particular attention to the lead tracts were performed. RESULTS: All leads were successfully removed in their entirety and required significantly less than 1 kg of traction force. The side helix disengaged from the vein as designed and resulted in no complications. No cardiac tissue was observed on any extracted lead. Gross pathology and histology were devoid of any helix-induced lesions in the vascular structures. The epicardium over the side helix was normal and the fibrotic reaction around the helix was not significantly different from that around the nonhelix portions of the study leads or the control lead. CONCLUSION: Extraction of the side helix, active fixation LV lead from the coronary veins in the sheep model is safe, without procedural complexity, and free of complications after long-term LV lead implant duration.