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Introduction Frequent right AQ4ventricular pacing (≥40%) with a transvenous pacemaker (TVP) is associated with the risk of pacing‐induced cardiomyopathy (PICM). Leadless pacemakers (LPs) have distinct physical and mechanical differences from TVP. The risk of PICM with LP is not known. To identify incidence, predictors, and long‐term outcomes of PICM in LP and TVP patients. Methods The study comprised all pacemaker‐dependent patients with LP or TVP who had left ventricular ejection fraction (LVEF) of ≥50 from 2014 to 2019. The incidence of PICM (≥10% LVEF drop) was assessed with an echocardiogram. Predictors for PICM were identified using multivariate analysis. Long‐term outcomes after cardiac resynchronization (CRT) were assessed in both groups. Results A total of 131 patients with TVP and 67 with LP comprised the study. All patients in the TVP group and the majority in the LP group underwent atrioventricular node ablation. The mean follow‐up duration in TVP and LP groups was 592 ± 549 and 817 ± 600 days, respectively. A total of 18 (13.7%) patients in TVP and 2 (3%) in LP developed PICM after a median duration of 254 (interquartile range: 470) days. The incidence of PICM was significantly higher with TVP compared with LP (p = .02). TVP as pacing modality was a positive (odds ratio [OR]: 1.07) while age was negative (OR: 0.94) predictor for PICM on multivariable analysis. Both patients in LP and all except two in the TVP group responded to CRT. Conclusion Incidence of PICM is significantly lower with LP compared with TVP in pacemaker‐dependent patients. Age and TVP as pacing modality were predictors for PICM.

Background Anesthesia-induced neurotoxicity research in the developing brain must rely upon an unimpeachable animal model and a standardized treatment approach. In this manner, identification of mechanisms of action may be undertaken. The goal of this study was to develop a novel, clinically relevant, translational way to use a piglet model to investigate anesthesia effects on the developing brain. Methods 29 newborn piglets were assigned to either: (1) control (no intervention, n = 10); (2) lipopolysaccharide (LPS; positive inflammatory control, n = 9); or (3) isoflurane anesthesia (n = 10). Positive inflammatory control animals were given 100 mcg/kg LPS from Escherichia coli intraperitoneally (IP) on the same day as those receiving isoflurane. Isoflurane was administered for 3 h while care was taken to ensure human perioperative conditions. To establish a clinical scenario, each animal was intubated and monitored with pulse oximetry, invasive and non-invasive blood pressure, electrocardiogram, temperature, end-tidal CO 2 , anesthetic concentration, and iSTAT blood analysis. All animals were sacrificed after 48 h using transcardiac perfusion of ice-cold, heparinized phosphate buffered saline (PBS) followed by 4 % paraformaldehyde (PFA). Brains were collected and histopathological analysis focused on the entorhinal cortex looking for degenerative changes due to its critical role in learning and memory. Reliable identification of entorhinal cortex was achieved by using colored ink on the surface of the brains, which was then cross-referenced with microscopic anatomy. Hematoxylin & eosin-stained high-power fields was used to quantify cells. ImageJ™ (National Institutes of Health, Bethesda, MD, USA) was used to count absolute number of progenitor glial cells (PGC) and number of PGCs per cluster. Immunohistochemistry was also utilized to ensure positive identification of cellular structures. Results Histopathological sections of 28 brains were analyzed. One animal in the LPS group died shortly after administration, presumably from inadvertent intravascular injection. There was an acute basal ganglia ischemic infarct in one isoflurane-treated animal. A large number of small, round nucleated cells were seen throughout layer II of the entorhinal cortex in all animals. These cells were identified as PGCs using immunohistochemistry and light microscopy. Although there was no difference in the absolute number of PGCs between the groups, animals given isoflurane or LPS demonstrated a significant increase in cells forming ‘clusters’ in the entorhinal cortex. An apparent change in the pattern of doublecortin labeling also suggests changes in neuronal precursors and undifferentiated neurons. Conclusions This study represents the first novel use of a clinically relevant neonatal piglet model to study anesthesia effects on the developing brain. LPS induces neuroinflammatio...