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With the exponential growth of cardiovascular implantable electronic devices (CIEDs) in pediatric patients, a new method of long-term surveillance, remote monitoring (RM), has become the standard of care. The purpose of this study was to determine the usefulness of RM as a monitoring tool in the pediatric population. A retrospective review was performed of 198 patients at the University of Iowa Children’s Hospital who had CIEDs. Data transmitted by RM were analyzed. The following data were examined: patient demographics; median interval between transmissions; detection of adverse events requiring corrective measures, including detection of lead failure; detection of arrhythmias and device malfunctions independent of symptoms; time gained in the detection of events using RM versus standard practice; the validity of RM; and the impact of RM on data management. Of 198 patients, 162 submitted 615 RM transmissions. The median time between remote transmissions was 91 days. Of 615 total transmissions, 16 % had true adverse events with 11 % prompting clinical intervention. Of those events requiring clinical response, 61 % of patients reported symptoms. The median interval between last follow-up and occurrence of events detected by RM was 46 days, representing a gain of 134 days for patients followed-up at 6-month intervals and 44 days for patients followed-up at 3 month-intervals. The sensitivity and specificity of RM were found to be 99 and 72 %, respectively. The positive and negative predictive values were found to be 41 and 99 %, respectively. RM allows for early identification of arrhythmias and device malfunctions, thus prompting earlier corrective measures and improving care and safety in pediatric patients.

More than 30 mutations in ACTA2, which encodes α-smooth muscle actin, have been identified to cause autosomal dominant thoracic aortic aneurysm and dissection. The mutation R256H is of particular interest because it also causes patent ductus arteriosus and moyamoya disease. R256H is one of the more prevalent mutations and, based on its molecular location near the strand-strand interface in the actin filament, may affect F-actin stability. To understand the molecular ramifications of the R256H mutation, we generated Saccharomyces cerevisiae yeast cells expressing only R256H yeast actin as a model system. These cells displayed abnormal cytoskeletal morphology and increased sensitivity to latrunculin A. After cable disassembly induced by transient exposure to latrunculin A, mutant cells were delayed in reestablishing the actin cytoskeleton. In vitro, mutant actin exhibited a higher than normal critical concentration and a delayed nucleation. Consequently, we investigated regulation of mutant actin by formin, a potent facilitator of nucleation and a protein needed for normal vascular smooth muscle cell development. Mutant actin polymerization was inhibited by the FH1-FH2 fragment of the yeast formin, Bni1. This fragment strongly capped the filament rather than facilitating polymerization. Interestingly, phalloidin or the presence of wild type actin reversed the strong capping behavior of Bni1. Together, the data suggest that the R256H actin mutation alters filament conformation resulting in filament instability and misregulation by formin. These biochemical effects may contribute to abnormal histology identified in diseased arterial samples from affected patients.