International Multisite Study of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Drug Proarrhythmic Potential Assessment.

To assess the utility of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as an in vitro proarrhythmia model, we evaluated the concentration dependence and sources of variability of electrophysiologic responses to 28 drugs linked to low, intermediate, and high torsades de pointes (TdP) risk categories using two commercial cell lines and standardized protocols in a blinded multisite study using multielectrode array or voltage-sensing optical approaches. Logistical and ordinal linear regression models were constructed using drug responses as predictors and TdP risk categories as outcomes. Three of seven predictors (drug-induced arrhythmia-like events and prolongation of repolarization at either maximum tested or maximal clinical exposures) categorized drugs with reasonable accuracy (area under the curve values of receiver operator curves ∼0.8). hiPSC-CM line, test site, and platform had minimal influence on drug categorization. These results demonstrate the utility of hiPSC-CMs to detect drug-induced proarrhythmic effects as part of the evolving Comprehensive In Vitro Proarrhythmia Assay paradigm.

Radiation safety and ergonomics in the electrophysiology laboratory: update on recent advances.

PURPOSE OF REVIEW: Risks associated with exposure to ionizing radiation in patients undergoing electrophysiology procedures and interventional cardiac electrophysiologists performing these procedures are a serious concern. Strategies to reduce radiation exposure are of obvious importance. In addition, interventional cardiac electrophysiologists have to perform procedures wearing heavy lead protection for prolonged periods, making them prone to cervical and lumbar spinal injuries. RECENT FINDINGS: Recently developed technologies, such as low-exposure radiographic imaging, novel radiographic imaging protection systems, nonfluoroscopic mapping systems using image integration, and remote catheter manipulation systems have been successful in reducing ionizing radiation exposure in the electrophysiology laboratory. The efficacy and safety of these technologies are being evaluated in clinical trials. In addition, economic analyses are being performed to evaluate these novel systems. The use of nonweight-bearing radiation protection devices and ergonomic design of the electrophysiology laboratory aim to reduce the incidence of occupational injuries in interventional cardiac electrophysiologists. SUMMARY: There is need for ongoing development and evaluation of new technologies to minimize exposure to ionizing radiation during electrophysiologic procedures. In addition, ergonomic planning of the electrophysiology laboratory and training of interventional cardiac electrophysiologists are crucial to occupational injury prevention.