Proarrhythmia Risk Assessment in @entity1 Induced Pluripotent Stem Cell-Derived Cardiomyocytes using the Maestro XXXX Platform.

@entity1 @entity4024 @entity1166 @entity9689 @entity9493 @entity6251 @entity943 @entity1370
UNASSIGNED: Evaluation of stem cell-derived cardiomyocytes (SC-CM) using @entity9689 ( @entity9689 ) has attracted attention as a novel model to detect drug-induced @entity943 . An experiment was conducted to determine if @entity9689 recording from @entity1 induced pluripotent SC-CM (hiPSC-CM) could assess proarrhythmic risk. Ten @entity9493 blockers, 4 @entity4024 blockers, and 1 IKs blocker were evaluated blindly. Eight drugs are associated with @entity1166 ( @entity1166 ) and four are not. Multiple parameters, including field potential duration (FPD), @entity4024 slope, @entity4024 amplitude, beat rate (BR), and early after-depolarization (EAD) were recorded. @entity6251 ( @entity6251 ) that elicited a significant change were calculated. Our results determined that FPD and EAD were unable to distinguish torsadogenic from benign compounds, @entity4024 slope and amplitude could not differentiate @entity4024 channel blockade from @entity9493 blockade, BR had an inconsistent response to pharmacological treatment, and that hiPSC-CM were, in general, insensitive to IKs inhibition. A ratio was calculated that relates @entity6251 for evoking FPD prolongation, or triggering EAD, to the @entity1 therapeutic unbound Cmax ( @entity6251 /Cmax). The key finding was that the ratio was sensitive, but specificity was low. Consistently, the ratio had high positive predictive value and low negative predictive value. In conclusion, @entity9689 recordings of hiPSC-CM were sensitive for FPD and EAD detection, but unable to distinguish agents with low- and high-risk for TdPs. While some published reports suggested great potential for @entity9689 recordings in hSC-CM to assess preclinical @entity1370 , the current evaluation implies that this model would have a high false positive rate in regard to proarrhythmic risk.
