B-AB01-03 HIGH-RESOLUTION REAL-TIME LEFT-VENTRICULAR ENDOCARDIAL ACTIVATION-REPOLARIZATION MAPPING IN AN IN-VIVO CANINE MODEL OF DRUG-INDUCED LONG-QT 1 SYNDROME AND TORSADES DE POINTES

Abstract

Congenital loss of function or drug-induced inhibition of IKs causes repolarization lability, predisposing to QT prolongation (LQT1) and sympathetically-evoked torsades de pointes (TdP). High-resolution in-vivo mapping of endocardial activation-repolarization times (AT, RT), gradients and focal excitation conspiring to TdP in LQT1 is lacking. To study arrhythmogenic mechanisms of TdP in a canine model of drug-induced LQT1 using real-time and high-resolution electroanatomical mapping. IKs inhibition (HMR1556 0.025-0.05 mg/kg/min) was applied in three fentanyl/etomidate-anesthetized dogs; anesthesia to maintain near-normal autonomic responsiveness. The AcQMap3D noncontact imaging and mapping catheter (Acutus Medical, US) was positioned in the LV. Isoproterenol (1.25-2.5 mcg/kg) induced TdP. AT, RT (Wyatt), RTmax-min (ΔRT), local RT dispersion (per 5.5 mm) and TdP initiation/propagation were studied. IKs block prolonged QTc by 40% (386±22 ms) and mean RT by 44% (309±20 ms), as recorded with the AcQMap3D catheter (AT/RT errors 2.9±4.0/5.4±6.7 ms; cross-correlation 1.0±0.1; time difference 0.8±1.8 ms). ΔRT increased by 23% (85±7 ms) and max local RT dispersion by 19% (80±9 ms). Isoproterenol induced regional RT shortening (base>apex) and beat-to-beat instability, increasing ΔRT significantly by 122% (189±62 ms) and local RT dispersion by 91% (153±51 ms; Figure). Focal triggers of TdP emerged from regions bordering high RT dispersion, driving reentrant excitation. High-resolution mapping in an in-vivo LQT1/TdP model uniquely identifies spatiotemporal RT instabilities, focal excitation and TdP.