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Background: The anesthetized, complete chronic atrioventricular block (CAVB) dog model allows reproducible inducibility of torsades de pointes (TdP) arrhythmias due to ventricular remodeling and after a challenge with an I Kr blocker. High-rate pacing (HRP) prevents ventricular arrhythmias but has long-term detrimental effects on cardiac function when applied continuously. Temporal dispersion of repolarization, quantified as short-term variability (STV), increases before ventricular arrhythmias and has been proposed as a marker to guide HRP., Objective: The purpose of this proof-of-principle study was to show that automatically determined STV can guide HRP to prevent imminent ventricular arrhythmias., Methods: Eight CAVB dogs were implanted with an implantable cardioverter-defibrillator (ICD) with software to automatically determine STV (STV ICD ) in real time. During HRP, STV was measured offline from right ventricular (RV) electrograms (EGMs) and left ventricular (LV) monophasic action potential durations (MAPDs) (STV RV,EGM/LV,MAPD ). The CAVB dogs were challenged twice with dofetilide (0.025 mg/kg intravenously over 5 minutes or until the first TdP). In experiment 1, the individual STV ICD threshold before the first arrhythmic event was determined and programmed into the ICD. In experiment 2, HRP with 100 bpm was initiated automatically once the STV ICD threshold was reached., Results: In experiment 1, 8 of 8 dogs had repetitive TdP, and STV ICD increased from 0.96 ± 0.42 ms to 2.10 ± 1.26 ms (P <.05). In experiment 2, all dogs reached the STV threshold. HRP decreased STV RV,EGM/LV,MAPD from 2.02 ± 1.12 ms to 0.78 ± 0.28 ms, which was accompanied by prevention of TdP in 7 of 8 dogs., Conclusion: STV can guide HRP automatically by an ICD to prevent ventricular arrhythmias., (Copyright © 2020 The Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)