Not all Long-QTs Are the Same, Proarrhytmic Quantification with Action Potential Triangulation and Alternans

• Type of Material: Article
• Authors: Ilija Uzelac, Georgia Institute of Technology; Shahriar Iravanian, Emory University; Elizabeth M Cherry, Georgia Institute of Technology; Flavio H Fenton, Georgia Institute of Technology
• Language: English
• Date: 2021-01-01
• Publisher: IEEE Xplore
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2021 Computing in Cardiology
• Final Published Version (URL): http://dx.doi.org/10.23919/CinC53138.2021.9662721
• Title of Journal or Parent Work: Computing in Cardiology
• Volume: 2021-September
• Keywords: Proarrhytmic Quantification; Long-QT

Abstract

Long-QT is commonly associated with an increased risk of polymorphic ventricular tachycardia from drug therapy. However, not all drugs prolonging QT interval are proar-rhythmic. This study aimed to characterize cellular and tissue mechanisms under which QT-interval prolonging drugs and their combination are proarrhythmic, examining arrhythmia susceptibility due to action potential (AP) triangulation and spatial dispersion of action potential duration (APD). Additionally, we aimed to elucidate that Tor-sades de Pointe (TdP) associated with long-QT are not necessarily caused by early-after-depolarization (EADs) but are related to the presence of AP alternans in both time and space. Isolated Guinea Pig hearts were Langendorff perfused, and optical mapping was done with a voltage dye-sensitive dye. Two commonly used drugs at the beginning of the COVID-19 pandemic, hydroxychloroquine (HCQ) and Azithromycin (AZM), were added to study the effects of QT interval prolongation. Alternans in time and space were characterized by performing restitution pacing protocols. Comparing APs, HCQ prolongs APD during phase-III repolarization, resulting in a higher triangulation ratio than AZM alone or AZM combined with HCQ. Lower triangulation ratios with AZM are associated with phase-II prolongation, lower arrhythmia, and lower incidence of spatially discordant alternans.