Beyond Alternans: Detection of Higher-Order Periodicity in Ex-Vivo Human Ventricles Before Induction of Ventricular Fibrillation.

• Type of Material: Article
• Authors: Shahriar Iravanian, Emory University; Illija Uzelac, Georgia Institute of Technology; Anand Shah, Emory University; Mikael J Toye, Georgia Institute of Technology; Michael Lloyd, Emory University; Michael Burke, Emory University; Mani Daneshmand, Emory University; Tamer Attia, Emory University; John Vega, Emory University; Faisal Merchant, Emory University; Elizabeth M Cherry, Georgia Institute of Technology; Neal Bhatia, Emory University; Flavio H Fenton, Georgia Institute of Technology
• Language: English
• Date: 2023-05-02
• Publisher: bioRxiv
• Publication Version: Preprint (Prior to Peer Review)
• Copyright Statement: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1101/2023.05.01.539003
• Title of Journal or Parent Work: bioRxiv
• Grant/Funding Information: This study was supported in part by the NIH under grant 1R01HL143450-01 and the NSF under CMMI-1762553.
• Keywords: Ventricular Fibrillation

Abstract

BACKGROUND: Repolarization alternans, defined as period-2 oscillation in the repolarization phase of the action potentials, is one of the cornerstones of cardiac electrophysiology as it provides a mechanistic link between cellular dynamics and ventricular fibrillation (VF). Theoretically, higher-order periodicities (e.g., period-4, period-8,…) are expected but have very limited experimental evidence. METHODS: We studied explanted human hearts, obtained from the recipients of heart transplantation at the time of surgery, using optical mapping technique with transmembrane voltage-sensitive fluorescent dyes. The hearts were stimulated at an increasing rate until VF was induced. The signals recorded from the right ventricle endocardial surface just before the induction of VF and in the presence of 1:1 conduction were processed using the Principal Component Analysis and a combinatorial algorithm to detect and quantify higher-order dynamics. RESULTS: A prominent and statistically significant 1:4 peak (corresponding to period-4 dynamics) was seen in three of the six studied hearts. Local analysis revealed the spatiotemporal distribution of higher-order periods. Period-4 was localized to temporally stable islands. Higher-order oscillations (period-5, 6, and 8) were transient and primarily occurred in arcs parallel to the activation isochrones. DISCUSSION: We present evidence of higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex-vivo human hearts before VF induction. This result is consistent with the period-doubling route to chaos as a possible mechanism of VF initiation, which complements the concordant to discordant alternans mechanism. The presence of higher-order regions may act as niduses of instability that can degenerate into chaotic fibrillation.