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Free, publicly-accessible full text available May 1, 2024
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Free, publicly-accessible full text available May 1, 2024
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Abstract Aims The mechanisms of transition from regular rhythms to ventricular fibrillation (VF) are poorly understood. The concordant to discordant repolarization alternans pathway is extensively studied; however, despite its theoretical centrality, cannot guide ablation. We hypothesize that complex repolarization dynamics, i.e. oscillations in the repolarization phase of action potentials with periods over two of classic alternans, is a marker of electrically unstable substrate, and ablation of these areas has a stabilizing effect and may reduce the risk of VF. To prove the existence of higher-order periodicities in human hearts.
Methods and results We performed optical mapping of explanted human hearts obtained from recipients of heart transplantation at the time of surgery. Signals recorded from the right ventricle endocardial surface were processed to detect global and local repolarization dynamics during rapid pacing. A statistically significant global 1:4 peak was seen in three of six hearts. Local (pixel-wise) analysis revealed the spatially heterogeneous distribution of Periods 4, 6, and 8, with the regional presence of periods greater than two in all the hearts. There was no significant correlation between the underlying restitution properties and the period of each pixel.
Conclusion We present evidence of complex higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex vivo human hearts. We infer that the oscillation of the calcium cycling machinery is the primary mechanism of higher-order dynamics. These higher-order regions may act as niduses of instability and may provide targets for substrate-based ablation of VF.
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Dual voltage-calcium fluorescence optical recordings are increasingly appealing to characterize complex spa-tiotemporal cardiac dynamics within ex-vivo whole-heart ex-perimental preparations. Synchrony among voltage and calcium signals allows us to unveil novel multi-scale and multi-physics couplings at the ventricular scale and quantify features that define the intrinsic nonlinearities of the observed phenom-ena. Within such a complex scenario, we propose a rigorous methodological analysis comparing and contrasting multiple cardiac alternans onset and evolution indicators for rabbit pacing-down restitution protocols. We introduce a novel integral index quantified upon voltage and calcium signals, validated against well-accepted post-processing analyses, and generalized in terms of statistical restitution curves obtained under four different thermal states. Our study suggests that such a novel indicator can further advance our predictability on alternans onset, linking the concurrent evolution to an innovative quan-tification of the characteristic length obtained for both voltage and calcium at different thermal states.more » « less
