Key result
Rapid pacing induces period-4 dynamics prior to VF in ~50% of ex-vivo human hearts.
Why the study?
Higher-order periodicities beyond repolarization alternans are theoretically expected to link cellular dynamics to ventricular fibrillation, but have very limited experimental evidence.
The detection of higher-order periodicities in ex-vivo human ventricles provides experimental evidence for the period-doubling route to chaos as a mechanism for ventricular fibrillation initiation.
Hypothesis-generating for period-doubling in human VF; leaves open in vivo relevance and should not change practice.
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.
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Iravanian et al. (2023) studied Explanted human hearts (Ventricular Fibrillation) (n=6). Increasing pacing rate vs. Baseline pacing (500 ms) was evaluated on Detection of a 1:4 peak (period-4 dynamics) before induction of ventricular fibrillation. Progressively increasing pacing rates induced a prominent and statistically significant 1:4 peak corresponding to period-4 dynamics in three of six studied ex-vivo human hearts prior to VF induction.
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