An Integrated Electrophysiological and Structural Investigation of Cardiac Arrythmias Mechanisms in an Ex-Vivo Rabbit Model
The effective treatment of complex cardiac arrhythmias is currently limited by a disconnect between clinical diagnostics and the underlying pathophysiology. While 12-lead ECGs lack spatial resolution and invasive catheters provide only localized contact data, neither alone captures the full spatiotemporal complexity of fibrillation. This study compared panoramic optical mapping, electrical contact mapping, and tissue structure to link cellular activity directly with clinical signals and the underlying substrate.
Simultaneous optical and electrical recordings in ex vivo rabbit hearts (n=16) were performed. Independent Component Analysis (ICA) was used to isolate atrial signals from ventricular noise. It was followed by comparing the mapping modalities using Dominant Frequency (DF), Fluorescence, Potential, Organization Index, and Local Activation Time (LAT) maps. Finally, the functional data was correlated with Hematoxylin & Eosin histology to quantify nuclear density, myofiber disarray, and interstitial space expansion.
ICA successfully isolated high-fidelity signals for comparison. In organized rhythms, spatial maps and activation times aligned closely and identified similar regions of earliest activation. DF matched between optical and electrical modalities during sinus rhythm (Sinus Rythm: 2.72 vs 2.80 Hz) and sinus tachycardia (ST: 4.73 vs 4.67 Hz). Notably, optical activation consistently preceded electrical earliest activation time points.
Modality agreement was not as similar as the rhythms became disorganized. In atrial fibrillation (AF) within the right atrium, optical mapping indicated a DF of 5.97 ± 0.89 Hz, while electrical electrodes recorded fractionated signals with lower frequencies (5.08 ± 2.50 Hz) and low organization (OI: 0.33 ± 0.13). Similar trends were observed in the left AF, where DF aligned closely between optical (2.30 Hz) and electrical (2.28 Hz) modalities, but electrical recordings significantly underestimated organization (OI: 0.15) compared to optical mapping (OI: 0.74).
Ventricular fibrillation (VF) displayed spatial pattern divergence between fluorescence and potential maps, although LAT maps indicated similar earliest activation regions. VF DF measured 5.40 ± 0.60 Hz optically compared to 6.40 ± 0.51 Hz electrically. Histological analysis confirmed arrhythmic hearts possessed significantly higher nuclear density and structural remodeling. These samples exhibited interstitial expansion and disarray scores of 1–2 relative to 0 in controls.
This study establishes a direct link between structural heterogeneity and functional divergence. Arrhythmic hearts displayed acute remodeling characterized by significant myofiber disarray and interstitial space expansion. This interstitial widening acts as a functional surrogate for microstructural uncoupling, which disrupts lateral gap junction communication and stabilizes re-entrant drivers. This work defines the physical limits of surface-based mapping. This study demonstrate that while contact electrodes capture the temporal periodicity of fibrillation, the spatial complexity of the arrhythmogenic substrate requires a multimodal approach for characterization.