Local Entropy as Determinant for Wavebreaks and Ventricular Arrhythmia in Langendorff-Perfused Guinea-Pig Hearts

Ilija Uzelac and Flavio Fenton
Georgia Institute of Technology


Aims: Alternans or beat to beat variations are manifested through variations of action potential duration (APD), both temporally and spatially. Out of phase alternans (spatially discordant alternans) are known promoters of arrhythmogenesis, leading to waveblocks and wave-reentry. Steepness of restitution-based curves of APD versus diastolic interval are commonly used as predictor arrhythmias, however with limited applicability on a whole heart scale. In this study we use optical mapping method to obtain APD maps before the initiation of ventricular arrhythmia and non-linear technique of local entropy calculation for further insights on APD dispersion complexity. Local entropy and its short and long-term variability are aimed to be determinants of wavebreaks and arrhythmogenesis.

Methods: Isolated rabbit hearts were Langendorff perfused and stained with Di-4-ANBDQPQ Vm dye. Series of images were obtained at 128 x 128 pixels at 500 FPS. Hearts were paced at PCLs from 400 to 130 ms or until arrhythmia occurs. Spatial maps of APD dispersion were calculated for both even and odd beats, and subsequent APD dispersion maps for both even and odd beats as a local difference in APD from the mean APD value. Micro-states were defined as pairs of local APD values from both even and odd dispersion maps. Entropy was defined statistically as probability of occurrence of a given micro-state in respect to neighboring micro-states.

Results: Discordant alternans occurring at fast PCLs lead to conduction block with further degradation into complex ventricular arrhythmia. Increased APD dispersion lead to local entropy decrease, which proved to be suitable determinant for prognosis of wavebreaks, and their localization through classification of local entropy values across different PCLs.

Conclusions: Waveblocks and reentry are typically caused by discordant alternans and through calculations of locally defined entropy, a prognosis can be made about arrhythmia induction and its spatial localization.