Spatial heterogeneity of APD under long QT conditions: characterisation and relationship to sinus activation sequence

Abstract Aims Enhanced spatial variation in ventricular action potential duration (APD) is known to contribute to arrhythmia development under long QT conditions, although the causes of APD variation are unclear. Specifically, between-individual variation in the locations of pro-arrhythmic long APD islands and associated repolarisation gradients is difficult to explain in the context of established regional variation in electrophysiology. This study aimed to explore the mechanisms underlying the spatial heterogeneity of ventricular APD under baseline and long QT conditions. Methods and Results New Zealand White rabbit hearts (n = 26) were Langendorff-perfused with oxygenated Tyrode’s solution and loaded with blebbistatin and FluoVolt. Optical mapping of transmembrane voltage from the anterior epicardial surface of the right (RV) and left ventricles (LV) during sinus rhythm revealed a strong inverse relationship between activation time and APD90 in all hearts (linear regression slope: -0.85 ± 0.17, r2: 0.60 ± 0.12, p  Conclusion Ventricular sites with distinct sinus activation times exhibit different electrophysiological properties which contribute to enhanced spatial heterogeneity of APD under long QT conditions.