Background: Sudden cardiac death remains the leading cause of death, claiming more than 1000 lives per day in the United States alone. Noninvasive means to diagnose rhythm disorders of the heart have relied heavily on the 12-lead electrocardiogram and, to a lesser extent, on higher-resolution body-surface mapping. These lack sensitivity and specificity due to the smoothing effect of the torso volume conductor. In contrast, noninvasive electrocardiographic imaging (ECGI) reconstructs potentials, electrograms, and activation sequences directly on the heart surface from body-surface electrocardiograms and has been applied in animal as well as clinical studies. This presentation summarizes the application of ECGI for imaging epicardial arrhythmogenic substrates and associated properties, in particular, dispersion of myocardial repolarization, fractionated electrograms, and heterogeneous multipolar potential distributions. Methods: Electrocardiographic imaging was evaluated in a canine model of temperature-induced dispersion of myocardial repolarization through localized wan-ning and cooling and in 3 patients with preserved left ventricular ejection fraction (>= 50%) undergoing open heart surgery. Noninvasively reconstructed epicardial potentials, electrograrns (and derived measures), as welt as activation sequences were compared with their measured counterparts. Results: Epicardial measures of dispersion of repolarization (activation recovery intervals [ARIs] and QRST integrals) accurately reflected the underlying repolarization properties: prolonged ARIs and increased QRST (warming), shortened ARIs and decreased QRST (cooling), and gradients of adjacent prolonged and shortened ARIs (increased and decreased QRST) during simultaneous warming and cooling. In open-heart surgery patients, ECGI reflected the underlying arrhythmogenic substrate by noninvasively reconstructing fractionated electrograms (cross-correlation with measured electrograms = 0.72 +/- 0.25), regions of heterogeneous multipolar potential distributions, and areas of slow conduction. Conclusion: These studies demonstrate that ECGI can capture and localize noninvasively important electrophysiologic properties of the heart. Its clinical significance lies in mapping arrhythmogenic substrates, evaluation and guidance of therapy, and risk stratification. (c) 2007 Elsevier Inc. All rights reserved.