Improved Activation Time Assignment of Unipolar Electrograms from Ischemic Canine Epicardium EDWARD B. CAREF, PH.D., GJIN NDREPEPA, M.D., GIOIA TURITTO, M.D., MARK RESTIVO, PH.D., and NABIL EL-SHERIF, M.D. From the State University of New York Health Science Center at Brooklyn and NY Harbor VA Healthcare System, Brooklyn, New York Aims: The present study attempts to develop an objective, statistically based set of criteria for activation time determination from unipolar electrograms (U-EGMs) using a standard of activation related to biophysical theory. Methods: A high-resolution assembly of U-EGMs obtained from the epicardial surface of the canine postinfarction heart were analyzed in order to achieve the best prediction of local versus distant activation. An activation time standard (ATS) consisted of three properties: (1) propagation of activation, evidenced by a linear temporal shift of waveforms from closely spaced U-EGMs with little or no decay in amplitude; (2) cycle length-dependent changes of those propagating waveforms; and (3) evidence of electrotonic deflections, seen as nonpropagating potentials having decaying amplitude with distance. Results: A number of U-EGM features were calculated and subjected to analysis by comparing their occurrence with the ATS. A discriminant function analysis incorporating multiple features (Voltage, −dV/dt and Ratio) of major U-EGM deflections improved prediction of activation time of complex fractionated EMGs from ischemic canine epicardium to 90%. Conclusion: A unique discriminant function based on sound biophysical principles markedly improved prediction of activation time of complex U-EGMs from ischemic canine epicardium. A computerized version of the algorithm could be developed to provide more accurate activation maps for both basic and clinical use. (PACE 2011; 34:1105–1115) biomedical engineering, electrocardiogram, electrophysiology—basic, mapping, new technology Introduction Accurate activation mapping techniques are required in both the basic and clinical settings to extend our understanding and treatment of arrhythmias. Reconstruction of the electrical ac- tivation sequence assumes accurate identification of local myocardial activation. Detection moment of activation is usually based on extracellular signals that only indirectly indicate the process of activation occurring at the cellular membrane. 1 Because extracellular signals result from weighted spatial averaging of electrical activity occurring throughout the heart, 2 they do not exclusively reflect local activity. This lack of selectivity is a significant problem when multiphasic waveforms are recorded. This is commonly seen in recordings from infarcted and scarred tissue 3,4 and more This work was supported by Department of Veterans Affairs Medical Research Fund grants to Drs. El-Sherif and Restivo, and a Fulbright Award to Dr. Ndrepepa. Address for reprints: Nabil El-Sherif, M.D., Cardiology Division, NY Harbor VA Healthcare System, 800 Poly Place, Brooklyn, NY 11209. Fax: 718-630-3740; e-mail: nelsherif@aol.com Received December 12, 2010; revised February 5, 2011; accepted March 2, 2011. doi: 10.1111/j.1540-8159.2011.03116.x recently from left atrium in patients with chronic atrial fibrillation. 5 In these cases, it is difficult to determine that deflections are due to local activation or whether the tissue near the electrode even is capable of excitation. The majority of theoretical and experimental work on the analysis of extracellular electrograms (EGMs) has been reported for unipolar record- ings. 6–13 However, while many experimental studies were designed to test the accuracy of EGM features to predict the moment of activation and were compared with an activation time standard (ATS), no suitable standard was applied. Recently, noncontact three-dimensional mapping systems have been widely utilized in electrophysiological laboratories for mapping of cardiac activation. Synthesized “virtual” unipolar EGMs (U-EGMs) are utilized to localize the site of origin of focal ventricular tachycardias, 14 for understanding the underlying mechanism(s) of complex fractionated atrial EGMs in patients with atrial fibrillation, 5 and in confirming isthmus block during radiofrequency ablation of atrial flutter. 15 However, the theoretical basis of the “virtual” U-EGM is not clear. The present study attempts to develop an objective, statistically based set of criteria for activation time determination from U-EGMs using a standard of activation related to biophysical C 2011, The Authors. Journal compilation C 2011 Wiley Periodicals, Inc. PACE, Vol. 34 September 2011 1105