Over 7 million people worldwide die annually from erratic heart rhythms (cardiac arrhythmias), and many more are disabled. Yet there is no imaging modality to identify patients at risk, provide accurate diagnosis and guide therapy. Standard diagnostic techniques such as the electrocardiogram (ECG) provide only low-resolution projections of cardiac electrical activity on the body surface. Here we demonstrate the successful application in humans of a new imaging modality called electrocardiographic imaging (ECGI), which noninvasively images cardiac electrical activity in the heart. In ECGI, a multielectrode vest records 224 body-surface electrocardiograms; electrical potentials, electrograms and isochrones are then reconstructed on the heart's surface using geometrical information from computed tomography (CT) and a mathematical algorithm. We provide examples of ECGI application during atrial and ventricular activation and ventricular repolarization in (i) normal heart (ii) heart with a conduction disorder (right bundle branch block) (iii) focal activation initiated by right or left ventricular pacing, and (iv) atrial flutter.Disruptions of the regular heart rhythm, called cardiac arrhythmias, constitute a major cause of death and disability among the world's population. Although modern medicine relies heavily on noninvasive imaging modalities such as CT or magnetic resonance imaging to guide therapy, an equivalent modality for imaging cardiac arrhythmias is not yet available. Noninvasive diagnosis of arrhythmias is currently based on the standard 12-lead ECG, which involves measuring electric potentials from very few points on the body surface. Taken far away from the heart, these measurements lack sensitivity (may fail to detect abnormal activity) and specificity (may fail to accurately classify the arrhythmia or determine its location). Here we describe ECGI 1 , a new noninvasive imaging modality for cardiac electrophysiology and arrhythmias. This technique images potentials, electrograms and activation sequences (isochrones) on the epicardium, the outer surface of the heart. The ECGI methodology used in the human studies presented here builds on 20 years of development in our laboratory (Fig. 1). Many aspects of the approach were tested and validated experimentally in normal and abnormal canine hearts 2-7 . Building on these animal studies, we recently developed ECGI for human application. In this report we describe the first ECGI application in human subjects using our current imaging methodology.

Knowledge of normal human cardiac excitation stems from isolated heart or intraoperative mapping studies under nonphysiological conditions. Here, we use a noninvasive imaging modality (electrocardiographic imaging) to study normal activation and repolarization in intact unanesthetized healthy adults under complete physiological conditions. Epicardial potentials, electrograms, and isochrones were noninvasively reconstructed. The normal electrophysiological sequence during activation and repolarization was imaged in seven healthy subjects (four males and three females). Electrocardiographic imaging depicted salient features of normal ventricular activation, including timing and location of the earliest right ventricular (RV) epicardial breakthrough in the anterior paraseptal region, subsequent RV and left ventricular (LV) breakthroughs, apex-to-base activation of posterior LV, and late activation of LV base or RV outflow tract. The repolarization sequence was unaffected by the activation sequence, supporting the hypothesis that in normal hearts, local action potential duration (APD) determines local repolarization time. Mean activation recovery interval (ARI), reflecting local APD, was in the typical human APD range (235 ms). Mean LV apex-to-base ARI dispersion was 42 ms. Average LV ARI exceeded RV ARI by 32 ms. Atrial images showed activation spreading from the sinus node to the rest of the atria, ending at the left atrial appendage. This study provides previously undescribed characterization of human cardiac activation and repolarization under normal physiological conditions. A common sequence of activation was identified, with interindividual differences in specific patterns. The repolarization sequence was determined by local repolarization properties rather than by the activation sequence, and significant dispersion of repolarization was observed between RV and LV and from apex to base.noninvasive electrocardiographic imaging ͉ normal cardiac activation and repolarization ͉ normal sinus rhythm U nderstanding normal cardiac excitation provides a necessary baseline for understanding abnormal cardiac electrical activity and rhythm disorders of the heart, a major cause of death and disability. So far, knowledge of normal human cardiac excitation has been obtained mostly through extrapolation from animal studies, including canine (1, 2) and chimpanzee (3). In addition, human data have been obtained from intraoperative epicardial mapping (4-7) and isolated human hearts (8). Extrapolation of animal studies to humans is limited by interspecies differences in anatomy and electrophysiology. Also, the animal and human studies were conducted under nonphysiological conditions (e.g., anesthesia effects and heart exposure during intraoperative mapping; effects of isolation and absence of neural inputs, mechanical loading, and normal perfusion in isolated heart studies). Until now, it has not been possible to study cardiac excitation in intact healthy subjects under normal physiological conditions because of the unavailabili...

Results suggest that (1) when accompanied by fusion, LV pacing alone can be as effective as biventricular pacing for electrical resynchronization; (2) right ventricular pacing is not effective for resynchronization; and (3) efficacy of CRT depends strongly on the patient-specific electrophysiologic substrate.

OBJECTIVES/BACKGROUND-Cardiac arrhythmias are a leading cause of death and disability. Electrocardiographic imaging (ECGI) is a noninvasive imaging modality that reconstructs potentials, electrograms, and isochrones on the epicardial surface from body surface measurements. We previously demonstrated in animal experiments through comparison with simultaneously measured epicardial data the high accuracy of ECGI in imaging cardiac electrical events. Here, images obtained by noninvasive ECGI are compared to invasive direct epicardial mapping in open heart surgery patients.METHODS-Three patients were studied during sinus rhythm and right ventricular endocardial and epicardial pacing (total of five datasets). Body surface potentials were acquired preoperatively or postoperatively using a 224-electrode vest. Heart-torso geometry was determined preoperatively using computed tomography. Intraoperative mapping was performed with two 100-electrode epicardial patches. CONCLUSIONS-Despite limitations due to nonsimultaneous acquisition of the surgical and noninvasive data under different conditions, the study demonstrates that ECGI can capture important features of cardiac electrical excitation in humans noninvasively during a single beat. It also shows that general excitation patterns and electrogram morphologies are largely preserved in open chest conditions. RESULTS-Noninvasive

The results demonstrate that, in the clinical application, it is not necessary to include torso inhomogeneities for noninvasive reconstructions of epicardial potentials, EGMs, and activation sequences.