Activation and repolarization of the normal human heart under complete physiological conditions

Abstract

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...

Computer Three‐Dimensional Anatomical Reconstruction of the Human Sinus Node and a Novel Paranodal Area

“…The leading pacemaker site can, however, move spontaneously along the terminal crest of the right atrium, a phenomenon known as the wandering pacemaker. In open heart surgery, patients and in healthy individuals, the leading pacemaker site has been shown to be located anywhere along the terminal crest between the openings of the superior and inferior caval veins (Boineau et al, 1988;Ramanathan et al, 2004;Ramanathan et al, 2006). Such findings are in agreement with studies on smaller mammals.…”

Left Ventricular Form and Function Revisited: Applied Translational Science to Cardiovascular Ultrasound Imaging

“…Recent investigations in humans have confirmed that the earliest epicardial electrical break-through occurs in the right ventricular free wall and the anterior LV wall, and then travels in an apex-to-base direction (36). The basal posterior wall is the last region to be activated, which occurs during the down-slope of the R-wave (36). The timing and sequence of electrical excitation in the ventricles is influenced by the impulse propagating through the His-Purkinje system and the anistropic nature of myocardium where propagation velocities are faster along rather than across the fibers (35,37).…”

“…Recent investigations in humans have confirmed that the earliest epicardial electrical break-through occurs in the right ventricular free wall and the anterior LV wall, and then travels in an apex-to-base direction (36). The basal posterior wall is the last region to be activated, which occurs during the down-slope of the R-wave (36).…”

Application of the Method of Fundamental Solutions to Potential-based Inverse Electrocardiography

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