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.

Fig. 1.

Epicardial potentials during ventricular activation (subject no. 1). (A) Five milliseconds before epicardial breakthrough. Cartoon (Right) represents activation front as a dipole layer approaching the RV epicardium generating positive potentials (+ sign). Positive potentials and local maxima cover the RV (Left). (B) RVB. Upon breakthrough, a local intense potential minimum (blue, −) appears at the breakthrough site (Left); the cartoon (Right) shows a schematic of the activation front and dipole source distribution at this time. (C) Epicardial potential map during the middle of QRS (40 ms; Lead II of ECG is shown for timing). Multiple breakthroughs are seen (minima, dark blue): RVB, labeled 1; left-anterior-paraseptal breakthrough, labeled 2; inferior-RVB, labeled 3; and apical breakthrough, labeled 4. Lateral view shows extensive maximum on LV apex (+ sign). (D) Epicardial potential map during late QRS (60 ms; see Lead II). Apical maximum seen at 40 ms has migrated towards LV posterolateral base (posterior view). (E) Summary of early activation sites imaged by ECGI. Numbers and their corresponding locations indicate number of subjects that had a breakthrough at that location. RV, right ventricle; LV, left ventricle; Ao, aorta.

Fig. 2.

Morphology of selected electrograms over entire RV and LV. (A) Anterior and posterior heart outlines showing electrogram locations (anatomical positions listed below). (B) Electrograms from subject no. 1 from RV locations 1–4 (Left) and from LV locations 5–8 (Right). RVOT, RV outflow tract.

Fig. 3.

Ventricular and atrial isochrones. Ventricular epicardial isochrones from subjects nos. 1 (A), 3 (B), and 4 (C). Numbers indicate location of early activation sites (adapted from figure 2C of ref. 9). (D) Atrial activation isochrones from subject no. 4. LAA, left atrial appendage; PV, pulmonary veins; SVC, superior vena cava. RVOT, RV outflow tract.

Fig. 4.

Ventricular repolarization (subject no. 1). (A) Anterior and diaphragmatic views of epicardial potential maps during T wave. Maps during T wave onset (Upper) and peak (Lower) are shown (see Lead II for timing). (B) Epicardial recovery-time isochrones. (C) Epicardial ARI map.