Noninvasive cardiac activation imaging of ventricular arrhythmias during drug-induced QT prolongation in the rabbit heart

Abstract

Background: Imaging myocardial activation from noninvasive body surface potentials promises to aid in both cardiovascular research and clinical medicine.

Objective: To investigate the ability of a noninvasive 3-dimensional cardiac electrical imaging technique for characterizing the activation patterns of dynamically changing ventricular arrhythmias during drug-induced QT prolongation in rabbits.

Methods: Simultaneous body surface potential mapping and 3-dimensional intracardiac mapping were performed in a closed-chest condition in 8 rabbits. Data analysis was performed on premature ventricular complexes, couplets, and torsades de pointes (TdP) induced during intravenous administration of clofilium and phenylephrine with combinations of various infusion rates.

Results: The drug infusion led to a significant increase in the QT interval (from 175 ± 7 to 274 ± 31 ms) and rate-corrected QT interval (from 183 ± 5 to 262 ± 21 ms) during the first dose cycle. All the ectopic beats initiated by a focal activation pattern. The initial beat of TdPs arose at the focal site, whereas the subsequent beats were due to focal activity from different sites or 2 competing focal sites. The imaged results captured the dynamic shift of activation patterns and were in good correlation with the simultaneous measurements, with a correlation coefficient of 0.65 ± 0.02 averaged over 111 ectopic beats. Sites of initial activation were localized to be ~5 mm from the directly measured initiation sites.

Conclusions: The 3-dimensional cardiac electrical imaging technique could localize the origin of activation and image activation sequence of TdP during QT prolongation induced by clofilium and phenylephrine in rabbits. It offers the potential to noninvasively investigate the proarrhythmic effects of drug infusion and assess the mechanisms of arrhythmias on a beat-to-beat basis.

Keywords: 3-dimensional; 3-dimensional cardiac electrical imaging; 3D; 3DCEI; BSPM; CC; CL; Cardiac imaging; Cardiac mapping; EAD; ECG; Electrocardiography; LE; LV; PVC; QT prolongation; QTc; RV; RVOT; Rabbit model; TAT; TdP; Torsades de pointes; UFCT; body surface potential map; correlation coefficient; cycle length; early afterdepolarization; electrocardiographic/electrocardiogram; left ventricle/ventricular; localization error; premature ventricular complex; rate-corrected QT; right ventricle/ventricular; right ventricular outflow tract; torsades de pointes; total activation time; ultrafast computed tomography.

Figure 1

(A) The drug infusion protocol. (B) Example of torsades de pointes. (C) The change of cycle length, QT interval, and rate-corrected QT (QT_c) interval during the drug infusion.

Figure 2

Comparison between the measured and imaged activation sequences for two premature ventricular contractions (A) and (B) in rabbit 1. The activation sequence is color coded from red to blue, corresponding to earliest and latest activations. ECG lead I is shown with red boxes indicating the beats analyzed. The activation sequence is displayed on epicardial and endocardial surfaces, respectively, in an anterior view. The measured initial site and the estimated initial site of activation are marked by a black asterisk and a purple arrow.

Figure 3

Comparison between measured and imaged activation sequences for a couplet (A) and (B) in rabbit 7. The epicardial and endocardial surfaces are displayed in a right anterior view for the beat in (A) and in a left top view for the beat in (B), respectively.

Figure 4

Comparison between measured and imaged activation sequences for a premature ventricular complex preceding ventricular asystole in rabbit 8. The epicardial and endocardial surfaces are displayed respectively in an anterior view.

Figure 5

(A) Selected channels of ECG tracings (CH1-CH9) in body surface potential mapping for 3DCEI and ECG lead I for a ten-beat torsades de pointes (TdP) in rabbit 2. “L” indicates the initiation site located in the left ventricle and “R” indicates the initiation site located in the right ventricle. (B) Selected bipolar electrograms for the first two beats of this TdP. In the left column, red dots and letters from a to j represent the locations for the selected plunge-needle electrodes in the heart. In the middle and right columns, the activation time for each bipolar electrogram is displayed in red for the first two beats of this TdP. Panels (C), (D), and (E) show the comparison between measured and imaged activation sequences for beat 2, beat7, and beat 9 of this TdP, respectively. The epicardial and endocardial surfaces are displayed in an anterior view.

Figure 6

Comparison between measured and imaged activation sequences for a six-beat TdP in rabbit 3. Panels (A), (B), and (C) show the activation sequence for the first three beats, respectively. The epicardial and endocardial surfaces are displayed in an anterior view (A), a left anterior view (B), and a right posterior view (C) respectively.