Transvenous pacing leads are regularly placed in the right ventricular (RV) apex. Pediatric patients can develop myopathic changes after long-term RV apical pacing. Left ventricular (LV) mechanical dyssynchrony, estimated with echocardiography, may explain the acute decrease in LV function and long-term histopathologic changes. Ts-4w is an established echocardiographic measurement of LV synchrony, using tissue Doppler imaging (TDI). The purpose of this study was to determine whether TDI could identify acute changes in LV synchrony during pacing from different RV sites. We prospectively measured Ts-4w and Doppler-derived cardiac output after 5 minutes of pacing in 19 subjects undergoing catheter ablation. Each subject underwent pacing at 4 sites in random order: high right atrium, high RV septum (septal), RV outflow tract, and RV apex. Ts-4w was measured during sinus rhythm and each pacing protocol, with a value >65 ms defining mechanical dyssynchrony. Ts-4w during high right atrial (32.6 ± 17.6 ms) and septal (28.9 ± 10.9 ms) pacing were not different from sinus rhythm (39.5 ± 15.5 ms). RV apex (85.7 ± 18.4 ms) and RV outflow tract (84.2 ± 20.4 ms) pacing induced mechanical dyssynchrony (p <0.0001). In conclusion, TDI demonstrated significant differences in LV synchrony related to pacing site. Ts-4w may be useful to determine ideal lead placement because it correlates with acutely improved hemodynamics.
There are limited studies in pediatrics regarding the study of tissue Doppler imaging (TDI) and ventricular dyssynchrony. We wished to determine whether TDI, by assessing mechanical synchrony, could be used to optimize pacemaker lead placement in pediatric subjects. Specifically, the purpose of this study was to determine whether TDI could demonstrate significant changes in left ventricular (LV) synchrony when pacing from different right ventricular (RV) sites. A second objective was to examine whether a relation existed between dyssynchrony and noninvasive measurements of cardiac output in the acute setting when pacing. Our primary hypothesis was that there was significantly more LV dyssynchrony when pacing in the RV apex compared to pacing in other areas.
Methods
The study population consisted of patients undergoing electrophysiologic study and catheter ablation of an arrhythmogenic substrate at Children’s Medical Center (Dallas, Texas). Subjects were required to have echocardiographic documentation of a structurally normal heart before the study. Exclusion criteria included abnormal cardiac function, defined as an ejection fraction <50% and/or fractional shortening <30%, documented structural cardiac abnormality, and lack of signed parental informed consent.
From September 2007 to April 2008, 19 patients were investigated. There were 9 male and 10 female subjects (mean age 12.7 ± 3.1 years) referred for catheter ablation of re-entrant supraventricular tachycardia (i.e., atrioventricular nodal reentrant tachycardia or atrioventricular reentrant tachycardia). The study was approved by the University of Texas Southwestern Medical Center (Dallas, Texas) and Children’s Medical Center institutional review boards, and all subjects’ parents gave informed consent before enrollment.
Studies were performed with a patient under general anesthesia. For electrophysiologic study and catheter ablation, 4 pacing catheters were placed in the usual locations (high right atrium, His, RV apex, and coronary sinus) through a femoral vein approach. Confirmation of catheter placement was made by electrogram and fluoroscopic image. Based on clinical indications, catheter ablation was performed with radiofreqency energy or cryotherapy at the discretion of the attending electrophysiologist. Subsequent electrophysiologic testing confirmed tachycardia substrate elimination in all patients.
Pacing and echocardiographic data acquisition was performed during the postablation waiting period, thus not increasing procedure duration. All patients had stable sinus rhythm. None had preexcitation or conduction delay. After baseline measurements during sinus rhythm, a randomized pacing order was assigned to each patient for the high right atrium (superior right atrium in proximity to superior vena cava–right atrial junction), septal (just beneath the annulus of the septal and anterior tricuspid valve leaflets), RV outflow tract (mid septal position adjacent to the moderator band insertion), and RV apex (most distal and inferior location obtainable). Random permutation was used to generate all possible pacing orders. Each was placed in a blank envelope to be selected (before each study) by support personnel initiating the actual pacing. Pacing was performed at 2 times diastolic threshold with a standard 5Fr or 6Fr quadripolar catheter, the distal pacing electrodes of which had 2-mm spacing. The high right atrial site was used as a control for the effect of pacing rate alone. Pacing rate was 30% above a patient’s baseline heart rate to suppress any intrinsic heart rhythm. After 5 minutes of pacing, data collection commenced, and a washout time of 2 minutes was used between pacing conditions. The principal investigator (A.J.V.) was blinded to each study condition, positioned separately, and thus unable to view fluoroscopic images or physiologic monitors during data acquisition.
Apical 2-chamber and 4-chamber echocardiographic views were obtained during each pacing condition and at baseline with a 4-MHz transducer (Sequoia C256, Acuson Corp., Mountain View, California). In addition, a parasternal long-axis view was acquired at the onset of the case to measure aortic annulus size. Standard 2-dimensional and color Doppler data (3-second clips) were saved in cine-loop format. For TDI, frame rates and pulse repetition frequencies varied depending on the sector width of the range of interest.
In each pacing condition, TDI analysis was performed by placing the sample volume in the LV basal portions of the septal and lateral walls (using apical 4-chamber images) and the anterior and inferior walls (using apical 2-chamber images). Pulse-wave Doppler images of the aortic outflow tract were also acquired to estimate an echocardiographically derived estimate of cardiac output using the following equation: cardiac output (liters per minute) = HR (beats per minute) × CSA (square centimeters) × TVI (centimeters), where HR represents paced (or baseline) heart rate, CSA cross-sectional area of the aortic valve annulus (valve annulus squared × 0.785), and TVI time velocity integral by planimetry of the area under the Doppler curve of the aortic valve. Each parameter obtained echocardiographically was repeated 3 consecutive times, and an average was used for analysis.
All echocardiographic data were stored for off-line analysis using commercially available software (KinetDx, Siemens, Malvern, Pennsylvania). Images were examined by the primary investigator, where cardiac output (derived from the equation) was determined, and tissue Doppler estimates of LV dyssynchrony were quantified. Cardiac output for each condition was normalized to individual subjects’ baseline output for analysis.
Synchrony was defined and measured using previous standards incorporating Ts-4w in adults because there are no established standards for pediatric patients. Using the concept of electromechanical delay, defined as the delay between onset of the QRS complex on surface electrocardiogram and peak systolic velocity of a chamber wall derived by TDI, dyssynchrony was quantified as the time difference between the shortest and longest electromechanical delays among the 4 LV walls. Studies in adults have established the normal value for Ts-4w to be 35 ± 20 ms and adult patients who are paced in the RV apex have a Ts-4w of 87 ± 45 ms. Bax et al determined optimum ventricular synchrony as that resulting in clinical improvement and reverse remodeling. Using receiver operating curve modeling a value of 65 ms provided the best distinction between responders and nonresponders. For our study a cutoff >65 ms was used to define dyssynchrony.
Statistical calculations were performed using SAS 9.1 (SAS Institute, Cary, North Carolina). Results are presented as mean ± SD. Data were compared using repeated measures analysis of variance for within-subjects comparisons. Multiple comparisons were performed using the Tukey-Kramer method. Using adult reference values for dyssynchrony yielded >95% power for repeated measures test and >80% for multiple paired comparisons. For all comparisons, a p value <0.05 was considered statistically significant.
Results
There were no significant biases in gender or indication for electrophysiologic study (9 male and 10 female subjects). Mean age of the study population was 12.7 ± 3.1 years (range 8.5 to 17.2).
Figure 1 shows each subject’s respective Ts-4w measurement during each pacing condition. Overall, there was no significant difference in mechanical synchrony, as measured by Ts-4w, among the baseline (39.5 ± 15.5), high right atrial (32.5 ± 17.6), and septal (28.9 ± 10.9) conditions. RV outflow tract (84.2 ± 20.4) and RV apex (85.7 ± 18.4) pacing resulted in significant dyssynchrony, well above the >65-ms cutoff. Ts-4w values during RV outflow tract and RV apex pacing were not significantly different (p = 0.78) but were significantly prolonged compared to control conditions (p <0.0001), high right atrial pacing (p <0.0001), and septal pacing (p <0.0001).
