Effect of Coupling Interval and Pacing Cycle Length on Morphology of Paced Ventricular Complexes
Implications for Pace Mapping
Background Ventricular pace mapping is performed by comparing the QRS morphology of ventricular paced complexes to that of a template arrhythmia, either a premature ventricular depolarization or a QRS complex during ventricular tachycardia. The objective of this study was to evaluate the effect of coupling interval and pacing cycle length on QRS morphology.
Methods and Results The study population consisted of 20 patients (mean age, 38±16 years) undergoing a clinically indicated electrophysiology procedure. In the first 10 patients, the effect of coupling interval on the morphology of single paced ventricular complexes was evaluated visually and by signal processing techniques. Visually apparent differences in QRS morphology occurred in a mean of 4/12 electrocardiographic leads with a change in coupling interval of ≥100 ms. In the next 10 patients, the QRS complex morphology during ventricular overdrive pacing at cycle lengths of 600 and 300 ms was found to differ significantly in a mean of 4/12 leads. The QRS morphology during overdrive pacing differed significantly from that of a single paced complex whenever the pacing cycle length differed from the coupling interval of the single paced complex by >80 ms.
Conclusions The morphology of single paced QRS complexes may vary, depending on coupling interval, and the QRS morphology during overdrive pacing is affected by the pacing cycle length. During ventricular pace mapping, the coupling interval or cycle length of the template arrhythmia should be matched during pacing. If not, rate-dependent changes in QRS morphology that are independent of the pacing site may confound the results of pace mapping.
Pace mapping has proven useful in identifying target sites for ablation of ventricular tachycardia, particularly when the ventricular tachycardia is idiopathic.1 In addition, pace mapping of ventricular premature depolarizations may be useful in patients undergoing catheter ablation of symptomatic ventricular ectopy2 or in patients with documented but noninducible ventricular tachycardia in whom ventricular premature depolarizations that have the same morphology as the ventricular tachycardia complexes serve as a surrogate template for the ventricular tachycardia. Although it is known that ventricular premature depolarizations arising at the same site of origin may have different morphologies,3 4 5 no prior studies have examined the effect of variables such as coupling interval or pacing cycle length on the configuration of ventricular paced complexes. Depending on the degree of effect, the accuracy of pace mapping might be significantly impaired by changes in QRS morphology that are cycle length–dependent instead of site-dependent. Therefore, the purpose of this study was to examine quantitatively the effect of coupling interval on the morphology of single paced ventricular complexes and the effects of pacing cycle length on QRS morphology during ventricular overdrive pacing.
Rationale of Study Design
Pace mapping of ventricular premature depolarizations may be performed by comparing the morphology of the ventricular premature depolarization either to the morphology of single paced ventricular complexes or to the QRS morphology during ventricular overdrive pacing. Pace mapping of ventricular tachycardia is performed by comparing the QRS morphology during overdrive pacing to that of the tachycardia. Therefore, this study was designed to investigate the effects of both coupling interval and pacing rate on QRS morphology. In the first phase of the study, the effect of coupling interval on the configuration of single paced ventricular complexes was investigated; in the second phase, a single paced ventricular complex was compared with QRS morphology during ventricular overdrive pacing, and the effect of pacing cycle length on the QRS morphology during ventricular overdrive pacing was determined.
Characteristics of Subjects
The study group consisted of 20 patients who underwent an electrophysiology procedure at the University of Michigan Medical Center for evaluation and treatment of paroxysmal supraventricular tachycardia (15 patients), idiopathic ventricular tachycardia (3 patients), or atrial flutter (2 patients). Exclusion criteria consisted of atrial fibrillation, a sinus cycle length <600 ms, structural heart disease, or treatment with an antiarrhythmic medication. There were 6 men and 14 women, and their mean age was 38±16 years (±SD).
The electrophysiology procedures were performed after informed consent was obtained and in the fasting state. Quadripolar electrode catheters were positioned in the heart as clinically indicated. The 12-lead ECG and intracardiac electrograms were displayed on an oscilloscope and recorded on paper using a Mingograph 7 recorder (Siemens-Elema). Bipolar pacing was performed using the distal pair of electrodes of the quadripolar catheter, with an interelectrode distance of 2 mm. Pacing was performed with a programmable stimulator (Bloom Associates) using a stimulus strength of twice diastolic threshold and a stimulus duration of 2 ms.
The study protocol was performed, on completion of the radiofrequency ablation component of the electrophysiology procedure, during the 30-minute waiting period to confirm a successful outcome. Electrode catheters were positioned in the high right atrium and right ventricular apex. A right ventricular electrogram and either the frontal plane leads or precordial leads were recorded on paper at 25 mm/s, and an output from the recorder was connected to an FM magnetic tape recorder (Teac 130 TE), which had a sampling frequency of 12 kHz. Analog to digital conversion was performed from the digital analog tape at a sampling frequency of 1 kHz per channel, and the data were stored in separate files for later splicing. Data manipulations and analyses were performed in Matlab (Mathworks) using programs specifically designed for this study.
Single Paced Ventricular Complexes
There were 10 patients enrolled in the first component of the study. Atrial pacing was performed at a cycle length of 600 ms for eight beats, with a 1-second pause between pacing trains. A single ventricular extrastimulus was introduced at the maximal ventricular coupling interval, with the coupling interval then shortened in steps of 20 ms to the point of ventricular refractoriness. The pacing protocol was performed once while recording the frontal plane leads and a second time while recording the precordial leads. After digitization, each paced premature ventricular complex and the preceding QRS complex were windowed and saved to separate files for later analysis.
Ventricular Overdrive Pacing
The second component of the study was also performed in 10 patients. To simulate a single ventricular premature depolarization, atrial pacing was performed for eight beats at a cycle length of 600 ms and a single ventricular extrastimulus was introduced at a ventricular coupling interval of 400 ms. Ventricular overdrive pacing then was performed in trains of 12 stimuli at cycle lengths of 500, 450, 400, 350, and 300 ms; there was a 4-second pause between the pacing trains. To evaluate the effect of pacing cycle length on QRS morphology, ventricular pacing was also performed in trains of 12 stimuli at the longest cycle length to capture the ventricle without fusion and at a cycle length equal to the shortest coupling interval resulting in capture of a single ventricular extrastimulus. All pacing protocols were performed once while recording the frontal plane leads and a second time while recording the precordial leads.
In a pilot study, it was found that the QRS morphology during ventricular overdrive pacing was stable after the fifth beat of the pacing trains. Therefore, after digitalization of the recordings, the last five QRS complexes of each pacing train were averaged and stored in separate files for later analysis.
To quantitate the differences between two QRS complexes, previous investigators have used several signal processing techniques.6 7 8 9 10 One of the techniques consists of determination of the correlation coefficient between two signals, with a value greater than 0.9 identifying identical QRS complexes and a value less than 0.7 identifying a difference between two QRS complexes.10 This was one of the techniques used to compare QRS complexes in the present study. However, a limitation of this technique is that it is not sensitive to differences in amplitude (Fig 1⇓). Therefore, to increase the sensitivity in identifying differences between QRS complexes, the root mean square of the difference between two QRS complexes was also determined (Fig 1⇓). The root mean square of two signals is derived by taking the difference of the two signals at 1-ms intervals; this results in both positive and negative numbers for the duration of the signal (200 ms in our study). Every number is then raised to the second power before taking the square root of the mean. In our study, before performing root mean square analysis, a correlation coefficient as close as possible to a value of 1 was used to align QRS complexes. Based on the results of a pilot study, a root mean square of the difference that was >0.1 was considered to indicate a visually apparent difference in QRS morphologies, and a root mean square of the difference value of ≤0.1 was considered an indication that two QRS complexes did not differ significantly (Fig 2⇓).
Analysis of Paced QRS Complexes
For each patient in the first component of the study, the paced ventricular complex that had the longest coupling interval was used as the template for comparison with the other paced ventricular complexes. The correlation coefficient and root mean square of the difference signal between the template and each of the other paced ventricular complexes were determined.
In the second component of the study, the single paced ventricular complex that had a ventricular coupling interval of 400 ms was used as the template for comparison with the average of the last five QRS complexes of each overdrive pacing train. The root mean square of the difference signal between the template and the averaged QRS complex of each pacing train was determined.
Visual comparisons of the template paced ventricular complex and the last QRS complex of each pacing train were performed in each of the 12 ECG leads by two observers. The comparisons were graded on a scale of zero to 12, depending on the number of leads in which the QRS complexes appeared visually indistinguishable. The QRS morphology during overdrive ventricular pacing cycle lengths at two cycle lengths also was compared visually.
Continuous variables are expressed as mean±SD. ANOVA was used when comparing the changes in QRS morphology between more than two groups. Simple and square polynomial regression analysis was performed to evaluate the effect of coupling interval or pacing cycle length on QRS morphology (Statview, Abacus Concepts, Inc). A value of P<.05 was considered significant.
Single Paced Ventricular Complexes
In each of 10 patients, a single paced QRS complex at a coupling interval of 630±138 ms (range, 728 to 437) was used as the template for comparison with the paced ventricular complexes at shorter coupling intervals ranging from 720 to 200 ms. The differences in coupling interval between the template QRS complex and the other paced QRS complexes were calculated, and the paced QRS complexes were pooled into groups of 50 ms differences in coupling interval. Based on analysis by correlation coefficient, the QRS complexes had the same morphology as that of the template in a mean of 9.7±0.6 to 11.8±0.4 of 12 leads for differences in coupling interval of between 50 and 350 ms (Fig 3⇓). On the basis of the root mean square of the difference analysis, the QRS complexes had the same morphology as that of the template in a mean of 8.2±3.4 to 9.9±2.2 of 12 leads when the difference in coupling intervals ranged from 100 to 350 ms (Fig 4⇓).
For each of the 12 ECG leads, a regression analysis was performed between the difference in the coupling intervals of the template and paced QRS complexes and the root mean square of the difference between the template and the paced QRS complexes. This allowed identification of the critical difference in coupling intervals at which the QRS configuration became different. For example, Fig 5⇓ demonstrates the regression analysis for lead V4. At a root mean square of the difference of 0.1 V, the coupling interval difference is 260 ms. Therefore, in lead V4, paced QRS complexes can be expected to differ in morphology when their coupling intervals differ by more than 260 ms. This type of analysis is presented in tabular fashion in Table 1⇓. In all leads, there was a significant correlation between the root mean square of the difference and the coupling interval difference of the template and paced QRS complexes. The critical coupling interval at which QRS complexes differed based on the root mean square of the difference analysis ranged from 200 to 400 ms in the precordial leads (mean, 298±74 ms) and from 525 ms to extrapolated values of 900 ms in the frontal plane leads (mean, 720±181 ms, P<.001 compared with precordial leads, Table 1⇓). An example of the effect of coupling interval on the morphology of single paced QRS complexes is shown in Fig 6⇓.
Computerized Comparison of Premature Ventricular Complex and Paced QRS Morphology
Single paced ventricular complexes at a mean coupling interval of 403±2 ms served as a template for comparison with paced complexes at cycle lengths of 301±3, 353±6, 401±1, 450±2, and 500±1 ms. The root mean square of the difference between the single paced complex and the QRS complexes at the different pacing cycle lengths was correlated using a square polynomial regression analysis (Fig 7⇓). The root mean square of the difference was 0.03±0.01 V when comparing the single paced complex at a coupling interval of 400 ms to the ventricular complexes at a pacing cycle length of 400 ms. Differences from the template increased as the pacing cycle length was shortened or lengthened from 400 ms. Pacing cycle lengths of 340 and 460 ms corresponded to a root mean square of the difference of 0.1 V, indicating that visually apparent differences in the QRS complexes could be expected at pacing cycle lengths 60 ms shorter or longer than the coupling interval of the template QRS complex. Table 2⇓ shows the regression coefficient and the pacing cycle lengths that corresponded to a root mean square of the difference of 0.1 for each of the 12 leads (mean, 330±41 and 478±38 ms). The change in pacing cycle length compared with 400 ms was less for cycle lengths shorter than 400 ms than for cycle lengths longer than 400 ms (70±41 versus 78±38 ms, P<.01).
The morphology of the single paced complex at a coupling interval of 400 ms was compared visually with that of the last complex of a pacing train at cycle lengths of 300, 350, 400, 450, and 500 ms. Only at overdrive pacing cycle lengths of 500, 450, and 300 ms were the pace map scores statistically different from the template: 11.0±0.7, 11.2±1.2, and 10.7±2.7 (P<.02, ANOVA), respectively (Fig 8⇓).
Comparison of QRS Complexes During Ventricular Overdrive Pacing
Ventricular overdrive pacing was performed at two cycle lengths, 606±110 ms and 312±33 ms, with a mean difference of 293±107 ms. Differences in QRS morphology were evaluated visually by two observers. The mean pace map score was 7.5±2.1. There was no significant interobserver variation (7.7±2.1 versus 8.0±2.4, P=.35). Fig 9⇓ is an example from one of the 10 patients.
The results of this study demonstrate that the morphology of single paced QRS complexes may be significantly altered by changes in coupling interval and that the QRS complex morphology during trains of ventricular pacing may be significantly affected by changes in the pacing rate. Using a root mean square of the difference analysis, the morphology of single paced QRS complexes may be altered by changes in coupling interval as small as 200 ms, and the QRS complex morphology during overdrive pacing often differs from that of a single paced complex generated at the same site when the pacing cycle length differs from the coupling interval of the single complex by 80 ms or more. Furthermore, the rate-dependent changes in QRS configuration detected by root mean square of the difference analysis are often visually apparent. Therefore, when pace mapping is performed using a ventricular premature depolarization as a template, it is important that the coupling interval of the spontaneous premature complex be matched by the coupling interval of single paced ventricular complexes or by the cycle length of a pacing train.
In addition, when pace mapping of ventricular tachycardia is performed, it is important that the pacing cycle length be similar to the tachycardia cycle length. If the pacing cycle length of the paced complexes differs from the coupling interval of spontaneous premature depolarizations or from the cycle length of the ventricular tachycardia by more than approximately 80 ms, it is likely that the accuracy of the pace map will be confounded by changes in QRS morphology that are rate-dependent instead of site-dependent.
Previous investigators have used the maximum correlation coefficient between two digitized QRS complexes as a measure of similarity in morphology.6 10 In this study, it was found that the root mean square of the difference between QRS complexes was a more sensitive measure of change in morphology. Correlation coefficient analysis does not account for differences in QRS amplitude, whereas the root mean square of the difference analysis does detect differences in amplitude. The fact that the root mean square of the difference analysis demonstrated greater rate-dependent changes in QRS configuration than did the correlation coefficient analysis indicates that rate-dependent changes in the QRS are often manifest as a change in amplitude instead of a change in shape. It has been demonstrated that for optimal spatial resolution of pace mapping, amplitude changes need to be taken into account.11 12 13
An advantage of using a computerized evaluation of differences in QRS morphology is that a quantitative analysis is possible and that more subtle changes can be incorporated into statistical analyses. In addition, a computerized approach allows the averaging of several complexes, thereby increasing the signal-to-noise ratio and reducing the effects of possible confounding factors that may distort the QRS morphology, such as P waves.
Morphology of Single Paced Ventricular Complexes
The QRS morphology of single paced ventricular complexes was affected by changes in coupling interval in all 12 ECG leads. However, the magnitude of the change in coupling interval required to bring out a difference in QRS configuration detectable by root mean square of the difference analysis was significantly shorter in the precordial leads than in the frontal plane leads. This indicates that the precordial leads are more sensitive to coupling interval-dependent changes in QRS morphology, at least when ventricular premature depolarizations are introduced at the right ventricular apex. It is possible that the larger size of the QRS complexes in the precordial leads allows for easier detection of differences in configuration. Whether the precordial leads are also more sensitive than the frontal plane leads to site-dependent changes in QRS morphology is unknown.
Single Paced Complexes Compared With Overdrive Pacing
The results of this study demonstrate that the morphology of single ventricular complexes accurately reflects the QRS morphology of a train of complexes arising from the same location, but only when the cycle length of the train is within 60 ms of the coupling interval of the single complex.
When pacing at cycle lengths shorter than the coupling interval of the single complex, less of a change in cycle length was needed to bring out changes in QRS morphology than when pacing at cycle lengths longer than the coupling interval. This is consistent with rate-dependent aberration of the QRS complex due to greater degrees of incomplete repolarization of ventricular tissue as the cycle length progressively shortens. Alternatively, the QRS complex may become progressively more distorted by overlap with the T wave as the pacing cycle length shortens.
No difference in QRS morphology was noted when comparing a paced ventricular complex at a coupling interval of 400 ms to overdrive pacing at a cycle length of 400 ms. The fact that overdrive pacing at cycle lengths 60 ms shorter or longer than the coupling interval of the single complex resulted in changes in QRS morphology indicates that similar changes in QRS morphology would be expected to occur when comparing overdrive pacing at a cycle length of 400 ms to other pacing cycle lengths. Therefore, when pace mapping for ventricular tachycardia, pacing at cycle lengths which are more than 60 ms shorter or longer than the ventricular tachycardia cycle length may introduce changes in QRS configuration that are independent of the pacing site.
A possible limitation of this study is that all of the patients had structurally normal hearts. Therefore, the findings of this study may not apply to patients with heart disease. Whether the rate-dependent changes in QRS morphology noted in this study would be unaffected, exaggerated, or attenuated in patients with structural heart disease remains to be determined. In addition, none of the patients were being treated with an antiarrhythmic drug, and therefore the results of this study may not be applicable in the setting of antiarrhythmic drug therapy.
Another limitation is that pacing was performed only at the right ventricular apex, and therefore the results may not be applicable to the right ventricular outflow tract or to left ventricular pace mapping.
When pace mapping is used to identify target sites for ablation of a ventricular arrhythmia, an identical or nearly identical match of QRS complexes usually is necessary in 11 or 12 of 12 ECG leads.12 13 Because the spatial resolution of pace mapping is on the order of 5 to 10 mm even when strict criteria are used to compare spontaneous and paced complexes, and since typical lesions created by radiofrequency energy are approximately 5 mm in diameter,14 15 successful ablation is unlikely if there is an inadequate match of QRS complexes in more than one lead.11 However, if the possibility of rate-dependent changes in QRS morphology is not recognized, a pace map in which all 12 leads show an excellent match of QRS morphologies may not be possible to achieve.
When premature ventricular depolarizations are used as a template for pace mapping, paced complexes should be introduced at the same coupling interval as the spontaneous complexes. Alternatively, if pace mapping is performed with trains of pacing stimuli, the cycle length of the pacing train should be equal to the coupling interval of the spontaneous premature complex. Another implication of this study is that pace mapping for ventricular tachycardia should be performed at the same cycle length as that of the ventricular tachycardia. If the effects of coupling interval or pacing cycle length on QRS morphology during pace mapping are not recognized and controlled for, the probability of localizing an effective target site for ablation may be significantly compromised.
- Received March 28, 1996.
- Revision received July 2, 1996.
- Accepted July 8, 1996.
- Copyright © 1996 by American Heart Association
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