Mechanisms Causing Sustained Ventricular Tachycardia With Multiple QRS Morphologies
Results of Mapping Studies in the Infarcted Canine Heart
Background Sustained reentrant ventricular tachycardias (VTs) with different QRS morphologies have been observed to occur spontaneously and during programmed stimulation in human hearts. We determined mechanisms that can cause tachycardias with multiple morphologies in a canine model of myocardial infarction by mapping reentrant circuits.
Methods and Results Reentrant VT with multiple QRS morphologies was induced in 11 canine hearts with 4-day-old infarcts. Comparison of activation maps of the reentrant circuits in the epicardial border zone associated with each morphology indicated two basic mechanisms. Less frequently, VTs of different morphologies in the same heart were caused by reentrant circuits in different regions of the infarct. Most commonly, the reentrant circuits associated with different morphologies were in the same region. Three different factors caused different exit routes from circuits in the same region, leading to the multiple morphologies. (1) The reentrant wave front for each morphology rotated around the same line of block but in different directions. (2) Reentrant circuits associated with each morphology were similar, but there were small changes in the extent of the central line of block. (3) Reentrant circuits with completely different sizes and shapes caused different morphologies.
Conclusions In this canine model, tachycardias with multiple morphologies most commonly arise from reentrant circuits in the same region of the infarct, suggesting that most often only one area has electrophysiological properties necessary to sustain reentry.
Between 25% and 40% of patients with sustained monomorphic ventricular tachycardia (VT) caused by a reentrant mechanism and associated with ischemic heart disease have been shown to have spontaneous episodes of tachycardia with multiple QRS morphologies.1,2 A larger percentage of patients (25% to 67%) have had tachycardias with multiple morphologies induced by programmed stimulation during electrophysiological studies.1–4 Patients with multiple-tachycardia morphologies are less likely to have successful electrophysiology-guided antiarrhythmic therapy,4 map-guided endocardial resection,5 or catheter ablation.6,7
The mechanisms causing multiple VT morphologies are unclear. On the basis of clinical mapping studies using either single-site, sequential activation mapping or limited simultaneous multielectrode mapping, several possible mechanisms have been proposed. One is that tachycardias with different morphologies arise from different reentrant circuits, located either in widely separated or in closely adjacent areas.1,5,8,9 A second proposed mechanism is that multiple morphologies are caused by different exit routes from the same reentrant circuit.1,9,10
For additional details concerning the mechanisms that might cause tachycardias with multiple QRS morphologies, mapping of the pattern of activity in the reentrant circuit or circuits associated with the different tachycardia morphologies is necessary. At the present time, such detailed mapping is not done routinely in clinical studies, although it has sometimes been done.8,9,11 Reentrant circuits can be mapped, however, during sustained VT in a canine model of myocardial infarction.12,13 As in the clinical cases, multiple tachycardia QRS morphologies occur in the same heart, providing the unique opportunity to determine mechanisms that can cause VTs with multiple morphologies. A preliminary report of our results has been presented in abstract form.14
Canine Model of Myocardial Infarction
Adult mongrel dogs weighing 30 to 40 kg underwent a two-stage ligation of the left anterior descending coronary artery (LAD) ≈1 cm from its origin, producing a transmural anterior septal myocardial infarction.13,15 Four to 5 days later, electrophysiological studies were performed on the dogs that survived.
For the electrophysiological study, the animals were anesthetized with intravenous pentobarbital sodium (30 mg/kg), intubated, and ventilated. The heart was exposed via a median sternotomy, and a flexible electrode array was sutured over the infarcted area,15 with its margins extending onto noninfarcted myocardium. A heating lamp was used to maintain the temperature at the surface of the heart between 37°C and 38°C. Blood pressure recorded with a femoral artery catheter and two ECG leads (I and II or III) were continuously displayed on an Electronics for Medicine DR12 oscillographic recorder.
Electrode Array and Recording Instrumentation
The electrode array for mapping the epicardial border zone in the infarcted region13,15 consisted of 292 bipolar electrodes. Each bipole was formed by two 1-mm-diameter silver disks 2 mm apart. The electrodes were arranged in two overlapping groups. One group of 192 electrodes was spaced evenly over the entire 9×13-cm array (interelectrode distance of 5 to 10 mm), and the other group of 192 was concentrated in a 5.5×5.5-cm square at the center (5 to 7.5 mm between each bipole).15 One of the two groups could be selected with a switch box for simultaneous recording. The signals were led to preamplifiers with automatic gain control and then were multiplexed, digitized, and stored on wide-band tape (Ampex PCM System)13 along with the two surface ECGs and blood pressure. Stimulating electrodes in the electrode array were at the basal margin, the left lateral margin, and the center as well as on the right ventricle adjacent to the LAD.15
VT was initiated by single or double extrastimuli (2 to 4 times diastolic threshold) during pacing at different basic cycle lengths or by rapid overdrive pacing from all pacing sites. Sustained VT was defined as tachycardia originating in the ventricles lasting longer than 30 seconds, during which blood pressure remained at a mean value of >50 mm Hg. All VTs were monomorphic.
The QRS morphology of the tachycardias was classified from two orthogonal ECG limb leads as follows: (1) R in which the complex was predominantly an R wave with a small or no Q wave and S wave, (2) QS in which the complex had a small or no R wave, (3) RS in which the complex had an R wave at least 1/4 of the amplitude of the S wave, and (4) QR in which the complex had a Q wave at least 1/4 of the amplitude of the R wave. An experiment was classified as having tachycardias with different QRS morphologies if the morphology was different in at least one of the two leads. This classification is not quantitative and lacks a high degree of sensitivity; it may sometimes have failed to distinguish between different morphologies. However, it does possess a high degree of specificity, ensuring that what we classified as different morphologies always were different morphologies.
We have previously described our methods for determining local activation times, drawing isochrones, and designating regions of conduction block.13,15 We also determined the probable exit route of the reentrant impulse from the circuit to the ventricles and correlated the exit route with the QRS morphology. Since the epicardial border zone lacks, for the most part, intramural connections,13 the reentrant impulse usually enters the rest of the ventricle from one of its margins at the edges of the electrode array.16 Therefore, the region of the electrode margin that is activated within 20 ms before the onset of the QRS during tachycardia is designated as the exit route.16 This was also verified by pacing during sinus rhythm from the site designated as the exit route to show that the QRS had a morphology similar to that during tachycardia.
Occurrence of VTs With Multiple Morphologies
In 17 of 42 experiments with sustained VT, tachycardias with more than 1 morphology were induced: 2 morphologies in 14 experiments, 3 morphologies in 2 experiments, and 5 morphologies in 1 experiment. Complete reentrant circuits were mapped in the epicardial border zone for all tachycardia morphologies in 11 of the 17 hearts, 3 of which had more than 2 morphologies, for a total of 27 morphologies. Fourteen of these morphologies were induced a total of 60 times with the same reentrant circuit and exit route associated with the same morphology on more than one induction for 12 of the 14. Two morphologies had both the same and different circuits, but the exit routes were the same for each induction of a given morphology. Thirteen morphologies were induced only once. Mechanisms for multiple morphologies are based on the data obtained from these 11 hearts.
Different Morphologies Due to Reentrant Circuits Around Lines of Block Located at Different Sites
This group of tachycardias in three experiments is characterized by reentrant circuits around lines of functional block (not present during sinus rhythm) at distinctly different sites in the epicardial border zone (located at least 1 cm apart). Reentrant circuits at different sites were associated with different exit routes to the ventricles that caused the different QRS morphologies. In Fig 1A⇓, recorded during one episode of tachycardia (cycle length, 204 ms), the QRS complexes are classified as R waves in both leads I and II. In Fig 1B⇓, recorded during another episode in the same heart (cycle length, 175 ms), the QRS complexes are classified as QS in both leads.
The reentrant circuit that is shown in Fig 2A⇓ was associated with the QRS morphology of the tachycardia in Fig 1A⇑. A single loop (arrows) occurs around a long functional line of block located toward the apical area of the epicardial border zone (longest dark black line); electrograms in the circuit are displayed to the left. Several other shorter lines of block are not part of the circuit. To the right are electrograms from a region that is not part of this reentrant circuit but that were in the circuit associated with the second tachycardia morphology (see below).
During this tachycardia, the junction of the LAD and apical margins of the electrode array (asterisks in Fig 2A⇑) was designated as the exit route from the reentrant circuit. Fig 1A⇑ shows that electrograms recorded at these margins of the border zone (37 and 21 enclosed by the diamonds on the map in Fig 2A⇑) occur just before the onset of the QRS complex. Electrograms recorded from other sites around the margin occur during or at the end of the QRS. The QRS complex during pacing from the LAD-stimulating electrodes resembles the QRS during tachycardia (Fig 1C⇑), although it has a deeper initial Q wave, probably because it is not at the exact same site designated as the exit route.
The activation map during the tachycardia with the second morphology (Fig 1B⇑), shown in Fig 2B⇑, consists of a single reentrant loop (arrows) around a functional line of block in the center of the epicardial border zone, ≈4 cm from the line of block associated with the first reentrant circuit. The reentrant wave front is moving in the opposite direction. Several other short lines of block are not associated with it. The electrograms at the right are from sites around the circuit, the same sites that were not part of the circuit during the tachycardia in Fig 2A⇑ (at the right). Conversely, the electrograms shown at the left in Fig 2B⇑ are from the sites at which the first reentrant circuit was located (Fig 2A⇑, left) and are not in this second circuit.
During this second tachycardia, the LL margin of the epicardial border zone was designated as the exit route (asterisks on map in Fig 2B⇑). As shown in Fig 1B⇑, the electrogram (LL) recorded at this site occurred just before the onset of the QRS, whereas electrograms recorded at other margins occurred during or just after the QRS. Pacing from the electrodes on the lateral margin near the designated exit site resulted in a QRS complex that resembled the QRS during tachycardia (Fig 1D⇑).
The activation maps described in Fig 2⇑ are representative of the maps from other experiments in this group. When reentrant circuits occurred at different sites, at least one of the circuits consisted of only one wave front circulating around a single line of block in the mapped region rather than a figure-eight circuit.12
Different Morphologies Associated With Circuits in the Same Area of the Epicardial Border Zone
In all 11 experiments, reentrant circuits and their central lines of functional block associated with different QRS morphologies in each heart were located in the same region of the epicardial border zone, including the three experiments that had circuits at distinctly different locations, because each had several different morphologies at one of the different sites. Despite the similar location of circuits associated with different morphologies in this group, each morphology was associated with a distinctly different exit route from the circuit.
Propagation of Wave Fronts in Opposite Directions Around Similar Reentrant Circuits
In eight hearts, different QRS morphologies were associated with reentrant wave fronts moving in opposite directions around the same line of block. Fig 3A⇓ and 3B⇓ shows ECGs of two tachycardias in one of these hearts. The QRS in panel A (cycle length, 227 ms) is classified as QS in both leads, and the QRS in panel B (cycle length, 240 ms) is classified as QR in lead I and R in lead II. The activation map of the VT in Fig 3A⇓ is shown in Fig 4A⇓. One reentrant wave front moves in a counterclockwise direction (arrows) around a long line of functional block toward the LL margin. Electrograms in the circuit are below. Another long line of functional block formed parallel and to the left of the first one. Activation moves clockwise around the upper end of this line from the 20-ms isochrone to the 90-ms isochrone. (This wave front may have conducted slowly across the line of apparent block, because the 20-ms isochrone is parallel to the line.13) This clockwise wave front lags behind the counterclockwise wave front, which is already halfway through the central common pathway (between the two lines of block) by 90 ms and does not finish a complete revolution. The exit site is designated between the apex and the lateral margin (asterisks).
The activation map of the VT in Fig 3B⇑ is shown in Fig 4B⇑. The line of block toward the lower right and lateral margin is in exactly the same location as it was during the first tachycardia in Fig 4A⇑. However, the reentrant wave front moves around this line in the opposite (clockwise) direction (see electrograms in the circuit below the map recorded from the same sites as in A). The midportion of the second line of block at the upper left is also unchanged, but the ends are slightly altered. Arrival of the wave front that moves counterclockwise around this line of block, at the apical entrance to the central common pathway, also lags behind arrival of the wave front from the opposite line of block, and it may not complete a reentrant cycle. The exit site occurred between the LAD margin and the base (asterisks).
In other experiments in this group, reversal of the reentrant wave front around the same line of block also resulted in switching of the exit route from one margin of the array to the opposite margin.
Propagation of Wave Fronts in the Same Direction Around Similar Reentrant Circuits
In three hearts, different QRS morphologies were associated with reentrant wave fronts moving in the same direction around the same line of block. Fig 3C⇑ and 3D⇑ shows ECG tracings from one of these hearts. In 3C, the morphology is classified as QR in lead I and as R in lead II (cycle length, 220 ms). In 3D, the QRS is narrower and is classified as QS in lead I and R in lead II (cycle length, 278 ms).
In Fig 5A⇓ (the circuit associated with the QRS in Fig 3C⇑), two wave fronts (arrows) rotate around nearly parallel lines of functional block in a figure-eight pattern.12 The counterclockwise wave front entered the central common pathway ≈50 ms after the clockwise wave front and therefore did not complete the circuit. Activation also may occur slowly and simultaneously across the lower line of block between circled activation times 48 and 98 (small straight arrows), because the isochrones on the distal side of this line are parallel to it.13 The fractionated electrogram recorded at site 48 (see electrograms below) is also consistent with this interpretation. This is characteristic of anisotropic reentry.13 The LAD margin was designated as the exit route (asterisks).
The reentrant circuit shown in Fig 5B⇑ was associated with the second QRS morphology (Fig 3D⇑). The wave front in the central common pathway between the lines of block moves toward the LAD margin as before. However, the clockwise wave front turns to the right earlier than in Fig 5A⇑ and moves more rapidly through the region (circled electrograms with activation times 51, 63, and 92) in which there was a line of apparent block during the reentry that was described in Fig 5A⇑. Activation time is 29 ms between circled electrode sites 63 and 92, whereas in the map in Fig 5A⇑, the time was 50 ms (between circled sites 48 and 98, which are the same sites as in B). Therefore, the right line of block is shortened. The counterclockwise wave front still trails the clockwise wave front as it enters the apical end of the central common pathway. Activation of the LAD margin (asterisks) and the left lateral margin (asterisks) occur nearly simultaneously and are both designated as the exit routes. The earlier activation at the LL margin (compared with Fig 5A⇑) resulting in its becoming an exit route was a consequence of the change in the right line of block. This example shows that only small changes in the reentrant circuit can result in alteration of the QRS morphology.
Different Reentrant Circuits and Lines of Block in the Same Region
In three hearts, different QRS morphologies were associated with different reentrant circuits at the same site. Fig 6⇓ shows ECGs of two different tachycardias in one of these hearts. The morphology in panel A (cycle length, 165 ms) is classified as RS. The morphology in panel B (cycle length, 156 ms) is classified as QS. The activation map during the tachycardia in Fig 6A⇓ shows a double loop (figure-eight) reentrant circuit (Fig 7A⇓, center panel), with rotation of two wave fronts (arrows) around two lines of functional block. Electrograms around the right circuit are shown at the left. The LAD margin (asterisks) is the exit route. An electrogram from this margin activated at 48 ms (enclosed in the diamond on the map) is shown below the ECG in Fig 6A⇓. Also shown in Fig 6A⇓ are electrograms recorded from other margins of the electrode array that were activated after the onset of the QRS.
The map during the VT with the second morphology (Fig 6B⇑) is shown in Fig 7B⇑. It shows a single circuit (arrows) (electrograms at the right) around a small unexcited area (cross-hatches) that showed occasional activation, indicating a high degree of conduction block. The apical margin represents the exit route (asterisks). An electrogram recorded from the apical margin activated at 65 ms (enclosed within the diamond on the map) occurred just before the onset of the QRS and is shown below the ECG in Fig 6B⇑, along with electrograms recorded from the other margins of the electrode array. Note that the LAD margin is now activated late. Therefore, the two tachycardias described are located in the same area with overlapping reentrant circuits. Each circuit has a different size and shape and exit route.
Mode of Onset of VTs With Multiple Morphologies
Initiation by Programmed Stimulation of Tachycardias With Different Morphologies
In five experiments, sustained VTs with different QRS morphologies were associated with different sites of stimulation. The initial lines of block that formed during conduction of the premature impulses from different sites were in distinctly different regions. This in turn influenced either where the stable line(s) of block formed in the reentrant circuit, the direction in which the reentrant wave front circled around the stable line of block, or both. Fig 8A⇓ is initiation of tachycardia by a premature stimulus delivered through the lateral electrodes (coupling interval, 135 ms at a basic drive cycle of 280 ms), and Fig 8B⇓ shows initiation with the premature stimulus through the LAD electrodes in the same heart (coupling interval, 150 ms; basic drive cycle, 280 ms). The maps in Fig 9A⇓ through D are from the initiation at the lateral margin (ECG in Fig 8A⇓). Activation of the border zone (arrows) during the basic drive did not show any evidence of conduction block (Fig 9A⇓). The premature impulse, however, blocked (small arrows and horizontal heavy black line) (Fig 9B⇓), with propagation around both ends of this line to the opposite side (large curved solid and open arrows). The wave fronts then conducted retrogradely through this line of block (Fig 9C⇓, isochrones 10 to 40) to form the reentrant circuit shown in Fig 9D⇓. In this case, the line of block at the center of the single reentrant circuit is part of the same line of block that occurred during block of the initiating premature impulse. Exit from the epicardial border zone occurred at the LL margin (asterisks). The activation maps of initiation of the second morphology in this heart from the LAD margin (Fig 8B⇓) are shown in Fig 10⇓. Fig 10A⇓ shows activation by the basic drive. Conduction block of the premature impulse (Fig 10B⇓) occurred toward the LAD margin (heavy black line) at a different site from the block caused by lateral stimulation (compare with Fig 9B⇓). Conduction of the premature impulse occurred around both ends of the line of block to the opposite side (curved solid arrows). Reemergence of the premature impulse retrogradely through the line of block (shaded region) is shown in Fig 10C⇓. This resulted in the formation of two widely separated smaller lines of block, perpendicular to the first one, around which two wave fronts rotated during sustained tachycardia (Fig 10D⇓). The exit route from this circuit was at the LAD margin (asterisks). In this example, the initial line of block did not become part of the line of block in the stable reentrant circuit, which is a much more common occurrence than the pattern shown in Fig 9⇓. One of the reentrant wave fronts in Fig 10D⇓ moved in the opposite direction to the reentrant wave front in Fig 9D⇓ because of the different site of initiation. In other experiments (not shown), lines of block occurred in the same place despite the different sites of stimulation, but the reentrant wave fronts rotated in opposite directions because of the different initiation sites.
Sustained tachycardias with different QRS morphologies were initiated in five hearts by stimulation at the same site with the same (four experiments) or different (one experiment) stimulation patterns (Fig 8C⇑ and 8D⇑). Like the activation maps shown in Figs 9⇑ and 10⇑, when stimulation at the same site resulted in different QRS morphologies, the lines of block caused by premature activation occurred in different regions, causing different reentrant circuits, although the direction of activation was usually the same.
Spontaneous Change in Tachycardia Morphology
In one experiment (described in Figs 3C⇑ and 3D⇑ and 5), the morphology of a monomorphic tachycardia that was stable changed spontaneously (Fig 11⇓). Spontaneous shortening of one of the lines of block (Fig 5⇑) resulted in a change in the exit route from the LAD margin (LAD electrograms indicated by asterisk, which precede onset of QRS during the first two beats in Fig 11⇓) to simultaneous exits from the border zone at both the LAD and lateral (LL) margins (LAD and LL electrograms indicated by asterisks, which precede QRS during the last two beats). The reason for the change in the line of block is not apparent.
In this canine model of healing myocardial infarction, sustained VTs with different QRS morphologies can be induced in the same heart by programmed stimulation, similar to observations in some patients with sustained tachycardia.1–4 Detailed mapping allowed us to determine the mechanisms for the different QRS morphologies.
Multiple Morphologies Caused by Reentrant Circuits in Different Regions
There is a relatively low incidence of reentrant circuits at separate sites causing sustained tachycardias with multiple morphologies both in this laboratory model (≈18% of multiple morphologies) and in infarcted human hearts (11% to 47%).1,5 In the canine model, in which functional anisotropic reentry is an important cause of tachycardia,13 it appears that only limited regions of the epicardial border zone are capable of forming stable lines of functional block and have anisotropic conduction properties suitable for maintaining sustained reentry after programmed stimulation. The appropriate characteristics of block and conduction probably depend on how the infarction process has shaped the microanatomy of the epicardial border zone, which influences its electrophysiological properties. The functional lines of block of stable reentrant circuits form in the thinnest regions, in which there are boundaries between myocardium with normal gap junctional distribution and gap junctional disarray.17 The cause of the disarray and how it predisposes a region to conduction block are not known. It is possible that in hearts with reentrant circuits in different regions, such boundaries occur at several different locations while occurring in only one region in hearts that do not have stable circuits at different sites. The occurrence of multiple regions with appropriate properties for lines of block and anisotropic conduction would seem to be more likely in hearts with larger infarcts or several discrete infarcted regions, but we did not quantify infarct size in this study. Patients with multiple infarcts, in whom total infarct size might also be larger, are more likely to have more than one tachycardia morphology occurring spontaneously, arising at sites that are designated as being different by clinical criteria.1,2,5
The cause of reentry in human hearts with healing or healed infarction may sometimes be functional11,18 and other times have an anatomic basis.19 Nevertheless, it is still necessary that different regions have appropriate anatomic and electrophysiological properties to support different stable reentrant circuits if multiple morphologies are to result from circuits at different sites. The likelihood of this occurring may be related to the extent of ischemic damage.
Multiple Morphologies Associated With Reentrant Circuits Located in the Same Region
We found that different QRS morphologies are most commonly associated with reentrant circuits in the same region of the infarcted ventricles, as have clinical studies based on activation mapping, often with less spatial resolution.1,6,8–11,20–23 Our results provide new information on possible mechanisms whereby functional reentrant circuits in the same region can lead to different QRS morphologies.
In anatomic reentrant circuits, exit routes to the ventricles are most likely through anatomically distinct pathways. The number and location of these pathways may determine whether multiple-morphology tachycardias occur. Conversely, functional anisotropic reentrant circuits in the canine model are connected to the ventricles around their entire circumference at the margins of the epicardial border zone. The exit route is most often at either the LAD or lateral apical margins; the wave front conducts most rapidly along the longitudinal axis of the muscle fiber bundles toward these margins, whereas conduction toward the base or apical margins is in the slow transverse direction, leading to delayed activation at these margins.13,16 Usually the exit route is only at one margin (LAD or lateral-apical) instead of both. This is the margin that is reached when the ventricles have recovered excitability. Activation of both margins usually occurs within half a reentrant cycle; one margin is usually activated during diastole and the other during the QRS or T wave, while the ventricles are refractory. Illustration of this point is the pattern of activation in Fig 5A⇑. The LAD margin is activated at 105 to 110 ms (asterisks), just before the onset of the QRS, while the lateral margin is activated nearly half a reentrant cycle later during the end of the QRS (Fig 11⇑). In general, when the LAD region is activated first, the QRS complex is predominantly positive in both leads (Figs 1A⇑, 3B⇑, and 3C⇑), whereas it exhibits a QS pattern when the lateral region is activated first (Figs 1B⇑ and 3A⇑). In our series of experiments, the most common cause for tachycardias with different morphologies was rotation of the reentrant wave front in opposite directions around the same line of functional block. Because of the different direction of rotation, the wave front exited the central common pathway in a different direction and a different margin of the border zone was activated during diastole for each morphology (see Fig 4⇑). Rotation of a reentrant wave front in opposite directions has previously been described for experimental anatomic circuits.24,25 It has also been postulated to occur in humans in cases in which complete circuits could not be mapped.20–23
Based on clinical mapping studies, it has also been proposed that a common mechanism for multiple-morphology tachycardias is reentrant wave fronts rotating in the same direction in the same reentrant circuit but with different exit routes.9,10,22 In our series of experiments, we rarely found the exact same circuit to be associated with different tachycardia morphologies, as might occur in anatomic circuits in which the reentrant pathway is fixed; there was often a slight change in the circuit. Because of the delicate balance between margins of the border zone that are activated when the ventricles are excitable and borders activated when they are not, a very small change in a reentrant circuit caused by a change in the length of one of the functional lines of block, for example, can lead to a change in the exit route and a change in QRS morphology (Fig 5⇑). In other instances, although located in the same region, reentrant circuits associated with different tachycardia morphologies were markedly different (Fig 7⇑).
Initiation of Tachycardias With Multiple QRS Morphologies
The reason why different morphologies occurred in our series of experiments was mostly related to the activation pattern during initiation with programmed stimulation (although in one example shown in Fig 11⇑, the QRS morphology changed spontaneously during tachycardia). In clinical evaluation of patients with sustained VT, programmed stimulation has resulted in initiation of tachycardias with multiple morphologies, some of which were not observed to occur spontaneously, and the likelihood of multiple morphologies is increased with more aggressive stimulation protocols.1–4 Spontaneously occurring tachycardias were not documented in our experiments, and the stimulation protocols that initiated multiple morphologies were not more aggressive than in experiments in which only a single morphology was induced. Seventy-five percent of the morphologies were induced by single premature stimuli, and the remainder were initiated by doubles or overdrive. However, more aggressive protocols might have induced additional morphologies. The different sites or patterns of programmed stimulation resulted in different lines of block of the premature impulses. This in turn influenced the location of the reentrant circuit. Also, the site of stimulation influenced the direction that the reentrant wave front propagated around the line of block (Figs 9⇑ and 10⇑).
Limitations and Conclusions
We recorded only two surface ECG leads and, therefore, may have underestimated the number of different tachycardia morphologies. A quantitative approach involving determination of the frontal axis or recording additional leads would have been more sensitive. It is possible that sometimes, when the QRS morphology in the two recorded leads appeared identical, differences might have been evident in other leads. However, the purpose of the study was not to document the incidence of multiple morphologies in this animal model but rather the mechanism for multiple morphologies. Therefore, the limited sensitivity of our method does not affect the results. Our criteria for designating that morphologies were different was highly specific and to a large extent eliminated the possibility that different morphologies were actually the same. The accuracy of pacing at the margins of the electrode array during sinus rhythm to confirm exit routes is also limited by the availability of only two ECG leads and by the fixed locations of the stimulating electrodes, which did not allow stimulation at the exact sites designated as exit routes. Also, there is the question of the clinical relevance of this animal model, in which reentry occurs in the epicardial border zone. Clinically occurring reentrant VT often involves subendocardial1,5,8–11 reentrant circuits, although circuits have been found to occur in epimyocardium.26 The role of anisotropy in causing reentry in human hearts is also unknown. Nevertheless, experimental studies on animal models are useful for suggesting possible mechanisms of clinical events. Our study shows how changes in the direction of wave front rotation or length of lines of block in functional reentrant circuits localized in the same region of the ventricle have profound effects on exit routes and QRS morphologies. The results also emphasize the possibility that despite large differences in early sites of activation, which may represent exit routes, tachycardias with different morphologies may have similar sites of origin. In clinical studies with limited mapping sites, many of these tachycardias could be misclassified as having different sites of origin despite circuits in the same region, because the exit sites were separated by 4 to 5 cm. Our results suggest that multiple VT morphologies may be eliminated by ablating one discrete area that may serve as the central common pathway for two circuits moving in opposite directions or different circuits in the same region with different exit routes.
This study was supported by grant R32HL-31393 from the National Heart, Lung, and Blood Institute, National Institutes of Health.
- Received May 5, 1997.
- Revision received July 24, 1997.
- Accepted August 2, 1997.
- Copyright © 1997 by American Heart Association
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