Effect of Subendocardial Resection on Sinus Rhythm Endocardial Electrogram Abnormalities
Background Patients with sustained ventricular tachycardia after acute myocardial infarction frequently have characteristic abnormalities of left ventricular endocardial electrical activity, including fractionated (prolonged, multicomponent, low-amplitude), split (having discrete widely separated deflections), and late (extending after the end of the QRS complex) electrograms. The exact cause and source of these electrograms are not clear.
Methods and Results In this study, endocardial electrograms from 18 patients were recorded with a 20-electrode array from the same area immediately before and immediately after resection of subendocardial tissue at the time of surgery for ventricular tachycardia. Electrograms could be compared before and after resection from 298 of 360 (83%) of the electrodes. Before resection, split electrograms were present in 130 (44%) and late components in 81 (27%) of the recordings. Recordings made after resection showed fewer abnormalities, including complete absence of split electrograms as well as all previously recorded late components (P<.02). Mean electrogram amplitude increased from 0.5±0.8 to 1.0±1.6 mV (P<.0001) because of removal of the attenuating effect of endocardial scar; mean duration decreased from 112±38 to 65±27 ms (P<.0001) mainly because of loss of late and split components. Overall electrogram contour was very similar aside from these changes.
Conclusions These data show that (1) some of the signal recorded on the endocardial surface is derived from deeper tissue layers and (2) split and late electrogram components appear to be generated by cells in the superficial endocardial layers, since they are eradicated by removal of this tissue. These findings correspond well with previous histological studies of resection specimens that show bundles of surviving muscle cells separated by layers of dense scar that act as an insulator.
In patients with uniform sustained ventricular tachycardia (VT) in the setting of a healed myocardial infarction, abnormal electrical activity can frequently be recorded from the left ventricular endocardium during normal sinus rhythm (NSR).1 2 3 4 5 These abnormal electrograms have been classified in several ways: fractionated (prolonged, multicomponent, low amplitude), late (lasting beyond the end of the surface QRS complex), and split (having two or more discrete electrogram components). There is evidence that these abnormal electrograms account for characteristic abnormalities in the surface signal-averaged ECG (the “late potential”).4 6 In many patients undergoing subendocardial resection for VT, the signal-averaged ECG is normalized (loss of a preoperative low-amplitude late potential).7 8 9 We hypothesized that subendocardial resection removed the tissue responsible for the genesis of the surface late potential as well as other endocardial electrogram abnormalities. We investigated this possibility by recording endocardial NSR electrograms from the same location (left ventricular apical septum) before and immediately after subendocardial resection during surgery for sustained VT. We sought to determine whether the abnormal electrograms recorded were intrinsic to the endocardium or represented electrical activity originating in deeper layers.
The study group in this series consisted of 18 men 55±9 years old (mean±SD; range, 37 to 68 years), all of whom had a history of anteroseptal myocardial infarction from 2 weeks to 24 years previously. Each patient had multiple episodes of sus- tained uniform-morphology VT, and all had undergone electrophysiological studies at which programmed ventricular stimulation yielded an inducible sustained uniform morphology of VT despite the subsequent addition of antiarrhythmic drug ther- apy. In each patient, the decision was made to undergo surgical treatment (map-guided subendocardial resection) for VT.
All patients underwent elective map-guided subendocardial resection according to the following protocol: The heart was approached via median sternotomy in the usual fashion and, after establishment of normothermic cardiopulmonary bypass, an aneurysmotomy was made at the left ventricular apex. Right and left ventricular stainless steel bipolar plunge endocardial electrodes were inserted for recording and pacing. Throughout the study, recordings were made of surface leads I, II, III, and V5R, right and left ventricular endocardial reference electrograms, and the mapping electrodes. VT was initiated by programmed stimulation and endocardial mapping performed with a roving bipolar or quadripolar electrode probe. At the conclusion of VT mapping, a 2×3-cm electrode array (consisting of 20 bipoles with 1-mm interelectrode distance; Fig 1A⇓) was placed on an area of the apical septum that was to be resected (Fig 2A⇓). This was in all cases on or near a septal endocardial site from which earliest electrical activity during at least one VT could be recorded. The array was oriented in such a fashion that one edge of the array was aligned with the ventriculotomy incision to facilitate reproducibility of placement of the array after resection. In the first several cases, a marking suture was affixed to the endocardium at one corner of the array; this proved unnecessary for accurate placement and was not continued during the remainder of the study. Recordings were made with the electrode array during sinus rhythm, after which the electrode array was removed and subendocardial resection was performed on the normothermic heart (Fig 2B⇓). Immediately after resection, the electrode array was placed back in the same location as before resection, aligning with previously determined landmarks (Fig 2D⇓). Recordings were then repeated during sinus rhythm. In three cases, the resected specimen was fit back in situ, the electrode array was placed over the specimen, and recordings were repeated during sinus rhythm. After these recordings, the remainder of the surgical procedure was performed, which included endocardial cryoablation in 10 patients and instillation of cardioplegia into the aortic root and coronary artery bypass graft surgery in 8 patients.
Electrograms recorded with the electrode array were written on paper at a speed of 200 mm/s, and measurements were made of amplitude (peak to peak) and electrogram duration (onset to offset); reproducibility and accuracy of measurements were consistently ±0.1 mV in amplitude and ±5 ms in duration. Electrograms were classified according to the following criteria (see Fig 1B⇑): normal, amplitude >0.6 mV and duration <70 ms (all other electrograms were classified as abnormal); fractionated, abnormal electrogram with amplitude <0.3 mV and duration >90 ms; split, abnormal electrogram with two or more discrete components separated by at least 30 ms of electrical quiescence; and late, an abnormal electrogram, a portion of which extended beyond the end of the surface QRS complex. Electrograms could be classified in more than one way (eg, fractionated and late).
Statistical analysis was performed with the paired t test (comparing electrogram parameters before and after resection), and qualitative abnormalities were compared by χ2 analysis; statistical significance was ascribed to differences with P<.05.
Electrograms could be analyzed from 301 of 360 (84%) of the electrodes before resection and from 311 of 360 (86%) after resection (the difference is accounted for by extremely low-amplitude signals before resection having increased in amplitude after resection). Before resection, 15 electrograms (5%) were normal, 63 (21%) fractionated, and 223 (74%) abnormal but not fractionated, compared with 161 (52%) normal, 24 (8%) fractionated, and 126 (40%) abnormal/nonfractionated after resection (P<.001). Split potentials were present in 130 recordings (44%) before resection but in none after resection; late electrogram components were present in 81 recordings (27%) before and 5 (2%) after resection. All of the latter 5 electrograms were from a single patient and were recorded at sites lacking late components before resection.
Among 298 electrograms that could be compared before and after resection (ie, recorded from the same electrode), the mean amplitude increased from 0.5±0.8 to 1.0±1.6 mV (P<.0001) and the mean duration decreased from 112±38 to 65±27 ms (P<.0001). Increases in amplitude of >0.2 mV were present in 146 recordings (49%), a similar decrease in amplitude was present in 37 (12%), and 115 electrograms (39%) changed by ≤0.2 mV after resection. Among the same electrograms, 242 (81%) decreased by >5 ms in duration, 43 (14%) increased in duration by the same amount, and 13 (5%) showed ≤5 ms change in duration. Examples of changes in electrograms after resection are shown in Figs 3⇓ and 4⇓. A summary of how each type of electrogram was affected by resection is shown in Fig 5⇓. In general, signals recorded from each electrode were less abnormal after resection than before resection because of the combination of increased amplitude and decreased duration as noted above. Among these 298 paired recordings, the proportion of normal electrograms increased from 5% to 52% (15 to 154) of the total, abnormal electrograms decreased in prevalence from 74% to 40% (220 to 120), and fractionated electrograms decreased from 21% to 8% (63 to 24); this shift was significant at the P<.03 level. Similarly, the marked changes in the prevalence of split and late electrograms after resection was significant (P<.02).
In the 3 patients who had the resected specimen replaced in situ and recordings repeated with the array, a total of 50 recordings could be compared (before resection versus after replacement of specimen). Among these, the mean amplitude decreased from 1.0±1.5 to 0.7±1.0 mV (P<.002), and the mean duration decreased from 118±50 to 66±21 ms (P<.0001). In each case, the morphology of the electrograms after specimen replacement was very similar to that recorded before resection, except for the absence of late and split potentials (Fig 4⇑).
One patient died of low cardiac output in the perioperative period. The remaining patients underwent postoperative electrophysiological stimulation to assess the efficacy of surgery in preventing inducibility of VT. The stimulation protocol included delivery of one, two, and three ventricular extrastimuli after at least two drive cycle lengths from two right ventricular sites and burst pacing at cycle lengths from 350 to 250 ms except for 1 patient who suffered a perioperative pulmonary embolus; stimulation was performed with epicardial pacing wires (one site) and included quadruple extrastimuli after four drive cycle lengths. Among these 17 patients, 1 had inducible sustained monomorphic VT.
Preoperative and postoperative signal-averaged ECGs were comparable in 10 of the patients (in the remainder, either one of the studies had not been performed or a new bundle branch block or complete heart block was present after surgery, precluding direct comparison). Among these patients, 7 had a positive study (a low-amplitude late potential) before surgery. In 4 of these patients, the low-amplitude late potential was absent after surgery, whereas the study became positive in 2 additional patients who had negative studies before surgery. One patient had negative studies before and after surgery. The 1 patient with persistence of inducible VT after surgery had a normal study before surgery that became abnormal after surgery; the patient in whom endocardial late electrograms were first recorded after resection had abnormal signal-averaged ECGs before and after surgery.
This is the first study to directly compare characteristics of endocardial electrograms recorded before and immediately after resection of arrhythmogenic ventricular tissue. In this study, there was an overall tendency for electrograms to change to less abnormal types after resection; that is, fractionated electrograms generally became either abnormal or even normal, and abnormal electrograms tended to become normal. Of greater interest, late and split components were uniformly eliminated by resection.
The observed increase in electrogram amplitude after resection appears to be due to removal of scar tissue that had attenuated the signal from deeper layers. This is evidenced by both the similarity in basic electrogram morphology before and after resection (except for the tendency toward an increase in signal amplitude after resection) and the striking similarity in electrogram morphology when the preresection recordings were compared with those made after replacement of the specimen (Fig 4⇑). The decrease in overall electrogram duration after resection was primarily due to removal of late electrogram components; in all sites from which either late or split components were recorded before resection, these components were absent in the postresection recordings. This indicates that these electrogram components were generated by cells in the more superficial layers of endocardium that had been removed with the resection. The absence of these components in recordings made after replacement of the specimen is further evidence of their endocardial origin.
Low-amplitude late components were first observed after resection in five recordings (not present in preresection recordings). This is probably explained by the signal-attenuating effect of the overlying scar tissue, the removal of which allowed the late components to be observed. This also suggests that although late components are almost always recorded from the superficial endocardial layers, this is not uniformly the case.
Split and Late Electrograms
A large proportion of recordings made during NSR in this study showed split electrograms: two activations recorded from the same area but at different times. These activations clearly do not derive from the same cells, since the interval between discrete activations is far less than a ventricular or Purkinje effective refractory period. Rather, the two or more discrete spikes in these electrograms appear to represent activations of bundles of cells anatomically near those giving rise to the other discrete activations recorded in the same electrode but insulated from the effects of depolarization of these cells by interposed scar tissue.10 11 Similar split potentials can be observed during VT (Fig 3⇑). Previous models of VT have generally been two-dimensional and have depicted the cells responsible for split potentials as separated in the same (horizontal) plane.12 13 The present study suggests that the cells responsible for the discrete components of a split electrogram are separated in the vertical plane: the later-occurring component is recorded from the endocardial surface and the earlier component from subjacent myocardial layers, since the later components of these electrograms are uniformly eradicated by subendocardial resection.
The discrete endocardial late and split potentials resemble His-Purkinje potentials. The subendocardial Purkinje network remains relatively intact after acute infarction10 and thus would be expected to produce recordable depolarizations. Although many patients in this study had normal QRS durations in NSR and no evidence of His-Purkinje dysfunction to account for the delayed activation of portions of the Purkinje network, these remain a possible cause of portions of late and split electrograms. This study did not specifically address the potential role of the Purkinje network in the genesis of these electrograms.
The proportions of endocardial split (44%) and late (28%) electrograms in this study were larger than in prior studies1 2 3 5 9 14 ; this is probably a result of differences in mapping techniques. Previous studies have sampled the entire left ventricular endocardium, much of which had relatively normal electrogram characteristics; in this study, electrograms were sampled only in abnormal areas with a much higher likelihood of recording these potentials.
Implications for VT Mapping
El Sherif et al15 have shown that the wave front in canine infarction models of VT circulates in a figure-eight manner incorporating a central zone of slow conduction. There is some evidence of this type of reentry pattern in humans, demonstrated with multipolar electrode balloon arrays13 16 during intraoperative mapping. However, not all activation patterns during VT are compatible with a figure-eight model, at least at the resolution of the recording techniques.13 17 Many VTs appear to have a “focal” origin (that is, an effective point source for the onset of endocardial activation) without any clear reentrant loop on the endocardium. These tachycardias could still be based on a figure-eight pattern of reentry, but a portion of the reentrant loop may be intramural rather than entirely within the superficial endocardial layers.
Previous studies have shown a poor correlation between sites from which late or split electrograms were recorded in NSR and sites from which the earliest diastolic activity during VT was recorded,5 18 19 whereas other studies have shown a relation between NSR late/split electrograms and middiastolic potentials recorded at the same sites during VT.20 Such a relation is demonstrated in Fig 3⇑. The present study does not resolve this issue, although it shows that the pathophysiology underlying late and split electrograms—spatial separation of surviving muscle bundles—is the same as that in current models of VT. In cases in which the earliest diastolic activity in VT is recorded from sites that show these delayed electrogram components in NSR, the evidence that they appear to derive from the superficial (endocardial) layers serves as an explanation for both the capacity of subendocardial resection to cure VT and why catheter ablation techniques that target middiastolic potentials21 22 can be successful in eliminating VT. Although prior investigations suggested that late and split electrograms recorded in NSR represent slow conduction along the endocardial surface, the present study suggests that they are instead the result of depolarization of different layers of cells not necessarily activated in sequence.
Previous studies have correlated resection of endocardial areas from which late electrograms were recorded at the time of surgery with changes in the signal-averaged ECG.7 8 9 These studies showed that when surgery is successful in eliminating inducible VT after surgery, the signal-averaged ECG is frequently normalized; when VT is still inducible, the signal-averaged ECG generally remains abnormal. However, some patients with persistence of inducible VT had no postoperative late potential, whereas others with a persistent late potential had a successful surgical outcome. The results of signal-averaged ECGs in the present study are similar to what has been reported previously, although only a small sample could be analyzed.
There are at least three possible explanations for the persistence of an abnormal signal-averaged ECG after even successful subendocardial resection: First, some of the late electrogram components responsible for the surface late potential could derive from residual endocardial scar tissue that was not resected. Second, some of the late electrogram components may originate in deeper (nonresected) layers, as was the case in one of our patients. Last, the surface ECG may be altered by resection (development of bundle branch block or complete heart block requiring ventricular pacing), making comparison of preoperative and postoperative signal-averaged ECGs impossible.
The most important potential limitation in this study is the ability to replace the recording array after resection precisely over the area from which recordings were made before resection. As noted above, marking sutures were initially used to facilitate identical electrode positioning, but further experience showed this to be unnecessary. The similarity of electrogram morphologies recorded from the same electrode before and after resection suggests good reproducibility in positioning of the array. In addition, the large proportion of late and split potentials observed in this study were recorded from several different electrodes on the array; a shift of a few millimeters in the placement of the array after resection would not be expected to result in failure to record any of these potentials. It is possible that tissue trauma incurred during resection could transiently depolarize some cells, causing their component of the electrogram to not be recorded after resection. Although this possibility cannot be excluded, the effect would have to be very selective (affecting only late and split components), since other parts of the signal from the same electrodes generally increased in amplitude.
Finally, this series of patients was relatively homogeneous: all were men with anterior wall myocardial infarctions. The same results may not necessarily apply to patients with VT in the setting of inferior wall infarctions.
This study provides new insight into the nature of some of the abnormal endocardial electrogram types observed in patients with VT. Specifically, our data show that “endocardial” recordings may actually be generated by cells in multiple tissue layers, since removal of the superficial endocardial tissue eradicates both the latest-occurring portion of a split electrogram as well as true late components (ie, extending beyond the end of the surface QRS complex). These findings correspond with the known histological abnormalities in resection specimens, which have shown strata of surviving muscle bundles separated by layers of dense collagenous scar.
In cases in which split and late electrograms are recorded in sinus rhythm from sites showing middiastolic activity during VT, the VT circuit may traverse a course incorporating some of the deeper layers rather than being exclusively endocardial. Removal or ablation of these sites can still cure VT by eliminating a critical component of the circuit, rather than the entire circuit. Use of advanced mapping tools, such as multipolar electrode arrays,13 16 should allow more precise characterization of the relation between endocardial sinus rhythm electrogram abnormalities and critical components of VT circuits.
The authors wish to acknowledge the careful work of Carol Wood in the preparation of this manuscript.
- Received May 16, 1994.
- Revision received August 2, 1994.
- Accepted November 26, 1994.
- Copyright © 1995 by American Heart Association
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