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J Am Coll Cardiol, 2003; 41:2228-2236, doi:10.1016/S0735-1097(03)00492-3 © 2003 by the American College of Cardiology Foundation |
* Cardiac Arrhythmia Service, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
Electrophysiology Section, Cardiology Division, Na Homolce Hospital, Prague, Czech Republic
Manuscript received March 30, 2001; revised manuscript received January 29, 2003, accepted February 6, 2003.
* Reprints requests and correspondence: Dr. Vivek Y. Reddy, Cardiac Arrhythmia Service, Massachusetts General Hospital, 32 Fruit St., Gray-Bigelow 109, Boston, Massachusetts 02114, USA.
vreddy{at}partners.org
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Abstract |
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BACKGROUND: Ventricular tachycardia associated with chronic myocardial infarction (MI) is frequently hemodynamically intolerable and associated with multiple electrocardiographic morphologies. Because traditional mapping techniques are contingent on hemodynamic stability for adequate VT mapping, VT ablation therapy for many patients has been disappointing.
METHODS: High-density electroanatomic mapping was performed during either sinus rhythm in 11 consecutive patients with a history of MI and ventricular arrhythmias. The RF ablation was performed using an irrigated-tip ablation catheter. All inducible VTs were targeted for catheter ablation during sinus rhythm.
RESULTS: The RF ablation lesions were placed in a linear fashion traversing the border zones of infarcted and normal tissue (mean of 3.4 linear lesions/patient). With this strategy, the target VT was eliminated in 9 of 11 patients (82%). Furthermore, when targeting all inducible monomorphic VTs, complete procedural success was achieved in 7 of 11 patients (64%). During the follow-up period (mean 13.1 ± 1.9 weeks), spontaneous VT was only noted in the two patients with no acute procedural benefit.
CONCLUSIONS: By identifying potentially arrhythmogenic tissue during sinus rhythm, substrate mapping can guide the ablation of a majority of inducible VTs using an irrigated RF ablation catheter. This emerging therapeutic paradigm may be considered in the management of patients with multiple hemodynamically unstable monomorphic VTs.
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10%) of patients experience VT that is hemodynamically tolerated sufficiently well to allow adequate mapping, and even these patients frequently exhibit inducible hemodynamically unstable VTs with multiple electrocardiographic (ECG) morphologies (9). Thus, catheter ablation of VT has largely been relegated to an adjunctive role even at experienced centers. The anatomic substrate for VT in these patients is predominantly located at the border zone between the normal and scarred myocardium (10). This arrhythmogenic zone has distinguishing electrogram (EGM) characteristics during sinus rhythm: low amplitude and prolonged duration (11). Using an electroanatomic mapping system (CARTO, Biosense-Webster Inc., Diamond Bar, California), it is possible to construct three-dimensional maps overlaying these EGM characteristics onto the LV chamber geometry. In a seminal study by Marchlinski et al. (12), the infarcted myocardium was identified using bipolar voltage amplitude criteria, and catheter-based RF ablation lesions were placed in a linear fashion to control drug-refractory unstable VT in nine post-MI patients. However, that study was directed to a specific population of patients with drug-refractory VT. In an effort to better define the potential of electroanatomic mapping-based substrate-ablation of VT, we examined: 1) the ability of EGM characteristics during normal sinus rhythm to delineate the scarred myocardium in patients with a history of MI and VT/VF, and 2) the use of this "substrate mapping" strategy to guide the ablation of all inducible VTs using a novel saline-irrigated RF ablation catheter.
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Methods |
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Electroanatomic mapping. Catheter access to the LV was achieved via the retrograde aortic approach, and in two patients an additional trans-septal approach. The LV electroanatomic mapping was performed using the CARTO system as previously described (14). Endocardial EGMs were recorded using deflectable Navistar catheters (BioSense-Webster Inc.) with a 4-mm-tip distal electrode. After intravenous heparin infusion, mapping was performed (using a fill threshold <20 mm) with an emphasis on fully defining the border zones of the infarcted tissue. The peak-to-peak bipolar voltages associated with each point were displayed upon the endocardial cast.
Reference values for electroanatomic maps. Reference values for distinguishing normal from abnormal tissue were established by mapping the LV of the seven control patients during normal sinus rhythm (mean of 69 points/patient). The mean bipolar voltage value obtained was 8.4 ± 7.8 mV (range 0.5 to 44.7 mV) and, most importantly, the 95% voltage amplitude cutoff was >1.53 mV. That is, only 5% of the points obtained were less than this value. Accordingly, normal tissue was defined as bipolar voltage >1.5 mV, and dense scar was arbitrarily defined as <0.5 mV (12). Accordingly, the color display was set to span 0.5 to 1.5 mV. As previously described, endocardial surface areas were calculated assuming multiple rectangular or trapezoidal shapes of either abnormal (<1.5 mV, bipolar voltage) or densely scarred (<0.5 mV, bipolar voltage) tissue (12). Using the CARTO electronic calipers to measure distances, the scar dimensions were estimated to best fit with either a circle, ellipsoid, rectangle, or combination of these shapes, and then the area(s) of this shape calculated.
RF catheter ablation. As a general strategy, pace-mapping (using bipolar pacing) was performed during sinus rhythm in the border zone between scar and normal tissue to approximate the exit site of each inducible VT. When seen, a delay in stimulus to QRS interval during pace-mapping within the scar was used to identify putative proximal sites within the VT circuit. Sequential point lesions were placed to create two bisecting linear ablation lines: one from the exit site back into the dense scar, and the other perpendicular to the first line at the exit site. These lesions typically were extended till either pacing could not capture the tissue, or the pace-maps revealed exit of the wavefront from the opposite side of the scar. The lesions were placed <10 mm apart. Potentially adverse effects on LV function were minimized by placing lesions exclusively in abnormal tissue (bipolar voltage <1.5 mV).
A few lesions (<5%) were placed using a 4-mm-tip temperature-controlled nonirrigated ablation catheter (Navistar, Biosense-Webster Inc.). Radiofrequency current was applied in 60-s intervals using a target temperature of 55°C to 60°C. However, the majority of RF lesions (> 95%) were placed using a saline-irrigated 3.5-mm-tip ablation catheter (Navistar, Biosense-Webster Inc.). This catheter is equipped with a central lumen and a "showerhead" configuration at the catheter tip. To actively cool the ablation electrode, saline (0.45% to 0.9%) was infused through the saline-irrigated catheter at 2 ml/min during catheter manipulation to maintain lumen patency, or at 15 to 30 ml/min during RF delivery. The RF lesions were placed in 60-s intervals under power control of 25 to 50 W with impedance monitoring. The activated coagulation time was maintained over 220 s. The RF energy applications were "tagged" for display on the CARTO system, and the final length of each linear lesion was measured.
Attempts were made to localize and ablate the target (and usually slowest) VT first. The target VT was defined as either the clinically spontaneous MMVT (in seven patients) or inducible MMVT(s) during electrophysiologic testing (in the remaining four patients) (Table 2). After every pair of bisecting linear lesions, programmed ventricular stimulation was repeated to induce any residual VT(s), which were in turn targeted for ablation. All patients underwent programmed stimulation using up to triple extrastimuli and rapid pacing from two RV and one to two LV sites after all ablation lesions were applied. A successful procedure was defined as either: 1) inability to induce any sustained VT; 2) induction of only a morphologically indeterminate VT with no isoelectric segment (e.g., a "sine wave"-like morphology [SWVT]); or 3) induction of only VF. Partial success was defined as elimination of one or more VTs (including the target VT) but persistence of at least one other inducible VT. Failure was defined as persistent inducibility of the "clinical" or predominant VT.
Postprocedure management and follow-up. Patients received intravenous heparin overnight, and those who underwent RF ablation were also prescribed coumadin for three months (international normalized ratio >2.0). Patients underwent echocardiography to re-evaluate LV function before discharge from the hospital. Before ablation, 7 of 11 patients were being treated with amiodarone. This drug treatment was unchanged during the follow-up period. During follow-up every three months, the ICDs were interrogated.
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Results |
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High-density endocardial electroanatomic mapping of the LV was accomplished by acquiring 285 ± 110 discrete points/patient (range 166 to 535 points). Despite the frequent presence of large areas of wall motion dysfunction during LV contrast ventriculography, bipolar voltage amplitude mapping identified a discrete scar and border zone in all patients. The endocardial surface area demonstrating abnormal bipolar voltage criteria was 61 ± 35 cm2, and ranged from 15 to 117 cm2. The area of dense scar occupied 22 ± 17 cm2, and ranged from 2 to 54 cm2 (Table 1). This corresponded to the area of aneurysmal dilation observed during echocardiography or contrast ventriculography.
RF catheter ablation using an irrigated-tip catheter. The results of three representative patients who underwent catheter ablation using the irrigated-tip ablation catheter are shown in Figures 1 to 3. Shown in Table 3, a mean of 37 ± 23 lesions were applied per patient (range 11 to 86) for a total of 3.4 ± 1.8 linear lesions (range 1 to 6). The average length of these lesions was 3.4 ± 1.2 cm (range 1.6 to 7.2 cm). Using noninducibility of VT as the end point, complete success was achieved in 7 of 11 (64%) patients and partial success in 2 of 11 patients. Of note, in both patients with partial success, Patients #9 and #11 (Fig. 3), all VTs inducible by RV stimulation (including the clinically spontaneous VT) were successfully ablated. However, LV stimulation after ablation induced another VT, which was not eliminated by further RF ablation in either patient. Thus, elimination of the target VT was achieved in 9 of 11 (82%) patients. Two patients were deemed failures because the target VTs remained inducible.
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Fluoroscopy times decreased from a mean of 75 min in the first six cases to 45 min in the last five cases. There was no echocardiographic evidence of deterioration of overall or regional LV systolic function following the ablation procedure.
Short-term follow-up. All patients were followed in the ICD clinic for a minimum of 12 months (mean 13.1 ± 1.9 months; range 12 to 16 months). There were no ICD therapies or detection of VT in any patient in whom either complete or partial acute procedural success was achieved. However, both patients in whom the ablation procedure failed to eliminate the target VT experienced clinical VT recurrences: 1) Patient #3 received three appropriate ICD therapies, and 2) Patient #4 developed MMVT requiring cardioversion while in the hospital, prompting ICD implantation (this patient later underwent a second ablation procedure using the substrate-based approach, and has since remained free of VT for over a year). In sum, the VT frequency decreased from a mean of 8.4 VT episodes (range 0 to 88) to 0.3 episodes (range 0 to 3) postablation. Delayed complications were not seen during follow-up in any patient.
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Discussion |
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The substrate-based ablation strategy. The arrhythmogenic substrate for VT resides at least partly in the border zone between densely infarcted/fibrotic tissue and normal tissue. Over the past three decades, two effective surgical strategies have been developed: 1) subendocardial resection— involving removal of the subendocardial layer containing the arrhythmogenic tissue, and 2) encircling endocardial ventriculotomy—whereby circumferential surgical lesions are placed through the border zone, presumably interrupting potential VT circuits (15–19) (Fig. 4). This experience was critical in establishing the concepts on which substrate-based ablation is based: 1) the arrhythmogenic substrate is predominantly located in the subendocardium; 2) this substrate has distinguishing EGM characteristics; and 3) removal or interruption of this arrhythmogenic tissue can abolish VT.
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Localization of the VT circuit. Using techniques similar to those previously described (12), pace-mapping was performed at the border zone of the infarct to identify the putative exit point of each induced VT. Despite the fact that ventricular activation with pace-mapping during sinus rhythm results in omnidirectional spread of activation (unlike activation during re-entrant VT, which proceeds directionally out of the scar), there was still a good match between the pace-map and VT ECG morphologies. This is likely due to the fact that the "antidromic" wavefront during pace-mapping (the spread of activation proceeding into the scar) encounters diseased tissue—thereby contributing minimally to the surface QRS morphology. Points within the VT circuit were occasionally identified by pace-mapping in close proximity to the exit site but farther into the scarred myocardium. The duration of latency from stimulation to the onset of QRS complex was observed. Notwithstanding the fact that this inevitably results in the identification of irrelevant "inner loop" and "adjacent bystander" sites as well as the desired "isthmus" sites (21), this strategy nonetheless provides a general idea of the orientation of the VT circuit.
RF catheter ablation. The ability to identify the anatomic substrate during sinus rhythm obviates the need for hemodynamic stability during VT because mapping during sustained VT is not required. Indeed, activation mapping was not performed in this study (and entrainment mapping only performed in Patient #5). Because all inducible VTs, hemodynamically stable or unstable, were targeted for ablation, the question of how to gauge success was raised. Most previous studies had defined a successful VT ablation procedure as noninducibility of either the clinically documented VT(s) or hemodynamically stable VT(s). In our study, the only ventricular tachyarrhythmias not targeted for ablation were VF and SWVT. The definition of "sine wave"-like VT was not dependent on the rate of the VT but rather on the indeterminate nature of the rhythm’s ECG morphology. Indeed, the rates of the two SWVTs noted in this series (cycle length 301 ms and 311 ms) were actually slower than were many VTs seen in other patients that were targeted for ablation. The clinical significance of postablation inducible SWVT (as well as inducible VF) can only be assessed by prospective clinical trials.
Unlike most previous studies, programmed stimulation was also performed from the LV before a procedure was deemed successful. Indeed, the two patients labeled as partial successes may have been classified as complete successes if only RV stimulation had been performed. Despite this relatively rigorous definition of a successful ablation procedure, it was possible to ablate a majority of the VTs. In most cases, failure was due to an inability to achieve adequate electrode-tissue contact at the desired location, a limitation that should improve with further refinements in catheter design. The fluoroscopy exposure and procedure times will likely similarly diminish with these advances.
The approach used in the patient who had both hemodynamically stable and unstable VT was similar to that used in patients with only unstable VT. A sinus rhythm substrate map of the LV was created, and pace-mapping was performed to identify the putative exit site. Traditional entrainment techniques during tachycardia were then applied to identify the critical isthmus in the VT circuit. While a single point lesion at the isthmus site sufficed to eliminate the target VT, it is known that multiple morphologies of VT can originate from a common mass of tissue (22,23). Because the goal was to ablate all inducible VTs, linear ablation was performed incorporating the entrainment sites within the lesions. This strategy of combining the anatomic and entrainment data possesses several advantages: 1) identification of critical portions of the stable VT circuit is facilitated by knowledge of the location of the scar and border zones; 2) patient discomfort is minimized as most of the procedure is conducted during sinus rhythm; and 3) this strategy may eliminate not only the hemodynamically stable target VT, but all inducible VTs—which are often hemodynamically unstable.
This study also highlights the efficacy and safety of the saline-irrigated RF ablation catheter for VT ablation. This catheter was employed both because of its ability to generate deeper lesions, and because active cooling of the ablation electrode helps prevent the formation of coagulum and elevations of impedance. Notwithstanding the limited number of patients in this series, no evidence was seen of thromboembolic phenomena in this series in the over 400 RF lesions applied. This study does not address the relative efficacies of the irrigated and nonirrigated catheters—a comparison that must be evaluated in a prospective randomized fashion.
Follow-up. Ventricular arrhythmias did not recur in any patient whose initial procedural outcome was either a complete or partial success over a mean follow-up of 13.1 months. In both patients with failed ablations, VT recurred during the follow-up period. Despite the fact that this was a patient population at high risk for recurrent ventricular arrhythmias (3,13), these data must be interpreted with caution because of both the nonrandomized nature of this series, and the relatively short duration of follow-up. Also, because these patients were not necessarily the "typical" VT ablation candidates (i.e., patients who had previously experienced multiple recurrent VT episodes/ICD shocks), results of this study may not necessarily be applied to that population. This study would best be interpreted as provocative data to form the basis of larger prospective randomized clinical trials to fully assess the clinical utility of this approach. Also, the results of this study do not imply that patients undergoing substrate ablation procedures do not require ICDs when established indications are present. The potential impact of this ablation strategy on both the mechanisms and risk of sudden cardiac death are unknown.
Study limitations. The control patient data utilized in this study as well as earlier studies were obtained during normal sinus rhythm, but some of the patients in this study were mapped during RV pacing. Although evidence shows that this does not significantly affect the EGM voltage amplitude (24), this needs to be fully studied.
The mechanisms of elimination of VT is thought to be due to interruption of critical portions of the circuit, but this remains speculative. In fact, one cannot determine from this study the number or length of the linear lesions required for successful VT ablation as programmed stimulation was not repeated after every point lesion, but rather after completion of one to two linear lesions.
Although no increases in impedance or thromboembolic phenomena occurred in any of these cases, the number of patients in whom RF ablation was performed was limited. Indeed, a stroke occurred in 1 of 16 patients in the series reported by Marchlinski et al. (12), albeit not with the theoretically safer irrigated ablation catheter, as was used in our series.
Conclusions. The principal advantage of substrate mapping to guide VT ablation lies in the potential application of this strategy to virtually any morphologically discernible monomorphic VT irrespective of its hemodynamic effect. This raises the possibility that most patients with a history of MI and monomorphic VT may ultimately be candidates for catheter ablative therapy. Substrate mapping may represent a catheter-based method to replicate the highly efficacious results of substrate modification by surgical techniques, but with less attendant morbidity and mortality.
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