View metadata, citation and similar papers at core.ac.uk brought to you by CORE Journal of the American College of provided byVol. Elsevier 44, No.- Publisher 8, 2004 Connector © 2004 by the American College of Cardiology Foundation ISSN 0735-1097/04/$30.00 Published by Elsevier Inc. doi:10.1016/j.jacc.2004.08.034 EXPRESS PUBLICATION Mapping and Ablation of Polymorphic Ventricular After Lukasz Szumowski, MD, PHD,* Prashanthan Sanders, MBBS, PHD,† Franciszek Walczak, MD, PHD,* Mélèze Hocini, MD,† Pierre Jaïs, MD,† Roman Kepski, PHD,* Ewa Szufladowicz, MD, PHD,* Piotr Urbanek, MD,* Paweł Derejko, MD,* Robert Bodalski, MD,* Michel Haïssaguerre, MD† Warsaw, Poland; and Bordeaux,

OBJECTIVES The goal of this study was to describe the mapping and ablation of polymorphic ventricular tachycardia (VT) after myocardial infarction (MI). BACKGROUND The initiating mechanisms of polymorphic VT after MI have not been reported. METHODS Five patients (four males; age 61 Ϯ 7 years) with recurrent episodes of polymorphic VT after anterior MI (left ventricular ejection fraction 32 Ϯ 7%) despite revascularization and antiarrhythmic drugs were studied. All patients demonstrated frequent ventricular premature beats (PBs) initiating polymorphic VT. Pace mapping and activation mapping were used to identify the earliest site of PB activity. The presence of a Purkinje potential preceding PB defined its origin from the Purkinje network. Electroanatomic voltage mapping was performed to delineate the extent of MI. RESULTS The PBs were observed in all cases to arise from the Purkinje arborization in the MI border zone. These PBs were right bundle-branch block in all five patients, with morphologic variations in the limb leads in four; one also had a left bundle-branch block morphology. The coupling interval of the PB to the preceding QRS complex demonstrated significant variations (320 to 600 ms). During PB, the Purkinje potential at the same site preceded the QRS complex by 20 to 160 ms and was associated with different morphologies. Repetitive Purkinje activity was documented during polymorphic VT. Splitting of Purkinje activity and Purkinje to muscle conduction block were also observed. Ablation at these sites eliminated all PBs. At 16 Ϯ 5 months follow-up using defibrillator memory interrogation, no patient has had recurrence of . CONCLUSIONS The Purkinje arborization along the border-zone of scar has an important role in the mechanism of polymorphic VT in patients after MI. Ablation of the local Purkinje network allows suppression of polymorphic VT. (J Am Coll Cardiol 2004;44:1700–6) © 2004 by the American College of Cardiology Foundation

Monomorphic ventricular tachycardia (VT) in the presence Emerging evidence in patients with ventricular fibrillation of structural heart disease is largely attributed to anatomi- (VF) in a variety of clinical scenarios implicates an impor- cally bound macro–re-entry involving regions of myocardial tant role for triggers originating from the distal Purkinje scarring or the bundle branches. Improved understanding of arborization in the initiation of this malignant arrhythmia these mechanisms has led to the ability to map and identify (10–14). This study describes the mapping and ablation of critical isthmuses that create the substrate necessary for polymorphic VT in relation to the three-dimensional ven- these , thus allowing their ablation (1–5). In tricular anatomy after myocardial infarction (MI). contrast, the mechanisms underlying the initiation and maintenance of polymorphic VT are poorly understood. METHODS Experimental studies have suggested the possibility that this arrhythmia may be maintained by migrating scroll waves, Study population. The study comprised five consecutive Ϯ Ϯ intramural re-entry, and Purkinje network re-entry (6–9). patients (four males; age 61 7 years [mean SD], range 50 to 67 years) with frequent episodes of polymorphic VT who underwent mapping and ablation. These patients were selected for ablation on the basis of repeated arrhythmia From the *Institute of Cardiology, Warsaw, Poland; and the †Hopital Cardi- ologique du Haut-Leveque and the Université Victor Segalen Bordeaux II, Bordeaux, despite drug therapy (including beta-blockers and amioda- France. This study was supported in part by a grant (3PO5C00723) from the State rone), complete revascularization, and correction of any Committee for Scientific Research, Poland. Dr. Sanders is the recipient of a Neil electrolyte abnormality. All patients were observed to have Hamilton Fairley Fellowship from the National Health and Medical Research Council of Australia and the Ralph Reader Fellowship from the National Heart frequent premature beats (PBs) that occurred in isolation or Foundation of Australia. Presented at the 25th Annual Scientific Sessions of the initiated arrhythmia (Fig. 1) during hospitalization imme- NASPE Heart Rhythm Society, San Francisco, May 2004, and published in abstract diately after the arrhythmic storms. Medical therapy for form (Heart Rhythm 2004;1:S37). Manuscript received May 1, 2004; revised manuscript received July 29, 2004, arrhythmia in these patients included amiodarone, sotalol, accepted August 2, 2004. beta-blockers, and mexiletine. JACC Vol. 44, No. 8, 2004 Szumowski et al. 1701 October 19, 2004:1700–6 Ablation of Polymorphic VT

Surface electrocardiograms and bipolar endocardial elec- Abbreviations and Acronyms trograms were continuously monitored and stored on a MI ϭ myocardial infarction computer-based digital amplifier/recorder system with op- ϭ PB premature beat tical disk storage for off-line analysis (Bard Electrophysiol- VF ϭ ventricular fibrillation VT ϭ ventricular tachycardia ogy [Massachusetts] or EP MedSystems Work-Mate [New Jersey]). Intracardiac electrograms were filtered from 30 to 500 Hz, and measured with computer-assisted calipers at a sweep speed of 100 mm/s. Electroanatomic mapping. In four patients, left ventricu- Arrhythmias occurred in these patients after large ante- lar electroanatomic maps were created during sinus rhythm rior MI with residual left ventricular ejection fractions of 32 (Fig. 2), whereas in one patient with frequent PBs, mapping Ϯ 7% (range 22% to 40%). In three patients, polymorphic of the PB was performed using the CARTO mapping VT occurred early after MI (four, four, and eight days, system (Biosense-Webster) (Fig. 3). The system records the respectively). Two of these required Ͼ30 external defibril- 12-lead electrocardiograms and bipolar electrograms filtered lations because of induction/degeneration into VF, such at 30 to 400 Hz from the mapping catheter and the that ablation was performed during the initial hospitaliza- reference electrogram. Endocardial contact during point tion. In the third patient, although the arrhythmic episodes acquisition was facilitated by fluoroscopy and the catheter abated during the initial hospitalization, further recurrent icon on the CARTO system. Points were acquired if the episodes one month later necessitated ablation. The latter stability criteria in space (Յ6 mm) and local activation time two patients presented with recurrent polymorphic VT 150 (Յ5 ms) were met. The border-zone of the MI was defined and 170 days after MI (Table 1). as previously described, as the region demonstrating bipolar Electrophysiologic study. Written, informed consent was voltage amplitudes of between 0.5 and 1.5 mV (4). In obtained from all patients. In the two patients mapped addition to voltage mapping, we tagged points on the map during the week of MI, mapping was performed in the that demonstrated Purkinje potentials during sinus rhythm sedated ventilated state. The remaining patients were stud- (Figs. 2 and 3). ied in the fasted state with sedation using midazolam and Mapping and ablation. The origin of PBs in these patients nalbuphine. An intravenous dose of 0.5 mg/kg of heparin was localized by: 1) pace mapping techniques to localize was administered during mapping in the left ventricle. One concordance with PB morphology; and 2) mapping of the or two multielectrode catheters were introduced percutane- earliest endocardial site activation relative to the QRS ously through the femoral vessels including an 8-mm tip complex during PB. In one patient with frequent mono- quadripolar roving ablation catheter (Navi-Star, Biosense morphic PBs, an activation map of the PB was created to Webster Inc., California). The latter was introduced into localize its origin. The following definitions were utilized as the left ventricle by retrograde aortic catheterization. previously described to identify the origin of PB (10): 1) An

Figure 1. Examples of frequent isolated premature beats followed by the initiation of polymorphic ventricular tachycardia. 1702 Szumowski et al. JACC Vol. 44, No. 8, 2004 Ablation of Polymorphic VT October 19, 2004:1700–6

Table 1. Baseline Characteristics and Results PVT After No. of Coupling Interval PP to QRS Ablation Site RF Time Pt. No. MI (days) VPB Morph. VPB Morph. of VPB Duration (ms) (PP) (min) 1 8 3 RBBB sup, inf and int 360–500 20–30 Left free-wall and septum 32 axis 190–220 2 170 1 RBBB sup axis 400–440 20 Ant-Sept and low 23 posterior walls 3 4 4 RBBB sup, inf and int 400–500 20–40 Septum 18 axis, LBBB 160–190 4 150 3 RBBB sup, inf and int 500–600 20 Ant-Sept 14 axis 60–80, 116 5 4 2 RBBB sup and inf axis 320–480 30–40 Ant-Sept 9

Ant-Sept ϭ anteroseptal; inf ϭ inferior; int ϭ intermediate; LBBB ϭ left bundle-branch block; MI ϭ myocardial infarction; Morph ϭ morphology; PP ϭ Purkinje potential; Pt. ϭ patient; PVT ϭ polymorphic ventricular tachycardia; RBBB ϭ right bundle-branch block; RF ϭ radiofrequency application; sup ϭ superior; VPB ϭ ventricular premature beat.

initial sharp potential (Ͻ10 ms in duration) preceding the sinus rhythm; the difference from sinus rhythm being Ͻ40 larger, slower ventricular electrogram during sinus beats, ms in four patients and 60 to 170 ms in the last patient was considered to represent a Purkinje potential. Such a (Table 1). In four patients, a long-short sequence of potential preceding the local electrogram at the site of activation without abnormal prolongation of the QT inter- earliest activation during PB indicated the Purkinje origin of val was observed to initiate polymorphic VT. the PB. 2) In the absence of such a potential at the site of Mapping and localization of PBs. Pace mapping was used earliest activation, the PB was considered to be of myocar- as a guide to identify the region of interest to perform more dial origin. detailed activation mapping of PBs. The PBs observed Ablation was performed using radiofrequency energy during mapping were all localized to the left ventricle in the with a target temperature of 55°Cto70°C and a maximum region of the border-zone of the MI as defined by electro- power of 70 W, with a duration, to abolish PB and anatomic mapping, occurring within 1 cm of dense scar consolidating applications to minimize recurrence. In addi- (Fig. 2). In these patients with post-anterior MI, we ϭ tion, in patients with inducible monomorphic VT (n 3), observed the following localization of PB morphology to the activation and entrainment mapping of this VT was per- border-zone of the scar: inferior-axis PBs were located along formed to identify the critical isthmus and further ablation the anteroseptal region; intermediate-axis PBs were local- performed at these sites. After ablation, patients were ized to the anterior-lateral region; and superior-axis PBs monitored for three to five days and then followed using were localized to the apico-septal region. defibrillator memory interrogation. In all cases, at the earliest site of activation, PBs were preceded by Purkinje potentials indicating their origin from this structure (Figs. 3 and 4). During PB, the Purkinje RESULTS potential preceded the QRS complex by 20 to 160 ms. At Polymorphic VT was observed in all patients during their the same site, this varying conduction was associated with hospitalization. The cycle length of arrhythmia varied from different PB morphologies previously documented on an 600 to 200 ms (mean 332 Ϯ 73 ms) and also demonstrated electrocardiogram. Repetitive Purkinje activity, suggestive significant intra-individual variation between episodes of of successive beats being maintained by the Purkinje net- polymorphic VT. work, was observed to precede each QRS complex during PBs and polymorphic VT. All patients were observed to the initiation of VT (Fig. 5). In addition, in two patients the have frequent ventricular PBs in the immediate aftermath of Purkinje potential appeared to split during repetitive runs of recurrent episodes of polymorphic VT. Through in-hospital PBs, and in a further two patients, conduction block monitoring, these PBs were observed to trigger episodes of between the Purkinje potential and the ventricular muscle polymorphic VT (Fig. 1). These beats were right bundle- was observed (Fig. 6). branch block morphology in all five patients, with morpho- Radiofrequency ablation. Radiofrequency energy was de- logic variations in the limb leads in four patients. One livered for 19 Ϯ 9 min (range 9 to 32 min) at sites patient additionally had a left bundle-branch block mor- demonstrating the earliest PB activation (mean fluoroscopy phology PB. The coupling interval of the PBs to the duration was 49 Ϯ 25 min). In all cases, these were at sites preceding QRS complex demonstrated significant intra- where Purkinje potentials were observed to precede ventric- and inter-individual variation (320 to 600 ms), with 40 to ular activation (Table 1). During applications, bursts of 160 ms variation within a given individual. The QRS arrhythmia were observed before the eventual elimination of duration of the PBs was similar to that observed during all PBs. JACC Vol. 44, No. 8, 2004 Szumowski et al. 1703 October 19, 2004:1700–6 Ablation of Polymorphic VT

Figure 2. Electroanatomic bipolar voltage map of Patient #4 performed during sinus rhythm. The voltage map delineates the region of scar border-zone. Note that the premature beats originating from the Purkinje network are in this border-zone, where successful ablation was performed (brown tags). Purple tags represent sites recording Purkinje potentials in sinus rhythm, and white tags represent fractionated complex electrograms.

Figure 3. Electroanatomic bipolar voltage and activation map in Patient #3 performed during premature beats. The activation map demonstrates the centrifugal activation from the border-zone of the scar. The voltage map (right panel) delineates the region of scar border-zone. Note that the premature beats originating from the Purkinje network are in this border-zone, where successful ablation was performed (brown tags). Purple tags represents sites recording Purkinje potentials, and white tags represent fractionated complex electrograms. 1704 Szumowski et al. JACC Vol. 44, No. 8, 2004 Ablation of Polymorphic VT October 19, 2004:1700–6

the border-zone of the MI and could be successfully abolished by radiofrequency ablation. The damaged border-zone tissue of the scar resulting from MI has been demonstrated to play a crucial role in forming the substrate that sustains macro–re-entry and monomorphic VT (1–5). In such VT, studies based on activation and entrainment mapping allowed determination of the critical isthmus of slowed conduction that maintained VT and thus facilitated ablation (1,2). These isthmuses of surviving tissue within the border-zone of the scar can also be localized by electroanatomic mapping, with transection of these regions by ablation resulting in termination and elimination of arrhythmia (4,5). In contrast, the mecha- nisms underlying polymorphic VT have remained un- known. El Sherif et al. (15) have previously implicated the role of the Purkinje network in an experimental model of anthropleurine-induced torsade de pointes. Berenfeld and Jalife (7), using a three-dimensional model of polymorphic VT, have suggested an important role for Purkinje to muscle interactions in the initial stages of polymorphic VT. In addition, they observed that when the Purkinje network was removed from this model, polymorphic VT could no longer become sustained, suggesting its potential role in the substrate maintaining arrhythmia. However, Janse et al. (16) have reported contradictory data suggesting the persistence of poly- morphic VT in the absence of the Purkinje network. It Figure 4. Mapping at the site of earliest activity during premature beats. has been suggested that a core of non-stationary vortex- Note that the Purkinje potential (*) precedes the ventricular activation like re-entrant activity may result in the constantly during both sinus rhythm and the premature beat. Also, the width of the premature beat is quite similar to that during sinus rhythm. changing QRS morphology observed in polymorphic VT (9). As such, it seems unlikely that the ablation performed in the current cohort would be of sufficient Follow-up. The two patients in whom the procedure extent to prevent such a migrating cascade of activation. was performed as a life-saving maneuver during the first Interestingly, the Purkinje tissue cells have been demon- week after MI had no arrhythmia requiring defibrillation strated to be able to survive transmural infarction in exper- after the procedure. However, they experienced some short, imental models, leading to speculation that their proximity self-terminating runs of PBs in the few days after the to the endocardium allows exposure to cavitary blood (17). procedure. The other three patients had occasional isolated These surviving Purkinje fibers crossing the border-zone of PBs during in-hospital monitoring after the ablation the MI demonstrate heightened automaticity, triggered procedure. activity, and supernormal excitability, which, when coupled All patients had defibrillators implanted; therefore, the with prolongation of the action potential duration in this follow-up was based on device memory of arrhythmia region, may result in the necessary milieu for polymorphic occurrence. None of these patients have had any defibrilla- VT (6,7,17–19). Emerging evidence in patients with VF in several tor therapies after ablation during a follow-up of 16 Ϯ 5 clinical conditions has identified that the Purkinje ar- months (range 10 to 24 months). All patients have been borization is a dominant source of triggers initiating VF continued on beta-blockers, angiotensin-converting enzyme (10–14). These studies have shown that ablation of these inhibitors, and amiodarone or sotalol. triggers was able to eliminate further arrhythmia. The observations in the current series of patients with poly- DISCUSSION morphic VT are remarkably similar, with all PBs in these patients originating from the Purkinje network located This study presents new information on the mechanisms of in the border-zone of the MI, regardless of the duration polymorphic VT after MI. Polymorphic VT in these pa- after the initial MI. In addition, we observed Purkinje tients was triggered and possibly maintained by activity potentials preceding runs of non-sustained polymorphic originating from the distal Purkinje arborization localized to VT, repetitive activation of the Purkinje system during JACC Vol. 44, No. 8, 2004 Szumowski et al. 1705 October 19, 2004:1700–6 Ablation of Polymorphic VT

Figure 5. Purkinje potential (*) preceding each beat of tachycardia, suggestive of driving the tachycardia. The morphology of the ventricular complexes, originating from the Purkinje fibers, is changing, suggesting different Purkinje-muscle outbreak. polymorphic VT, and persistent Purkinje activity despite CONCLUSIONS the absence of propagation to the ventricular myocardium. The Purkinje arborization within the border-zone of scar While these observations could support the notion of either automaticity or re-entry, they implicate the Purkinje ar- has an important role in the mechanism of polymorphic VT borization in the scar border-zone in the initiation and in patients after MI. Ablation of this network allows possibly in the maintenance of polymorphic VT in patients suppression of clinical arrhythmia. Although they need to after MI. be confirmed in a larger cohort with longer follow-up, these

Figure 6. Purkinje potential preceding both sinus and premature beats (*). The last beat demonstrates Purkinje to muscle conduction block. 1706 Szumowski et al. JACC Vol. 44, No. 8, 2004 Ablation of Polymorphic VT October 19, 2004:1700–6 results have major implications as they provide new insights QRS morphologies: results of mapping studies in the infarcted canine on the mechanisms of polymorphic ventricular arrhythmias. heart. Circulation 1997;96:3721–31. 9. Gray RA, Jalife J, Panfilov A, et al. Non-stationary vortex-like re-entrant activity as a mechanism of polymorphic ventricular tachy- Reprint requests and correspondence: Dr. Lukasz Szumowski, cardia in the isolated rabbit heart. Circulation 1995;91:2454–69. Institute of Cardiology, Alpejska 42, 04-620 Warsaw, Poland. 10. Haissaguerre M, Shoda M, Jais P, et al. Mapping and ablation of E-mail: [email protected]. idiopathic ventricular fibrillation. Circulation 2002;106:962–7. 11. Haissaguerre M, Extramiana F, Hocini M, et al. Mapping and ablation of ventricular fibrillation associated with long-QT and Bru- REFERENCES gada syndromes. Circulation 2003;108:925–8. 12. Haissaguerre M, Weerasooriya R, Walczak F, et al. 1. Stevenson WG, Khan H, Sager P, et al. Identification of re-entry of polymorphic VT or VF in multiple substrates. In: Santini M, editor. circuit sites during catheter mapping and radiofrequency ablation of Non-Pharmacological Treatment of Sudden Death. Bologna: Arianna ventricular tachycardia late after myocardial infarction. Circulation Editrice, 2003:237–53. 1993;88:1647–70. 13. Bansch D, Oyang F, Antz M, et al. Successful catheter ablation of 2. Wilber DJ, Kopp DE, Glascock DN, Kinder CA, Kall JG. Catheter electrical storm after myocardial infarction. Circulation 2003;108: ablation of the mitral isthmus for ventricular tachycardia associated 3011–6. with inferior infarction. Circulation 1995;92:3481–9. 14. Marrouche NF, Verma A, Wazni O, et al. Mode of initiation and 3. Stevenson WG, Friedman PL, Kocovic D, Sager PT, Saxon LA, Pavri ablation of ventricular fibrillation storms in patients with ischemic B. Radiofrequency catheter ablation of ventricular tachycardia after . J Am Coll Cardiol 2004;43:1715–20. myocardial infarction. Circulation 1998;98:308–14. 15. El Sherif N, Caref EB, Yin H, Restivo M. The electrophysiological 4. Marchlinski FE, Callans DJ, Gottlieb CD, Zado E. Linear ablation mechanism of ventricular arrhythmias in the long QT syndrome. lesions for control of unmappable ventricular tachycardia in patients Tridimensional mapping of activation and recovery patterns. Circ Res with ischemic and nonischemic cardiomyopathy. Circulation 2000; 1996;79:474–92. 101:1288–96. 16. Janse MJ, Kleber AG, Capucci A, Coronel R, Wilms-Schopman F. 5. Soejima K, Suzuki M, Maisel WH, et al. Catheter ablation in patients Electrophysiological basis for arrhythmias caused by acute isch- with multiple and unstable ventricular after myocardial emia. Role of the subendocardium. J Mol Cell Cardiol 1986;18: infarction: short ablation lines guided by reentry circuit isthmuses and 339–55. sinus rhythm mapping. Circulation 2001;104:664–9. 17. Friedman PL, Stewart JR, Fenoglio JJ, Jr., Wit AL. Survival of 6. Arnar DO, Bullinga JR, Martins JB. Role of the Purkinje system in subendocardial Purkinje fibres after extensive myocardial infarction in spontaneous ventricular tachycardia during acute ischemia in a canine dogs. Circ Res 1973;33:597–611. model. Circulation 1997;96:2421–9. 18. Chialvo DR, Michaels DC, Jalife J. Supernormal excitability as a 7. Berenfeld O, Jalife J. Purkinje-muscle reentry as a mechanism of mechanism of chaotic dynamics of activation in cardiac Purkinje fibers. polymorphic ventricular arrhythmias in a three-dimensional model of Circ Res 1990;66:525–45. the ventricles. Circ Res 1998;82:1063–77. 19. Kupersmith J, Li ZY, Maidonado C. Marked action potential prolon- 8. Costeas C, Peters NS, Waldecker B, Ciaccio EJ, Wit AL, Coromilas gation as a source of injury current leading to border zone arrhythmo- J. Mechanisms causing sustained ventricular tachycardia with multiple genesis. Am Heart J 1994;127:1543–53.