Mapping and Ablation of Ventricular Fibrillation Associated With Early Repolarization Syndrome

Introduction

Early repolarization (ER), highly prevalent in young populations, was initially thought to be a benign electrocardiographic finding for several decades.¹ However, a decade ago, several studies showed that ER, characterized by high-amplitude J wave and horizontal/descending ST-segment elevation in the inferior or lateral leads or both, is associated with an increased risk of ventricular fibrillation (VF) and sudden cardiac death.^2–4 The discovery of the inferolateral ER marker as a risk for sudden death in patients who are otherwise healthy and have no structural heart disease, known as ER syndrome (ERS), has spurred concern, awareness, and interest among electrophysiologists and cardiologists.

Together with the Brugada syndrome (BrS), the ERS has been included in the family of the J-wave syndrome (JWS) as distinct electrocardiographic phenotypes that affect the junction (J) between the QRS complex and the ST segment in inferolateral leads. On the basis of studies in the canine wedge preparation, the underlying electrophysiological mechanism of the syndrome was initially attributed to heterogeneity of the voltage gradient during repolarization across the ventricular wall.⁵ However, according to emerging evidence on the role of an arrhythmogenic substrate in BrS,⁶ one must explore the possibility that alternative mechanisms, including conduction abnormalities (eg, local depolarization abnormality or a combination of both repolarization and depolarization abnormalities), play a role in the pathophysiology of the ERS.⁶

Currently, ERS treatment options are limited to 2 established modalities: (1) pharmacological treatment with quinidine for long-term prevention of recurrent VF and isoproterenol for acute treatment of patients with implantable cardioverter-defibrillator (ICD) storm from frequent VF episodes, and (2) ICD for sudden death prophylaxis in patients with life-threatening ventricular tachyarrhythmias. Thus far, there have been a few case reports of successful catheter ablation of VF triggers for treatment of patients with ERS with electric storm.^7–9 Better characterization of the arrhythmogenic substrate and VF drivers in ERS is needed to identify targets for ablation therapy. Thus, we carried out a multicenter collaborative study aiming to map patients who experienced frequent VF episodes associated with inferolateral ER to determine the role of catheter ablation for the treatment of symptomatic patients with ERS.

Methods

We declare that all supporting data are available within the article and its online supplementary files.

Study Population

We retrospectively studied symptomatic patients with ERS who either survived recurrent VF episodes or had cardiac or unknown syncope or agonal respiration during sleep. These patients were recruited from 4 institutions in 5 locations, Chulalongkorn University and Pacific Rim Electrophysiology Research Institute (Bangkok and Los Angeles); University of Bordeaux, France; University of Tsukuba, Japan; and St. George’s University Hospitals NHS Foundation Trust, United Kingdom (Table 1). All patients underwent echocardiography or magnetic resonance imaging examination to exclude structural heart disease. Patients with inferolateral JWS without concomitant spontaneous Brugada electrocardiographic pattern also underwent provocation test with sodium channel blockers (ajmaline, procainamide, and pilsicainide). Patients with combined inferolateral J-wave and Brugada patterns, either spontaneously or after sodium channel blockade, were included. We excluded patients with severe anoxic brain damage from previous cardiac arrests and those with structural heart diseases or precipitating factors that could give rise to ER pattern or VF (ie, ischemia, coronary vasospasm, drug abuse, and hyperkalemia). Only 32 patients (62%) had a complete genetic testing. The study was approved by the respective institutional review boards, and all patients signed an informed consent.

Electrophysiological Studies and Mapping of the VF Substrate

Invasive Mapping

Detailed epicardial and endocardial electroanatomical mapping was performed during sinus rhythm with the Carto Navigation System (Biosense Webster, Inc, Diamond Bar, CA). We paid specific attention to sites with activation times coinciding with the electrocardiographic J wave. The electrograms (EGMs) occurring within (and possibly after) the J wave were considered to belong to the depolarization if they were sharp and in temporal and spatial continuity with the depolarization field mapped at the end of the QRS complex. An abnormal EGM was defined as a bipolar EGM that had low voltage (≤1 mV) and split EGM or fractionated EGM lasting ≥70 milliseconds. Such abnormal areas were tagged and defined as VF ventricular substrate, as described previously.^10,11 The European and Thai study sites used ajmaline (1–mg/kg doses up to 100 mg) to unmask areas with abnormal EGM, whereas the Japanese and the US sites used pilsicainide and procainamide for the same purpose. None of the sites used warm saline during mapping of the VF substrates.

Programmed electric stimulation for VF induction (S1-S1 at 600, 500, and 400 milliseconds and up to triple ventricular extrastimuli) was performed via the quadripolar catheter in the apex of the right ventricle (RV) or its outflow tract (RVOT). Cardioversion/defibrillation was performed to restore sinus rhythm after 10 seconds of VF.

Noninvasive Mapping With Electrocardiographic Imaging

Patients studied at Bumrungrad Hospital, Bangkok, Thailand, and at Hôpital Cardiologique du Haut Lévèque, Bordeaux-Pessac, France, between January 2016 and June 2018 also underwent the electrocardiographic imaging (ECGI) mapping procedure with the CardioInsight system (Medtronic, St. Paul, MN). The ECGI methodology has been described.^12,13 Patient-specific geometry and body surface ECG recordings were acquired through a 252-electrode vest attached to the skin. The chest-heart geometry was created before the procedure with a low-dose computed tomography to localize vest electrode positions relative to the ventricular epicardial surface. A 3D model of the heart was created with dedicated software (CardioInsight).

The patients were then transferred to the electrophysiology laboratory while wearing the vest, which remained in the same position during the invasive mapping and ablation procedures. Body surface ECG recordings from the vest electrodes were acquired before and during the invasive mapping procedure. On the basis of the inverse solution, the system automatically displays epicardial wave-front patterns on the 3D reconstruction of the patient’s heart. In this manner, activation mapping was performed during spontaneous or induced VF. After adequate filtering, dynamic wave-front propagation maps were generated with phase mapping. The wave-front patterns were displayed on the epicardial surface (patterns detailed below), serving as VF maps.^12,13

We analyzed the VF maps during an initial organized period of VF (the initial 5 seconds), as previously described; cardioversion was performed if VF lasted >10 seconds.¹⁴ VF drivers were defined as either focal breakthroughs when centrifugal activation originated from a given site or full reentrant activity with a high activation frequency. The wave-front maps, derived from phase mapping, display the electric wave front at the π/2 phase value of each ECGI-calculated unipolar EGM, serving as a surrogate for local activation. Focal breakthroughs are detected when this wave front emerges from a point and activates a portion of the heart. Rotations are detected when the rotational core, or singularity point, of a rotating wave front is within a 2.5-cm area for ≥1.5 rotations. We then created spatiotemporal density maps displaying the number, location, and spatial extent (of reentry trajectories) of VF drivers, and the colored hexagon represents the number and location of epicardial focal breakthrough (see below).

Mapping of VF Triggers

Our aim was to identify the site of earliest activation relative to the onset of the QRS complex of the premature ventricular contraction (PVC) triggering VF. Obviously, this was possible only when these PVCs were frequent enough to map. An initial sharp potential (<10 milliseconds in duration) preceding the larger and slower ventricular EGM by <15 milliseconds during sinus rhythm represented a peripheral Purkinje fiber, whereas longer intervals indicated proximal Purkinje fascicle activation. A Purkinje potential preceding a spontaneous ventricular activation was interpreted as an indication of a Purkinje origin of that premature beat.

Ablation Protocol and Clinical End Points

Ablations were invariably performed with irrigated-tip catheters, using contact-force catheters when these became available in 2013. We used a contact force >5 g at all target sites; and radiofrequency power was titrated between 20 and 50 W, depending on the contact force, guided by close continuous observation of the voltage reduction of the late fractionated EGM and the disappearance of mid and late components of the fractionated potentials during ablation, as previously described.¹¹

The ablation targets were VF trigger areas, as defined above; VF substrates, defined as areas that harbor abnormal ventricular EGMs based solely on electroanatomical mapping; or both. The ablation end point for VF triggers was the elimination of the PVC-VF triggers; for VF substrates, it was the elimination of all abnormal late fractionated EGMs. Noninducibility of sustained ventricular arrhythmias was not our ablation end point, although it was carried out at the discretion of operators in the majority of our patients. We defined inducible ventricular tachycardia/VF as induced ventricular tachycardia/VF lasting ≥10 seconds.

All patients were followed up at 1 month after the ablation session and every 3 months thereafter. Our clinical end points were death and the long-term incidence of VF episodes, monitored by ICD interrogation.

Statistical Analysis

We used the Student t test and Wilcoxon rank-sum test for continuous variables and the Pearson χ² test or Fisher exact test for categorical variables for comparisons between groups. The Wilcoxon rank-sum test was also used to compare the number of episodes before and after ablation All data were analyzed with SAS version 9.2.

Results

We evaluated 58 patients with symptomatic ERS (51 cardiac arrest survivors and 7 with syncope). Of the 58, 6 were excluded from the study because of anoxic brain damage after cardiac arrest. The remaining 52 patients (4 women; mean age, 37±14 years) were enrolled in the study (Table 1). The clinical characteristics of each patient are included in the Table I in the online-only Data Supplement. All patients except 1 (who refused ICD) had an ICD for VF therapy; all except 2 patients had frequent VF episodes (ranging from 1–>150 episodes in the previous 3 months before the procedure). Twenty-two patients had been on quinidine, which was either ineffective or not tolerated in 18 of 22 patients (82%). None of the patients had structural heart disease.

VF Substrates

Of the 52 patients, combined endocardial and epicardial mapping could be performed in 51 patients. One patient had VF storms with frequent VF episodes during the procedure, precluding detailed mapping. In this patient, however, VF triggers were mapped and ablated.

We found 2 distinct phenotypes (Table 2). Forty patients (group 1) harbored an arrhythmogenic substrate on the epicardium characterized by fractionated EGMs exhibiting low voltage (<1 mV) and fractionation with prolonged duration (≥70 milliseconds; Figure 1A). In contrast, 11 patients (group 2) had inferolateral ERS on their ECG but did not have any abnormal EGMs despite detailed epicardial mapping. Group 1 patients were older and more often male than group 2 patients (mean age, 38 versus 29 years; P=0.051; 100% men in group 1 compared with 36% women in group 2; P=0.001).

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Nineteen percent of the group 1 patients had SCN5A mutation, but none of the group 2 patients did. Group 2 had a much higher incidence of J-wave elevation in both inferior and lateral leads than did group 1 (82% versus 28%; P=0.009). Most group 1 patients (82.5%) had concomitant Brugada electrocardiographic pattern, whereas there were none in group 2 patients (P<0.0001).

The presence of Brugada electrocardiographic pattern subcategorizes group 1 patients into 2 subgroups (Table 3): Group 1A (n =33) patients had a combination of J-wave pattern (at the inferior leads, lateral leads, or both) and a Brugada electrocardiographic pattern (21 spontaneous and 12 unmasked after sodium channel blocker); group 1B patients (n=7) had only J-wave pattern. Of significance, sodium channel blockade accentuated the J-wave pattern in inferolateral leads in 6 group 1A patients (Figure I in the online-only Data Supplement). VF substrates in group 1B were more predominantly located at the inferior RV epicardium (compared with the RVOT/RV epicardium in group 1A with concomitant Brugada pattern).

Globally in group 1 (n=40), abnormal fractionated late potentials were present at the epicardium of the RVOT/anterior RV in 38 patients (95%) and at the inferior aspect of the RV in 34 patients (85%). In addition, 4 patients (10%) had abnormal potentials in the LV epicardium, at the posterior/lateral area (n=2), at the apical-septal area (n=1), and at the interventricular groove (n=1; epicardial projection of the LV septum). Only 1 patient had abnormal endocardial EGMs (at the inferior aspect of the RV close to the tricuspid annulus along with anterior RVOT epicardial substrate).

Group 2 patients (n=11) had no identifiable epicardial or endocardial abnormal depolarization coinciding with the inferolateral J wave. Sodium channel blockade did not lead to aggravation of the J-wave pattern in these patients. Figure 2 shows an example of normal EGMs recorded from the endocardium and epicardium of both ventricles. The patient had left Purkinje system as VF triggers. Ablation of these triggering sites was successful. Although VF was inducible before ablation, it was not inducible after ablation. The patient had no VF recurrence without antiarrhythmic drug for 7.5 years.

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VF Triggers

We identified VF triggers in 14 patients. Twelve of the 14 patients (86%) had VF triggers emanating from the Purkinje system: 9 (75%) from the left and 3 from the right Purkinje network. In the remaining 2 patients, the foci of the PVC VF triggers were at the RV inferior wall in 1 patient and left ventricular (LV) posterior wall in the other. An example of a PVC triggering a VF episode during an arrhythmic storm is shown in Figure 1B and 1C.

VF Drivers: Results of Noninvasive Maps in VF

We performed ECGI noninvasive mapping of VF (2 spontaneous and 30 induced VF) in 32 patients (25 in group 1, and 7 in group 2). The mean VF cycle length, measured at 5 seconds after initiation, was significantly shorter in patients without abnormal epicardial signals (157±15 milliseconds in group 2 versus 190±10 milliseconds in group 1; P<0.001).

Group 1 Patients With ERS With Late Depolarization (n=25)

The distribution of VF driving activities in group 1 patients (both with or without Brugada electrocardiographic pattern) is shown over the 6 compartments on the ventricular surface (Figure 3): (1) anterior RVOT/RV, (2) inferior RV, (3) inferior LV, (4) LV posterolateral, (5) interventricular septum, and (6) interventricular groove. In group 1, the presence of focal/reentrant drivers, detected by ECGI and abnormal late fractionated EGMs colocalized in the same regions, occurred predominantly at the RV epicardium (100% correlation). Examples of the noninvasive mapping and its correlation with the location of abnormal late fractionated EGM areas are shown in Figure 4. The drivers in group 1 patients with JWS distributed in the anterior RVOT/RV (region 1) and the RV inferior wall (region 2) in 100% and 88%, respectively (Figure 3A).

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Figure 5 demonstrates a striking similarity between a spontaneous VF episode and induced VF in 1 of the group 1A patients. In this patient, the distribution of VF drivers and focal activities not only colocalizes with low-voltage late potentials but also is similar between spontaneous and induced VF (Figure 5A). Moreover, the culprit PVC that initiated VF was also located at the same area (right inferolateral RV epicardium), where rotational activities sustain VF were abundant (Figure 5B).

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Group 2 Patients Without Late Depolarization (n=7)

In contrast to group 1 patients, group 2 patients had VF driving activities located predominantly in the inferior ventricular wall, which distributed among 3 inferior wall regions: 100% at the inferior septum at the interventricular groove (region 6), 100% at the inferior LV (region 3), and 60% at the inferior RV (region 2; Figure 3B).

Catheter Ablation

Forty-three of the 52 patients underwent catheter ablations because of recurrent VF. The remaining 9 patients who did not undergo ablation include 5 group 2 patients with no identifiable VF substrates and 4 group 1 patients who preferred quinidine therapy.

For the 43 patients who underwent catheter ablation, the median number of ablation procedures was 1 (mean, 1.4±0.6 procedures). Details of each individual patient’s ablation and mapping data are also provided in Tables II and III in the online-only Data Supplement. Of these patients, 36 were ERS group 1 patients with mappable abnormal substrate, and 6 were ERS group 2 patients; 1 patient had incomplete detailed mapping. Group 2 patients had no identifiable late depolarization abnormalities serving as targets for ablations, but all had identifiable VF triggers mainly in the left posteroinferior Purkinje network (n=5) and only 1 from the right posterior Purkinje network. Ablations at these sites prevented VF recurrence in all. For 1 patient, who was not classified in any group, VF trigger from the left posteroinferior Purkinje network was ablated successfully, and in turn, the VF storms were ablated.

Thirty-one group 1 patients underwent ablation based exclusively on substrate mapping; 5 had both substrate plus VF trigger ablation. The ablated substrate locations were predominantly at the epicardium of the anterior RVOT/RV (100%) and inferior wall RV (32 of the 36, 89%); thus, almost all these patients (n=32, 89%) had ablated substrates in both sites. In only a minority of the patients, the substrates were also present elsewhere: in the LV posterolateral in 4 patients (11%) and in the endocardial inferior RV close to the tricuspid valve in 1 patient. The ablation areas were larger (20±6 cm²) than those of group 2 patients (4±0.7 cm²) undergoing VF trigger ablations (P<0.0001).

Figure 6 shows an example of abnormal EGM sites from another group 1B patient who had multiple ICD discharges for VF recurrences. As shown, the abnormal fractionated late potentials and the VF drivers colocalized in the anterior RVOT, inferior RV epicardium, and LV posterior wall apical areas (Figure 6A and 6B). Ablations at these areas eliminated all fractionated signals, prevented both spontaneous and induced VF, and normalized the ER pattern in the ECG of this patient (Figure 6C). Overall, ablations normalized Brugada electrocardiographic pattern in all group 1A patients except 1 (97%) and resulted in disappearance of the ER pattern in 32 of the 39 patients (82%); follow-up ECGs were missing for 2 patients (Table II in the online-only Data Supplement).

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Preablation inducible VF was present in 32 of 36 (89%) group 1 and 5 of 6 (83%) group 2 patients,. After ablation, only 4 of 23 (17%) group 1 retested patients had inducible VF (P<0.001); neither of the 2 group 2 patients who had repeat programmed stimulation had inducible VF.

Clinical Outcomes and Complications

Table 4 shows the effect of catheter ablation on the VF recurrent outcome. After a single procedure, 29 of 43 patients (67%) remained free of VF recurrences without antiarrhythmic medications; the number increased to 39 of the 43 (91%) after the repeat procedure (mean, 1.4±0.6 procedures) with the mean follow-up period of 31±26 months from the last ablation (P<0.0001). The remaining 4 patients, who had VF recurrences after ablation, had only 1 ablation session and declined a second procedure on the basis of a drastic reduction of VF episodes. Only 1 patient developed a serious complication (hemopericardium). During the follow-up period, all patients who underwent an ablation therapy are alive and well, except for 1 patient who died of gunshot wounds 3 months after the ablation. In contrast, 2 siblings from group 2 who did not undergo ablation treatment and were treated developed intractable VF despite quinidine therapy, causing fatal multiorgan failure in 1 patient and prompting cardiac transplantation (unfortunately unsuccessful) for the other.

Discussion

We present the first systematic study of mapping and ablation of inferolateral ERS in humans. Key observations are the following. First, patients with ERS express 1 of the 2 distinct groups: depolarization abnormalities predominantly at the RV epicardium and the absence of depolarization abnormality areas. Second, late depolarization areas colocalize with VF drivers. Third, these abnormal depolarization areas represent good target sites for ablation. Fourth, ablations at these sites prevent both VF induction and VF recurrences. Fifth, the Purkinje network is the leading underlying electrophysiological abnormality causing VF in patients with ERS devoid of depolarization abnormalities.

Patients with identifiable arrhythmogenic substrate in the epicardium (group 1) differed from patients without abnormal signals despite extensive epicardial/endocardial mapping (group 2): They were older and invariably male (compared with 33% women in group 2). In addition, no group 2 patients had SCN5A mutations compared with 19% in group 1. All group 1 patients who were treated with quinidine failed to respond to the drug, whereas 50% of the group 2 patients responded to the quinidine.

We learned from our observations that depolarization abnormalities play an important role in the underlying mechanism of the ERS. Thus, the term ER may not be appropriate because it implies repolarization abnormality as the main mechanism of the syndrome. Thus, we now refer to ERS as JWS.

Electrophysiological Substrate of JWS

Our present study is also the first in humans to use both invasive detailed epicardial and endocardial mapping and noninvasive mapping studies simultaneously during sinus rhythm and VF. The mapping studies unequivocally demonstrate the presence of abnormal late-depolarization abnormalities in most patients with JWS, particularly in those with coexisting spontaneous or drug-induced BrS. The spatial distribution of these abnormal EGMs is clustered predominantly in the RV epicardium, including the RV inferior wall, sometimes in the LV, and very rarely in the RV endocardium. The presence of anterior RVOT/RV substrates confirmed our previous report that these areas are the most common substrate of the BrS, but the incidence of VF substrates in the RV inferior epicardium (86%) in our patients with inferolateral-JWS is much higher than that of pure BrS without concomitant inferolateral J wave augmentation and horizontal/descending ST-segment elevation.^10,11 Four patients also had abnormal areas of EGMs along the posterior and lateral aspect of the LV. The presence of abnormal EGMs in the LV shares some similarity with the observation of late epicardial depolarization associated with structural heart disease and ventricular tachycardia^14,15 and supported by computer simulation data that conduction slowing, caused by reduced sodium current in the lateral ventricular myocardium, can provoke J waves, which coincide with delayed activation.¹⁶ This dovetails well with our observation that ajmaline accentuated the J-wave pattern in our group 1 patients, supporting the notion that a J wave can be the manifestation of late depolarization located at any part of the RVs or LVs, provided that it occurs late enough to infringe the terminal QRS complex.¹⁶ Ajmaline may either attenuate or accentuate inferolateral J waves,^17,18 and a study by Bastiaenen et al¹⁷ suggests that the patients whose J waves persist or are even accentuated by ajmaline are more likely to have a history of arrhythmic symptoms, like all the patients in our study.

The presence of the conduction delay and late fractionated EGMs in our patients raises the possibility that structural abnormalities too subtle to be picked up by current imaging technologies play a key role in the pathogenesis of JWS. Our group and others have shown that subclinical structural abnormalities of the RVOT epicardium and myocardium constitute VF substrates exhibiting abnormal late potential EGMs in patients with BrS.^19,20 It is therefore likely that a similar phenomenon is present in patients with JWS. Furthermore, although the RV is the dominant site of VF substrates, the LV epicardium in some patients also harbors these substrates. Therefore, one could infer from these findings that a large proportion of patients diagnosed today with ERS have subclinical fibrosis in both ventricles more easily identifiable in late activated areas such as the RVOT and RV inferior wall.

Our finding that the areas with abnormal EGMs colocalize with VF reentrant and focal activities that drive sustained VF further supports the concept that these areas are VF substrates. VF drivers detected from ECGI noninvasive mapping during VF were 100% concordant with the areas of abnormal late fractionated potentials in the RV epicardium.

However, this is not necessarily true for group 2 patients with no demonstrable areas with late depolarization abnormalities or fractionated EGMs. The findings that VF cycle length in this group is much shorter than that of group 1 and that more patients in this group responded to quinidine suggest that repolarization abnormality plays a major role in the underlying electrophysiological mechanism of group 2 patients with JWS.

The other important finding in group 2 patients is that the Purkinje network is the main culprit triggering VF. This observation dovetails with ECGI mapping that VF rotors and focal activities are consistently at the septum in group 2 patients (100%), possibly representing drivers and VF initiators emanating from the Purkinje systems. The other explanation of why reentrant rotors tended to anchor at the septum derives from the study in the rabbit heart and a computer model under the condition of reduced I_Na.^16,21 These studies show that when the RV is the source of drivers, propagation from the thinner RV has insufficient current to excite the septum and LV, causing sink-source mismatch and block predisposing the reentry anchored around the septum at the epicardium.^21,22 A similar mechanism has been described for BrS.²¹

Catheter Ablation: An Important Therapeutic Modality

Treatment of life-threatening ventricular arrhythmias of patients with inferolateral JWS is hitherto limited to only quinidine, which is unavailable in most parts of the world.²³ Although a few case reports have shown the benefit of catheter ablation in treating patients with a combined syndrome of BrS and JWS,^24,25 ours is the first and largest study to demonstrate the presence of VF substrates in patients with JWS and to define the effective strategy for ablation of JWS. Our study shows that percutaneous catheter ablations are effective in preventing recurrent VF episodes. This is relevant because currently there is no other established treatment for these patients, especially if quinidine is ineffective or not tolerated. Our study suggests that ablation can also be considered as a first treatment option for cardiac arrest survivors.

Although patients with JWS in group 2 did not have identifiable VF substrates, the majority could undergo successful catheter ablation within the Purkinje network that prevented VF recurrences during long-term follow-up.

Study Limitations

Our findings that the majority of our patients with JWS have late depolarization abnormality are possibly the result of referral biases, because the patients were often referred for catheter ablation after drug failure, including quinidine, which may be less effective in patients with depolarization abnormality. However, >60% of our study cohort was from Southeast Asia and did not have access to quinidine; thus, it is unlikely that the patient population was skewed by this form of selection bias.

Many of our patients were highly symptomatic (several had electric storms) and were referred for ablation as a last resort. Consequently, some patients might not have undergone full detailed mapping because of frequent VF episodes requiring multiple shocks in the laboratory. In addition, because we did not use intracardiac ultrasound for visualization of the papillary muscle, we cannot entirely exclude its role in generating Purkinje potentials that cause VF-triggering PVCs.

Conclusions

Our study demonstrates that electrophysiological mechanisms underlying JWS are complex. For the first time, we demonstrate that late depolarization abnormalities, predominantly in the RV epicardium, contribute to the underlying mechanism of the syndrome. We have also found that the Purkinje network of both ventricles, especially from the posterior and inferoposterior septal areas of the LV, plays an important role in giving rise to VF triggers and initiators. Such areas are important ablation target sites that were successfully ablated in our study, resulting in the prevention of recurrent VF episodes. Thus, we show that ablation of the VF substrate sites or VF triggers is an effective modality for the treatment of JWS and a welcome addition to the therapeutic armamentarium of this syndrome.

Further study to delineate the role of repolarization disorder and its interplay with late depolarization substrate will be needed. A randomization study to compare the treatment between quinidine and ablation is also warranted. On the basis of our findings, any symptomatic patients with JWS should be considered for ablation treatment.

Footnotes