Efficacy of Endocardial Ablation of Drug-Resistant Ventricular Fibrillation in Brugada Syndrome: Long-Term Outcome
Circulation: Arrhythmia and Electrophysiology
VIEW EDITORIAL:Endocardial Ablation Approach for Brugada Syndrome
Abstract
Background
Both endocardial trigger elimination and epicardial substrate modification are effective in treating ventricular fibrillation (VF) in Brugada syndrome. However, the primary approach and the characteristics of patients who respond to endocardial ablation remain unknown.
Methods
Among 123 symptomatic Brugada syndrome patients (VF, 63%; syncope, 37%), ablation was performed in 21 VF/electrical storm patients, the majority of whom were resistant to antiarrhythmic drugs.
Results
Careful endocardial mapping revealed that 81% of the patients had no specific findings, whereas 19% of the patients, who experienced the most frequent VF episodes with notching of the QRS in lead V1, had delayed low-voltage fractionated endocardial electrograms. Ablation of VF triggers followed by endocardial substrate modification was performed in the right ventricular outflow tract in 85% of the cases and in the right ventricle in 15%. VF triggers could not be completely eliminated in 1 patient and VF became noninducible in 14 (88%) patients among 16 patients who underwent VF induction with normalization of Brugada-type ECG in 3. During follow-up (56.14±36.95 months), VF recurrence was observed in 7 patients. Importantly, all patients who had nothing of QRS in lead V1 did not respond to endocardial ablation despite presence of VF-triggering ectopic beats during ablation.
Conclusions
With careful documentation of VF-triggering ectopic beats and detailed endocardial mapping, endocardial VF trigger elimination followed by endocardial substrate modification has an excellent long-term outcome, whereas presence of QRS notching in lead V1 was associated with high VF recurrence suggesting epicardial substrate ablation as effective initial approach.
Graphical Abstract
Introduction
See Editorial by Nademanee and Haïssaguerre
WHAT IS KNOWN?
•
Catheter ablation of ventricular fibrillation (VF) in Brugada syndrome can be performed by targeting the VF-triggering premature ectopic beats or by ablating the epicardial substrate.
•
Endocardial ablation of VF-triggering ectopy was an effective adjuvant therapy in sporadic case series of Brugada syndrome, whereas epicardial approach is also effective in preventing VF.
•
It remains unknown which approach (epi or endo) should be practiced first in Brugada patients and what kind of cases may respond to endocardial ablation.
WHAT THE STUDY ADDS?
•
With careful documentation of VF-triggering ectopic beats and detailed endocardial mapping, endocardial VF trigger elimination followed by endocardial substrate modification has an excellent long-term outcome.
•
However, presence of QRS notching in lead V1 is associated with high VF recurrence suggesting epicardial substrate ablation as effective initial approach in such population.
In Brugada syndrome (BrS), the right ventricular outflow tract (RVOT) is a major arrhythmogenic focus where isolated premature ventricular contractions (PVCs) can initiate ventricular fibrillation (VF).1–3
Local radiofrequency catheter ablation (RFCA) of PVCs that trigger VF was reported as an effective therapy in preventing VF in few cases3–5; however, little is known about the electrophysiological characteristics of endocardial substrate, and data about the long-term effect of trigger ablation and endocardial substrate modification in BrS are limited. Moreover, although substrate modification of RVOT epicardium could effectively prevent VF6 and eliminate Brugada phenotype,7 the primary approach (ie, trigger ablation or epicardial substrate modification) and the kind of cases that respond to endocardial ablation are unclear. This study aimed to clarify the aforementioned points with results of a long-term follow-up in a multicenter study.
Methods
Study Population
The original data are subject to the Institutional Review Board, and the data, analytic methods, and study materials will not be made available to other researchers for purposes of reproducing the results or replicating the procedure. During a long-term follow-up of 123 consecutive BrS patients who initially presented with VF (63%) or syncope (37%) associated with Brugada-type ECG (type 1:91%, type 2: 9%) in 10 different centers from 1999 to 2015, 21 patients developed recurrent implantable cardioverter-defibrillator (ICD) discharges or electrical storm resistant to medical therapy in the vast majority of the patents. The patients were divided into 2 groups: (1) nonablation group, including 102 BrS patients who were followed up conservatively, and (2) ablation group: consisting of 21 patients who underwent RFCA.
During admission, a standard investigation protocol was performed, including cardiac magnetic resonance imaging, cardiac catheterization with acetylcholine provocation when indicated, and an electrophysiology study when appropriate. An informed consent was obtained from all participants, and the study was approved by the local ethics committee.
Electrophysiological Study, Mapping, and Ablation
The procedure was performed under local anesthesia and conscious sedation. Ablation strategy and the flow chart of the study cohort are shown in Figure 1. Standard multielectrode catheters were placed in the His bundle region and RV apex through the right femoral vein. The RV, with its inflow and outflow tracts, was mapped with a 7F quadripolar catheter with a nonirrigated 4-mm- or 8-mm-tip distal electrode, embedded thermistor, interspacing of 2 to 5–2 mm, and deflectable tip (EP Technologies, San Jose, CA,; Biosense Webster, Diamond Bar, CA). In some patients, detailed RVOT mapping was performed using a 10-pole circumferential catheter (Lasso; Biosense Webster, Diamond Bar, CA). Endocardial electroanatomical mapping was performed using a 3-dimensional mapping system (CARTO 3, Biosense Webster, Diamond Bar, CA) or Ensite Velocity system (St. Jude Medical Inc, Milwaukee, WI).
VF-triggering PVCs were localized by mapping the earliest local electrogram relative to the onset of the QRS complex during a ventricular ectopy. To induce the triggering PVC, sodium channel blocker provocation with intravenous pilsicainide infusion (0.25 mg/kg for 5 minutes) was performed. The induced PVCs were identified as clinical or not based on the surface ECG and stored ICD electrogram morphology from spontaneous VF-triggering events. Ablation was performed using radiofrequency energy, with a target temperature of 55°C and a maximum power of 50 W, or using an externally irrigated 3.5-mm-tip catheter (Thermocool, Biosense Webster, Diamond Bar, CA). When an acceleration or a reduction in the incidence of PVCs was observed during the first 10 s of the application, the radiofrequency delivery was continued for 60 to 120 s. Otherwise, radiofrequency delivery was terminated, and the catheter was repositioned. Locations of abnormal electrograms, defined as fractionated electrograms (multicomponent with an amplitude of 50 ms), or isolated late potentials (inscribed entirely after the QRS complex), and low-voltage electrograms (<1 mv), were tagged during sinus rhythm mapping.
In 16 patients, programmed ventricular stimulation with up to triple extrastimuli was repeatedly performed from the RV apex and RVOT to induce VF.
Statistical Analysis
Data analysis was performed using the PASW Statistics 18 package (version 18.0.0, SPSS Inc, Chicago, IL). The significance of the differences between groups was assessed by the Student t test. Kaplan-Meier analysis was performed to estimate freedom from VF. A log-rank test was performed to compare event rates between groups. A P value <0.05 was considered statistically significant.
Results
Clinical Characteristics
Flowchart of the study cohort is shown in Figure 1. The ablation group consisted of 21 patients (male, 19; age, 43±14 years). Fourteen patients initially presented with VF, and 7 patients presented with syncope. Genetic screening for SCN5A mutation only was performed in 11 patients and revealed positive SCN5A mutation in 3 patients.
In brief, genomic DNA was extracted from peripheral blood with QIAamp DNA Blood Midi Kit (Qiagen, Venlo, The Netherlands) and SCN5A gene-coding exons were screened by polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing analyzer (ABI 3730; Applied Biosystems, Waltham, MA).
Among 21 BrS patients, 5 patients presented with electrical storm which was initially suppressed by intravenous isoproterenol infusion in 4 patients; however, the patients consistently experienced VF recurrence after tapering or discontinuation of isoproterenol infusion. These patients underwent emergency RFCA within 24 hours of the last VF onset, whereas 1 patient underwent emergency RFCA before trying antiarrhythmic medications. Sixteen patients underwent RFCA after developing frequent VF episodes 36±17 months after ICD implantation despite using 1.8±0.8 antiarrhythmic drugs. The nonablation group included 102 patients (female, 6; age, 48±12 years) who initially presented with VF (64%) or syncope (36%). These patients were followed up conservatively after ICD implantation.
Electrocardiographic Characteristics of the Ablation Cohort
Baseline ECG showed normal P-R interval (176±15 ms), slightly wide QRS complex (117±26 ms), and normal QT interval (406±17 ms) in all patients. Seventeen patients had type 1 Brugada ECG, and 4 patients had type 2. Brugada ECG was spontaneous in 16 patients and pilsicainide induced in 5. QRS notching in lead V1 was observed in 6 patients, among them 5 had notching at the nadir or downstroke of S wave. Signal average ECG was tested in 19 patients and revealed positive late potential in 15 patients.
In the electrophysiology laboratory, spontaneous or induced PVCs were identified as a VF trigger based on documented VF initiation on surface ECG in 19 patients and by comparison of the PVC near-field and far-field ICD electrogram morphology with a stored VF initiation on the ICD in 2 patients.
VF-triggering ectopic beat, documented in 12-lead ECG, exhibited left bundle branch block configuration with inferior axis in 16 patients (Figure 2A) and superior axis in 3 patients (Figure 2B). The precordial QRS transitional was seen in lead V3 in 4 patients, in V4 in 8 patients, and in V5 in 7 patients. The mean coupling interval of the clinical PVC was 415±57 ms.
Electrophysiological Characteristics of VF Triggers and Endocardial Substrate
The site of successful ablation, defined as the site of earliest local ventricular activation and perfect pacemap, was found at the RVOT in 18 patients, although VF-triggering PVCs were ablated at the RV anterior free wall in 2 patients and at the RV inflow tract in 1 patient. Purkinje potentials could be recorded at the ablation site in only 1 patient. Moreover, in the electrophysiology laboratory, clinical PVCs were observed spontaneously in 11 patients, particularly in patients who presented with electrical storm. In 4 patients, the PVCs were pilsicainide induced, whereas in the remaining patients, pacemap-guided ablation was performed (Figure 1).
Early activation map and good pacemap (Figure 2C) were obtained with local activation at the ablation catheter preceding the onset of the QRS complex by 31±13 ms. Substrate mapping revealed normal bipolar endocardial voltage in 20 patients, whereas unipolar voltage analysis revealed that 3 patients had low unipolar voltage.
Importantly, delayed low-voltage fractionated electrograms were observed in 4 patients. These fractionated electrograms were more obvious by increasing the standard voltage gain (Figure 3A) and were identified at the RVOT anterior wall in 3 patients and at the RV anterior wall, where Purkinje potentials preceded the QRS onset of the clinical PVC by 35 ms, in 1 patient.
Ablation End Point and Complications
After eliminating the VF-triggering ectopic beats, ablation lesion was extended to cover a larger area around the focus for 7 to 10 minutes to minimize the recurrence. In patients with low-voltage fractionated electrogram areas, additional ablation was performed. Pilsicainide was infused after ablation to ensure noninducilibity of clinical PVCs. VF-triggering PVCs remained inducible in only 1 patient after pilsicainide infusion for which additional radiofrequency applications failed to suppress these PVCs. Nonclinical PVCs were induced in 2 patients; hence, ablation was not performed.
Finally, depending on the operator’s preference, programmed ventricular stimulation was performed in 16 patients; however, VF was noninducible in 14 patients. Moreover, in 3 patients, normalization of ST-segment elevation was observed (Figure 3B). As a complication, steam pop was observed during RVOT ablation in 1 patient without sequelae, and the patient was followed up conservatively. Transient right bundle branch block was observed during catheter manipulation in 2 patients.
Long-Term Outcome
Ablation Group
Ablation results are summarized in Figure 4A. During a mean follow-up of 55 months (56.14±36.95 months; mean±SD), 7 patients developed VF recurrence. One patient had only a single ICD discharge 1 day after ablation and was followed up conservatively, whereas 3 patients developed few ICD discharges 6, 12, and 18 months after ablation, respectively, and were treated medically using a combination therapy of cilostazol and bepridil in 2 patients and Quinidine in 1 patient who is scheduled for epicardial ablation. In 3 patients, multiple appropriate ICD discharges were observed, and further VF recurrence was prevented by epicardial substrate ablation in 2 patients (with cryoablation through surgical thoracotomy in 1 patient) and by endocardial ablation in 1 patient.
Characteristics of Failed Endocardial Ablation Cases
Clinical characteristics and prognosis of failed endocardial ablation are demonstrated in Figures 4A through 4C. All 6 patients who had QRS notching in lead V1 developed VF recurrence (Figure 4B). Further analysis revealed that such patients had distinct characteristics (Table). Although there was no significant difference in the age, P-R interval, QRS duration, QT interval, coupling interval of VF-triggering PVC, late potentials on signal average ECG, or total ablation time between patients with and without QRS notch in lead V1, the former had more VF episodes (P<0.001). Of note, among 6 patients who had QRS notching in lead V1, 4 had fractionated endocardial electrograms and 3 patients had low unipolar voltage in the RVOT. An example of a failed endocardial ablation is shown in Figure 5. Endocardial mapping revealed normal RV voltage of a 28-year-old male who presented with 22 ICD discharges resistant to 3 antiarrhythmic drugs. Genetic analysis revealed SCN5A (A226D) mutation with negative tests for PKP2 (plakophilin-2) and RyR2 (ryanodine receptor) mutations. His ECG showed notching at the nadir of S wave in lead V1, and fractionated electrograms were found at the RV anterior wall. Despite ablating the fractionated electrogram sites and sites of early activation, VF-triggering PVC could not be eliminated, and VF recurrence was observed frequently. Eight years later, he developed RV lead infection which necessitated surgical thoracotomy. ECG, echocardiogram, and computed tomography scan were performed preoperatively; however, no evidence of RV dilatation or wall motion abnormalities was observed. Furthermore, preoperative endocardial mapping revealed normal unipolar and bipolar voltage of RV endocardium with extremely small residual electrograms (which were ablated by a prior session). Moreover, intraoperative epicardial mapping revealed a relatively low-voltage area with fractionated electrograms at the epicardial surface of previously ablated endocardial electrograms. Interestingly, coved-type ST-segment elevation was observed in the unipolar recordings of the ablation catheter at the fractionated electrogram areas, although fractionated electrogram-free areas revealed no such finding. Cryoablation at the fractionated electrogram sites prevented VF recurrence during further 5-year follow-up, with normalization of ST elevation in the precordial leads.
| Variant | QRS Notch in lead V1 (n=6) | No QRS Notching (n=15) | P Value |
|---|---|---|---|
| Age | 42±13 | 45±15 | 0.94 |
| Annual VF episodes | 18±8 | 4±2 | <0.001 |
| P-R, ms | 177±18 | 171±15 | 0.95 |
| QRS in V1, ms | 118±15 | 114±26 | 0.73 |
| QT, ms | 403±5 | 408±6 | 0.60 |
| Coupling interval of VF-triggering ectopic beats | 394±65 | 427±53 | 0.32 |
| Positive LP on SAECG (n) | 6/6 | 9/13 | 0.12 |
| Endocardial fractionated EGM | 4/6 | 0/15 | <0.01 |
| Unipolar low voltage | 3/6 | 0/15 | ns |
| Total RF time, min | 29±11 | 26±8 | 0.60 |
Values are expressed as mean±SD.
EGM indicates electrogram; LP, late potential; ns, not significant; RF, radiofrequency; SAECG, signal average ECG; and VF, ventricular fibrillation.
Nonablation Group
Among 102 patients, VF recurrence was found in 34 (33%) patients. Figure 4C shows Kaplan-Meier survival curve. Patients with QRS notching in V1 had the worst prognosis, although trigger elimination and endocardial substrate modification in those without QRS notching in lead V1 could significantly decrease VF recurrence without using any antiarrhythmic drugs compared with nonablation group (log-rank P<0.001).
Discussion
Main Findings
This study, which is the largest study of endocardial VF ablation in BrS with the longest follow-up period, has demonstrated the following: (1) VF-triggering ectopic originated from the RVOT in 85% of BrS cases and from the RV itself in the rest of the cases, (2) VF-triggering PVC elimination with additional substrate ablation resulted in an excellent long-term outcome, and (3) patients with QRS notch in lead V1 had more VF episodes than those without and did not respond to endocardial ablation.
These findings suggest that endocardial ablation of VF triggers with substrate modification is a reasonable initial approach in drug-resistant VF, and the presence of QRS notch and/or fractionated electrograms at the endocardial surface of the RVOT indicates that endocardial ablation is inadequate and epicardial approach could be an effective ultimate approach.
VF trigger ablation was elegantly reported by Haïssaguerre et al3 in 3 cases with a 7±6 months follow-up; however, such approach has not been validated systemically except in sporadic case reports.4,5 Moreover, whether VF trigger elimination is effective in preventing VF recurrence during long-term follow-up remained unclear.
Preferential Ablation Sites of VF-Triggering PVCs
In BrS, VF-triggering PVCs are almost identical, site-specific, and predominantly originate from the RVOT, which is the region hypothesized to provide slow discontinuous conduction and maximal refractoriness.6–9 A previous study showed that VF-triggering PVCs were spontaneously observed and successfully ablated in the RVOT in 4 cases3–5 and at the right Purkinje arborization in 1 case.3 Similarly, we found VF-triggering PVCs originated from the RVOT in 85% of the cases and from the RV itself in the rest of the cases. Only 1 patient had Purkinje potential recorded at the earliest ectopic activation site, whereas in 2 other patients, VF triggers had no clear Purkinje-related origin. This is the first study to report a non-Purkinje origin of VF triggers in the RV.
Effect of Trigger Elimination
After ICD implantation, 33% of symptomatic patients had VF recurrence during a ≈10-year follow-up. This high VF recurrence rate was reduced by RFCA without using antiarrhythmic drugs in all patients.
Although there is growing evidence that BrS, unlike idiopathic VF, patients have subtle structural changes that constitute an important substrate that predisposes patients to VF,6–9 ablation of VF triggers with endocardial substrate modification has a favorable result, which is almost similar to that reported in idiopathic VF.10
Our results are plausible because VF-triggering PVCs in BrS are almost identical and, in some patients, VF was initiated by the same index PVC.1–6 A study of explanted heart from Brugada phenotype showed that VF-triggering ectopic arose from the RV endocardium, not epicardium.9 This explains why majority of VF-triggering PVCs could be eliminated by endocardial approach. Furthermore, endocardial ablation of RVOT free wall is expected to modify the epicardial substrate because the RVOT free wall is relatively thin. In our study, endocardial ablation normalized the precordial ST-segment elevation in 3 cases and rendered VF noninducible in 14 patients among 16 patients who underwent programmed stimulation after ablation indicating some degree of substrate modification. Although Sroubek et al11 found that triple extrastimuli are nonspecific and lack of induction with programmed stimulation alone does not reliably identify low-risk patients, presence of VF/electrical storm before ablation indicates that such patients are at high risk of subsequent VF events which were reduced by catheter ablation as evidenced by long-term follow-up.
An important practical consideration is the documentation of triggering PVCs. Trigger ablation strategy might be hampered by rare occurrence of PVCs in BrS patients12; however, we could effectively overcome this limitation by (1) performing ablation shortly after VF/storm onset and before the culprit PVC subsides and (2) precise documentation of triggering PVCs. In the current era of good-quality ICD recordings and remote ICD monitoring of VF triggers, pacemap-guided ablation is a reasonable approach. Although VF trigger PVCs were infrequent to enable activation map in some patients, pacemap-guided ablation was effective and absence of frequent PVCs during ablation did not result in unfavorable outcome. In contrast, presence of QRS notching in lead V1 and abnormal endocardial substrate resulted in unfavorable outcome despite presence of VF-triggering PVCs in the electrophysiology laboratory. Hence, careful monitoring of VF-triggering PVC is a crucial issue because drug-induced PVCs do not necessarily represent the culprit PVC.
Endocardial Substrate in BrS
There is mounting evidence that localized conduction abnormalities in the RVOT contribute to the arrhythmogenic substrate responsible for the clinical phenotype of coved-type ST-segment elevation and ventricular arrhythmias in BrS.6–9 Nademanee et al6 reported that fractionated electrograms were exclusively localized in the anterior RVOT epicardium. With careful endocardial mapping, we also found that endocardial fractionated electrograms were present in the most malignant Brugada phenotype (ie, in patients with extremely frequent VF episodes who had evidence of subtle conduction delay represented by QRS notching in lead V1). Although ablating RVOT-fractionated electrograms normalized the ST-segment elevation in 3 patients, VF recurrence was still observed.
One might argue that the presence of endocardial fractionated electrograms might reflect an underlying RV cardiomyopathy. In our cases, however, the long-term follow-up revealed no imaging or ECG evidence of cardiomyopathies. For instance, in a 13-year follow-up, no underlying cardiomyopathy was noted, and endocardial electroanatomical mapping repeated 8 years after the initial endocardial RFCA session, revealed normal RV/RVOT voltage, and confirmed elimination of previously ablated endocardial electrograms.
Finally, patients with QRS notch in lead V1 did not respond to endocardial ablation, and the reason is incompletely clear. Our data indicate that such patients had the highly malignant arrhythmogenic substrate (very frequent VF episodes) with presence of low-voltage fractionated electrograms not only in epicardium but also in the RV endocardium (with lesser extent). In addition, using an experimental BrS model, Morita et al13 found that local epicardial delay causes multiple spikes at the late phase of the QRS complex, thereby resulting in fragmented QRS complex. Clinically, they found that patients with fragmented QRS complex were at high risk of developing subsequent arrhythmic events. This finding is consistent with our findings and may explain why some BrS patients continue to experience VF recurrence, whereas others do not. Recently, progression of abnormal electroanatomical substrate and fractionated electrograms with arrhythmia recurrence has been reported,14 emphasizing the potential role of electroanatomic mapping in monitoring disease progression and in prognostic stratification of BrS.
Initial Management of VF in BrS
In atrial fibrillation triggers, most commonly ectopic beats from the thoracic veins are well known in initiating atrial fibrillation,15 whereas atrial fibrillation maintenance has drawn significant attention to the role of the substrate.16
Similarly, but to a lesser extent, our results suggest that VF in BrS can effectively be managed by trigger elimination (mostly in the RVOT) with substrate modification through endocardial approach. With the development of new catheter designs and mapping technologies, and greater physician experience, trigger ablation is a reasonable initial approach in drug-resistant VF. However, when VF-triggering ectopic cannot be documented and in patients with QRS notch in lead V1 and fractionated endocardial electrograms, endocardial approach might be ineffective; therefore, epicardial substrate modification is potentially an effective ultimate approach in such cases.
This study has limitations. First, the number of ablated patients is small, which reflects the rarity of BrS patients with drug-resistant VF. Of note, we did not include BrS patients who responded to medical treatment. Second, postablation programmed ventricular stimulation was performed depending on the operator’s preference and was not performed in all patients. Third, sodium channel blocker was not used to assess the endocardial substrate.
Conclusions
With careful documentation of VF-triggering ectopic beats, trigger endocardial ablation with endocardial substrate modification has an excellent long-term outcome in drug-resistant VF, although presence of QRS notch in lead V1 in patients with extremely frequent VF episodes indicates inadequacy of endocardial ablation as initial management; hence, epicardial approach might be a reasonable first step.
References
1.
Kakishita M, Kurita T, Matsuo K, Taguchi A, Suyama K, Shimizu W, Aihara N, Kamakura S, Yamamoto F, Kobayashi J, Kosakai Y, Ohe T. Mode of onset of ventricular fibrillation in patients with Brugada syndrome detected by implantable cardioverter defibrillator therapy. J Am Coll Cardiol. 2000;36:1646–1653.
2.
Morita H, Fukushima-Kusano K, Nagase S, Takenaka-Morita S, Nishii N, Kakishita M, Nakamura K, Emori T, Matsubara H, Ohe T. Site-specific arrhythmogenesis in patients with Brugada syndrome. J Cardiovasc Electrophysiol. 2003;14:373–379.
3.
Haïssaguerre M, Extramiana F, Hocini M, Cauchemez B, Jaïs P, Cabrera JA, Farré J, Farre G, Leenhardt A, Sanders P, Scavée C, Hsu LF, Weerasooriya R, Shah DC, Frank R, Maury P, Delay M, Garrigue S, Clémenty J. Mapping and ablation of ventricular fibrillation associated with long-QT and Brugada syndromes. Circulation. 2003;108:925–928. doi: 10.1161/01.CIR.0000088781.99943.95
4.
Darmon JP, Bettouche S, Deswardt P, Tiger F, Ricard P, Bernasconi F, Saoudi N. Radiofrequency ablation of ventricular fibrillation and multiple right and left atrial tachycardia in a patient with Brugada syndrome. J Interv Card Electrophysiol. 2004;11:205–209. doi: 10.1023/B:JICE.0000048571.19462.54
5.
Nakagawa E, Takagi M, Tatsumi H, Yoshiyama M. Successful radiofrequency catheter ablation for electrical storm of ventricular fibrillation in a patient with Brugada syndrome. Circ J. 2008;72:1025–1029.
6.
Nademanee K, Veerakul G, Chandanamattha P, Chaothawee L, Ariyachaipanich A, Jirasirirojanakorn K, Likittanasombat K, Bhuripanyo K, Ngarmukos T. Prevention of ventricular fibrillation episodes in Brugada syndrome by catheter ablation over the anterior right ventricular outflow tract epicardium. Circulation. 2011;123:1270–1279. doi: 10.1161/CIRCULATIONAHA.110.972612
7.
Brugada J, Pappone C, Berruezo A, Vicedomini G, Manguso F, Ciconte G, Giannelli L, Santinelli V. Brugada syndrome phenotype elimination by epicardial substrate ablation. Circ Arrhythm Electrophysiol. 2015;8:1373–1381. doi: 10.1161/CIRCEP.115.003220
8.
Nademanee K, Raju H, de Noronha SV, Papadakis M, Robinson L, Rothery S, Makita N, Kowase S, Boonmee N, Vitayakritsirikul V, Ratanarapee S, Sharma S, van der Wal AC, Christiansen M, Tan HL, Wilde AA, Nogami A, Sheppard MN, Veerakul G, Behr ER. Fibrosis, connexin-43, and conduction abnormalities in the Brugada syndrome. J Am Coll Cardiol. 2015;66:1976–1986. doi: 10.1016/j.jacc.2015.08.862
9.
Coronel R, Casini S, Koopmann TT, Wilms-Schopman FJ, Verkerk AO, de Groot JR, Bhuiyan Z, Bezzina CR, Veldkamp MW, Linnenbank AC, van der Wal AC, Tan HL, Brugada P, Wilde AA, de Bakker JM. Right ventricular fibrosis and conduction delay in a patient with clinical signs of Brugada syndrome: a combined electrophysiological, genetic, histopathologic, and computational study. Circulation. 2005;112:2769–2777. doi: 10.1161/CIRCULATIONAHA.105.532614
10.
Knecht S, Sacher F, Wright M, Hocini M, Nogami A, Arentz T, Petit B, Franck R, De Chillou C, Lamaison D, Farré J, Lavergne T, Verbeet T, Nault I, Matsuo S, Leroux L, Weerasooriya R, Cauchemez B, Lellouche N, Derval N, Narayan SM, Jaïs P, Clementy J, Haïssaguerre M. Long-term follow-up of idiopathic ventricular fibrillation ablation: a multicenter study. J Am Coll Cardiol. 2009;54:522–528. doi: 10.1016/j.jacc.2009.03.065
11.
Sroubek J, Probst V, Mazzanti A, Delise P, Hevia JC, Ohkubo K, Zorzi A, Champagne J, Kostopoulou A, Yin X, Napolitano C, Milan DJ, Wilde A, Sacher F, Borggrefe M, Ellinor PT, Theodorakis G, Nault I, Corrado D, Watanabe I, Antzelevitch C, Allocca G, Priori SG, Lubitz SA. Programmed ventricular stimulation for risk stratification in the Brugada syndrome: a pooled analysis. Circulation. 2016;133:622–630. doi: 10.1161/CIRCULATIONAHA.115.017885
12.
Krittayaphong R, Veerakul G, Nademanee K, Kangkagate C. Heart rate variability in patients with Brugada syndrome in Thailand. Eur Heart J. 2003;24:1771–1778.
13.
Morita H, Kusano KF, Miura D, Nagase S, Nakamura K, Morita ST, Ohe T, Zipes DP, Wu J. Fragmented QRS as a marker of conduction abnormality and a predictor of prognosis of Brugada syndrome. Circulation. 2008;118:1697–1704. doi: 10.1161/CIRCULATIONAHA.108.770917
14.
Notarstefano P, Pieroni M, Guida R, Rio T, Oliva A, Grotti S, Fraticelli A, Bolognese L. Progression of electroanatomic substrate and electric storm recurrence in a patient with Brugada syndrome. Circulation. 2015;131:838–841. doi: 10.1161/CIRCULATIONAHA.114.013773
15.
Haïssaguerre M, Jaïs P, Shah DC, Takahashi A, Hocini M, Quiniou G, Garrigue S, Le Mouroux A, Le Métayer P, Clémenty J. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med. 1998;339:659–666. doi: 10.1056/NEJM199809033391003
16.
Allessie MA, Boyden PA, Camm AJ, Kléber AG, Lab MJ, Legato MJ, Rosen MR, Schwartz PJ, Spooner PM, Van Wagoner DR, Waldo AL. Pathophysiology and prevention of atrial fibrillation. Circulation. 2001;103:769–777.
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© 2018 American Heart Association, Inc.
History
Received: 12 July 2017
Accepted: 26 June 2018
Published in print: August 2018
Published online: 20 August 2018
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Disclosures
Dr Nogami has received lecture honoraria from St. Jude Medical and Boston Scientific and an endowment from Medtronic and Johnson & Johnson. Dr Tajiri has received endowment from St. Jude Medical co. The other authors report no conflicts.
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- Electrophysiological Characteristics and Ablation Outcomes in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia, Journal of the American Heart Association, 12, 24, (2023)./doi/10.1161/JAHA.123.031768
- Future direction of substrate‐based catheter ablation in Brugada syndrome and other inherited primary arrhythmia syndromes: Systematic review and meta‐analysis, Journal of Arrhythmia, 39, 6, (909-927), (2023).https://doi.org/10.1002/joa3.12947
- Outcomes of catheter ablation in high-risk patients with Brugada syndrome refusing an implantable cardioverter defibrillator implantation, Europace, 26, 1, (2023).https://doi.org/10.1093/europace/euad318
- Trigger and Substrate Mapping and Ablation for Ventricular Fibrillation in the Structurally Normal Heart, Journal of Cardiovascular Development and Disease, 10, 5, (200), (2023).https://doi.org/10.3390/jcdd10050200
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