Published online before print August 18, 2003, doi: 10.1161/01.CIR.0000088781.99943.95
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(Circulation. 2003;108:925.)
© 2003 American Heart Association, Inc.
Brief Rapid Communications |
Mapping and Ablation of Ventricular Fibrillation Associated With Long-QT and Brugada Syndromes
From the Hopital Cardiologique du Haut-Leveque, Bordeaux-Pessac, France.
Correspondence to Professor Michel Haïssaguerre, Hôpital Cardiologique du Haut-Lévêque, Avenue de Magellan, 33604 Bordeaux-Pessac, France. E-mail jacques.clementy{at}pu.u-bordeaux2.fr
Received March 4, 2003; de novo received June 3, 2003; revision received July 9, 2003; accepted July 10, 2003.
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Abstract |
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Background— The long-QT and Brugada syndromes are important substrates of malignant ventricular arrhythmia. The feasibility of mapping and ablation of ventricular arrhythmias in these conditions has not been reported.
Methods and Results— Seven patients (4 men; age, 38±7 years; 4 with long-QT and 3 with Brugada syndrome) with episodes of ventricular fibrillation or polymorphic ventricular tachycardia and frequent isolated or repetitive premature beats were studied. These premature beats were observed to trigger ventricular arrhythmias and were localized by mapping the earliest endocardial activity. In 4 patients, premature beats originated from the peripheral right (1 Brugada) or left (3 long-QT) Purkinje conducting system and were associated with variable Purkinje-to-muscle conduction times (30 to 110 ms). In the remaining 3 patients, premature beats originated from the right ventricular outflow tract, being 25 to 40 ms ahead of the QRS. The accuracy of mapping was confirmed by acute elimination of premature beats after 12±6 minutes of radiofrequency applications. During a follow-up of 17±17 months using ambulatory monitoring and defibrillator memory interrogation, no patients had recurrence of symptomatic ventricular arrhythmia but 1 had persistent premature beats.
Conclusion— Triggers from the Purkinje arborization or the right ventricular outflow tract have a crucial role in initiating ventricular fibrillation associated with the long-QT and Brugada syndromes. These can be eliminated by focal radiofrequency ablation.
Key Words: long-QT syndrome • death, sudden • ablation • arrhythmia
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Introduction |
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The long-QT syndrome (LQTS) and Brugada syndrome are established causes of sudden cardiac death associated with abnormal ventricular repolarization.1–6 The cornerstone of their management has been the implantation of a defibrillator (or ß-blockers in LQTS). Recently, the importance of triggers in idiopathic ventricular fibrillation (VF) and their successful catheter ablation have been demonstrated.7 These triggers originated dominantly from the Purkinje system or right ventricular outflow tract (RVOT). The present study describes the mapping and ablation of malignant ventricular arrhythmias in patients with LQTS or the Brugada syndrome.
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Methods |
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Seven patients with LQTS (2 men/2 women; age, 37±8 years) or Brugada syndrome (2 men/1 woman; age, 39±7 years) underwent mapping and ablation of triggers inducing polymorphic ventricular tachycardia or VF. These patients presented with documented episodes of polymorphic ventricular tachycardia or VF (1 to 21 episodes), 3 with a family history of sudden death. Whereas patients with the Brugada syndrome had 14±8 episodes of VF, those with LQTS had 6±4 episodes of VF or syncope before mapping. The LQTS was diagnosed in 4 patients on the basis of established criteria with a corrected QT interval of >460 ms; KCNQ1, SCN5A, and HERG channelopathies were excluded. The Brugada syndrome was diagnosed by abnormal QRST complexes in leads V1 and V2 with a coved ST-segment elevation in 3 patients, one who had a familial SCN5A channelopathy (2850delT). No patient had evidence of structural heart disease according to physical examination, echocardiography, and right/left ventricular ejection fraction. Exercise testing in all and coronary angiography in 4 patients excluded myocardial ischemia.
The LQTS was diagnosed at the time of ventricular arrhythmia. Two patients with Brugada syndrome were initially asymptomatic, having undergone prophylactic insertion of a defibrillator, and later presented (9 months and 3 years, respectively) with clinical episodes of VF (5 and 17, respectively); in the third, a defibrillator was inserted after 12 episodes of syncope.
Patients were hospitalized within 2 weeks of symptoms or multiple VF episodes (in 5), and were then documented to have ventricular premature beats (11 559±13 111/24 hours, range 661 to 32 400). The triggering role of premature beats in the initiation of VF was observed by ambulatory monitoring or stored electrograms of the defibrillator. Premature beats in the LQTS had a coupling interval of 503±29 ms; they were monomorphic in 2 patients (1 with left bundle-branch block–inferior axis typical of RVOT [Figure 1] and 1 with right bundle-branch block with superior axis), and polymorphic and repetitive (sometimes bidirectional) with a positive morphology in lead V1 in 2 patients (Figure 2). The latter had varying cycle lengths of 280 to 420 ms with repetitive beats lasting 3 to 45 beats, which were well tolerated during hospitalization. Premature beats in the Brugada syndrome were monomorphic in all, with a RVOT morphology in 2 (coupling interval of 340±20 and 408±15 ms) and with left bundle-branch block–superior axis in 1 (coupling interval 278±29 ms). The monomorphic RVOT premature beats were first observed at the time of VF in 1 patient, whereas in 2 patients, they had been documented (with a normal QRS/QT in sinus rhythm) 14 and 11 years before they triggered VF, after development of abnormal QRST. Exercise testing and isoproterenol infusion eliminated all premature beats, excluding catecholaminergic polymorphic ventricular tachycardia.
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Medical treatment in the LQTS had included ß-blockers alone or combined with class IC drugs (3), verapamil (2), and amiodarone (1). No drug therapy had been attempted in 2 patients with Brugada syndrome, while quinidine failed in 1 patient. A defibrillator was implanted in 5 patients but not in 2 patients with LQTS who had frequent polymorphic ventricular tachycardias.
Electrophysiological Study
Written informed consent was obtained from all patients. Mapping was performed in the fasted state with sedation using midazolam and nalbuphine. An intravenous dose of 0.5 mg/kg of heparin was administered during mapping in the left ventricle. Two to four multielectrode catheters were introduced percutaneously through the femoral vessels, including a 4-mm-tip quadripolar roving ablation catheter equipped with a thermocouple (Biosense Webster). The latter was introduced into the left ventricle by retrograde aortic or transseptal catheterization for the patients with left ventricular premature beats. Surface ECGs and bipolar endocardial electrograms were filtered at 30 to 500 Hz and recorded with a polygraph (model Laboratory system or Midas, 1 to 4 kHz and 10 kHz sampling rate, respectively).
In patients with Brugada syndrome, induction of sustained VF was attempted using 1 to 3 programmed extrastimuli at the right ventricular apex and (if negative) from the RVOT at twice the diastolic threshold.
Localization and Ablation of Triggers
Mapping the earliest electrogram relative to the onset of the ectopic QRS complex localized the triggers. An initial sharp potential (<10 ms in duration) preceding the larger and slower ventricular electrogram by <15 ms during sinus rhythm represented a peripheral Purkinje component, whereas longer intervals indicated proximal Purkinje fascicle activation. Such a potential preceding ventricular activation during premature beats indicated the latter originated from the Purkinje system.8,9 Ablation was performed using radiofrequency (RF) energy with a target temperature of 55°C to 60°C and a maximum power of 50 watts, with a duration that included the time to abolish premature beats and consolidating applications to minimize recurrence.
Patients were monitored for 3 to 5 days after ablation, and 24-hour ambulatory monitoring was performed at 1 month. Patients were followed up at their referral hospital for recurrence of presyncope, syncope, or defibrillator shocks.
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Results |
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The procedural and fluoroscopy durations were 169±57 minutes (range 90 to 240) and 42±21 minutes (range 17 to 69), respectively.
Long-QT Syndrome
In 1 patient, premature beats originated from the RVOT and were ablated by 6 minutes of RF application. In 2 patients, polymorphic ventricular beats originated from the peripheral Purkinje arborization in the left ventricle, including the ramifications of anterior or posterior fascicles (which produced inferior and superior axis morphologies, respectively), and from the intervening region in intermediate morphologies (Figure 2). In 1 patient, premature beats originated from the posterior fascicle. During premature beat, the earliest Purkinje potential preceded the local endocardial muscle activation by a conduction interval of 34±17 ms, whereas during sinus rhythm it preceded the ventricular muscle activity by 5 to 15 ms. Repetitive beats were also preceded by Purkinje activity (Figure 2) with a variable delay ranging from 20 to 110 ms (52±24).
The ablation of Purkinje beats produced, during the first minute of local RF application, temporary exacerbation of arrhythmia (increased the number of premature beats and polymorphic ventricular tachycardia) followed by a disappearance of premature beats. Different morphologies were progressively eliminated by ablation at multiple sites using 12 to 24 minutes of RF applications. Electrograms after ablation showed the abolition of the local Purkinje potential, but the QRS complex during sinus rhythm remained unchanged.
Brugada Syndrome
In 2 patients, RVOT triggers were eliminated by 7 to 10 minutes of RF applications at the earliest site (25 and 40 ms ahead of QRS onset). Noteworthy is that VF inducibility was modified after ablation; initially, VF was reproducibly induced from the right ventricular apex with 2 extrastimuli (S1500, S2240, and S3220 ms in both patients), but the same repeated maneuvers after ablation were negative. Whereas 3 extrastimuli from 2 sites were negative in 1 of these patients, it ultimately induced VF in the other (S2240, S3220, and S4180 ms). In the third patient, premature beats with left bundle-branch block and superior axis originated from the anterior right ventricular Purkinje network and were ablated with 10 minutes of RF application. VF was not inducible in this patient.
Follow-Up
During a mean follow-up period of 17±17 months (LQTS 24±20 months; Brugada 7±6 months), there has been no recurrence of VF, syncope, or sudden cardiac death in any patient. One patient with LQTS was maintained on a ß-blocker. Another had a late recurrence of premature beats; she refused further procedures and continued ß-blocker treatment. In other patients, repeated ambulatory monitoring showed none or a few (0 to 12) isolated premature beats per 24 hours.
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Discussion |
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This study demonstrates the important role of focal triggers in the development of malignant ventricular arrhythmias associated with the LQTS and Brugada syndrome, with dramatic improvement after ablation.
These patients fulfilled established criteria for the LQTS or Brugada syndrome and presented with malignant arrhythmias that were associated with frequent isolated or repetitive premature beats and multiple VF in most. Patients were rapidly hospitalized to facilitate mapping of spontaneous triggers. Although they are consecutive patients, this cohort may represent a selected subset, and these results may not be applicable to patients with a paucity of premature beats. However, even in reports with infrequent premature beats, the morphology of these beats was similar to our patients.10,11 Triggering beats were elicited from the Purkinje system (notably in LQTS) or from the RVOT (notably in Brugada syndrome) and confirmed by elimination of triggers and malignant arrhythmia after ablation.
The present report provides new insights into the initiation of VF associated with abnormal repolarization. The finding of focal triggers is in agreement with previous observations that in 67% of patients with Brugada syndrome, initiation of VF was preceded by similar isolated premature beats.10 These have a right ventricular origin dominantly from the RVOT, with the latter region hypothesized to support maximal electrical gradient. However, the long coupling interval of triggers or their Purkinje origin would not support epicardial phase 2 reentry.3 In the LQTS, there are scarce data about morphology of beats initiating malignant arrhythmias because of their sporadic occurrence and the efficacy of ß-blockers; however, narrow complex beats ("fascicular") occurring in isolation or in polymorphic/bidirectional runs can be recognized in previous reports.11 The initiating role of the Purkinje system may result from automaticity, reentry, or triggered activity and is sensitive to various clinical factors.6,12,13
The cohort studied is small but involves two causes of sudden death that have been considered concurrently because they affect ventricular repolarization with similar triggers and polymorphic arrhythmia, which can be eliminated by ablation. These results are strikingly similar to those of idiopathic VF, considered implicitly not to involve an abnormal substrate, and therefore indicate a broader role of focal triggers in VF initiation. Though they need to be confirmed in a larger cohort with longer follow-up, such results have major implications as they provide new insights that may lead to a possible cure for VF.
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References |
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1. Consensus statement of the Joint Committees of the Unexplained Cardiac Arrest Registry of Europe and of the Idiopathic Ventricular Fibrillation Registry in the United States. Survivors of out-of-hospital cardiac arrest with apparently normal heart: need for definition and standardized clinical evaluation. Circulation. 1996; 95: 265–272.
2. Belhassen B, Viskin S. Idiopathic ventricular tachycardia and fibrillation. J Cardiovasc Electrophysiol. 1993; 4: 356–368.[Medline] [Order article via Infotrieve]
3. Antzelevitch C, Brugada P, Brugada J, et al. The Brugada Syndrome. Armonk, NY: Futura Publishing; 1999.
4. Wellens HJJ, Lemery R, Smeets JL, et al. Sudden arrhythmic death without overt heart disease. Circulation. 1992; 85: I-92–I-97.[Medline] [Order article via Infotrieve]
5. Schwartz PJ, Locati E, Priori SG, et al. The idiopathic long QT syndrome. In: Zipes DP, Jalife J, eds. Cardiac Electrophysiology: From Cell to Bedside. Philadelphia, Pa: WB Sanders Co; 1990: 589–605.
6. Jackman WM, Friday KJ, Anderson JL, et. al. The long QT syndromes: a critical review, new clinical observations and a unifying hypothesis. Prog Cardiovasc Dis. 1988; 31: 115–172.[CrossRef][Medline] [Order article via Infotrieve]
7. Haissaguerre M, Shoda M, Jais P, et. al. Mapping and ablation of idiopathic ventricular fibrillation. Circulation. 2002; 106: 962–967.
8. Nakagawa H, Beckman KJ, McClelland JM, et. al. Radiofrequency catheter ablation of idiopathic left ventricular tachycardia guided by a Purkinje potential. Circulation. 1993; 88: 2607–2617.
9. Myerburg RJ, Stewart JW, Hoffman BF. Electrophysiological properties of the canine peripheral conducting system. Circ Res. 1970; 26: 361–372.
10. Kakishita M, Kurita T, Matsuo K, et al. 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.
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12. El-Sherif N, Chinushi M, Caref EB, et al. Electrophysiological mechanism of the characteristic electrocardiographic morphology of torsade de pointes tachyarrhythmias in the long-QT syndrome. Circulation. 1997; 96: 4292–4299.
13. Berenfeld O, Jalife J. Purkinje-muscle reentry as a mechanism of polymorphic ventricular arrhythmias in a 3-dimensional model of the ventricles. Circ Res. 1998; 82: 1063–1077.
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