CLINICAL STUDY
Epicardial electrogram of the right ventricular outflow tract in patients with the brugada syndrome
Using the epicardial lead
Satoshi Nagase, MD*,*,
Kengo Fukushima Kusano, MD, PhD*,
Hiroshi Morita, MD, PhD*,
Yoshihisa Fujimoto, MD, PhD*,
Mikio Kakishita, MD, PhD*,
Kazufumi Nakamura, MD, PhD*,
Tetsuro Emori, MD*,
Hiromi Matsubara, MD, PhD* and
Tohru Ohe, MD, PhD, FACC*
* Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Manuscript received September 11, 2001;
revised manuscript received February 14, 2002,
accepted March 27, 2002.
* Reprint requests and correspondence: Dr. Satoshi Nagase, Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
snagase{at}cc.okayama-u.ac.jp
Part of this manuscript was presented at the 22nd Annual Scientific Sessions of the North American Society of Pacing and Electrophysiology, May 2 to 5, 2001, Boston, Massachusetts, and published in abstract form (Pacing Clin Electrophysiol 2001;24 Suppl II:II677).
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Abstract
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OBJECTIVES: We tried to record an epicardial electrogram directly, and we examined local electrograms before and after administration of a class IC anti-arrhythmic drug in patients with the Brugada syndrome.
BACKGROUND: Electrical heterogeneity of the epicardium in the right ventricular outflow tract (RVOT) has been thought to be related to the Brugada syndrome. However, an epicardial abnormality has not been demonstrated in patients with the Brugada syndrome.
METHODS: In five patients with a Brugada-type electrocardiogram (ECG), local unipolar electrograms were recorded at the epicardium and endocardium of the RVOT. To record the epicardial electrogram directly, we introduced an electrical guidewire into the conus branch (CB) of the right coronary artery. The duration of the local electrogram after termination of the QRS complex (DP) was measured before and after class IC anti-arrhythmic drug administration. The signal-averaged electrocardiogram (SAECG) was also obtained in all patients.
RESULTS: A definite DP was observed at the epicardium, but not at the endocardium. After administration of a class IC anti-arrhythmic drug, the DP at the epicardium was prolonged from 38 ± 10 ms to 67 ± 24 ms. The late potential corresponding to the DP at the epicardium was observed in all patients on the SAECG.
CONCLUSIONS: An epicardial electrogram can be recorded from the CB. Recording from the CB enables identification of an epicardial abnormality in patients with the Brugada syndrome. These abnormal electrograms may be related to a myocardial abnormality in the epicardium of patients with the Brugada syndrome.
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Abbreviations and Acronyms
| | CB = conus branch | | DP = local electrogram after termination of the QRS complex | | ECG = electrocardiogram/electrocardiographic | | LAS40 = duration of low-amplitude signals <40 µV in the terminal filtered QRS complex | | LP = late potential | | RMS40 = root mean square voltage of the terminal 40 ms in the filtered QRS complex | | RVOT = right ventricular outflow tract | | RVOT-FW = free wall of the right ventricular outflow tract | | SAECG = signal-averaged electrocardiogram | | VF = ventricular fibrillation |
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The Brugada syndrome is an idiopathic ventricular fibrillation (VF) characterized by ST-segment elevation in the precordial leads, and is augmented by sodium channel blockers (1–3). It has been suggested that electrical heterogeneity, especially at the epicardium of the right ventricle, causes the ST-segment elevation and is related to the occurrence of polymorphic ventricular arrhythmias (4,5). However, studies using body surface mapping or the signal-averaged electrocardiogram (SAECG) have suggested that a conduction delay exists in the anterior wall of the right ventricle or the right ventricular outflow tract (RVOT) in patients with the Brugada syndrome (6,7). However, endocardial mapping in a routine electrophysiologic study failed to demonstrate this electrical abnormality.
The conus branch (CB) arises at the right coronary ostium or within the first few millimeters of the right coronary artery. It runs on the surface of the free wall of the right ventricular outflow tract (RVOT-FW). Therefore, an electrogram obtained at the CB may reflect an epicardial electrogram at the RVOT-FW. In this study, we analyzed electrograms recorded at the CB and examined the effects of class IC anti-arrhythmic drugs in patients with the Brugada syndrome.
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Methods
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Study group.
Five male patients (age 45 ± 11 years) with the Brugada syndrome were studied. All patients had persistent ST-segment elevation in the precordial leads. In three patients, episodes of VF or aborted sudden cardiac death were observed (i.e., symptomatic patients). In the other two patients, no episodes of VF or aborted sudden cardiac death were observed, but VF was demonstrated with single or double extrastimulation at the RVOT-FW in the electrophysiologic study (i.e., asymptomatic patients). Routine studies, including cardiac echocardiography, coronary angiography, right and left ventriculography, radionucleography and endomyocardial biopsy, showed no evidence of structural heart disease.
Electrophysiologic study
After obtaining written, informed consent, an electrophysiologic study was performed in all patients.
After right coronary arteriography, an electrical guidewire (FloWire, Cardiometrics, California) was introduced into the CB through the right coronary artery. A local unipolar electrogram at the epicardium of the RVOT-FW was recorded at the tip of the wire, using a 30- to 400-Hz bandwidth. A local unipolar electrogram at the endocardium was recorded using a 30- to 400-Hz bandwidth, by a quadripolar 6F deflectable catheter positioned at the endocardium at the RVOT-FW (Fig. 1A).
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Figure 1 (A) Fluoroscopic 30° right anterior oblique (RAO) and 60° left anterior oblique (LAO) views of the position of the electrical guidewire introduced into the conus branch through the right coronary artery for epicardial mapping (Epi), as well as the quadripolar deflectable catheter at the endocardium of the free wall at the right ventricular outflow tract for endocardial mapping (Endo). (B) Surface electrocardiographic leads V1, V2 and V5 and intracardiac electrograms of the epicardium (Epi) and endocardium (Endo) at the free wall at the right ventricular outflow tract before (Pre) and after (Post) the administration of a class IC anti-arrhythmic drug in Patient 1 (asymptomatic patient). A definite local electrogram was recorded after termination of the QRS complex at the epicardium (arrows), and the duration of the local electrogram after termination of the QRS complex after class IC anti-arrhythmic drug administration was more prolonged at the epicardium than at the endocardium in Patient 1.
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The duration of the local electrogram after termination of the QRS complex (DP) was measured before and after class IC anti-arrhythmic drug administration. Termination of the QRS complex was defined in lead V5. Pilsicainide (0.7 to 1.0 mg/kg) was administered to Patients 1 to 4, and flecainide (1.0 mg/kg) was administered to Patient 5 as a bolus over a period of 10 min.
SAECG
The SAECG (ART 1200EPX; noise level <0.3 µV, high-pass filtering of 40 Hz using a bidirectional four-pole Butterworth) was performed in all patients. The filtered QRS duration, the root mean square voltage of the terminal 40 ms in the filtered QRS complex (RMS40) and the duration of low-amplitude signals <40 µV in the terminal filtered QRS complex (LAS40), were measured with SAECG. A late potential (LP) was considered to be positive when two criteria (RMS40 <20 µV and LAS40 >40 ms) were met.
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Results
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A definite DP was observed at the epicardium, but not at the endocardium. After administration of a class IC anti-arrhythmic drug, the duration of the DP at the epicardium was prolonged from 38 ± 10 ms to 67 ± 24 ms (Fig. 1B). An LP corresponding to the DP at the epicardium was observed in all patients on the SAECG (Fig. 2).
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Figure 2 (A to E) Surface electrocardiographic leads V2 and V5, intracardiac electrograms of the epicardium (Epi) at the free wall at the right ventricular outflow tract and signal-averaged electrocardiogram (SAECG) in Patients 1 (A), 2 (B), 3 (C), 4 (D) and 5 (E). Patients 1 and 2 are asymptomatic patients, and Patients 3, 4 and 5 are symptomatic patients. The late potentials, represented by the shaded area, are positive in all patients, showing the root mean square voltage of the terminal 40 ms in the filtered QRS complex (RMS40) <20 µV and the duration of low-ampltitude signals <40 µV in the terminal filtered QRS complex (LAS40) >40 ms, and correspond to a delayed potential after the QRS complex at the epicardium (arrows) in all patients. f-QRS = filtered QRS duration.
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Discussion
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The Brugada syndrome is an idiopathic VF of uncertain etiology (1–3). Several studies have suggested that electrical heterogeneity is related to the genesis of the Brugada syndrome (4,5). A depressed right ventricular epicardial action potential dome is the basis for the ST-segment elevation and leads to phase 2 re-entry as a trigger for episodes of polymorphic ventricular arrhythmias. However, the existence of a conduction delay at the RVOT has been suggested in many reports (6,7). In addition, several clinical studies have suggested that spontaneous episodes of VF are triggered by premature ventricular contractions originating from the right ventricular free wall (8,9). However, this electrical abnormality was not demonstrated by endocardial mapping in a routine electrophysiologic study.
In patients with the Brugada syndrome, class IC anti-arrhythmic drug administration could augment ST-segment elevation in the precordial leads, and spontaneous VF has sometimes been observed (3,10).
The CB arises at the right coronary ostium or within the first few millimeters of the right coronary artery. It runs on the surface of the RVOT-FW. In this study, we were able to directly record a unipolar epicardial electrogram at the RVOT-FW, by using an electrical guidewire introduced into the CB. There was a delayed potential at the QRS complex in the epicardium of the RVOT-FW, which was not demonstrated by endocardial mapping. Class IC anti-arrhythmic drug administration augmented ST-segment elevation and also augmented the DP in the epicardium. An LP was observed on the SAECG in all patients and corresponded to the DP recorded on the epicardial electrogram. These abnormal electrograms were thought to reflect a myocardial abnormality in the epicardium.
Because the CB is attached to the left ventricular cavity through the low resistance of blood, it is quite possible that the DP recorded in the CB reflects not only local electrograms at the RVOT, but also remote regions such as the left ventricle. To exclude that possibility, left ventricular endocardial mapping was performed in all patients, and the DP was not demonstrated at the left ventricular endocardium in any of the patients. Furthermore, left ventricular epicardial electrograms of the great cardiac vein through the coronary sinus were recorded in some patients who did not show a DP.
Conclusions.
Recording from the CB enables identification of an epicardial abnormality in patients with the Brugada syndrome. Class IC anti-arrhythmic drug administration worsens these abnormalities, which may play an important role in the occurrence of VF in patients with the Brugada syndrome.
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References
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1. Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden death: a distinct clinical and electrocardiographic syndrome. J Am Coll Cardiol. 1992;20:1391–1396[Abstract]
2. Brugada J, Brugada R, Brugada P. Right bundle-branch block and ST-segment elevation in leads V1 through V3: a marker for sudden death in patients without demonstrable structural heart disease. Circulation. 1998;97:457–460[Abstract/Free Full Text]
3. Brugada R, Brugada J, Antzelevitch C, et al. Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts. Circulation. 2000;101:510–515[Abstract/Free Full Text]
4. Yan GX, Antzelevitch C. Cellular basis for the Brugada syndrome and other mechanisms of arrhythmogenesis associated with ST-segment elevation. Circulation. 1999;100:1660–1666[Abstract/Free Full Text]
5. Gussak I, Antzelevitch C, Bjerregaard P, et al. The Brugada syndrome: clinical, electrophysiological and genetic aspects. J Am Coll Cardiol. 1999;33:5–15[Abstract/Free Full Text]
6. Kasanuki H, Ohnishi S, Ohtuka M, et al. Idiopathic ventricular fibrillation induced with vagal activity in patients without obvious heart disease. Circulation. 1997;95:2277–2285[Abstract/Free Full Text]
7. Ikeda T, Sakurada H, Sakabe K, et al. Assessment of noninvasive markers in identifying patients at risk in the Brugada syndrome: insight into risk stratification. J Am Coll Cardiol. 2001;37:1628–1634[Abstract/Free Full Text]
8. 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[Abstract/Free Full Text]
9. Takagi M, Aihara N, Kuribayashi S, et al. Localized right ventricular morphological abnormalities detected by electron-beam computed tomography represent arrhythmogenic substrates in patients with the Brugada syndrome. Eur Heart J. 2001;22:1032–1041[Abstract/Free Full Text]
10. Takenaka S, Kusano FK, Hisamatsu K, et al. Relatively benign clinical course in asymptomatic patients with Brugada-type electrocardiogram without family history of sudden death. J Cardiovasc Electrophysiol. 2001;12:2–6[CrossRef][Medline]
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Abstract
Methods