Changes in body surface potential distributions induced by isoproterenol and Na channel blockers in patients with the Brugada syndrome

Izumida, Naomi; Asano, Yuh; Doi, Satomi; Wakimoto, Hiroko; Fukamizu, Seiji; Kimura, T; Ueyama, Tsuyoshi; Sakurada, Harumizu; Kawano, Seiko; Sawanobori, Tohru; Hiraoka, Masayasu

doi:10.1016/j.ijcard.2003.05.025

Cited by 15 publications

(13 citation statements)

References 30 publications

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“…Similar to Scn5a 1798insD/ϩ mice, we and others have previously shown the presence of RV conduction slowing in patients with this disorder. [17][18][19][20] In addition, Van Veen et al 21 have also recently shown the presence of conduction slowing and lengthening of the effective refractory period preferentially in the RV of Scn5a heterozygous knock-out mice. Although regional differences in transmural ion channel distribution as well as RV and LV size differences may play a role, 22,23 the mechanism for a predominant role for the RV remains unclear.…”

Section: Remme Et Almentioning

confidence: 97%

Overlap Syndrome of Cardiac Sodium Channel Disease in Mice Carrying the Equivalent Mutation of Human SCN5A -1795insD

et al. 2006

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Background-Patients carrying the cardiac sodium channel (SCN5A) mutation 1795insD show sudden nocturnal death and signs of multiple arrhythmia syndromes including bradycardia, conduction delay, QT prolongation, and right precordial ST-elevation. We investigated the electrophysiological characteristics of a transgenic model of the murine equivalent mutation 1798insD. Methods and Results-On 24-hour continuous telemetry and surface ECG recordings, Scn5a 1798insD/ϩ heterozygous mice showed significantly lower heart rates, more bradycardic episodes (pauses Ն500 ms), and increased PQ interval, QRS duration, and QTc interval compared with wild-type mice. The sodium channel blocker flecainide induced marked sinus bradycardia and/or sinus arrest in the majority of Scn5a 1798insD/ϩ mice, but not in wild-type mice. Epicardial mapping using a multielectrode grid on excised, Langendorff-perfused hearts showed preferential conduction slowing in the right ventricle of Scn5a 1798insD/ϩ hearts. On whole-cell patch-clamp analysis, ventricular myocytes isolated from Scn5a

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Section: Remme Et Almentioning

confidence: 97%

Overlap Syndrome of Cardiac Sodium Channel Disease in Mice Carrying the Equivalent Mutation of Human SCN5A -1795insD

et al. 2006

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“…Of note, this delay increased with class IC drug challenge. In another study [127], BSM localized areas of conduction delay to the RVOT. Conduction delay here increased with I Na blockers and decreased after isoproterenol.…”

Section: Right Ventricular Conduction Slowingmentioning

confidence: 98%

“…Rather, we should perhaps aim for clarification of the contribution of each mechanism in individual Brugada syndrome patients, so as to render rational and effective therapy, tailored to each of these mechanisms, a realistic aim in the near future. Table 1 Clinical and experimental evidence to suggest the electrophysiological mechanism of Brugada syndrome Support for repolarization disorder hypothesis Sodium channel blockers exacerbate/provoke ST elevations [27] Linkage with SCN5A mutations exhibiting reduced sodium current [3] Quinidine normalizes ECG and prevents arrhythmias [80,81,116] More prevalent phenotype in males [5,20,105] ST elevations are usually facilitated by slow heart rates [23,50] ST elevations are accompanied by epicardial action potential abbreviation [88] ''Spike-and-dome'' configuration of epicardial monophasic AP during heart surgery [90] ST elevation is associated with reduced ejection time of RV but not of LV [91] Support for depolarization disorder hypothesis Sodium channel blockers exacerbate/provoke ST elevations [27] Linkage with SCN5A mutations exhibiting reduced sodium current [3] ECG signs of general conduction slowing: axis deviation, PQ/QRS prolongation, sinus/AV node dysfunction [1,9,34,40,42 -45] High prevalence of late potentials [50,92,94,112,125] Late potentials indicate increased risk of arrhythmic events [94,125] Flecainide induces greater QRS widening in Brugada s. patients than controls [29] Conduction delay in right ventricular outflow tract (body surface mapping) [24,127] Longer HV interval predicts VT/VF inducibility [126] ST elevation correlates with delay in right ventricle contraction [91] Arrhythmogenic area is confined to small RVOT region (initiating PVCs, VT/VF inducibility, efficacy of catheter ablation) [58,132] Structural derangements, including fibrosis, in histological stud...…”

Section: Synthesismentioning

confidence: 99%

Pathophysiological mechanisms of Brugada syndrome: Depolarization disorder, repolarization disorder, or more?

Meregalli¹,

Wilde²,

Tan³

2005

Cardiovascular Research

333

266

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After its recognition as a distinct clinical entity, Brugada syndrome is increasingly recognized worldwide as an important cause of sudden cardiac death. Brugada syndrome exhibits autosomal dominant inheritance with SCN5A, which encodes the cardiac sodium channel, as the only gene with a proven involvement in 20-30% of patients. Its signature feature is ST segment elevation in right precordial ECG leads and predisposition to malignant ventricular tachyarrhythmias. The pathophysiological mechanism of ST elevation and ventricular tachyarrhythmia, two phenomena strongly related, is controversial. Here, we review clinical and experimental studies as they provide evidence to support or disprove the two hypotheses on the mechanism of Brugada syndrome that currently receive the widest support: (1) nonuniform abbreviation of right ventricular epicardial action potentials ("repolarization disorder"), (2) conduction delay in the right ventricular outflow tract ("depolarization disorder"). We also propose a schematic representation of the depolarization disorder hypothesis. Moreover, we review recent evidence to suggest that other derangements may also contribute to the pathophysiology of Brugada syndrome, in particular, right ventricular structural derangements. In reviewing these studies, we conclude that, similar to most diseases, it is likely that Brugada syndrome is not fully explained by one single mechanism. Rather than adhering to the notion that Brugada syndrome is a monofactorial disease, we should aim for clarification of the contribution of various pathophysiological mechanisms in individual Brugada syndrome patients and tailor therapy considering each of these mechanisms.

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“…23,24 Recently, Izumida et al have shown, using a ventricular activation time isochronal map, that in patients with BS, delayed conduction is noted on the upper anterior chest and the delay was decreased by sodium-channel blockers or isoproterenol; however, these drugs did not affect the QRST integral map pattern. 25 Izumida et al suggested that the ST elevation of BS was primarily caused by an abnormality in depolarization rather than in repolarization. 25 Taking all the results together, it is possible that abnormalities of repolarization, depolarization or both around the right ventricular outflow tract are the pathophysiological mechanism underlying the arrhythmogenecity in the high risk patients with Brugada-type resting ECG patterns.…”

Section: Specific Features Of Qrst Integral Mappingmentioning

confidence: 99%

“…25 Izumida et al suggested that the ST elevation of BS was primarily caused by an abnormality in depolarization rather than in repolarization. 25 Taking all the results together, it is possible that abnormalities of repolarization, depolarization or both around the right ventricular outflow tract are the pathophysiological mechanism underlying the arrhythmogenecity in the high risk patients with Brugada-type resting ECG patterns.…”

Section: Specific Features Of Qrst Integral Mappingmentioning

confidence: 99%

Characteristic Features of QRST Integral Mapping in Patients With High Risk Brugada Syndrome

Kanahara

Kai

Toyomasu

et al. 2007

Circ J

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rugada syndrome (BS) is associated with a high risk of sudden cardiac death secondary to life-threatening arrhythmias; that is, ventricular tachycardia and fibrillation (VT/VF) in young and otherwise healthy adults. 1-4 ECG abnormalities constitute the hallmark of BS and include a coved or saddleback-type ST-segment elevation in the right precordial leads (V1-3) accompanied by T wave alterations, with or without some degree of right bundle branch block in the absence of identifiable structural cardiac abnormalities. However, there are a substantial number of patients who show Brugada-type ECGs but do not develop fatal arrhythmias. Therefore, it is important in the clinical practice to discriminate patients with the Brugada-type resting ECG who are at a high risk for lifethreatening ventricular arrhythmias from those at low risk. However, at present there is not a non-invasive method of risk stratification.Among the approaches to detect patients at risk of lifethreatening ventricular arrhythmias, QRST integral mapping is of particular interest. The spatial distributions of the QRST integrals reflect an anatomic and electrophysiological substrate for fatal ventricular arrhythmias. 5-10 It has Circulation Journal Vol. 71, January 2007 been shown that QRST integral mapping is capable of assessing the vulnerability to ventricular arrhythmias in various heart diseases. [11][12][13][14] Accordingly, we investigated whether patients with Brugada-type resting ECGs and life-threatening arrhythmias can be non-invasively characterized using QRST integral mapping. If so, QRST integral mapping could be a new non-invasive screening method to discriminate between high and low risk patients with regard to life-threatening arrhythmias. In the present study, QRST isointegral maps and QRST integral departure maps were created in patients with Brugada-type resting ECGs with at least 1 of the following: aborted sudden death, a history of spontaneous sustained VT/VF or programmed electrical stimulation (PES)-inducible sustained VT/VF. These findings were compared with those of Brugada-type ECG patients who had not experienced such cardiac events. Methods Study GroupsThis retrospective study included 24 consecutive patients with Brugada-type resting ECGs, all of whom underwent body-surface QRST isointegral mapping at Kurume University Hospital from January 1997 to August 2005. The enrolled patients had no evidence of structural abnormalities of the heart based upon cardiac echocardiograms, coronary angiograms, and right and left ventriculograms. None of the patients enrolled in this study was taking antiarrhythmic drugs. The present study was approved by the Ethical Committee for Clinical Research of Kurume University, and all subjects gave written informed consent.The Brugada-type ECGs were recognized as having type- Characteristic Features of QRST Integral Mapping in Patients With High Risk Brugada SyndromeMasaaki Kanahara, MSc; Hisashi Kai, MD*; Koji Toyomasu, MD**; Teruhisa Yoshida, MD*; Tatsuro Hiraki, MD*; Kimitaka Sagawa, MD...

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Changes in body surface potential distributions induced by isoproterenol and Na channel blockers in patients with the Brugada syndrome

Cited by 15 publications

References 30 publications

Overlap Syndrome of Cardiac Sodium Channel Disease in Mice Carrying the Equivalent Mutation of Human SCN5A -1795insD

Overlap Syndrome of Cardiac Sodium Channel Disease in Mice Carrying the Equivalent Mutation of Human SCN5A -1795insD

Pathophysiological mechanisms of Brugada syndrome: Depolarization disorder, repolarization disorder, or more?

Characteristic Features of QRST Integral Mapping in Patients With High Risk Brugada Syndrome

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