Delay in Right Ventricular Activation Contributes to Brugada Syndrome

Tukkie, Raymond; Søgaard, Peter; Vleugels, Jim; Groot, I. K. L. M. de; Wilde, Arthur A.M.; Tan, Hanno L.

doi:10.1161/01.cir.0000118467.53182.d1

Cited by 170 publications

(136 citation statements)

References 34 publications

Supporting

Mentioning

123

Contrasting

Unclassified

Order By: Relevance

“…21 Although there is convincing experimental evidence to support this hypothesis, an additional involvement of altered conduction in the pathophysiological sequence leading to this complex disease cannot be excluded. 22,23 Indeed, the frontier between the Brugada syndrome and progressive conduction diseases remains unclear, because in the same family, the same mutation can induce both diseases. 24 Whether the pathophysiology of the Brugada syndrome also involves myocardial fibrosis (either diffuse or localized in the upper right ventricle) remains to be established, particularly for the fraction of Brugada patients carrying a SCN5A mutation leading to haploinsufficiency.…”

Section: Discussionmentioning

confidence: 99%

Mouse Model of SCN5A -Linked Hereditary Lenègre’s Disease

et al. 2005

View full text Add to dashboard Cite

Background— We have previously linked hereditary progressive cardiac conduction defect (hereditary Lenègre’s disease) to a loss-of-function mutation in the gene encoding the main cardiac Na + channel, SCN5A . In the present study, we investigated heterozygous Scn5a -knockout mice ( Scn5a +/− mice) as a model for hereditary Lenègre’s disease. Methods and Results— In Scn5a +/− mice, surface ECG recordings showed age-related lengthening of the P-wave and PR- and QRS-interval duration, coinciding with previous observations in patients with Lenègre’s disease. Old but not young Scn5a +/− mice showed extensive fibrosis of their ventricular myocardium, a feature not seen in wild-type animals. In old Scn5a +/− mice, fibrosis was accompanied by heterogeneous expression of connexin 43 and upregulation of hypertrophic markers, including β-MHC and skeletal α-actin. Global connexin 43 expression as assessed with Western blots was similar to wild-type mice. Decreased connexin 40 expression was seen in the atria. Using pangenomic microarrays and real-time PCR, we identified in Scn5a +/− mice an age-related upregulation of genes encoding Atf3 and Egr1 transcription factors. Echocardiography and hemodynamic investigations demonstrated conserved cardiac function with aging and lack of ventricular hypertrophy. Conclusions— We conclude that Scn5a +/− mice convincingly recapitulate the Lenègre’s disease phenotype, including progressive impairment with aging of atrial and ventricular conduction associated with myocardial rearrangements and fibrosis. Our work provides the first demonstration that a monogenic ion channel defect can progressively lead to myocardial structural anomalies.

show abstract

Section: Discussionmentioning

confidence: 99%

Mouse Model of SCN5A -Linked Hereditary Lenègre’s Disease

et al. 2005

View full text Add to dashboard Cite

show abstract

“…8,[17][18][19] Depolarization abnormality is reflected in prolonged HV intervals, abnormal late potential and abnormal delayed potential in the epicardial region of the right ventricular outflow tract. 8,16,[20][21][22] A widening of the S wave in the right precordial leads, reflecting an underlying right ventricular conduction delay, was frequently observed in symptomatic patients and might be an important indicator of increased risk. 23 However, rate-dependent changes in the conduction abnormality have not been fully elucidated.…”

Section: Rate-dependent Changes In S Wave and Qrs Durationmentioning

confidence: 99%

Bradycardia-Dependent ECG Changes in Brugada Syndrome

Mizumaki

Fujiki

Nishida

et al. 2006

Circ J

View full text Add to dashboard Cite

rugada syndrome (BS), a distinct subtype of idiopathic ventricular fibrillation (VF), is characterized by a distinctive ST segment elevation in the right precordial leads. [1][2][3] The mechanism responsible for this ST segment elevation and genesis of VF is still under investigation. Several possible mechanisms have been proposed for the ST segment elevation in BS. Among them are conduction delay, accentuation of the action potential notch and loss of the action potential dome in the right ventricular outflow epicardium. 3,4 In BS, unlike other diseases, VF and sudden death mainly occur in the resting state, predominantly during sleep. 5,6 The typical ECG changes are variable over time and are modulated by exercise or pharmacological interventions that interact with autonomic nervous activities. 5,[7][8][9] We recently reported an inadequate prolongation of the QT interval (short QT interval) at longer RR intervals 10 and an augmentation of the ST elevation through vagal activity in patients with BS. 11 The nighttime onset of VF episodes may be related to both a shorter QT interval and an enhanced ST elevation during bradycardia at night. This could be because of a slow recovery from the inactivation of prominent Ito. 12 However, it is still unclear how the RR intervals affect the ECG changes in BS and whether rate dependent changes in the ECG would be different between symptomatic and asymptomatic patients. The present study was therefore designed to examine the effects of the RR intervals on ECG changes during an electrophysiologic study (EPS) in both symptomatic and asymptomatic patients. Methods Study PopulationTwenty-one consecutive male patients with BS were studied: 9 were symptomatic with either documented VF or episodes of unexplained syncope, and the other 12 were asymptomatic without either spontaneous VF or inducible VF during the EPS. The study protocol was approved by the institutional review board and written informed consent was given by all patients before participation. We diagnosed BS in accordance with recently established ECG criteria. 3 Patients with coved-type ST elevation accompanied by Jwave amplitude ≥2 mm in one of the leads V1-3 were included. 3 For patients with saddle-back-type ST elevation (type 2 or 3), coved-type ST elevation ≥2 mm induced by pilsicainide, a class Ic antiarrhythmic drug, was required. 3 In all patients, physical examination, chest X-ray, 2-dimensional-echocardiography, exercise test and thallium or 99m Tc-tetrofosmin myocardial single photon emission computed tomography failed to disclose apparent evidence of organic heart disease. Patients with diabetes mellitus, long QT syndrome or electrolyte abnormality and patients taking any drugs were excluded from the present study. EPS and Analysis of ECGsEPS was performed in all 21 patients after all antiarrhythmic drugs had been discontinued for at least 5 halflives of the drug. A steerable 6F octapolar catheter with Background In patients with Brugada syndrome (BS), ventricular fibrillation (VF) occurs mainly during ...

show abstract

“…A recent report showed that such fractionated QRS may have some relationship with their arrhythmic events in patients with type 1 ECG (Morita et al 2008). Other study also showed that right ventricular conduction is delayed in patients with Brugada syndrome (Tukkie et al 2004). Depolarization abnormalities noted in these studies may contribute to the development of late potentials in patients with Brugada syndrome.…”

Section: Late Potentials By Sa-ecgmentioning

confidence: 83%

Prognostic Significance of Late Potentials in Outpatients with Type 2 Brugada Electrocardiogram

Fukuda

Kondo

Segawa

et al. 2016

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Brugada syndrome is characterized by distinguishing electrocardiogram (ECG) patterns (coved and saddleback types with day-to-day variation) and occurrence of lethal tachy-arrhythmias. The appearance of coved type ECG (type 1) is required for the diagnosis of Brugada syndrome, whereas the significance of saddleback type ECG (type 2), which is inadequate for the diagnosis, has not been fully established. We enrolled 34 consecutive patients with type 2 ECG on outpatient-clinic. Among them, 7 patients were ventricular fibrillation (VF) survivors who were diagnosed as Brugada syndrome with transient appearance of type 1 ECG, and showed type 2 ECG on their first outpatient-clinic visit after the VF event (VF group). The remaining 27 were asymptomatic and never showed type 1 ECG on repeated ECG examinations (control group). The VF group showed significantly longer RJ intervals in leads V1 and V2 and QTc intervals in lead V2 compared with the control group (P < 0.030, P < 0.017, and P < 0.030, respectively). Late potentials, detected on the signal-averaged ECG (SA-ECG), reflect conduction abnormalities and are known as one of the risk markers of arrhythmic events. Among the 34 patients, late potentials were negative in 12 patients belonging to the control group. In conclusion, the SA-ECG could be helpful to identify high-risk patients for its high negative predictive value as the first step, and ECG parameters, including RJ intervals in leads V1 and V2 and QTc interval in lead V2, could be useful for further risk stratification in patients with type 2 Brugada ECG.

show abstract

Delay in Right Ventricular Activation Contributes to Brugada Syndrome

Cited by 170 publications

References 34 publications

Mouse Model of SCN5A -Linked Hereditary Lenègre’s Disease

Mouse Model of SCN5A -Linked Hereditary Lenègre’s Disease

Bradycardia-Dependent ECG Changes in Brugada Syndrome

Prognostic Significance of Late Potentials in Outpatients with Type 2 Brugada Electrocardiogram

Contact Info

Product

Resources

About