High-Density Substrate Mapping in Brugada Syndrome

Lambiase, Pier D.; Ahmed, Ayesha; Ciaccio, Edward J.; Brugada, Ramón; Lizotte, Éric; Chaubey, Sanjay; Ben-Simon, Ron; Chow, Anthony; Löwe, Martin; McKenna, William J.

doi:10.1161/circulationaha.108.771401

Cited by 144 publications

(27 citation statements)

References 40 publications

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“…Together, these two properties provide conditions for sustained reentrant excitation. Their coexistence in the substrate of BrS patients has been suggested by other recent studies; 27–28 it is consistent with the high incidence of arrhythmic SCD. Interestingly, most arrhythmic events occur during bradycardia.…”

Section: Discussionsupporting

confidence: 86%

Cardiac Electrophysiological Substrate Underlying the ECG Phenotype and Electrogram Abnormalities in Brugada Syndrome Patients

et al. 2015

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Background Brugada syndrome (BrS) is a highly arrhythmogenic cardiac disorder, associated with an increased incidence of sudden death. Its arrhythmogenic substrate in the intact human heart remains ill-defined. Methods and Results Using noninvasive ECG imaging (ECGI), we studied 25 BrS patients to characterize the electrophysiologic substrate, and 6 patients with right bundle branch block (RBBB) for comparison. Seven normal subjects provided control data. Abnormal substrate was observed exclusively in the right ventricular outflow tract (RVOT) with the following properties (compared to normal controls; p<0.005): (1)ST-segment elevation (STE) and inverted T-wave of unipolar electrograms (EGMs) (2.21±0.67 vs. 0 mV); (2)delayed RVOT activation (82±18 vs. 37±11 ms); (3)low amplitude (0.47±0.16 vs. 3.74±1.60 mV) and fractionated EGMs, suggesting slow discontinuous conduction; (4)prolonged recovery time (RT; 381±30 vs. 311±34 ms) and activation-recovery intervals (ARIs; 318±32 vs. 241±27 ms), indicating delayed repolarization; (5)steep repolarization gradients (ΔRT/Δx= 96±28 vs. 7±6 ms/cm, ΔARI/Δx= 105±24 vs. 7±5 ms/cm) at RVOT borders. With increased heart rate in 6 BrS patients, reduced STE and increased fractionation were observed. Unlike BrS, RBBB had delayed activation in the entire RV, without STE, fractionation, or repolarization abnormalities on EGMs. Conclusions The results indicate that both, slow discontinuous conduction and steep dispersion of repolarization are present in the RVOT of BrS patients. ECGI could differentiate between BrS and RBBB.

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Section: Discussionsupporting

confidence: 86%

Cardiac Electrophysiological Substrate Underlying the ECG Phenotype and Electrogram Abnormalities in Brugada Syndrome Patients

et al. 2015

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“…Noncontact mapping of the RV demonstrated moderately prolonged total RV endocardial activation time of 82 ms in sinus rhythm versus <65 ms recorded in healthy controls 20 . Furthermore, the maximum endocardial activation gradient was only 0.22 mm/ms, which is 40% of that recorded in healthy controls by our group using this technique (0.51 ± 0.15 mm/ms) 21 . Fractionated and low-amplitude electrograms also were identified in the posterior RV wall and posterolateral RV outflow tract segments (Figure 1).…”

Section: Resultsmentioning

confidence: 40%

A novel desmocollin-2 mutation reveals insights into the molecular link between desmosomes and gap junctions

et al. 2011

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BackgroundCellular adhesion mediated by cardiac desmosomes is a prerequisite for proper electric propagation mediated by gap junctions in the myocardium. However, the molecular principles underlying this interdependence are not fully understood.ObjectiveThe purpose of this study was to determine potential causes of right ventricular conduction abnormalities in a patient with borderline diagnosis of arrhythmogenic right ventricular cardiomyopathy.MethodsTo assess molecular changes, the patient's myocardial tissue was analyzed for altered desmosomal and gap junction (connexin43) protein levels and localization. In vitro functional studies were performed to characterize the consequences of the desmosomal mutations.ResultsLoss of plakoglobin signal was evident at the cell junctions despite expression of the protein at control levels. Although the distribution of connexin43 was not altered, total protein levels were reduced and changes in phosphorylation were observed. The truncation mutant in desmocollin-2a is deficient in binding plakoglobin. Moreover, the ability of desmocollin-2a to directly interact with connexin43 was abolished by the mutation. No pathogenic potential of the desmoglein-2 missense change was identified.ConclusionThe observed abnormalities in gap junction protein expression and phosphorylation, which precede an overt cardiac phenotype, likely are responsible for slow myocardial conduction in this patient. At the molecular level, altered binding properties of the desmocollin-2a mutant may contribute to the changes in connexin43. In particular, the newly identified interaction between the desmocollin-2a isoform and connexin43 provides novel insights into the molecular link between desmosomes and gap junctions.

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“…119 The investigators identified marked regional endocardial conduction delay and heterogeneities in repolarisation in patients with BrS and proposed that the slow-conduction zones may have a role in the initiation and maintenance of ventricular arrhythmias.…”

Section: Inherited Arrhythmogenic Diseasesmentioning

confidence: 99%

Almanac 2011: Cardiac Arrhythmias and Pacing. The National Society Journals Present Selected Research that has Driven Recent Advances in Clinical Cardiology

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2011

Mater Sociomed

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High-Density Substrate Mapping in Brugada Syndrome

Cited by 144 publications

References 40 publications

Cardiac Electrophysiological Substrate Underlying the ECG Phenotype and Electrogram Abnormalities in Brugada Syndrome Patients

Cardiac Electrophysiological Substrate Underlying the ECG Phenotype and Electrogram Abnormalities in Brugada Syndrome Patients

A novel desmocollin-2 mutation reveals insights into the molecular link between desmosomes and gap junctions

Almanac 2011: Cardiac Arrhythmias and Pacing. The National Society Journals Present Selected Research that has Driven Recent Advances in Clinical Cardiology

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