Brugada syndrome in childhood: a potential fatal arrhythmia not always recognised by paediatricians. A case report and review of the literature

We report on a youngster followed by his paediatrician from birth until 14years of age for premature beats, most likely of ventricular origin. The sudden death of his sister provoked a re-assessment of his electrocardiograms (ECG), resulting in the diagnosis of Brugada syndrome and the subsequent implantation of a cardioverter defibrillator. This syndrome is a well known entity in adult cardiology, first described by Brugada and Brugada in 1992. It is considered to be the second most common cause of death in young adults after road traffic accidents. In children, however, the Brugada syndrome is not well known and we believe to be certainly underdiagnose

The role of exercise testing in congenital heart disease patients after coronary artery reimplantation

Introduction: The Ross procedure requires like the arterial switch operation (ASO) coronary artery reimplantation. There is no information on coronary artery stenosis at the site of the reimplantation in Ross patients as has been described for ASO patients. This study assessed therefore the prevalence of positive exercise tests (pETs) suggesting myocardial ischemia in Ross and ASO patients in comparison to tetralogy of Fallot patients (TOF), the latter not undergoing coronary artery reimplantation. The study evaluated further, whether a coronary artery complication was confirmed by a supplementary non- and/or invasive evaluation. Methods: Results of exercise tests, echocardiography, coronary computed tomography (CCT) and coronary angiography (CA) were retrospectively reviewed in 30 Ross, 14 ASO and 30 TOF patients. Results: Exercise capacity did not differ between groups. There was a trend to more frequent pETs in Ross patients (Ross vs. ASO vs. TOF, N, %): 8 (27) vs. 1 (7) vs. 2 (7) p = 0.062. CCT was performed in 30% Ross, 21% ASO, 3% TOF (p = 0.023); CA in 20% Ross, 21% ASO and 13% TOF patients (p = 0.727). None of these investigations revealed a coronary artery stenosis. Patients with pET showed a higher right ventricular outflow tract (RVOT) gradient (44 ± 30 vs. 22 ± 13 mmHg, p = 0.004) and more frequently a severe RVOT stenosis (27 vs. 0%, p < 0.006). Conclusions: pETs are rather related to RVOT stenosis than to coronary artery complications after Ross procedure, ASO and TOF repair. The role of exercise testing for detection of myocardial ischemia is limited and should be restricted to evaluation of exercise capacity

Analyses of a novel SCN5A mutation (C1850S): conduction vs. repolarization disorder hypotheses in the Brugada syndrome

Aims Brugada syndrome (BrS) is characterized by arrhythmias leading to sudden cardiac death. BrS is caused, in part, by mutations in the SCN5A gene, which encodes the sodium channel alpha-subunit Nav1.5. Here, we aimed to characterize the biophysical properties and consequences of a novel BrS SCN5A mutation. Methods and results SCN5A was screened for mutations in a male patient with type-1 BrS pattern ECG. Wild-type (WT) and mutant Nav1.5 channels were expressed in HEK293 cells. Sodium currents (INa) were analysed using the whole-cell patch-clamp technique at 37°C. The electrophysiological effects of the mutation were simulated using the Luo-Rudy model, into which the transient outward current (Ito) was incorporated. A new mutation (C1850S) was identified in the Nav1.5 C-terminal domain. In HEK293 cells, mutant INa density was decreased by 62% at −20 mV. Inactivation of mutant INa was accelerated in a voltage-dependent manner and the steady-state inactivation curve was shifted by 11.6 mV towards negative potentials. No change was observed regarding activation characteristics. Altogether, these biophysical alterations decreased the availability of INa. In the simulations, the Ito density necessary to precipitate repolarization differed minimally between the two genotypes. In contrast, the mutation greatly affected conduction across a structural heterogeneity and precipitated conduction block. Conclusion Our data confirm that mutations of the C-terminal domain of Nav1.5 alter the inactivation of the channel and support the notion that conduction alterations may play a significant role in the pathogenesis of Br

Decreased Excitability as a Protective Mechanism Against Repolarization Alternans-Induced Atrial Reentry

Introduction: We recently observed in human left atrium periods of intermittent 2:1 and 1:1 atrial capture, preceded by atrial repolarization alternans (Re-ALT) during rapid pacing. It remains undetermined whether Re- ALT plays a role in preventing 1:1 atrial capture over long periods of rapid pacing. Methods: We specifically developed a chronic ovine model of rapid atrial pacing using two pacemakers (PM) each with a single right atrial (RA) lead separated by ~2 cm. The 1st PM was used to record a broadband unipolar RA EGM and the 2nd one to deliver rapid pacing protocols (400 beats) at incremental rates. Activation time (AT), activation recovery interval (ARI) and beat-to-beat differences in atrial T-wave apex amplitude (ΔTa) were analyzed until the 1st beat of 2:1 capture. Results: Intermittent 2:1 capture (panel A of figure) was observed in all sheep (n=9) at a mean pacing CL of 156±26 ms. 167 episodes of intermittent 2:1 capture were analyzed. Importantly, atrial Re-ALT (panel B of figure) was observed before 2:1 capture in 73% and AT prolongation in 55% of the sequences. Only 10% of sequences showed an absence of Re-ALT and AT prolongation. Conclusions: Using an ovine model of rapid atrial pacing, our findings suggest that Re-ALT may be a mechanism causing transition from rapid 1:1 atrial capture to 2:1 capture. Because rapid atrial tachycardia slows propagation velocity and promotes fibrillatory conduction, transitions to 2:1 capture may reduce susceptibility to atrial fibrillation

Mechano-electrical contribution of ventricular contractions to the complexity of atrial fibrillation electrograms

Purpose: Intracardiac organization indices (OI) have been used to track the efficiency of stepwise radiofrequency catheter ablation (step-CA) of persistent atrial fibrillation (pers-AF). A better understanding of the components and complexity of AF electrograms (EGMs) is fundamental for tracking the organization of AF. It remains unknown whether ventricular contractions affect the complexity of AF EGMs by means of mechano-eletrical feedback. Our study is aimed at developing new methods to quantify the potential mechano-electrical contribution of ventricular contractions on AF complexity. Methods: During step-CA, a quadripolar catheter was placed into the right atrial appendage (RAA). Robust maximum positive peak detection was applied. The time difference between two adjacent peaks was regularly resampled resulting in the intra-cardiac variability (ICV) signal. ICV reflects the intrinsic atrial activation time variability as well as the potential mechano-electrical feedback of ventricular contractions (VC). A lowpass version impulses series of R wave locations was used as input to an adaptive interference canceller in order to suppress the VC contribution to ICV (VC-ICV). Results: Step-CA (including PVI, CFAE, roof and mitral isthmus lines) terminated 2/3 pers-AF into flutter. The mean contribution of the mechano-electrical feedback on AF complexity achieved 37%. The figure shows a representative example where the VC component (2.03 Hz) has been removed from the ICV, resulting in the atrial-ICV. All other components have been preserved. Conclusions: Our preliminary findings suggest that by means of mechano-electrical feedback, VC contribute up to 37% of the atrial complexity during pers-AF. It is also a first step in the elaboration of new organization indices free of ventricular contribution

Contribution of Left and Right Atrial Appendage Activities to ECG Fibrillation Waves

It was recently shown that atrial fibrillation (AF) waves on chest lead V1 adequately reflect right atrial appendage (RAA) activity during long standing persistent AF (pers-AF). The contribution of the left atrial (LA) activity to chest leads AF waves, however, remains unknown. Our study is aimed at evaluating the respective contribution of the RA and LA depolarization to ECG chest leads AF waves during pers-AF. Methods: Catheters (CAT) were introduced in 10 consecutive patients (60±5 y, AF duration 22±14 m) prior to ablation: 1) a quadripolar CAT in the RAA, 2) a decapolar CAT in the coronary sinus (CS) and 3) a duodecapolar CAT in the LA appendage (LAA). Local activation times were extracted from bipolar recordings using sliding windows. Chest lead V6 was placed in the back (V6b). Mean AF cycle length (AFCL) of leads V1 to V6b were computed as the inverse of the dominant frequency of ECG spectra after QRST cancellation, and compared to intracardiac RAA, LAA and CS AFCL using Pearson’s correlation coefficient. Results: The figure shows that the correlation between RAA and chest leads AFCL was maximal for V1 and progressively dropped till V5, with a moderate rise for V6b. LAA AFCL showed the opposite pattern with the highest correlation in V6B and the lowest one in V2. The correlation of CS AFCL was similar to the LAA one, but of lower magnitude. Conclusion: Our preliminary results suggest that the respective contribution of RAA and LAA activities can be estimated using a modified surface ECG. Whether this technique has the potential to guide ablation of LA and RA drivers in pers-AF needs further validation

Morphological Study of Intracardiac Signals as a New Tool to Track the Efficiency of Stepwise Ablation of Persistent Atrial Fibrillation

Intracardiac organization indices such as atrial fibrillation (AF) cycle length (AFCL) have been used to track the efficiency of stepwise catheter ablation (step-CA) of longstanding persistent AF, however with limited success. The morphology of AF activation waves reflects the underlying activation patterns. Its temporal evolution is a local organization indicator that could be potentially used for tracking the efficiency of step-CA. We report a new method for characterizing the structure of the temporal evolution of activation wave morphology. Using recurrence plots, novel organization indices are proposed. By computing their relative evolution during the first step of ablation vs baseline, we found that these new parameters are superior to AFCL to track the effect of step-CA “en route” to AF termination