Ajmaline‐Induced Abnormalities in Brugada Syndrome: Evaluation With ECG Imaging

Background The rate of sudden cardiac death (SCD) in Brugada syndrome (BrS) is ≈1%/y. Noninvasive electrocardiographic imaging is a noninvasive mapping system that has a role in assessing BrS depolarization and repolarization abnormalities. This study aimed to analyze electrocardiographic imaging parameters during ajmaline test (AJT). Methods and Results All consecutive epicardial maps of the right ventricle outflow tract (RVOT‐EPI) in BrS with CardioInsight were retrospectively analyzed. (1) RVOT‐EPI activation time (RVOT‐AT); (2) RVOT‐EPI recovery time, and (3) RVOT‐EPI activation‐recovery interval (RVOT‐ARI) were calculated. ∆RVOT‐AT, ∆RVOT‐EPI recovery time, and ∆RVOT‐ARI were defined as the difference in parameters before and after AJT. SCD‐BrS patients were defined as individuals presenting a history of aborted SCD. Thirty‐nine patients with BrS were retrospectively analyzed and 12 patients (30.8%) were SCD‐BrS. After AJT, an increase in both RVOT‐AT [105.9 milliseconds versus 65.8 milliseconds, P <0.001] and RVOT‐EPI recovery time [403.4 milliseconds versus 365.7 milliseconds, P <0.001] was observed. No changes occurred in RVOT‐ARI [297.5 milliseconds versus 299.9 milliseconds, P =0.7]. Before AJT no differences were observed between SCD‐BrS and non SCD‐BrS in RVOT‐AT, RVOT‐EPI recovery time, and RVOT‐ARI ( P =0.9, P =0.91, P =0.86, respectively). Following AJT, SCD‐BrS patients showed higher RVOT‐AT, higher ∆RVOT‐AT, lower RVOT‐ARI, and lower ∆RVOT‐ARI ( P <0.001, P <0.001, P =0.007, P =0.002, respectively). At the univariate logistic regression, predictors of SCD‐BrS were the following: RVOT‐AT after AJT (specificity: 0.74, sensitivity 1.00, area under the curve 0.92); ∆RVOT‐AT (specificity: 0.74, sensitivity 0.92, area under the curve 0.86); RVOT‐ARI after AJT (specificity 0.96, sensitivity 0.58, area under the curve 0.79), and ∆RVOT‐ARI (specificity 0.85, sensitivity 0.67, area under the curve 0.76). Conclusions Noninvasive electrocardiographic imaging can be useful in evaluating the results of AJT in BrS.

Incidental Findings of Brugada Syndrome Type-1 and Epsilon-Like Pattern in Otherwise Healthy Man: a Case Report

Background: Brugada Syndrome (BrS) and arrhythmogenic right ventricle dysplasia (ARVD) are rare cardiomyopathies predisposing to sudden cardiac death (SCD). Comprehending the electrocardiographic features of these cardiomyopathies are crucial especially in emergency settings.Case presentation: A 25-year old medical student presented with no complaints, but had episodes of syncope, chest pain, and palpitations of unknown origin 10 years ago. The initial assessment showed stable hemodynamics. During examination, the ECG demonstrated incomplete right bundle branch block, Brugada-type 1 pattern, with signs of Epsilon wave. The following year, assessment of the ECG was repeated and findings were found suggestive of Brugada syndrome, although his echocardiography showed no structural abnormality. According to ESC guidelines, asymptomatic Brugada patients should undergo electrophysiology study.Conclusion: Careful follow-up with electrophysiology study is recommended for this patient in order to identify the likelihood of true Brugada and suitability for radiofrequency ablation or implantation of implantable cardioverter defibrillator (ICD).

Why Is Only Type 1 Electrocardiogram Diagnostic of Brugada Syndrome? Mechanistic Insights From Computer Modeling

Background: Three types of characteristic ST-segment elevation are associated with Brugada syndrome but only type 1 is diagnostic. Why only type 1 ECG is diagnostic remains unanswered. Methods: Computer simulations were performed in single cells, 1-dimensional cables, and 2-dimensional tissues to investigate the effects of the peak and late components of the transient outward potassium current (I to ), sodium current, and L-type calcium current (I Ca,L ) as well as other potassium currents on the genesis of ECG morphologies and phase 2 reentry (P2R). Results: Although a sufficiently large peak I to was required to result in the type 1 ECG pattern and P2R, increasing the late component of I to converted type 1 ECG to type 2 ECG and suppressed P2R. Increasing the peak I to promoted spiral wave breakup, potentiating the transition from tachycardia to fibrillation, but increasing the late I to prevented spiral wave breakup by flattening the action potential duration restitution and preventing P2R. A sufficiently large I Ca,L conductance was needed for P2R to occur, but once above the critical conductance, blocking I Ca,L promoted P2R. However, selectively blocking the window and late components of I Ca,L suppressed P2R, countering the effect of the late I to . Blocking either the peak or late components of sodium current promoted P2R, with the late sodium current blockade having the larger effect. As expected, increasing other potassium currents potentiated P2R, with ATP-sensitive potassium current exhibiting a larger effect than rapid and slow component of the delayed rectifier potassium current. Conclusions: The peak I to promotes type 1 ECG and P2R, whereas the late I to converts type 1 ECG to type 2 ECG and suppresses P2R. Blocking the peak I Ca,L and either the peak or the late sodium current promotes P2R, whereas blocking the window and late I Ca,L suppresses P2R. These results provide important insights into the mechanisms of arrhythmogenesis and potential therapeutic targets for treatment of Brugada syndrome.

The Mechanism of Ajmaline and Thus Brugada Syndrome: Not Only the Sodium Channel!

Ajmaline is an anti-arrhythmic drug that is used to unmask the type-1 Brugada syndrome (BrS) electrocardiogram pattern to diagnose the syndrome. Thus, the disease is defined at its core as a particular response to this or other drugs. Ajmaline is usually described as a sodium-channel blocker, and most research into the mechanism of BrS has centered around this idea that the sodium channel is somehow impaired in BrS, and thus the genetics research has placed much emphasis on sodium channel gene mutations, especially the gene SCN5A, to the point that it has even been suggested that only the SCN5A gene should be screened in BrS patients. However, pathogenic rare variants in SCN5A are identified in only 20–30% of cases, and recent data indicates that SCN5A variants are actually, in many cases, prognostic rather than diagnostic, resulting in a more severe phenotype. Furthermore, the misconception by some that ajmaline only influences the sodium current is flawed, in that ajmaline actually acts additionally on potassium and calcium currents, as well as mitochondria and metabolic pathways. Clinical studies have implicated several candidate genes in BrS, encoding not only for sodium, potassium, and calcium channel proteins, but also for signaling-related, scaffolding-related, sarcomeric, and mitochondrial proteins. Thus, these proteins, as well as any proteins that act upon them, could prove absolutely relevant in the mechanism of BrS.

Association of atrial septal defect and Brugada syndrome in a young woman

We report a 25-year-old woman who was diagnosed with atrial septal defect (ASD). An ECG showed only first-degree atrioventricular block and incomplete right bundle branch block. One day after the percutaneous ASD closure, she had a slight fever and an ECG showed a type 1 Brugada pattern. ECG characteristics of ASD are similar to those of a Brugada ECG. This case is rare combination of Brugada syndrome with ASD.