Brugada syndrome (BrS) is a rare autosomal dominant inherited channel disorder characterized by a specific electrocardiographic pattern of right precordial ST-segment elevation. Clinically, patients may experience polymorphic ventricular tachycardia and ventricular fibrillation, leading to recurrent syncope and sudden cardiac death (SCD) in the absence of structural cardiomyopathy. The A-kinase anchor protein 9 (AKAP9) gene, located on chromosome 7, encodes the AKAP9 protein, which plays a crucial role in regulating the phosphorylation of slowly activating delayed rectifier potassium channels (IKs). Here, we present a rare case of BrS associated with an insertion mutation in AKAP9, resulting in a frameshift mutation.

Brugada syndrome (BrS) is an inherited arrhythmogenic disorder marked by distinctive ST-segment elevations on electrocardiograms (ECG) and an increased risk of sudden cardiac death. Characterized by mutations primarily in the SCN5A gene, BrS disrupts cardiac ion channel function, leading to abnormal electrical activity and arrhythmias. Although BrS primarily affects young, healthy males, it poses significant diagnostic challenges due to its often concealed or intermittent ECG manifestations and clinical presentation that can mimic other cardiac disorders. Current management strategies focus on symptom control and prevention of sudden death, with implantable cardioverter-defibrillators (ICD) serving as the primary intervention for high-risk patients. However, the complications associated with ICDs and the lack of effective pharmacological options necessitate a cautious and personalized approach. Recent advancements in catheter ablation have shown promise, particularly for managing ventricular fibrillation (VF) storms and reducing ICD shocks. Additionally, pharmacological treatments such as quinidine have been effective in specific cases, though their use is limited by availability and side effects. This review highlights significant gaps in the BrS literature, particularly in terms of long-term management and novel therapeutic approaches. The importance of genetic screening and tailored treatment strategies to better identify and manage at-risk individuals is emphasized. The review aims to enhance the understanding of BrS and improve patient outcomes, advocating for a multidisciplinary approach to this complex syndrome.

We describe the case of a 28-year-old man with Brugada syndrome who received single-shot adductor canal and sciatic nerve blocks for the management of post-operative pain related to extensive orthopedic injuries. Low-dose ropivacaine with glucocorticoid additives was administered without any EKG changes, arrhythmias, or syncopal sensations. The patient experienced pain relief for over 24 h and was monitored on telemetry with defibrillator pads as a cardiac precaution. This case adds a valuable data point in the limited canon of information on the safety and efficacy of regional anesthesia in Brugada syndrome for the perioperative physician.

BACKGROUND Brugada syndrome is characterized by specific electrocardiographic changes predisposing individuals to ventricular arrhythmias and sudden cardiac death. Cases of coexisting Brugada syndrome and ischemic stroke are seldom documented, and an underlying pathophysiological link is yet unknown. This article presents a case in which a patient exhibited both Brugada syndrome patterns and an ischemic stroke, prompting a comprehensive literature review to explore the potential association between Brugada syndrome and ischemic stroke. CASE REPORT A 49-year-old man, previously healthy, was admitted to the hospital after being discovered unconscious at his workplace. Physical exam showed low oxygen saturation, fever, and abnormal neurological findings. Head computed tomography revealed a significant posterior circulation ischemic stroke. An electrocardiogram revealed Brugada syndrome type II initially, progressing to type III pattern. Despite efforts, the patient\'s condition rapidly deteriorated, leading to death within 24 hours. As far as we\'re aware, Brugada patterns following a posterior circulation ischemic stroke have only been documented in 1 other instance, in which the patient was also diagnosed with atrial fibrillation. CONCLUSIONS Both our literature review and the presented case indicate that Brugada patterns may coexist with and even be associated with ischemic stroke. More extensive research is required to shed light on this potential association. The question of whether Brugada syndrome is a precursor to or a result of ischemic stroke remains unanswered. We propose that patients with ischemic stroke should undergo an evaluation for electrocardiographic signs indicative of Brugada syndrome, particularly if no clear causes, like cardioembolism, are evident.

BACKGROUND: Brugada syndrome (BrS) is an inherited arrhythmogenic syndrome characterized by cove-shaped ST-segment elevation in leads V1-V3 and incomplete or complete right bundle branch block. BrS exhibits autosomal dominant inheritance with incomplete penetrance and a male predominance. It carries a significant risk of sudden cardiac death due to ventricular fibrillation (VF).
METHODS: Recent studies have highlighted the presence of epicardial fibrosis as a proarrhythmic substrate in BrS, revolutionizing our understanding of the disease\'s pathophysiology. Catheter ablation has emerged as a crucial intervention for symptomatic BrS patients experiencing recurrent episodes of ventricular tachycardia (VT) or VF. By potentially obviating the need for implantable cardioverter-defibrillator (ICD) implantation, epicardial ablation offers a promising therapeutic approach.
CONCLUSIONS: This review emphasizes the significance of current evidence and ongoing research in shaping the role of epicardial ablation as a curative strategy in BrS management, highlighting its potential benefits and the necessity for further investigation.

BACKGROUND: A rare gene variant in SCN5A can be found in approximately 20%-25% of patients with Brugada syndrome (BrS).
OBJECTIVE: The aim of this systematic review and meta-analysis was to evaluate the differences in clinical characteristics of BrS patients with and without SCN5A rare variants and the prognostic role of SCN5A for ventricular arrhythmias in BrS.
METHODS: PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) were systematically searched from inception to January 2024 to identify all relevant studies. Studies were analyzed if they included patients diagnosed with BrS in whom genetic testing for SCN5A variants was performed and arrhythmic outcomes were reported.
RESULTS: A total of 17 studies with 3568 BrS patients, of whom 3030 underwent genetic testing for SCN5A variants, fulfilled the eligibility criteria and were included. Compared with SCN5A- patients, SCN5A+ BrS patients more frequently had spontaneous type 1 electrocardiogram, history of syncope, and documented arrhythmias. Furthermore, higher PQ and QRS intervals in SCN5A+ BrS patients compared with SCN5A- have been found. The pooled analysis demonstrated a significant association between the presence of SCN5A rare variants in BrS patients and the risk of major arrhythmic events, with a pooled odds ratio of 2.14 (95% confidence interval, 1.53-2.99; I2 = 29%).
CONCLUSIONS: SCN5A+ BrS patients showed a worse clinical phenotype compared with SCN5A-. The pooled analysis demonstrated a significant association between SCN5A+ mutation status and the risk of major arrhythmic events in BrS patients.

The development of the cardiogenetics field in Germany has been increasing since the mid-1990s with many national contributions, some of them were really important and groundbreaking. The starting point was and still is the patient and his family, e.g. with a familial form of arrhythmia or cardiomyopathy, the clarification of the genetic cause and the personalized treatment of those being affected. The scientific, always translationally oriented interest in identifying a causative gene and uncovering the underlying pathomechanisms has led to notable contributions for Brugada syndrome, short QT syndrome and cardiac conduction disorders or sinus node dysfunction, but also in DCM or ARVC. What is important, however, is always the way back (bench > bed side): implementation of national and international recommendations for cardiogenetic diagnostics in daily cardiological routine and the personalized care and therapy of those being affected.
UNASSIGNED: Die Entwicklung des Kardiogenetik in Deutschland hat seit der Mitte der 90er Jahre eine zunehmende Entwicklung mit vielen eigenen, zum Teil wichtigen und wegweisenden Beiträge. Ausgangspunkt war und ist immer noch der Patient mit seiner Familie, z. B. mit einer familiären Arrhythmieform oder einer Kardiomyopathie, die Aufklärung der genetischen Ursache und die personalisierte Behandlung der Betroffenen.  Das wissenschaftliche, immer transnational orientierte Interesse, ein ursächliches Gen zu identifizieren und den zugrundeliegenden Pathomechanismus aufzudecken, hat beim Brugada-Syndrom, Kurzen QT-Syndrom und Erregungsleitungsstörung oder Sinusknotendysfunktion, aber auch bei DCM oder ARVC zu beachteten Beiträgen geführt. Wichtig ist jedoch der Weg zurück (bench > bed side): Implementierung von nationalen wie internationalen Empfehlungen zur kardiogenetischen Diagnostik in die kardiologische Versorgung und die personalisierte Betreuung und Therapie Betroffener.

Brugada syndrome (BrS) is an inherited disorder that can cause ventricular fibrillation and sudden cardiac death in individuals with otherwise structurally normal hearts. Several provoking factors are known to potentially unmask or exacerbate a typical Brugada ECG pattern in predisposed subjects. Hypothyroidism has been suggested as one of these triggers, but the exact mechanisms underlying this relationship remain poorly understood. Moreover, the severity of thyroid dysfunction beyond which a Brugada-type ECG alteration might be triggered is still unclear. We report the case of a 33-year-old male who displayed a Brugada type 1 ECG pattern and was diagnosed with severe hypothyroidism (TSH > 100 mU/L with undetectable levels of fT4 and fT3). Hormonal replacement therapy with levothyroxine was initiated at increasing doses; serial biochemical and ECG controls were performed, initially every 3 weeks up to 15 weeks and afterward every 3 months. The regression of typical Brugada ECG waveforms could be seen at an early stage, when the patient was still taking a low dose of levothyroxine (37.5 µg/day, i.e., one-fourth of his final requirements of 150 µg/day), and laboratory tests still showed a marked alteration of thyroid hormonal parameters. Hypothyroidism may act as a trigger for Brugada-type ECG abnormalities, but a very severe alteration of the hormonal parameters is necessary to prompt these alterations. In our case, the initiation of replacement therapy with levothyroxine rapidly reversed the ECG modifications, even at a low subtherapeutic dose.

UNASSIGNED: Inherited Primary Arrhythmias Syndromes (IPAS), especially Brugada syndrome (BrS), have been associated with arrhythmogenic substrates that can be targeted through ablation. This meta-analysis evaluated the outcomes of catheter ablation (CA) in different types of IPAS based on procedural guidance and location.
UNASSIGNED: A systematic search was conducted across multiple databases to identify studies reporting on ventricular arrhythmia (VA) events before and after CA in IPAS, including BrS, Long-QT syndrome (LQTS), Early repolarization syndrome (ERS), and Idiopathic ventricular fibrillation (IVF). The primary outcomes were VA recurrence and VA burden, evaluated through conditional subgroup analysis. Procedural data were collected as secondary outcomes.
UNASSIGNED: A total of 21 studies involving 584 IPAS patients who underwent CA were included. Following a mean follow-up duration of 33.5 months, substrate-based ablation demonstrated efficacy in reducing VA recurrence across all types of IPAS [RR 0.23; 95% CI (0.13-0.39); p < .001; I 2 = 74%]. However, activation guidance ablation was found to be effective only in IVF cases. Although recurrences still occurred, CA was successful in reducing VA burden [MD -4.70; 95% CI (-6.11-(-3.29); p < .001; I 2 = 74%]. The mean size of arrhythmogenic substrate was 15.70 cm2 [95% CI (12.34-19.99 cm2)], predominantly distributed in the epicardial right ventricular outflow tract (RVOT) in BrS cases and LQTS [Proportion 0.99; 95% CI (0.96-1.00) and Proportion 0.82; 95% CI ( 0.59-1.00), respectively].
UNASSIGNED: Substrate-based CA has demonstrated effective prevention of VA and reduction in VA burden in IPAS cases.

Brugada syndrome is characterized by pronounced J-ST segment elevation in the right precordial leads on surface electrocardiograms. The etiological underpinnings of these distinctive features have been the subject of extensive debate, encompassing various theories related to repolarization anomalies and conduction irregularities. Genetic investigations have unveiled SCN5A, the gene encoding NaV1.5, a critical sodium channel, as the most frequently implicated causative gene, with mutations typically manifesting as loss of function. Nonetheless, the detection rate of SCN5A mutations remains below 20%, underscoring the intricate genetic landscape of the syndrome. Histological analyses have divulged localized structural irregularities, primarily marked by fibrotic alterations, within the right ventricular outflow tract. Electrophysiological inquiries employing direct epicardial mapping techniques have uncovered localized conduction impediments concomitant with modifications in unipolar morphologies within the J-ST segment. Thus, the theory positing conduction abnormalities emerges as a compelling mechanism accounting for J-ST segment elevation. However, the precise mechanisms governing the onset of life-threatening tachyarrhythmias remain shrouded in uncertainty. Recent clinical case reports have proffered evidence supporting the notion that phase 2 reentry, arising from the marked heterogeneity in action potentials within the epicardial domain, may serve as the instigator of premature ventricular contractions, ultimately culminating in ventricular fibrillation. In light of these developments, it becomes increasingly evident that comprehending the mechanisms underlying the electrocardiographic manifestations and lethal arrhythmias in Brugada syndrome necessitates the consideration of a multifaceted perspective, transcending the binary discourse of repolarization versus depolarization anomalies.