scholarly journals Brugada syndrome genetics is associated with phenotype severity

2020 ◽  
Author(s):  
Giuseppe Ciconte ◽  
Michelle M Monasky ◽  
Vincenzo Santinelli ◽  
Emanuele Micaglio ◽  
Gabriele Vicedomini ◽  
...  
Keyword(s):  
Brugada Syndrome ◽  
Phenotypic Expression ◽  
Genetic Determinants ◽  
Phenotype Correlation ◽  
Main Determinant ◽  
Non Invasive ◽  
Increased Risk ◽  
Arrhythmogenic Substrate ◽  
Scn5a Mutation

Abstract Aims  Brugada syndrome (BrS) is associated with an increased risk of sudden cardiac death due to ventricular tachycardia/fibrillation (VT/VF) in young, otherwise healthy individuals. Despite SCN5A being the most commonly known mutated gene to date, the genotype–phenotype relationship is poorly understood and remains uncertain. This study aimed to elucidate the genotype–phenotype correlation in BrS. Methods and results Brugada syndrome probands deemed at high risk of future arrhythmic events underwent genetic testing and phenotype characterization by the means of epicardial arrhythmogenic substrate (AS) mapping, and were divided into two groups according to the presence or absence of SCN5A mutation. Two-hundred probands (160 males, 80%; mean age 42.6 ± 12.2 years) were included in this study. Patients harbouring SCN5A mutations exhibited a spontaneous type 1 pattern and experienced aborted cardiac arrest or spontaneous VT/VF more frequently than the other subjects. SCN5A-positive patients exhibited a larger epicardial AS area, more prolonged electrograms and more frequently observed non-invasive late potentials. The presence of an SCN5A mutation explained >26% of the variation in the epicardial AS area and was the strongest predictor of a large epicardial area. Conclusion  In BrS, the genetic background is the main determinant for the extent of the electrophysiological abnormalities. SCN5A mutation carriers exhibit more pronounced epicardial electrical abnormalities and a more aggressive clinical presentation. These results contribute to the understanding of the genetic determinants of the BrS phenotypic expression and provide possible explanations for the varying degrees of disease expression.

scholarly journals Novel CineECG Derived From Standard 12-Lead ECG Enables Right Ventricle Outflow Tract Localization of Electrical Substrate in Patients With Brugada Syndrome

2020 ◽  
Vol 13 (9) ◽  
Author(s):  
Peter M. van Dam ◽  
Emanuela T. Locati ◽  
Giuseppe Ciconte ◽  
Valeria Borrelli ◽  
Francesca Heilbron ◽  
...  
Keyword(s):  
Right Ventricle ◽  
Brugada Syndrome ◽  
Predictive Value ◽  
Normal Subjects ◽  
Outflow Tract ◽  
Arrhythmogenic Substrate ◽  
The Right ◽  
Type 3 ◽  
Electrocardiogram Ecg

Background: In Brugada syndrome (BrS), diagnosed in presence of a spontaneous or ajmaline-induced type-1 pattern, ventricular arrhythmias originate from the right ventricle outflow tract (RVOT). We developed a novel CineECG method, obtained by inverse electrocardiogram (ECG) from standard 12-lead ECG, to localize the electrical activity pathway in patients with BrS. Methods: The CineECG enabled the temporospatial localization of the ECG waveforms, deriving the mean temporospatial isochrone from standard 12-lead ECG. The study sample included (1) 15 patients with spontaneous type-1 Brugada pattern, and (2) 18 patients with ajmaline-induced BrS (at baseline and after ajmaline), in whom epicardial potential duration maps were available; (3) 17 type-3 BrS pattern patients not showing type-1 BrS pattern after ajmaline (ajmaline-negative); (4) 47 normal subjects; (5) 18 patients with right bundle branch block (RBBB). According to CineECG algorithm, each ECG was classified as Normal, Brugada, RBBB, or Undetermined. Results: In patients with spontaneous or ajmaline-induced BrS, CineECG localized the terminal mean temporospatial isochrone forces in the RVOT, congruent with the arrhythmogenic substrate location detected by epicardial potential duration maps. The RVOT location was never observed in normal, RBBB, or ajmaline-negative patients. In most patients with ajmaline-induced BrS (78%), the RVOT location was already evident at baseline. The CineECG classified all normal subjects and ajmaline-negative patients at baseline as Normal or Undetermined, all patients with RBBB as RBBB, whereas all patients with spontaneous and ajmaline-induced BrS as Brugada. Compared with standard 12-lead ECG, CineECG at baseline had a 100% positive predictive value and 81% negative predictive value in predicting ajmaline test results. Conclusions: In patients with spontaneous and ajmaline-induced BrS, the CineECG localized the late QRS activity in the RVOT, a phenomenon never observed in normal, RBBB, or ajmaline-negative patients. The possibility to identify the RVOT as the location of the arrhythmogenic substrate by the noninvasive CineECG, based on the standard 12-lead ECG, opens new prospective for diagnosing patients with BrS.

P947dST-Tiso index, a new shallow ECG marker in response to ajmaline for predicting ventricular fibrillation induction in Brugada patients

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
S Iacopino ◽  
P Sorrenti ◽  
G Fabiano ◽  
G Campagna ◽  
A Petretta ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ventricular Fibrillation ◽  
Brugada Syndrome ◽  
Drug Induced ◽  
Non Invasive ◽  
T Wave ◽  
First Case ◽  
Potential Risk Factors

Abstract Introduction - No study has been performed to investigate the role of drug-induced ECG morphology modifications as potential risk factors for the development of malignant arrhythmias in patients with Brugada syndrome. Purpose - The aim of this study is to introduce a new index to improve asymptomatic patient stratification  and to report the first case of a patient with Brugada syndrome undergoing ajmaline testing that has been evaluated using a diagnostic 252-lead ECG vest. Methods - From December 2018 to April 2019, 26 consecutive patients [mean age 39.9 (30–59) years, 18 male] with no cardiovascular risk factors underwent ajmaline testing. By evaluating ECG recordings after ajmaline administration, we calculated an index that we called "dST-Tiso", that is the duration of the positive component of the ST-T wave to the isoelectric line, in V1 and/or V2. Results- Out of 26 patients, 16 (61.5%) had a positive test, with type 1 (coved-type) ECG diagnostic pattern in leads V1-V2 from the 2nd, 3rd and 4th intercostal spaces.  The mean recorded dST-Tiso value was 239 ± 76 ms. The ECG showed T-wave above the isoelectric line in 5 patients with a significantly higher dST-Tiso value (on average 360 ± 56 ms), and biphasic T-waves below the isoelectric line in 11 patients with a dST-Tiso value of 209 ± 42 ms (Mann-Whitney, p = 0.039). All patients with positive ajmaline test underwent programmed electrical stimulation (PES). Ventricular fibrillation was induced during PES in all 5 patients with stretched dST-Tiso. In the remaining 11 patients without stretched dST-Tiso, no ventricular arrhythmia was induced by PES.  Fig 1 Moreover, using non-invasive high-density electrocardiographic mapping (252-lead ECG vest), 3 patients with dST-Tiso positive pattern received a second ajmaline protocol, with assessment of both the depolarization and repolarization phases. Conclusion - The ECG pattern of prolonged dST-Tiso seems to have a significant impact on safety during PES and may have potential for stratifying risk of sudden death in patients with PES-induced ventricular tachycardia/fibrillation. Abstract Figure 1. Patients’ flowchart.

Brugada Syndrome – Report of Familial Occurrence Diagnosed in the Emergency Department

2020 ◽  
Vol 6 (1) ◽  
pp. 17-19
Author(s):  
Mojtaba Fazel ◽  
Fatemeh Hamidi ◽  
Elham Afshari
Keyword(s):  
Emergency Department ◽  
Ventricular Fibrillation ◽  
Rare Disease ◽  
Male Patient ◽  
Brugada Syndrome ◽  
Genetic Disorder ◽  
Clinical Manifestations ◽  
St Segment ◽  
Increased Risk

AbstractIntroduction: Brugada syndrome represents the clinical manifestation of a rare disease with genetic etiology. The syndrome is characterized by ventricular dysrhythmias associated with syncope or sudden cardiac death in the lack of any structural cardiac disease. The diagnosis of Brugada syndrome is established if a type 1 electrocardiographic (ECG) pattern of ST-segment and QRS morphology is present, in association with certain clinical manifestations and/or familial history.Case presentation: A 31-year-old male patient, without any medical history, presented in the emergency department (ED) of a clinical center. His only complaints consisted in palpitations, chest discomfort, and emotional stress related to the recent death of his wife. Earlier on the same day, his wife, a 25-year-old female was brought via emergency medical services (EMS) to the ED after presenting ventricular fibrillation. The female patient presented a long term history of chest pain and one year prior to this episode she presented idiopathic ventricular fibrillation, for which she had undergone implantation of an automated cardioverter defibrillator. As the couple were cousins, the EMS specialist suspected the presence of a familial cardiac disorder. The electrocardiogram of the male patient revealed a coved-type ST-segment elevation of 4 mm in leads V1–V3 compatible with type 1 Brugada syndrome.Conclusion: In case of Brugada syndrome, a genetic disorder associated with increased risk of SCD, the patient's first-degree relatives should be investigated as well, in order to identify the presence of the syndrome and to prevent SCD. As the sole established effective therapeutic measure for patients diagnosed with Brugada syndrome, ICD implantation should be considered in order to decrease the risk of syncope and SCD. This case is particular because a rare disease with familial etiology was identified in both husband and wife, who were cousins.

Non-invasive assessment of the arrhythmogenic substrate in Brugada syndrome using signal-averaged electrocardiogram: clinical implications from a prospective clinical trial

EP Europace ◽  
2019 ◽  
Author(s):  
Giuseppe Ciconte ◽  
Vincenzo Santinelli ◽  
Gabriele Vicedomini ◽  
Valeria Borrelli ◽  
Michelle M Monasky ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Brugada Syndrome ◽  
Predictive Value ◽  
Area Under The Curve ◽  
Late Potentials ◽  
Non Invasive ◽  
Arrhythmogenic Substrate ◽  
Risk Stratification Tool ◽  
Group 2 ◽  
Group 1

Abstract Aims Brugada syndrome (BrS) represents a major cause of sudden cardiac death in young individuals. The risk stratification to forecast future life-threatening events is still controversial. Non-invasive assessment of late potentials (LPs) has been proposed as a risk stratification tool. However, their nature in BrS is still undetermined. The purpose of this study is to assess the electrophysiological determinants of non-invasive LPs. Methods and Results Two hundred and fifty consecutive patients with (Group 1, n = 96) and without (Group 2, n = 154) BrS-related symptoms were prospectively enrolled in the registry. Signal-averaged electrocardiogram (SAECG) was performed in all subjects before undergoing epicardial mapping. Group 1 patients exhibited larger arrhythmogenic substrates (AS; 5.8 ± 2.8 vs. 2.6 ± 2.1 cm2, P < 0.001) with more delayed potentials (220.4 ± 46.0 vs. 186.7 ± 42.3 ms, P < 0.001). Late potentials were present in 82/96 (85.4%) Group 1 and in 31/154 (20.1%) Group 2 individuals (P < 0.001). Patients exhibiting LPs had more frequently a spontaneous Type 1 pattern (30.1% vs. 10.9%, P < 0.001), SCN5A mutation (34.5% vs. 21.2%, P = 0.02), and exhibited a larger AS with longer potentials (5.8 ± 2.7 vs. 2.2 ± 1.7 cm2; 231.2 ± 37.3 vs. 213.8 ± 39.0 ms; P < 0.001, respectively). Arrhythmogenic substrate dimension was the strongest predictor of the presence of LPs (odds ratio 1.9; P < 0.001). An AS area of at least 3.5 cm2 identified patients with LPs (area under the curve 0.88, 95% confidence interval 0.843–0.931; P < 0.001) with a sensitivity of 86%, specificity 88%, positive predictive value 85%, and negative predictive value 89%. Conclusion The results of this study support the role of the epicardial AS as an electrophysiological determinant of non-invasive LPs, which may serve as a tool in the non-invasive assessment of the BrS substrate, as SAECG-LPs could be considered an expression of the abnormal epicardial electrical activity. ClinicalTrials.gov number (NCT02641431; NCT03106701).

scholarly journals The numerous denominations of the Brugada syndrome and proposal about how to put an end to an old controversy - a historical-critical perspective

2020 ◽  
Vol 30 (3) ◽  
pp. 480-491
Author(s):  
Joseane Elza Tonussi Mendes ◽  
Kjell Nikus ◽  
Raimundo Barbosa-Barros ◽  
Andrés Ricardo Pérez-Riera
Keyword(s):  
Brugada Syndrome ◽  
Critical Perspective ◽  
Phenotype Correlation ◽  
First Report ◽  
The Past ◽  
Genotype Phenotype Correlation ◽  
Independent Entity

Backgroung: The eponymous Brugada Syndrome (BrS) in honor of its discovery as an independent entity by the Spanish/ Catalan Brugada brothers, Pedro and Josep, has deserved numerous denominations derived mainly from the clinical genotype/phenotype correlation. The purpose of this manuscript is to present and analyze the nomenclatures that this intriguing and challenging syndrome has received over the past 28 years. We also compared the main features between cases from the first report of the Brugada brothers and an article by Martini et al. The nomenclatures used by these authors are closely linked to the BrS, but the cases (except one) presented in the article by Martini et al do not present the type 1 Brugada ECG pattern, which is mandatory for the diagnosis of BrS.

Abstract 1825: Abnormal ECG Markers suggest that Accentuated Intracardiac Conduction Delay is The Common and Distinguishing Feature of Patients with Spontaneous Type 1 ECG or SCN5A Mutation in Brugadas Syndrome

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Juliane Theilade ◽  
Raffaella Bloise ◽  
Janny Nastoli ◽  
Elena Ronchetti ◽  
S. Facchinetti ◽  
...  
Keyword(s):  
Brugada Syndrome ◽  
Relative Size ◽  
Conduction Delay ◽  
List Type ◽  
Late Potentials ◽  
Loss Of Function ◽  
Intraventricular Conduction ◽  
Qrs Duration ◽  
Scn5a Mutation

The conclusive diagnosis of Brugada Syndrome (BrS) is established in patients (pts) with spontaneous type 1 ECG or in carriers of a loss of function SCN5A mutation. We carried out a systematic analysis of ECG recordings in BrS pts to test the hypothesis that the presence of intraventricular (Intra-Ven) and atrioventricular (A-Ven) conduction delay is the distinguishing common feature of pts with SCN5A mutations (Mut+) and in pts with a spontaneous type 1 ECG pattern (spont-ECG). We assessed the following 5 ECG parameters: late potentials (quantified as RMS at 40 Hz), aVR sign (relative size of the R and q waves in aVR), QRS complex fragmentation (defined as an additional R′ or notching of the of S wave), PQ and QRS duration. We studied 200 consecutive BrS pts to define whether the prevalence of ECG markers correlate with 1) the presence of a SCN5A mutation (Mut+) or 2) the presence of a spontaneous type 1 pattern ECG (spont-ECG). Results are summarized in the table . Interestingly, Mut+ not only presented prolonged PQ (p<0.003 vs Mut÷) as previously reported but more significantly they showed the presence of abnormal markers of intraventricular conduction (QRS duration, aVR sign and late potentials). Similarly, also the presence of a spont-ECG was associated with prolonged PQ and QRS intervals and with late potentials. Based on our ECG analysis we propose that Brugada syndrome is a disease characterized by impairment of A-Ven and Intra-Ven conduction, the presence of a mutation in the SCN5A gene and, the presence of a spontaneous type 1 ECG identify patients with accentuated conduction defects. These findings suggest that the presence of interventricular conduction delay is a landmark of BrS and should be considered as diagnostic markers in BrS.

scholarly journals Brugada Syndrome Caused by Autonomic Dysfunction in Multiple Sclerosis

2019 ◽  
Vol 2019 ◽  
pp. 1-5 ◽  
Author(s):  
Michel Ibrahim ◽  
Garly Saint-Croix ◽  
Rosario Colombo
Keyword(s):  
Multiple Sclerosis ◽  
Autonomic Dysfunction ◽  
Brugada Syndrome ◽  
Neurological Deficits ◽  
Type I ◽  
Increased Risk ◽  
Risk Of Falls ◽  
Balance Problems ◽  
Brugada Pattern

Only one case report has previously described a patient with multiple sclerosis and a type 1 Brugada pattern on the electrocardiogram. Patients with multiple sclerosis have several neurological deficits including sensory symptoms, acute or subacute motor weakness, gait disturbance, and balance problems that may lead to an increased risk of falls. Concurrent autonomic dysfunction and neurologic consequences of multiple sclerosis may precipitate both mechanical falls and falls with loss of consciousness. While mechanistically different, the type 1 Brugada pattern presents similarly with syncope due to an insufficient cardiac output during dysrhythmia. In such patients, intracardiac defibrillators have shown to prevent sudden cardiac death in patients with the Brugada syndrome. In light of these similarly presenting but unique clinical entities, MS patients who develop a syncopal event in the setting of a spontaneous type I Brugada pattern pose a diagnostic and therapeutic dilemma. This case illustrates an approach to the risks and benefits of an ICD placement in an MS patient with the type 1 Brugada pattern.

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