Antoine Andorin

Impact of clinical and genetic findings on the management of young patients with Brugada syndrome

BACKGROUND Brugada syndrome (BrS) is an arrhythmogenic disease associated with sudden cardiac death (SCD) that seldom manifests or is recognized in childhood. OBJECTIVES The objectives of this study were to describe the clinical presentation of pediatric BrS to identify prognostic factors for risk stratification and to propose a data-based approach management. METHODS We studied 106 patients younger than 19 years at diagnosis of BrS enrolled from 16 European hospitals. RESULTS At diagnosis, BrS was spontaneous (n = 36, 34%) or drug-induced (n = 70, 66%). The mean age was 11.1 ± 5.7 years, and most patients were asymptomatic (family screening, (n = 67, 63%; incidental, n = 13, 12%), while 15 (14%) experienced syncope, 6(6%) aborted SCD or symptomatic ventricular tachycardia, and 5 (5%) other symptoms. During follow-up (median 54 months), 10 (9%) patients had life-threatening arrhythmias (LTA), including 3 (3%) deaths. Six (6%) experienced syncope and 4 (4%) supraventricular tachycardia. Fever triggered 27% of LTA events. An implantable cardioverter-defibrillator was implanted in 22 (21%), with major adverse events in 41%. Of the 11 (10%) patients treated with hydroquinidine, 8 remained asymptomatic. Genetic testing was performed in 75 (71%) patients, and SCN5A rare variants were identified in 58 (55%); 15 of 32 tested probands (47%) were genotype positive. Nine of 10 patients with LTA underwent genetic testing, and all were genotype positive, whereas the 17 SCN5A-negative patients remained asymptomatic. Spontaneous Brugada type 1 electrocardiographic (ECG) pattern (P = .005) and symptoms at diagnosis (P = .001) were predictors of LTA. Time to the first LTA event was shorter in patients with both symptoms at diagnosis and spontaneous Brugada type 1 ECG pattern (P = .006). CONCLUSION Spontaneous Brugada type 1 ECG pattern and symptoms at diagnosis are predictors of LTA events in the young affected by BrS. The management of BrS should become age-specific, and prevention of SCD may involve genetic testing and aggressive use of antipyretics and quinidine, with risk-specific consideration for the implantable cardioverter-defibrillator.

Age of First Arrhythmic Event in Brugada Syndrome: Data From the SABRUS (Survey on Arrhythmic Events in Brugada Syndrome) in 678 Patients

Background Data on the age at first arrhythmic event (AE) in Brugada syndrome are from limited patient cohorts. The aim of this study is 2-fold: (1) to define the age at first AE in a large cohort of patients with Brugada syndrome, and (2) to assess the influence of the mode of AE documentation, sex, and ethnicity on the age at first AE. Methods and Results A survey of 23 centers from 10 Western and 4 Asian countries gathered data from 678 patients with Brugada syndrome (91.3% men) with first AE documented at time of aborted cardiac arrest (group A, n=426) or after prophylactic implantable cardioverter–defibrillator implantation (group B, n=252). The vast majority (94.2%) of the patients were 16 to 70 years old at the time of AE, whereas pediatric (<16 years) and elderly patients (>70 years) comprised 4.3% and 1.5%, respectively. Peak AE rate occurred between 38 and 48 years (mean, 41.9±14.8; range, 0.27–84 years). Group A patients were younger than in Group B by a mean of 6.7 years (46.1±13.2 versus 39.4±15.0 years; P<0.001). In adult patients (≥16 years), women experienced AE 6.5 years later than men (P=0.003). Whites and Asians exhibited their AE at the same median age (43 years). Conclusions SABRUS (Survey on Arrhythmic Events in Brugada Syndrome) presents the first analysis on the age distribution of AE in Brugada syndrome, suggesting 2 age cutoffs (16 and 70 years) that might be important for decision-making. It also allows gaining insights on the influence of mode of arrhythmia documentation, patient sex, and ethnic origin on the age at AE.

Gender Differences in Patients with Brugada Syndrome and Arrhythmic Events: Data from a Survey on Arrhythmic Events in 678 Patients

BACKGROUND There is limited information on gender differences in patients with Brugada syndrome (BrS) who experienced arrhythmic events (AEs). OBJECTIVE The purpose of this study was to compare clinical, electrocardiographic (ECG), electrophysiological, and genetic characteristics between males and females in patients with BrS with their first AE. METHODS The multicenter Survey on Arrhythmic Events in BRUgada Syndrome collected data on the first AE in 678 patients with BrS including 619 males (91.3%) and 59 females (8.7%) aged 0.27-84 years (mean age 42.5 ± 14.1 years) at the time of AE occurrence. RESULTS After excluding pediatric patients, it was found that females were older than males (49.5 ± 14.4 years vs 43 ± 12.7 years, respectively; P = .001). Higher proportions of females were observed in the pediatric and elderly populations. In Asians, the male to female ratio for AEs was ≈9-fold higher than that in White. Spontaneous type 1 BrS ECG was associated with an earlier onset of AEs in pediatric females. A similar prevalence (≈65%) of spontaneous type 1 BrS ECG was present in males and females above the age of 60 years. Females less frequently showed spontaneous type 1 BrS ECG (41% vs 69%; P < .001) or arrhythmia inducibility at electrophysiology study (36% vs 66%; P < .001). An SCN5A mutation was more frequently found in females (48% vs 28% in males; P = .007). CONCLUSION This study confirms that female patients with BrS are much rarer, display less type 1 Brugada ECG, and exhibit lower inducibility rates than do males. It shows for the first time that female patients with BrS with AE have higher SCN5A mutation rates as well as the relationship between gender vs age at the onset of AEs and ethnicity.

Fever-related arrhythmic events in the multicenter Survey on Arrhythmic Events in Brugada Syndrome

BACKGROUND The literature on fever-related arrhythmic events (AEs) in Brugada syndrome (BrS) is currently limited to few case reports and small series. OBJECTIVE The present study aimed to describe the characteristics of fever-related AE in a large cohort of patients with BrS. METHODS The Survey on Arrhythmic Events in Brugada Syndrome is a multicenter study on 678 patients with BrS with first AE documented at the time of aborted cardiac arrest (n = 426) or after prophylactic implantable cardioverter-defibrillator implantation (n = 252). RESULTS In 35 of 588 patients (6%) with available information, the AE occurred during a febrile illness. Most of the 35 patients were male (80%), Caucasian (83%), and proband (70%). The mean age at the time of AE was 29 ± 24 years (range 0.3-76 years). Most patients (80%) presented with aborted cardiac arrest and 6 (17%) with arrhythmic storm. Family history of sudden death, history of syncope, and spontaneous type 1 Brugada electrocardiogram were noted in 17%, 40%, and 71% of patients, respectively. Ventricular fibrillation was induced at electrophysiology study in 9 of 19 patients (47%). An SCN5A mutation was found in 14 of 28 patients (50%). The highest proportion of fever-related AE was observed in the pediatric population (age <16 years), with a disproportionally higher event rate in the very young (age 0-5 years) (65%). Males were involved in all age groups and females only in the pediatric and elderly groups. Fever-related AE affected 17 Caucasians aged <24 years, but no Asians aged <24 years. CONCLUSION The risk of fever-related AE in BrS markedly varies according to age group, sex, and ethnicity. Taking these factors into account could help the clinical management of patients with BrS with fever.

APPROPRIATE PRIMARY PROPHYLACTIC IMPLANTATION OF DEFIBRILLATOR IN PATIENTS WITH BRUGADA SYNDROME: IS THERE ANY DIFFERENCE BETWEEN PATIENTS FROM WESTERN AND ASIAN COUNTRIES? DATA FROM A MULTICENTER SURVEY INVOLVING 246 PATIENTS WITH ARRHYTHMIC EVENTS

Background: There is limited information regarding characteristics of patients with Brugada syndrome (BrS) who received a prophylactically implantable cardioverter-defibrillator (ICD) that delivered appropriate therapy. We sought to compare patients’ characteristics and indications of prophylactic

0332 : QUIDAM Study: assessment of hydroquinidine therapy in the management of Brugada syndrome patients at high arrhythmic risk and implanted with an ICD

Background During last decades, the knowledge in pathophysiological mechanisms of Brugada Syndrome improved. ICD implantation is the only effective treatment to decrease arrhythmic mortality in high-risk patients. Based on experimental and clinical data hydroquinidine seems to be a promising alternative for the management of ventricular arrhythmia and SCD but need to be evaluated. Methods Fifty patients were included in this French multicentric, randomised, double-blind study. Hydroquinidine or placebo treatment was given during two 18 months cross-over phases. Arrhythmic events, ECG parameters and clinical events were evaluated. Results Twenty-six (52%) patients completed the study. Thirty-four (68%) presented side effects, mainly gastrointestinal, related to hydroquinidine therapy in whom 13 had to stopped. One appropriate ICD shock, one ventricular fibrillation with self-resolution and one inappropriate ICD shock occurred in absence of hydroquinidine therapy. Not one of these event occurred under hydroquinidine. No statistical analysis has been done, regarding this low number of arrhythmic events. Hydroquinidine, at short (3 hours after first taking) or long-term, significantly lengthen QT interval, QTc (respectively 404 vs 417sm and 409 vs 433ms), Tpe and Tpe max (respectively 94,8 vs 106,6 ms and 89,4 vs 107,7ms) without any change on J-point elevation nor Tpe/QTc ratio. QTc interval was significantly longer (433 vs 417ms) during long than short-term treatment without any other effect on ECG parameters. Conclusion High rates of hydroquinidine side effects and low number of arrhythmic events give difficulties to conduct large studies to prove its efficiency in Brugada Syndrome. Hydroquinidine lengthens and increases the repolarisation dispersal, with electrocardiographic effects generally similar during short and long-term treatment. These considerations should not stop its use in daily clinical practice, especially for management of electrical storms. The author hereby declares no conflict of interest Download : Download full-size image Figure . Flow chart of QUIDAM study.

CO 2 The impact of clinical and genetic findings on the management of young Brugada syndrome patients

Aims - Brugada Syndrome (BrS) is an arrhythmogenic disease associated with sudden cardiac death (SCD) which seldom manifests and is recognized in childhood. We aim to describe the pediatric BrS clinical presentation to identify prognostic factors for risk stratification, and to propose a data-based approach management. Methods and results - We studied 106 patients, under 19 years of age at diagnosis with spontaneous (n=36) or drug-induced (n=70) BrS from 16 European hospitals. At diagnosis, mean age was 11.1±5.7 years and most patients were asymptomatic [family screening (n=67), incidental (n=13)] while 15 had experienced syncope, 6 aborted SCD or symptomatic ventricular tachycardia, 2 supraventricular tachycardia (SVT), 3 palpitations or presyncope. During follow-up (median: 54 months), 10 patients had life-threatening arrhythmias (LTA) including 3 deaths. Six experienced syncope and 4 SVT. Fever triggered 27% of LTA events. An ICD was implanted in 22 with major adverse events in 41%. Of the 11 patients treated with hydroquinidine, 8 remained asymptomatic. Genetic testing was performed in 75 patients and SCN5A rare variants were identified in 58; among the 32 pediatric probands tested 15 were genotype positive. Of the 10 patients with LTA the 9 with genetic testing were all genotype positive whereas the 17 SCN5A negative patients remained asymptomatic. Spontaneous BrS type 1 ECG (p=0.005) and symptoms at diagnosis (p=0.0015) were predictors of lta. Time to the first LTA event was shorter in patients with both symptoms at diagnosis and spontaneous BrS type 1 ECG pattern (p=0.01) (figure 1). Conclusions - Spontaneous type 1 ECG and symptoms at diagnosis are predictors of LTA events in the young affected by BrS. The management of BrS should become age-specific and prevention of SCD may involve genetic testing, aggressive use of anti-pyretics and quinidine with risk-specific consideration for the ICD