Aviram Hochstadt

Female gender as independent risk factor of torsades de pointes during acquired atrioventricular block

BACKGROUND Female gender increases the risk of torsades de pointes (TdP) in the long QT syndrome, and this increased risk is assumed to be due to their longer QT interval. OBJECTIVE The purpose of this study was to study the interplay between gender, duration of the QT interval, and risk of TdP during AV block. METHODS We studied 250 patients (48% women) with AV block. QT interval was measured at the time of most severe bradycardia. We then constructed different receiver operating characteristic curves for the QTc of males and females for predicting TdP. RESULTS As expected, patients with TdP had longer QTc intervals than did patients with uncomplicated AV block (564 ± 81 ms vs 422 ± 62 ms, P < .001). This correlation between longer QTc and higher risk of TdP was true for both genders. However, the QT of females with TdP was shorter than the respective value for males with TdP. Despite similar severity of bradycardia, the QT was shorter for females (QT 672 ± 88 ms vs 727 ± 57 ms for females with TdP vs males with TdP, P = .022). The QTc/TdP risk curve for females was shifted to the left in comparison to the pertinent graph for males. Female gender was an independent predictor of TdP. CONCLUSION Women are at increased risk for developing TdP during AV block, but this increased risk is independent of their longer QT interval. Females develop TdP with QT intervals that are not necessarily arrhythmogenic for males.

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.

New formula for defining “normal” and “prolonged” QT in patients with bundle branch block

OBJECTIVES To predict the QT interval in the presence of normal QRS for patients with left bundle branch block (LBBB). BACKGROUND There is no acceptable method for simple and reliable QT correction for patients with bundle branch block (BBB). METHODS We measured the QT interval in patients with new onset LBBB who had a recent electrocardiogram with narrow QRS for comparison. 48 patients who developed in-hospital LBBB were studied. Patients who had similar heart rate before and after LBBB were included. We used linear regression, the Bogossian method, and our new fixed QRS replacement method to evaluate the most reliable correction method. RESULTS JTc (QTc-QRS) interval was preserved before and after LBBB (328.9 ± 25.4 ms before LBBB vs. 327.3 ms post LBBB (p = 0.550). Mean predicted preLBBB QTc difference was 1.3 ms, -21.3 ms and 1.6 ms for the three methods respectively (p < 0.001 for Bogossian comparison with the other methods). Coefficients of correlation (R) between actual preLBBB QTc with predicted preLBBB QTc were 0.707, 0.683 and 0.665 respectively (p > 0.3 for R comparisons between all methods). The average absolute difference in preLBBB QTc was 15.5 ms and 16.7 ms for the regression and fixed-gender methods (p value between the two = 0.321) and 25.5 ms for the Bogossian method, which was found to be significantly underperforming. CONCLUSIONS In patients with LBBB, replacing of the QRS duration after deriving the QTc interval with a fixed value of 88 ms for female and 95 ms for male provides a simple and reliable method for predicting the QTc before the development of LBBB.

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