Brugada Syndrome ECG Is Highly Prevalent in Schizophrenia Marieke T. Blom, Dan Cohen, Adrie Seldenrijk, Brenda W.J.H. Penninx, Giel Nijpels, Coen D.A. Stehouwer, Jacqueline M. Dekker and Hanno L. Tan Circ Arrhythm Electrophysiol. 2014;7:384-391; originally published online March 3, 2014; doi: 10.1161/CIRCEP.113.000927 Circulation: Arrhythmia and Electrophysiology is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2014 American Heart Association, Inc. All rights reserved. Print ISSN: 1941-3149. Online ISSN: 1941-3084

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Original Article Brugada Syndrome ECG Is Highly Prevalent in Schizophrenia Marieke T. Blom, MA, MSE; Dan Cohen, MD, PhD; Adrie Seldenrijk, MSc, PhD; Brenda W.J.H. Penninx, MSc, PhD; Giel Nijpels, MD, PhD; Coen D.A. Stehouwer, MD, PhD; Jacqueline M. Dekker, MSc, PhD; Hanno L. Tan, MD, PhD Background—The causes of increased risk of sudden cardiac death in schizophrenia are not resolved. We aimed to establish (1) whether ECG markers of sudden cardiac death risk, in particular Brugada-ECG pattern, are more prevalent among patients with schizophrenia, and (2) whether increased prevalence of these ECG markers in schizophrenia is explained by confounding factors, notably sodium channel–blocking medication. Methods and Results—In a cross-sectional study, we analyzed ECGs of a cohort of 275 patients with schizophrenia, along with medication use. We determined whether Brugada-ECG was present and assessed standard ECG measures (heart rate, PQ-, QRS-, and QT-intervals). We compared the findings with nonschizophrenic individuals of comparable age (the Netherlands Study of Depression and Anxiety [NESDA] cohort; N=179) and, to account for assumed increased aging rate in schizophrenia, with individuals 20 years older (Hoorn cohort; n=1168), using multivariate regression models. Brugada-ECG was significantly more prevalent in the schizophrenia cohort (11.6%) compared with NESDA controls (1.1%) or Hoorn controls (2.4%). Moreover, patients with schizophrenia had longer QT-intervals (410.9 versus 393.1 and 401.9 ms; both P450 ms; women >470 ms).16

Brugada-ECG and BrS The diagnosis of BrS requires typical ST-segment elevations in right precordial ECG leads (type 1 Brugada-ECG) and events suggestive of cardiac arrhythmia or a family history of BrS or SCD. In most BrS patients, the baseline ECG is only suspicious for BrS (type 2/3 Brugada-ECG). To confirm or refute this suspicion, they must undergo provocation testing with a sodium channel–blocking drug (Figure 1).10 Accordingly, patients with schizophrenia with baseline type 2/3 Brugada-ECG were invited for ajmaline testing in the


Academic Medical Center. All patients with type 1 Brugada-ECG (at baseline or after ajmaline testing) underwent DNA screening of SCN5A.17 SCN5A encodes the α-subunit of the cardiac sodium channel,18 which drives depolarization. Moreover, family screening was offered. In the NESDA and Hoorn cohorts, ajmaline testing could not be performed. Therefore, the prevalences of baseline Brugada-ECG (type 1 or 2/3) were compared between cohorts.

Confounders Risk factors for cardiovascular disease and SCD (previous myocardial infarction, hypertension, hypercholesterolemia, diabetes mellitus, body mass index [BMI]) were derived from patient files (Schizophrenia cohort) or from medication use and patient files (control cohorts).12,15 Drug use during ECG recording or ajmaline testing was derived from patient records (Schizophrenia cohort), questionnaire (Hoorn cohort), or drug container inspection (NESDA cohort). We assessed the use of sodium channel blockers,19 QTc-prolonging drugs,20 First-generation antipsychotics, second-generation antipsychotics, antidepressants, cardiovascular drugs (nitrates, β-blockers, calcium channel antagonists, antithrombotics), and ­lipid-lowering drugs.

Statistical Analysis To analyze differences between cohorts in the prevalence of comorbidities and medication use, we used χ2 statistics (Pearson/Fisher exact where appropriate) for categorical variables and ANOVA for continuous variables. We performed multivariate logistic regression analyses to assess differences between cohorts in Brugada-ECG, correcting for sex and factors that were significantly (P




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Brugada syndrome ECG is highly prevalent in schizophrenia.

The causes of increased risk of sudden cardiac death in schizophrenia are not resolved. We aimed to establish (1) whether ECG markers of sudden cardia...
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