Brugada Syndrome ECG Is Highly Prevalent in Schizophrenia

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 P<0.05), increased proportion of mild or severe QTc prolongation (13.1% and 5.8% versus 3.4% and 0.0% [NESDA], versus 5.1 and 2.8% [Hoorn]), and higher heart rates (80.8 versus 61.7 and 68.0 beats per minute; both P<0.05). The prevalence of Brugada-ECG was still increased (9.6%) when patients with schizophrenia without sodium channel–blocking medication were compared with either of the control cohorts. Conclusions—Brugada-ECG has increased prevalence among patients with schizophrenia. This association is not explained by the use of sodium channel–blocking medication.

[1]  M. Malik,et al.  QT/RR curvatures in healthy subjects: sex differences and covariates. , 2013, American journal of physiology. Heart and circulatory physiology.

[2]  Hanno L. Tan,et al.  Yield of Molecular and Clinical Testing for Arrhythmia Syndromes: Report of 15 Years’ Experience , 2013, Circulation.

[3]  C. Albert,et al.  A common missense variant in the neuregulin 1 gene is associated with both schizophrenia and sudden cardiac death. , 2013, Heart rhythm.

[4]  H. Tan,et al.  Sudden cardiac arrest associated with use of a non-cardiac drug that reduces cardiac excitability: evidence from bench, bedside, and community. , 2013, European heart journal.

[5]  Josemir W Sander,et al.  Epilepsy Is a Risk Factor for Sudden Cardiac Arrest in the General Population , 2012, PloS one.

[6]  P. Postema About Brugada syndrome and its prevalence. , 2012, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[7]  G. Christé,et al.  Sudden Death of Cardiac Origin and Psychotropic Drugs , 2012, Front. Pharmacol..

[8]  Ian M. Anderson,et al.  Antipsychotic-Related QTc Prolongation, Torsade de Pointes and Sudden Death , 2012, Drugs.

[9]  Jason H. Moore,et al.  Ion channels and schizophrenia: a gene set-based analytic approach to GWAS data for biological hypothesis testing , 2012, Human Genetics.

[10]  B. Penninx,et al.  Carotid atherosclerosis in depression and anxiety: Associations for age of depression onset , 2011, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[11]  D. Jeste,et al.  Divergent trajectories of physical, cognitive, and psychosocial aging in schizophrenia. , 2011, Schizophrenia bulletin.

[12]  H. Möller,et al.  Physical illness in patients with severe mental disorders. I. Prevalence, impact of medications and disparities in health care , 2011, World psychiatry : official journal of the World Psychiatric Association.

[13]  R. Perlis,et al.  L‐type calcium channels and psychiatric disorders: A brief review , 2010, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[14]  J. Suvisaari,et al.  Coronary heart disease and cardiac conduction abnormalities in persons with psychotic disorders in a general population , 2010, Psychiatry Research.

[15]  U. Ozbek,et al.  Open Access Research , 2022 .

[16]  C Michael Stein,et al.  Atypical antipsychotic drugs and the risk of sudden cardiac death. , 2009, The New England journal of medicine.

[17]  S. Priori,et al.  Drugs and Brugada syndrome patients: review of the literature, recommendations, and an up-to-date website (www.brugadadrugs.org). , 2009, Heart rhythm.

[18]  Antti Tanskanen,et al.  11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study) , 2009, The Lancet.

[19]  Josemir W. Sander,et al.  Sudden unexpected death in epilepsy: risk factors and potential pathomechanisms , 2009, Nature Reviews Neurology.

[20]  E. Behr,et al.  Drug-induced Brugada syndrome. , 2009, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[21]  G. Cascino,et al.  Identification of a possible pathogenic link between congenital long QT syndrome and epilepsy , 2009, Neurology.

[22]  A. IJsselmuiden,et al.  Antipsychotic Agents and Sudden Cardiac Death — How Should We Manage the Risk? , 2009 .

[23]  Philip D. Harvey,et al.  Is schizophrenia a syndrome of accelerated aging? , 2008, Schizophrenia bulletin.

[24]  P. Cuijpers,et al.  The Netherlands Study of Depression and Anxiety (NESDA): rationale, objectives and methods , 2008, International journal of methods in psychiatric research.

[25]  Karl-Jürgen Bär,et al.  Relationship between cardiovagal modulation and psychotic state in patients with paranoid schizophrenia , 2008, Psychiatry Research.

[26]  H. Huikuri,et al.  Schizophrenia and sudden cardiac death—A review , 2008, Nordic journal of psychiatry.

[27]  S. Saha,et al.  A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? , 2007, Archives of general psychiatry.

[28]  A. Castellanos,et al.  Emerging paradigms of the epidemiology and demographics of sudden cardiac arrest. , 2006, Heart rhythm.

[29]  A. Wilde,et al.  Pathophysiological mechanisms of Brugada syndrome: depolarization disorder, repolarization disorder, or more? , 2005, Cardiovascular research.

[30]  R. Hauer,et al.  Proposed diagnostic criteria for the Brugada syndrome: consensus report. , 2002, Circulation.

[31]  J M Dekker,et al.  Relation of impaired fasting and postload glucose with incident type 2 diabetes in a Dutch population: The Hoorn Study. , 2001, JAMA.

[32]  Takeo Takahashi,et al.  Prolonged QT interval in acute psychotic patients , 2000, Psychiatry Research.

[33]  L. Appleby,et al.  Sudden unexplained death in psychiatric in-patients , 2000, British Journal of Psychiatry.

[34]  G. Breithardt,et al.  Genetic basis and molecular mechanism for idiopathic ventricular fibrillation , 1998, Nature.

[35]  H. Wellens,et al.  Out-of-hospital cardiac arrest in the 1990's: a population-based study in the Maastricht area on incidence, characteristics and survival. , 1997, Journal of the American College of Cardiology.

[36]  Y. Rudy,et al.  Electrophysiologic effects of acute myocardial ischemia: a theoretical study of altered cell excitability and action potential duration. , 1997, Cardiovascular research.