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      Investigation of the Proarrhythmic Effects of Antidepressants according to QT Interval, QT Dispersion and T Wave Peak-to-End Interval in the Clinical Setting

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          Abstract

          Objective

          Some antidepressants have been implicated as risk factors for QT prolongation, which is a predictor of sudden cardiac death. However, the QT interval is considered an imperfect biomarker for proarrhythmic risk. Therefore, we reevaluated the risk of sudden cardiac death due to antidepressants using improved methods, namely, QT dispersion (QTD), T wave peak-to-end interval (Tp-e), and Tp-e/QT ratio.

          Methods

          We compared the effects of antidepressants on QTc (QT/RR 1/3), QTD, Tp-e, and Tp-e/QT ratio in 378 patients with mood disorder. We also compared each index between 165 healthy controls and 215 randomly selected age-matched patients.

          Results

          Age (p<0.01), sex (p<0.05), tricyclic antidepressant (TCA) use (p<0.05), and clomipramine (p<0.01) and mianserin (p<0.05) use in particular, significantly associated with a prolonged QTc. We also found that age (p<0.01), TCA use (p<0.05), and clomipramine (p<0.01) and mianserin (p<0.05) use in particular, significantly prolonged QTD. However, there was no correlation between each variable and Tp-e or Tp-e/QT ratio. Significant differences in QTc and QTD were found between the patients and healthy controls.

          Conclusion

          From our results, prediction of risk of sudden cardiac death by QTD, Tp-e, or Tp-e/QT ratio was inconsistent. Increased QTD may be more suitable for predicting sudden cardiac death due to antidepressants.

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          Most cited references28

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          Prolonged QTc interval and risk of sudden cardiac death in a population of older adults.

          This study sought to investigate whether prolongation of the heart rate-corrected QT (QTc) interval is a risk factor for sudden cardiac death in the general population. In developed countries, sudden cardiac death is a major cause of cardiovascular mortality. Prolongation of the QTc interval has been associated with ventricular arrhythmias, but in most population-based studies no consistent association was found between QTc prolongation and total or cardiovascular mortality. Only very few of these studies specifically addressed sudden cardiac death. This study was conducted as part of the Rotterdam Study, a prospective population-based cohort study that comprises 3,105 men and 4,878 women aged 55 years and older. The QTc interval on the electrocardiogram was determined during the baseline visit (1990 to 1993) and the first follow-up examination (1993 to 1995). The association between a prolonged QTc interval and sudden cardiac death was estimated using Cox proportional hazards analysis. During an average follow-up period of 6.7 years (standard deviation, 2.3 years) 125 patients died of sudden cardiac death. An abnormally prolonged QTc interval (>450 ms in men, >470 ms in women) was associated with a three-fold increased risk of sudden cardiac death (hazard ratio, 2.5; 95% confidence interval, 1.3 to 4.7), after adjustment for age, gender, body mass index, hypertension, cholesterol/high-density lipoprotein ratio, diabetes mellitus, myocardial infarction, heart failure, and heart rate. In patients with an age below the median of 68 years, the corresponding relative risk was 8.0 (95% confidence interval 2.1 to 31.3). Abnormal QTc prolongation on the electrocardiogram should be viewed as an independent risk factor for sudden cardiac death.
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            T(p-e)/QT ratio as an index of arrhythmogenesis.

            An increasing number of basic and clinical studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (T(p-e)) may correspond to the transmural dispersion of repolarization and that amplification of the T(p-e) interval is associated with malignant ventricular arrhythmias. In this review, we outline the utility of the T(p-e) interval and the T(p-e)/QT ratio as an electrocardiographic index of arrhythmogenesis for both congenital and acquired ion channel disease leading to ventricular arrhythmias. In healthy individuals, the T(p-e)/QT ratio has a mean value of approximately 0.21 in the precordial leads and it remains relatively constant between the heart rates from 60 to 100 beats per minute. Interestingly, the T(p-e)/QT ratio is significantly greater in the patients at risk for arrhythmic event such as those with long QT syndrome, Brugada syndrome, short QT syndrome, and also in patients with organic heart disease such as acute myocardial infarction. Functional reentry is the underlying mechanism for arrhythmogenesis associated with an increased T(p-e)/QT ratio.
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              An analysis of the time-relations of electrocardiogram

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                Author and article information

                Journal
                Psychiatry Investig
                Psychiatry Investig
                PI
                Psychiatry Investigation
                Korean Neuropsychiatric Association
                1738-3684
                1976-3026
                February 2019
                21 February 2019
                : 16
                : 2
                : 159-166
                Affiliations
                [1 ]Department of Psychiatry, Dokkyo Medical University School of Medicine, Tochigi, Japan
                [2 ]Department of Health Care, Dokkyo Medical University School of Medicine, Tochigi, Japan
                Author notes
                Correspondence: Yuji Ozeki, MD, PhD Department of Psychiatry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu-machi, Shimotsuga, Tochigi 321-0293, Japan Tel: +81-282-86-1111, Fax: +81-282-86-5187 E-mail: ozeki@ 123456dokkyomed.ac.jp
                Article
                pi-2018-12-11
                10.30773/pi.2018.12.11
                6393752
                30808123
                68c000b8-4ff6-4dd7-94bb-0b304a36ecf2
                Copyright © 2019 Korean Neuropsychiatric Association

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 September 2018
                : 3 December 2018
                : 11 December 2018
                Categories
                Original Article

                Clinical Psychology & Psychiatry
                antidepressants,sudden cardiac death,qt prolongation,qt dispersion,t peak-to-end,arrhythmia

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