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      Effects of Chronic Carbamazepine Treatment on the ECG in Patients with Focal Seizures

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          Abstract

          Background and Objectives

          Several mechanisms have been proposed for the sudden unexpected death in epilepsy patients, such as cardiac arrhythmias, a decrease in heart rate variability and the use of anti-epileptic drugs (AEDs). Although carbamazepine is commonly used as an AED, the exact working mechanism of this drug as well as its effect on the heart are not completely understood. The aim of this study was to determine whether chronic carbamazepine therapy in patients with focal seizures and impaired awareness has an effect on the electrocardiogram (ECG).

          Subjects and Methods

          This cross-sectional study included 36 patients with focal seizures and impaired awareness treated for 12–32 months with carbamazepine monotherapy and 38 healthy volunteers. A 5-min modified three-electrode chest lead ECG with lead II configuration was recorded using LabChart 7 ECG software module at 1000-Hz sampling frequency. All data analysis was performed using custom-made Matlab 2015b scripts. ECGs of patients and controls were compared with respect to heart rate, time intervals and measures of short- and long-term variation.

          Results

          There were no significant differences in heart rate and ECG time intervals between the patient and control groups. Measures on short- and long-term variability also did not show any significant group differences.

          Conclusion

          Our study shows that chronic use of carbamazepine as monotherapy does not have any significant effects on ECG time intervals or measures of short- and long-term variability.

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          Most cited references40

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          Do existing measures of Poincaré plot geometry reflect nonlinear features of heart rate variability?

          Heart rate variability (HRV) is concerned with the analysis of the intervals between heartbeats. An emerging analysis technique is the Poincaré plot, which takes a sequence of intervals and plots each interval against the following interval. The geometry of this plot has been shown to distinguish between healthy and unhealthy subjects in clinical settings. The Poincaré plot is a valuable HRV analysis technique due to its ability to display nonlinear aspects of the interval sequence. The problem is, how do we quantitatively characterize the plot to capture useful summary descriptors that are independent of existing HRV measures? Researchers have investigated a number of techniques: converting the two-dimensional plot into various one-dimensional views; the fitting of an ellipse to the plot shape; and measuring the correlation coefficient of the plot. We investigate each of these methods in detail and show that they are all measuring linear aspects of the intervals which existing HRV indexes already specify. The fact that these methods appear insensitive to the nonlinear characteristics of the intervals is an important finding because the Poincaré plot is primarily a nonlinear technique. Therefore, further work is needed to determine if better methods of characterizing Poincaré plot geometry can be found.
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            An analysis of the time-relations of electrocardiogram

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              Long-term outcomes in individuals with prolonged PR interval or first-degree atrioventricular block.

              Prolongation of the electrocardiographic PR interval, known as first-degree atrioventricular block when the PR interval exceeds 200 milliseconds, is frequently encountered in clinical practice. To determine the clinical significance of PR prolongation in ambulatory individuals. Prospective, community-based cohort including 7575 individuals from the Framingham Heart Study (mean age, 47 years; 54% women) who underwent routine 12-lead electrocardiography. The study cohort underwent prospective follow-up through 2007 from baseline examinations in 1968-1974. Multivariable-adjusted Cox proportional hazards models were used to examine the associations of PR interval with the incidence of arrhythmic events and death. Incident atrial fibrillation (AF), pacemaker implantation, and all-cause mortality. During follow-up, 481 participants developed AF, 124 required pacemaker implantation, and 1739 died. At the baseline examination, 124 individuals had PR intervals longer than 200 milliseconds. For those with PR intervals longer than 200 milliseconds compared with those with PR intervals of 200 milliseconds or shorter, incidence rates per 10 000 person-years were 140 (95% confidence interval [CI], 95-208) vs 36 (95% CI, 32-39) for AF, 59 (95% CI, 40-87) vs 6 (95% CI, 5-7) for pacemaker implantation, and 334 (95% CI, 260-428) vs 129 (95% CI, 123-135) for all-cause mortality. Corresponding absolute risk increases were 1.04% (AF), 0.53% (pacemaker implantation), and 2.05% (all-cause mortality) per year. In multivariable analyses, each 20-millisecond increment in PR was associated with an adjusted hazard ratio (HR) of 1.11 (95% CI, 1.02-1.22; P = .02) for AF, 1.22 (95% CI, 1.14-1.30; P < .001) for pacemaker implantation, and 1.08 (95% CI, 1.02-1.13; P = .005) for all-cause mortality. Individuals with first-degree atrioventricular block had a 2-fold adjusted risk of AF (HR, 2.06; 95% CI, 1.36-3.12; P < .001), 3-fold adjusted risk of pacemaker implantation (HR, 2.89; 95% CI, 1.83-4.57; P < .001), and 1.4-fold adjusted risk of all-cause mortality (HR, 1.44, 95% CI, 1.09-1.91; P = .01). Prolongation of the PR interval is associated with increased risks of AF, pacemaker implantation, and all-cause mortality.
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                Author and article information

                Contributors
                +31 43 388 1667 , tammo.delhaas@maastrichtuniversity.nl
                Journal
                Clin Drug Investig
                Clin Drug Investig
                Clinical Drug Investigation
                Springer International Publishing (Cham )
                1173-2563
                1179-1918
                25 July 2018
                25 July 2018
                2018
                : 38
                : 9
                : 845-851
                Affiliations
                [1 ]ISNI 0000 0001 1516 2246, GRID grid.416861.c, Autonomic Laboratory, Department of Neurophysiology, , National Institute of Mental Health and Neuro-Sciences (NIMHANS), ; Bangalore, India
                [2 ]ISNI 0000 0001 0481 6099, GRID grid.5012.6, Department of Biomedical Engineering, , Maastricht University, ; Maastricht, The Netherlands
                [3 ]ISNI 0000 0001 0481 6099, GRID grid.5012.6, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, ; Maastricht, The Netherlands
                [4 ]ISNI 0000 0001 1516 2246, GRID grid.416861.c, Department of Neurology, , National Institute of Mental Health and Neuro-Sciences (NIMHANS), ; Bangalore, India
                [5 ]ISNI 0000 0004 0480 1382, GRID grid.412966.e, Department of Paediatrics, , Maastricht University Medical Centre, ; Maastricht, The Netherlands
                Author information
                http://orcid.org/0000-0001-6897-9700
                Article
                677
                10.1007/s40261-018-0677-6
                6153966
                30047104
                b92d92de-10b8-45e0-9cda-1c0f6fd22ae3
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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                Original Research Article
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                © Springer Nature Switzerland AG 2018

                Pharmacology & Pharmaceutical medicine
                Pharmacology & Pharmaceutical medicine

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