Polytherapy with sodium channel-blocking antiepileptic drugs is associated with arrhythmogenic ST-T abnormality in patients with epilepsy

Ishizue, Naruya; Niwano, Shinichi; Saito, Masanori; Fukaya, Hidehira; Nakamura, Hironori; Igarashi, Tazuru; Fujiishi, Tamami; Yoshizawa, Tomoharu; Oikawa, Jun; Satoh, Akira; Kishihara, Jun; Murakami, Masami; Niwano, Hiroe; Miyaoka, Hiroaki; Ako, Junya

doi:10.1016/j.seizure.2016.06.004

Cited by 41 publications

(30 citation statements)

References 34 publications

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“…Atrioventricular (AV) conduction is the most frequent reported complication. ST changes, Brugada-like patterns, atrial fibrillation and QTc prolongation have also been reported but the association with AED treatment is less well established [72][73][74][75][76][77][78][79][80][81][82][83][84][85][86]. Most clinically relevant arrhythmias were related to AED overdose.…”

Section: Epilepsy and Cardiac Arrhythmiasmentioning

confidence: 99%

The heart of epilepsy: Current views and future concepts

Shmuely

Lende

Lamberts

et al. 2017

Seizure

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Cardiovascular (CV) comorbidities are common in people with epilepsy. Several mechanisms explain why these conditions tend to co-exist including causal associations, shared risk factors and those resulting from epilepsy or its treatment. Various arrhythmias occurring during and after seizures have been described. Ictal asystole is the most common cause. The converse phenomenon, arrhythmias causing seizures, appears extremely rare and has only been reported in children following cardioinihibitory syncope. Arrhythmias in epilepsy may not only result from seizure activity but also from a shared genetic susceptibility. Various cardiac and epilepsy genes could be implicated but firm evidence is still lacking. Several antiepileptic drugs (AEDs) triggering conduction abnormalities can also explain the co-existence of arrhythmias in epilepsy. Epidemiological studies have consistently shown that people with epilepsy have a higher prevalence of structural cardiac disease and a poorer CV risk profile than those without epilepsy. Shared CV risk factors, genetics and etiological factors can account for a significant part of the relationship between epilepsy and structural cardiac disease. Seizure activity may cause transient myocardial ischaemia and the Takotsubo syndrome. Additionally, certain AEDs may themselves negatively affect CV risk profile in epilepsy. Here we discuss the fascinating borderland of epilepsy and cardiovascular conditions. The review focuses on epidemiology, clinical presentations and possible mechanisms for shared pathophysiology. It concludes with a discussion of future developments and a call for validated screening instruments and guidelines aiding the early identification and treatment of CV comorbidity in epilepsy.

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Section: Epilepsy and Cardiac Arrhythmiasmentioning

confidence: 99%

The heart of epilepsy: Current views and future concepts

Shmuely

Lende

Lamberts

et al. 2017

Seizure

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show abstract

“…An abnormal ECG was recorded in 1 patient in the monotherapy subgroup and in 10 patients in the polytherapy subgroup (p = 0.05). As reported in the literature, polytherapy increases the risk of arrhythmia [7].…”

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confidence: 79%

“…However, an abnormal ECG trace requires the exclusion of heart disease and verification of the diagnosis of epilepsy. ECG changes could also be explained by the influence of epileptic discharges on the central autonomic nervous system, the effect of antiepileptic drugs (AEDs) and the presence of genetically determined disorders of ion channel function [1][2][3][4][5][6][7]. Detection of ECG changes is also important because of the phenomenon of sudden unexpected death in epilepsy (SUDEP) [2].…”

mentioning

confidence: 99%

Association between electrocardiographic and electroencephalographic changes in patients with epilepsy

Mańka-Gaca

Łabuz-Roszak

Machowska-Majchrzak

et al. 2020

aoms

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“…It appears, however, plausible that simultaneous administration of AEDs that bind to the same cellular targets increases the risk of target-related side effects. Therefore, it is not surprising that cardiac side effects such as atrioventricular block, sinus node dysfunction, or arrhythmogenic ST–T abnormalities were reported in the context of simultaneous intake of AED that inhibits VGSC (34–36). We think that cardiac side effects can indeed, if long lasting and severe enough, facilitate sudden cardiac death as a rare cause of SUDEP in some epilepsy patients.…”

Section: Discussionmentioning

confidence: 99%

Antiepileptic Drugs Impair Shortening of Isolated Cardiomyocytes

et al. 2017

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BackgroundMost antiepileptic drugs (AEDs) inhibit seizure generation by acting on voltage-dependent ion channels. Voltage-dependent sodium and calcium channels are commonly expressed in brain and heart, suggesting that AEDs may have considerable cardiodepressive effects, thereby facilitating sudden cardiac death as a potential cause of sudden unexpected death in epilepsy. Here, we investigated the effects of carbamazepine (CBZ), lamotrigine (LTG), and levetiracetam (LEV) alone and in combination on the shortening properties of isolated ventricular cardiomyocytes of wild-type mice.MethodsProperties of murine cardiomyocytes were determined by recording the sarcomere shortening with a video imaging system before, during, and after administration of AEDs in different concentrations and combinations. We assessed (i) the number of successful shortenings during continuous electrical stimulation (electromechanical coupling) and (ii) the shortening amplitude as well as other shortening-related properties upon repetitive electrical stimulation at 4 Hz. Data are given as mean ± SEM.ResultsAt 100 μM, CBZ (10 cells), LTG (11 cells), and LEV (11 cells) alone had no effect on the electromechanical coupling but reversibly reduced shortening amplitudes by 15 ± 4, 24 ± 3, and 11 ± 3%, respectively. Increasing the LTG concentration to 250 (21 cells) and 500 μM (4 cells) reversibly inhibited the electromechanical coupling in 62 and 100% of the experiments. Importantly, simultaneous application of CBZ, LTG, and LEV at 100 μM also impaired the electromechanical coupling in 8 of 19 cardiomyocytes (42%) and reduced the shortening amplitude by 21 ± 4%.ConclusionOur data show that AEDs reversibly impair cardiac excitation and contraction. Importantly, the blocking effect on electromechanical coupling appears to be additive when different AEDs are simultaneously applied. The translational value of these experimental findings into clinical practice is limited. Our results, however, suggest that rationale AED therapy may be important with respect to cardiac side effects and potential facilitation of serious cardiac dysfunction especially when AEDs are used in combination or at very high doses.

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Polytherapy with sodium channel-blocking antiepileptic drugs is associated with arrhythmogenic ST-T abnormality in patients with epilepsy

Abstract: ST-T abnormalities were frequently seen in patients using AEDs. The presence of Brugada-type ST elevation was associated with polytherapy with sodium channel-blocking AEDs.

Cited by 41 publications

References 34 publications

The heart of epilepsy: Current views and future concepts

The heart of epilepsy: Current views and future concepts

Association between electrocardiographic and electroencephalographic changes in patients with epilepsy

Antiepileptic Drugs Impair Shortening of Isolated Cardiomyocytes

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