Risk of cardiac events in Long QT syndrome patients when taking antiseizure medications

Abstract

Many antiseizure medications (ASMs) affect ion channel function. We investigated whether ASMs alter the risk of cardiac events in patients with corrected QT (QT) prolongation. The study included people from the Rochester-based Long QT syndrome (LQTS) Registry with baseline QT prolongation and history of ASM therapy (n = 296). Using multivariate Anderson-Gill models, we assessed the risk of recurrent cardiac events associated with ASM therapy. We stratified by LQTS genotype and predominant mechanism of ASM action (Na channel blocker and gamma-aminobutyric acid modifier.) There was an increased risk of cardiac events when participants with QT prolongation were taking vs off ASMs (HR 1.65, 95% confidence interval [CI] 1.36-2.00, P < 0.001). There was an increased risk of cardiac events when LQTS2 (HR 1.49, 95% CI 1.03-2.15, P = 0.036) but not LQTS1 participants were taking ASMs (interaction, P = 0.016). Na channel blocker ASMs were associated with an increased risk of cardiac events in participants with QT prolongation, specifically LQTS2, but decreased risk in LQTS1. The increased risk when taking all ASMs and Na channel blocker ASMs was attenuated by concurrent beta-adrenergic blocker therapy (interaction, P < 0.001). Gamma-aminobutyric acid modifier ASMs were associated with an increased risk of events in patients not concurrently treated with beta-adrenergic blockers. Female participants were at an increased risk of cardiac events while taking all ASMs and each class of ASMs. Despite no change in overall QT duration, pharmacogenomic analyses set the stage for future prospective clinical and mechanistic studies to validate that ASMs with predominantly Na channel blocking actions are deleterious in LQTS2, but protective in LQTS1.

Identifying patients with epilepsy at high risk of cardiac death: signs, risk factors and initial management of high risk of cardiac death

“…In this context, one may also discuss safety issues of ASM in epilepsy populations with inherited and acquired cardiac disease, as data are lacking on binding affinities and effects of ASM on mutant cardiac channels associated with arrhythmias. Indeed, in a recent cohort study on people with genetic long QT syndromes, the use of ASM was associated with an increased risk of cardiac events, especially in people with long QT syndrome type 2 [125]. Cardiac events were more frequent in female patients and upon sodium channel blocking agents, whilst co-administration of beta-adrenergic blocker medication attenuated the risk of cardiac events [125].…”

“…Indeed, in a recent cohort study on people with genetic long QT syndromes, the use of ASM was associated with an increased risk of cardiac events, especially in people with long QT syndrome type 2 [125]. Cardiac events were more frequent in female patients and upon sodium channel blocking agents, whilst co-administration of beta-adrenergic blocker medication attenuated the risk of cardiac events [125]. Given these considerations, one might expect frequently occurring new-onset cardiac arrhythmias in PWE after starting e.g.…”

Epilepsija ir COVID-19: neurologo, paciento ir nacionalinės sveikatos sistemos iššūkiai pandemijos metu

“…Ðir dies lai du mo su tri ki mus (QT in ter va lo pail gë ji mà EKG) ga li su kel ti azit ro mi ci nas ir chlo rok vi nas, taip pat kai ku rie VNE (pvz., kar ba ma ze pi nas, la ko za mi das, fe nitoi nas ir ru fi na mi das). To dël, ski riant ðiuos vais tus kar tu, bû ti na ste bë ti EKG [14,15]. In for ma ci ja apie VNE sà vei kà su prieð vi ru si niais vais tais pa tei kia ma nuo lat at nau ji na mame Li ver pu lio vais tø sà vei kos gru pës, Ba ze lio (Ðvei ca ri ja) ir Rad bou do (Ny der lan dai) uni ver si te ti niø li go ni niø tinkla la py je www.covid19-druginteractions.org.…”

Sudden cardiac death (SCD) and sudden unexpected death in epilepsy (SUDEP)

“…W większości przypadków (około 80%) przyczyną nagłych zgonów jest choroba wieńcowa, następnie pierwotne kardiomiopatie (około 10-15%) oraz choroby elektryczne serca (około 5-10%) -zespoły wydłużonego QT, zespół Brugadów oraz zespół Wolffa-Parkinso-na-White'a (WPW). U około 5% występuje idiopatyczne migotanie komór [9,10,11,12,13,14,15,16,17]. Ostre niedokrwienie mięśnia sercowego powoduje zaburzenia rytmu serca w wyniku złożonych mechanizmów wynikających z aktywacji współczulnej, przesunięcia równowagi jonowej, powstawania wolnych rodników w wyniku reperfuzji i zmian właściwości elektrycznych komórek, co prowadzi do wymykania się ośrodków obwodowych automatyzmu spod ośrodków nadrzędnych.…”

“…Do 12 roku życia większe zagrożenie występuje u płci męskiej, natomiast w późniejszym wieku u płci żeńskiej, prawdopodobnie ze względu na niekorzystny wpływ estrogenów. W około 40-50% występują epizody częstoskurczu komorowego torsade de points, manifestujące się omdleniem lub drgawkami [15,16,17,18]. Przebyte w przeszłości omdlenie, zarówno u pacjentów z LQTS, jak i z zespołem Brugadów, znacznie podnosi ryzyko nagłego zgonu.…”