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

Abstract

People with epilepsy have a threefold increased risk of dying prematurely, and a significant proportion is due to sudden cardiac death or acute myocardial infarctions. The causes of increased cardiovascular morbidity and mortality in epilepsy are manifold and include acute or remote effects of epileptic seizures, the longstanding epilepsy itself or antiseizure treatments. Seizurerelated cardiac arrhythmias are common and comprise bradyarrhythmia and asystole, atrial fibrillation and ventricular tachycardia. The most frequent clinically relevant seizure-related arrhythmia is ictal asystole that may require implantation of a cardiac pacemaker, whereas seizure-related ventricular tachycardias are only rarely reported. Takotsubo cardiomyopathy and myocardial infarction are rare complications and predominantly described in association with tonic-clonic seizures. Epilepsy-related cardiac complications include a disturbed cardiac autonomic nervous system and acquired dysfunction of the heart (recently defined as 'epileptic heart'), probably contributing to the abnormalities of cardiac repolarisation and elevated risk of sudden cardiac death in people with epilepsy. If successful, the use of antiseizure medication prevents seizure-related cardiac arrhythmias and remote cardiac complications. However, enzyme-inducing antiseizure medications have a negative impact on cardiovascular risk factors, which may further be aggravated by weight gain linked to specific antiseizure drugs. Given the severe consequences of cardiac risks, the aim of this educational review is to explain the many facets of cardiac complications and their underlying causes, and to enable the reader to recognize and manage these risks with the goal to mitigate the cardiac risks in people with epilepsy. Features of syncope are explained in detail, as syncope of all origins can be mistaken as epileptic seizures in people with or without epilepsy, and ictal syncope (i.e. seizure-induced syncope) can easily be ignored.

Atrioventricular Conduction in Mesial Temporal Lobe Seizures

“…Previous studies in apparently healthy subjects revealed an inverse correlation between PR intervals and HR, i.e., PR intervals shorten with increasing HR (9). Intriguingly, when considering the correlation between PR intervals and HR in our patients, PR interval shortening was significantly greater during left-hippocampal seizures, although absolute PR intervals and PR interval changes were within normal limits (4,9). This subtle finding is unlikely to have a clinical meaning, but may reflect a lateralized representation of the CAN with the left hemisphere being more important in the control of AV conduction.…”

“…These changes are mostly benign and may be used to detect and count epileptic seizures using wearable devices (3). Potentially lethal cardiac arrhythmias such as ventricular tachycardia or sustained asystole are rare and contribute to the elevated risk of premature mortality and sudden cardiac death in people with epilepsy (2,4).…”

“…Previous studies have predominantly reported increases and decreases of sinus node activity with subsequent changes in heart rate (HR) as well as lengthening or shortening of cardiac repolarization and QT intervals in association with seizures (4,5). Whilst ictal bradyarrhythmias and asystole occur rarely and almost exclusively in temporal lobe seizures spreading to the contralateral hemisphere, ictal increases of HR is a frequent phenomenon in temporal and frontal lobe epilepsies of both hemispheres (2).…”

Epileptic heart: A clinical syndromic approach

“…Ageing is associated with progressive cardiovascular pathology, which appears to be accelerated by a history of drug‐resistant seizures 20 . Certain ASMs may exacerbate SCD risk, such as those with sodium channel‐blocking effects, including carbamazepine, lamotrigine, and phenytoin 7–10 . Blockade of the cardiac sodium channels, particularly on a background of cardiovascular disease, can result in conduction abnormalities and lead to life‐threatening arrhythmias such as wide‐complex ventricular tachycardia.…”

“…The epileptic heart is defined as “a heart and coronary vasculature damaged by chronic epilepsy as a result of repeated surges in catecholamines and hypoxemia leading to electrical and mechanical dysfunction, and of adverse effects of certain antiseizure medications (ASMs), which may predispose to hyperlipidemia or arrhythmias. In some patients, acquired cardiac channelopathies in response to recurrent seizures may be involved.” Although the contemporary definition of sudden unexpected death in epilepsy (SUDEP; Table 1) excludes cardiac causes, 2–5 this semantic construct should not be interpreted as ruling out the involvement of heart disease as a factor in premature sudden death in individuals with chronic epilepsy 1,6–8 . Epidemiologic studies show that the incidence of sudden cardiac death (SCD) in individuals with chronic epilepsy is threefold greater than in the general population 9–12 and is 4.5‐fold greater than SUDEP as typically defined (Figure 1).…”