SUDEP and matters of the heart

[Part 2: Questions; Surges R]

 

 

SUDEP is likely to have a variety of causes and may occur in the presence or absence of seizures. The MORTEMUS study has convincingly shown that SUDEP is frequently caused by profound disturbances of respiration (i.e. apnea) and heart activity (bradycardia and asystole) occurring shortly after generalized tonic-clonic seizures. In contrast to this fatal seizure-related cardiorespiratory depression, life-threatening ventricular tachyarrhythmias have been hypothesized for decades as a potential cause of SUDEP, but only recently reported in a few near-SUDEP cases. 

 

There are a number of established risk factors of sudden cardiac death which increase the susceptibility to ventricular tachyarrhythmias. One important risk factor appears to be pathological cardiac repolarization. Cardiac repolarization is the phase of the cardiac cycle during which the electrical excitation of the heart muscle returns to the resting condition. The QT interval is an ECG indicator of cardiac repolarization. Prolongation of the QT interval above normal limits (which depend on age, gender and actual heart rate) is a well characterized risk factor for sudden cardiac death. Genetic forms, known as long QT syndromes, are due to mutation in various ionic channels responsible for the electrical properties of the heart. Pathological QT prolongations are also seen with the use of drugs such as some antibiotics and antidepressants. More than a decade ago, a genetic form of abnormally short QT intervals, also due to mutations in cardiac ionic channels, has been discovered. People with short QT syndromes display QT intervals below normal limits, suffer from syncope due to atrial fibrillation, ventricular tachycardia and fibrillation and have a high risk of sudden cardiac death. Interestingly, an increasing body of evidence suggests that gene mutations and genetic variants commonly linked to cardiac arrhythmias also cause epilepsy and vice versa, offering novel avenues of research that possibly lead to the identification of genetic markers of an increased SUDEP risk. QT dispersion is another measure of cardiac repolarization. It is defined as the difference between the longest and shortest QT interval on an ECG recording and reflects the regional heterogeneity of cardiac repolarization. Values above 50-60 ms have been shown to increase the risk of sudden cardiac death in apparently healthy people and in other medical conditions. 

 

Features of cardiac repolarization have recently been investigated in people with chronic epilepsy. QT dispersion was seen in up to one third of people with focal epilepsy. Changes of QT interval during seizures have also been examined in detail. Prolongation of QT interval was found in up to 12% of people with focal epilepsy. Transient abnormal shortening of QT interval has been observed to occur with almost every convulsive seizure in people with temporal lobe epilepsy. Antiepileptic drugs seem to have only minor effects on the QT interval. Valproate has no direct action on cardiac repolarization, but can enhance QT prolongation of co-administered drugs which themselves lengthen QT intervals and which are metabolised by specific liver enzymes (inhibited by valproate). In contrast, rufinamide, primidone and carbamazepine have been reported to shorten QT intervals. To date, the clinical importance of acquired QT shortening is unclear and is currently under investigation. 

 

Abnormalities of cardiac repolarization are common in people with chronic epilepsy. The question is, however, whether these abnormalities are benign or whether they increase the risk for sudden cardiac death as one plausible cause for SUDEP. In two recent case reports, ventricular tachycardia and fibrillation were described shortly after convulsive attacks. Importantly, cardiological investigations after successful cardiopulmonary resuscitation were unremarkable in these epilepsy patients, suggesting that seizure-related alterations of cardiac excitability have facilitated the life-threatening ventricular tachyarrhythmia. 

 

In summary, there is evidence that cardiac repolarization and ventricular tachyarrhythmia could cause sudden death in some people with epilepsy. The most important question is whether arrhythmia-related SUDEP can be predicted and prevented. To date, it is difficult to say who would benefit from preventive measures, which actions to be taken and at what time point. In any case, a 12-lead ECG should routinely be performed in every patient at least once. Mutations linked to genetic cardiac arrhythmias are increasingly recognized in SUDEP, suggesting that a genetic screening in a subgroup of patients (to be defined) may be helpful to identify people at higher risk. Potential measures to reduce the risk or to prevent SUDEP could, however, include anti-arrhythmic medication (such as beta-blockers which are used in some forms of long QT syndrome) and implantation of a defibrillator device (to stop ventricular tachycardia). Collaborative international, multi-centre efforts have been initiated to find out whether specific ECG features as well as genetic markers are helpful to identify people at higher risk for SUDEP and to develop strategies to prevent SUDEP due to cardiac arrhythmia.

 

 

Rainer Surges

Department of Epileptology

University Hospital Bonn, Germany

Updated May 2016; Original Dec 2014

 

 

How to cite:

Surges R. SUDEP and matters of the heart. In: Hanna J, Panelli R, Jeffs T, Chapman D, editors. Continuing the global conversation [online]. SUDEP Action, SUDEP Aware & Epilepsy Australia; 2016 [retrieved day/month/year]. Available from: www.sudepglobalconversation.com.

 

 

Further reading

Ebony, or Ebz as she was known to her friends, passed away in her bedroom on Sunday, 16th May  2010 - three weeks after we celebrated her 21st birthday. We never suspected that Ebony could be having seizures...

Sophie was born a very healthy, happy little girl.  She had her first tonic-clonic seizure when she was 6 months old and it lasted 45 minutes...

Karen was 10 when she suffered her first epileptic seizure and it was shortly after that she was diagnosed with generalized epilepsy. On 7 September 2008, I received a call that no parent could imagine or should receive...

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Bagnall RD, Crompton DE, Petrovski S, Lam L, Cutmore C, Garry SI, Sadleir LG, Dibbens LM, Cairns A, Kivity S, Afawi Z, Regan BM, Duflou J, Berkovic SF, Scheffer IE, Semsarian C. Exome-based analysis of cardiac arrhythmia, respiratory control, and epilepsy genes in sudden unexpected death in epilepsy. Ann Neurol. 2016;79(4):522-34.

Surges R, Sander JW. Sudden unexpected death in epilepsy: mechanisms, prevalence, and prevention. Curr Opin Neurol 2012;25(2):201-7.

Surges R, Taggart P, Sander JW, Walker MC. Too long or too short? New insights into abnormal cardiac repolarization in people with chronic epilepsy and its potential role in sudden unexpected death. Epilepsia 2010;51(5):738-44.

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