Epileptic Heart: Difference between revisions

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==Overview==
==Overview==
Chronic [[epileptic]] episodes and the subsequent [[catecholamine]] surges and [[hypoxia|hypoxic]] events may affect the [[heart]] and [[coronary]] [[vessels]] and result in the [[dysfunction]] of the [[heart]].  This [[condition]] is known as the "epileptic heart." This concept was first described by Dr. Richard L. Verrier and his colleagues in 2020.  
Chronic [[epileptic]] episodes and the subsequent [[catecholamine]] surges and [[hypoxia|hypoxic]] events may affect the [[heart]] and [[coronary]] [[vessels]] and result in the [[dysfunction]] of the [[heart]].  This [[condition]] is known as the "epileptic heart." This concept was first described by Dr. Richard L. Verrier and his colleagues in 2020.  
==Historical Perspective==
==Historical Perspective==


*Absence of [[cardiac]] activity during [[epilepsy|epileptic seizure]], first described by Dr. A.E. Russell, an English physician, in 1906.<ref name="Russell1906">{{cite journal|last1=Russell|first1=A.E.|title=CESSATION OF THE PULSE DURING THE ONSET OF EPILEPTIC FITS,|journal=The Lancet|volume=168|issue=4325|year=1906|pages=152–154|issn=01406736|doi=10.1016/S0140-6736(01)30477-4}}</ref>
*Absence of [[cardiac]] activity during [[epilepsy|epileptic seizure]] was first described by Dr. A.E. Russell, an English physician, in 1906.<ref name="Russell1906">{{cite journal|last1=Russell|first1=A.E.|title=CESSATION OF THE PULSE DURING THE ONSET OF EPILEPTIC FITS,|journal=The Lancet|volume=168|issue=4325|year=1906|pages=152–154|issn=01406736|doi=10.1016/S0140-6736(01)30477-4}}</ref>
*The epileptic heart was first described by Drs. Verrier, Pang, Nearing, and Schachter, in 2020.<ref name="VerrierPang2020">{{cite journal|last1=Verrier|first1=Richard L.|last2=Pang|first2=Trudy D.|last3=Nearing|first3=Bruce D.|last4=Schachter|first4=Steven C.|title=The Epileptic Heart: Concept and clinical evidence|journal=Epilepsy & Behavior|volume=105|year=2020|pages=106946|issn=15255050|doi=10.1016/j.yebeh.2020.106946}}</ref>
*The epileptic heart was first described by Drs. Verrier, Pang, Nearing, and Schachter, in 2020.<ref name="VerrierPang2020">{{cite journal|last1=Verrier|first1=Richard L.|last2=Pang|first2=Trudy D.|last3=Nearing|first3=Bruce D.|last4=Schachter|first4=Steven C.|title=The Epileptic Heart: Concept and clinical evidence|journal=Epilepsy & Behavior|volume=105|year=2020|pages=106946|issn=15255050|doi=10.1016/j.yebeh.2020.106946}}</ref>


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==Pathophysiology==
==Pathophysiology==


*The exact mechanisms involved in the epileptic heart are still being elucidated. However, the conceptual framework below provides helpful information on the development of [[heart disease]] in patients with [[epilepsy]].<ref name="VerrierSchachter2018">{{cite journal|last1=Verrier|first1=Richard L.|last2=Schachter|first2=Steven C.|title=Is heart disease in chronic epilepsy a consequence of seizures or a fellow traveler?|journal=Epilepsy & Behavior|volume=86|year=2018|pages=211–213|issn=15255050|doi=10.1016/j.yebeh.2018.06.027}}</ref>
*The exact mechanisms involved in the development of the epileptic heart are still being elucidated. However, the conceptual framework below provides helpful information on the development of [[heart disease]] in patients with [[epilepsy]].<ref name="VerrierSchachter2018">{{cite journal|last1=Verrier|first1=Richard L.|last2=Schachter|first2=Steven C.|title=Is heart disease in chronic epilepsy a consequence of seizures or a fellow traveler?|journal=Epilepsy & Behavior|volume=86|year=2018|pages=211–213|issn=15255050|doi=10.1016/j.yebeh.2018.06.027}}</ref>


{{familytree/start}}
{{familytree/start}}
{{familytree | | | | | | | | | A01 | | | | | |A01=[[Epilepsy]]}}
{{familytree | | | | | | | | | | A01 | | | | | |A01=Chronic [[epilepsy]]}}
{{familytree | | | | | | | | | |!| | | | | | | | }}
{{familytree | | | | | | | | | | |!| | | | | | | | }}
{{familytree | | | | | | | | | B01 | | | | | |B01=[[Cardiac]] effects}}
{{familytree | | |,|-|-|-|v|-|-|-|+|-|-|-|v|-|-|-|.| }}
{{familytree | | |,|-|-|-|-|-|-|^|-|-|-|-|-|-|.| }}
{{familytree | | C01 | | D01 | | D03 | | D05 | | C03 |C01=Repeated [[hypoxia]] and subsequent [[myocardial ischemia]]|C03=Catecholamine-induced cardiotoxicity|D01=Accelerated [[atherosclerosis]]|D03=[[Myocardial]] stunning|D05=Vacuolization of myocytes and [[fibrosis]]}}
{{familytree | | C01 | | | | | | | | | | | | C03 |C01=Repeated [[hypoxia]] and subsequent [[myocardial ischemia]]|C03=Cathecholamines-induced cardiotoxicity}}
{{familytree | | |!| | | |!| | | |!| | | |!| | | |!| }}
{{familytree | | |!| | | | | | | | | | | | | |!| }}
 
{{familytree | | |)|-|-|-|-|-|-|v|-|-|-|-|-|-|(| | | }}
{{familytree | | |`|-|-|-|^|-|-| E01 |-|-|^|-|-|-|'|E01=<div style="float: left; text-align: center; width: 20; padding:1em;"> '''<span style="color:navy;">Epileptic Heart</span>'''<br>
{{familytree | | |!| | | | | | |!| | | | | | |!| | | }}
{{familytree | | D01 | | | | | D03 | | | | | D05 |D01=Accelerated [[atherosclerosis]]|D03=[[Myocardial]] stunning|D05=Vacuolization of myocytes and [[fibrosis]]}}
{{familytree | | | | | | | | | |!| | | | | | | | }}
{{familytree | | | | | | | | | E01 | | | | | | | |E01=<div style="float: left; text-align: left; width: 20; padding:1em;"> '''<span style="color:navy;">Epileptic Heart</span>'''<br>
----
----
<span style="color:navy;">❑ </span> <span style="color:navy;">Instability in [[cardiac]] electrical system </span> <br> <span style="color:navy;">❑</span> <span style="color:navy;">T wave alternans</span> </div>}}
<span style="color:navy;">❑ </span> <span style="color:navy;">Cardiac electrical instability </span> <br> <span style="color:navy;">❑</span> <span style="color:navy;">[[T wave alternans]]</span> </div>}}
{{familytree/end}}
{{familytree/end}}
===Epilepsy and Cardiac Arrhythmia===
===Epilepsy and Cardiac Arrhythmia===
[[Cardiac]] [[arrhythmia]] have long been observed in [[patients]] with [[epilepsy]]. Three different mechanisms explain this association:<ref name="Shmuelyvan der Lende2017">{{cite journal|last1=Shmuely|first1=S.|last2=van der Lende|first2=M.|last3=Lamberts|first3=R.J.|last4=Sander|first4=J.W.|last5=Thijs|first5=R.D.|title=The heart of epilepsy: Current views and future concepts|journal=Seizure|volume=44|year=2017|pages=176–183|issn=10591311|doi=10.1016/j.seizure.2016.10.001}}</ref>
[[Cardiac]] [[arrhythmia]]<nowiki/>s have long been observed in [[patients]] with [[epilepsy]]. Three different mechanisms explain this association:<ref name="Shmuelyvan der Lende2017">{{cite journal|last1=Shmuely|first1=S.|last2=van der Lende|first2=M.|last3=Lamberts|first3=R.J.|last4=Sander|first4=J.W.|last5=Thijs|first5=R.D.|title=The heart of epilepsy: Current views and future concepts|journal=Seizure|volume=44|year=2017|pages=176–183|issn=10591311|doi=10.1016/j.seizure.2016.10.001}}</ref>


*Direct (causal) pathway
*Direct (causal) pathway
*Co-existence of [[epilepsy]] and [[cardiac]] [[arrhythmia]] in the context of [[genetic]] [[disorders]]:
*Co-existence of [[epilepsy]] and [[cardiac]] [[arrhythmia]] in the context of [[genetic]] [[disorders]]:
**[[Genes]] involved in [[epilepsy]]: [[SCN1A]], [[KCNA1]], and [[SCN8A]]
**[[Genes]] involved in [[epilepsy]]: [[SCN1A]], [[KCNA1]], and [[SCN8A]]
**[[Genes]] involved in [[heart]] [[diseases]]: [[KCNQ1]], [[KCNH2]], [[SCN5A]], [[RYR2]]
**[[Genes]] involved in inherited arrhythmogenic [[heart]] [[diseases]]: [[KCNQ1]], [[KCNH2]], [[SCN5A]], [[RYR2]]
*Resultant association:
*Resultant association:
**Certain [[anti-epileptic]] [[medications|medications with sodium channel blocking properties]] have been known to cause [[arrhythmia]].
**Certain [[anti-epileptic]] [[medications|medications with sodium channel blocking properties]] have been known to cause [[arrhythmia]].
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Three mechanisms have been suggested to explain the association between [[epilepsy]] and [[structural heart disease]]:<ref name="Shmuelyvan der Lende2017">{{cite journal|last1=Shmuely|first1=S.|last2=van der Lende|first2=M.|last3=Lamberts|first3=R.J.|last4=Sander|first4=J.W.|last5=Thijs|first5=R.D.|title=The heart of epilepsy: Current views and future concepts|journal=Seizure|volume=44|year=2017|pages=176–183|issn=10591311|doi=10.1016/j.seizure.2016.10.001}}</ref>
Three mechanisms have been suggested to explain the association between [[epilepsy]] and [[structural heart disease]]:<ref name="Shmuelyvan der Lende2017">{{cite journal|last1=Shmuely|first1=S.|last2=van der Lende|first2=M.|last3=Lamberts|first3=R.J.|last4=Sander|first4=J.W.|last5=Thijs|first5=R.D.|title=The heart of epilepsy: Current views and future concepts|journal=Seizure|volume=44|year=2017|pages=176–183|issn=10591311|doi=10.1016/j.seizure.2016.10.001}}</ref>


*Direct (causal) pathway in which [[structural heart disease]] may result in [[stroke]] and subsequent [[epilepsy]].  
*Direct (causal) pathway in which [[structural heart disease]] may result in embolic [[stroke]] and subsequent [[epilepsy]].
*Common [[risk factors]] contribute to the development of both [[epilepsy]] and [[structural heart disease]].
*Common [[risk factors]] contribute to the development of both [[epilepsy]] and [[structural heart disease]].
*Resultant pathway:  
*Resultant pathway:  
**[[Epilepsy]] may stimulate [[myocardial ischemia]] and [[Takotsubo syndrome|a Takotsubo-like syndrome]].
**[[Epilepsy]] may stimulate [[myocardial ischemia]] and [[Takotsubo syndrome|a Takotsubo-like syndrome]].
**[[Anti-epileptic|Certain anti-epileptic]] [[medications]] contribute to the development of [[arteriosclerosis]], [[weight]] gain, [[non alcoholic fatty liver disease|non-alcoholic fatty liver disease]] and [[metabolic syndrome]] and result in a poorer [[cardiovascular]] risk profile.
**[[Anti-epileptic|Certain anti-epileptic]] [[medications]] contribute to the development of [[arteriosclerosis]], [[weight]] gain, [[non alcoholic fatty liver disease|non-alcoholic fatty liver disease]] and [[metabolic syndrome]] and result in a poorer [[cardiovascular]] risk profile.<ref name="Hamed2014">{{cite journal|last1=Hamed|first1=Sherifa A.|title=Atherosclerosis in epilepsy: Its causes and implications|journal=Epilepsy & Behavior|volume=41|year=2014|pages=290–296|issn=15255050|doi=10.1016/j.yebeh.2014.07.003}}</ref><ref name="MintzerTrinka2018">{{cite journal|last1=Mintzer|first1=Scott|last2=Trinka|first2=Eugen|last3=Kraemer|first3=Günter|last4=Chervoneva|first4=Inna|last5=Werhahn|first5=Konrad J.|title=Impact of carbamazepine, lamotrigine, and levetiracetam on vascular risk markers and lipid-lowering agents in the elderly|journal=Epilepsia|volume=59|issue=10|year=2018|pages=1899–1907|issn=00139580|doi=10.1111/epi.14554}}</ref>
*On microscopic histopathological analysis of patients with [[epilepsy]] a range of pathologies has been reported. These changes include [[fibrosis]], myofibrillar degeneration, [[ventricular hypertrophy]], focal [[myocardial]] fibrosis, perivascular and interstitial myocardial fibrosis, and mild to moderate coronary atherosclerosis.<ref name="LeestmaWalczak1989">{{cite journal|last1=Leestma|first1=Jan E.|last2=Walczak|first2=Thaddeus|last3=Hughes|first3=John R.|last4=Kalelkar|first4=Mitra B.|last5=Teas|first5=Shaku S.|title=A prospective study on sudden unexpected death in epilepsy|journal=Annals of Neurology|volume=26|issue=2|year=1989|pages=195–203|issn=0364-5134|doi=10.1002/ana.410260203}}</ref><ref name="FalconerRajs1976">{{cite journal|last1=Falconer|first1=Bertil|last2=Rajs|first2=Jovan|title=Post-mortem findings of cardiac lesions in epileptics: A preliminary report|journal=Forensic Science|volume=8|year=1976|pages=63–71|issn=03009432|doi=10.1016/0300-9432(76)90048-0}}</ref><ref name="BardaiBlom2015">{{cite journal|last1=Bardai|first1=Abdennasser|last2=Blom|first2=Marieke T|last3=van Noord|first3=Charlotte|last4=Verhamme|first4=Katia M|last5=Sturkenboom|first5=Miriam C J M|last6=Tan|first6=Hanno L|title=Sudden cardiac death is associated both with epilepsy and with use of antiepileptic medications|journal=Heart|volume=101|issue=1|year=2015|pages=17–22|issn=1355-6037|doi=10.1136/heartjnl-2014-305664}}</ref>
 
==Causes==
[[Epileptic heart]] may be caused by the following:
 
*Accelerated [[atherosclerotic]] process due to side effect of longstanding [[antiepileptic]] therapy such as [[carbamazepine]], [[gabapentin]] on [[lipid profile]] <ref name="HookanaAnsakorpi2016">{{cite journal|last1=Hookana|first1=Eeva|last2=Ansakorpi|first2=Hanna|last3=Kortelainen|first3=Marja-Leena|last4=Junttila|first4=M. Juhani|last5=Kaikkonen|first5=Kari S|last6=Perkiömäki|first6=Juha|last7=Huikuri|first7=Heikki V|title=Antiepileptic medications and the risk for sudden cardiac death caused by an acute coronary event: a prospective case-control study|journal=Annals of Medicine|volume=48|issue=1-2|year=2016|pages=111–117|issn=0785-3890|doi=10.3109/07853890.2016.1140225}}</ref><ref name="GranbichlerOberaigner2014">{{cite journal|last1=Granbichler|first1=Claudia A.|last2=Oberaigner|first2=Willi|last3=Kuchukhidze|first3=Giorgi|last4=Bauer|first4=Gerhard|last5=Ndayisaba|first5=Jean-Pierre|last6=Seppi|first6=Klaus|last7=Trinka|first7=Eugen|title=Cause-specific mortality in adult epilepsy patients from Tyrol, Austria: hospital-based study|journal=Journal of Neurology|volume=262|issue=1|year=2014|pages=126–133|issn=0340-5354|doi=10.1007/s00415-014-7536-z}}</ref>
*Increased occurrence of [[arrhythmia]] due to hyperadrenergic state in [[seizure]] episodes <ref name="Baysal-KiracSerbest2017">{{cite journal|last1=Baysal-Kirac|first1=Leyla|last2=Serbest|first2=Nail Güven|last3=Şahin|first3=Erdi|last4=Dede|first4=Hava Özlem|last5=Gürses|first5=Candan|last6=Gökyiğit|first6=Ayşen|last7=Bebek|first7=Nerses|last8=Bilge|first8=Ahmet Kaya|last9=Baykan|first9=Betül|title=Analysis of heart rate variability and risk factors for SUDEP in patients with drug-resistant epilepsy|journal=Epilepsy & Behavior|volume=71|year=2017|pages=60–64|issn=15255050|doi=10.1016/j.yebeh.2017.04.018}}</ref>
*[[Cardiac]] autonomic dysfunction due to repeated [[siezue]] episodes, a predisposing factor of [[arrhythmia]] <ref name="DeGiorgioMiller2010">{{cite journal|last1=DeGiorgio|first1=Christopher M.|last2=Miller|first2=Patrick|last3=Meymandi|first3=Sheba|last4=Chin|first4=Alex|last5=Epps|first5=Jordan|last6=Gordon|first6=Steven|last7=Gornbein|first7=Jeffrey|last8=Harper|first8=Ronald M.|title=RMSSD, a measure of vagus-mediated heart rate variability, is associated with risk factors for SUDEP: The SUDEP-7 Inventory|journal=Epilepsy & Behavior|volume=19|issue=1|year=2010|pages=78–81|issn=15255050|doi=10.1016/j.yebeh.2010.06.011}}</ref>
*[[Arrhythmogenic]] effect of [[antiepileptic]] drugs due to blockage of [[sodium channels ]] on [[heart]] <ref name="ZaccaraLattanzi2019">{{cite journal|last1=Zaccara|first1=Gaetano|last2=Lattanzi|first2=Simona|title=Comorbidity between epilepsy and cardiac arrhythmias: Implication for treatment|journal=Epilepsy & Behavior|volume=97|year=2019|pages=304–312|issn=15255050|doi=10.1016/j.yebeh.2019.05.038}}</ref><ref name="RenouxDell'Aniello2015">{{cite journal|last1=Renoux|first1=Christel|last2=Dell'Aniello|first2=Sophie|last3=Saarela|first3=Olli|last4=Filion|first4=Kristian B|last5=Boivin|first5=Jean-François|title=Antiepileptic drugs and the risk of ischaemic stroke and myocardial infarction: a population-based cohort study|journal=BMJ Open|volume=5|issue=8|year=2015|pages=e008365|issn=2044-6055|doi=10.1136/bmjopen-2015-008365}}</ref>
 
*Susceptibility  to [[ventricular fibrillation]] before or after [[seizure]] episodes <ref name="KiechlBardai2012">{{cite journal|last1=Kiechl|first1=Stefan|last2=Bardai|first2=Abdennasser|last3=Lamberts|first3=Robert J.|last4=Blom|first4=Marieke T.|last5=Spanjaart|first5=Anne M.|last6=Berdowski|first6=Jocelyn|last7=van der Staal|first7=Sebastiaan R.|last8=Brouwer|first8=Henk J.|last9=Koster|first9=Rudolph W.|last10=Sander|first10=Josemir W.|last11=Thijs|first11=Roland D.|last12=Tan|first12=Hanno L.|title=Epilepsy Is a Risk Factor for Sudden Cardiac Arrest in the General Population|journal=PLoS ONE|volume=7|issue=8|year=2012|pages=e42749|issn=1932-6203|doi=10.1371/journal.pone.0042749}}</ref>
*Structural [[myocardium]] damage due to repeated [[seizures]], such as [[myocardial]] calcified lesions, myocardial stiffness, [[cardiomegaly]], [[ventricular hypertrophy]], [[left artial dilation]] <ref name="FineschiSilver2005">{{cite journal|last1=Fineschi|first1=V.|last2=Silver|first2=M.D.|last3=Karch|first3=S.B.|last4=Parolini|first4=M.|last5=Turillazzi|first5=E.|last6=Pomara|first6=C.|last7=Baroldi|first7=G.|title=Myocardial disarray: an architectural disorganization linked with adrenergic stress?|journal=International Journal of Cardiology|volume=99|issue=2|year=2005|pages=277–282|issn=01675273|doi=10.1016/j.ijcard.2004.01.022}}</ref><ref name="ZhaoZhang2019">{{cite journal|last1=Zhao|first1=Haiting|last2=Zhang|first2=Honghai|last3=Schoen|first3=Frederick J.|last4=Schachter|first4=Steven C.|last5=Feng|first5=Hua-Jun|title=Repeated generalized seizures can produce calcified cardiac lesions in DBA/1 mice|journal=Epilepsy & Behavior|volume=95|year=2019|pages=169–174|issn=15255050|doi=10.1016/j.yebeh.2019.04.010}}</ref>
*Neurogenic stunned myocardium similar to [[tukotsubo]], a reversible [[cardiomyopathy]] after a [[seizure]] episode <ref name="ChinBranch2005">{{cite journal|last1=Chin|first1=P. S.|last2=Branch|first2=K. R.|last3=Becker|first3=K. J.|title=Postictal neurogenic stunned myocardium|journal=Neurology|volume=64|issue=11|year=2005|pages=1977–1978|issn=0028-3878|doi=10.1212/01.WNL.0000163858.77494.7A}}</ref>
*Increased occurrence of [[atrial fibrillation ]] after [[seizure]] episode <ref name="NaylorChurilov2018">{{cite journal|last1=Naylor|first1=Jillian|last2=Churilov|first2=Leonid|last3=Johnstone|first3=Benjamin|last4=Guo|first4=Ruibing|last5=Xiong|first5=Yunyun|last6=Koome|first6=Miriam|last7=Chen|first7=Ziyi|last8=Thevathasan|first8=Arthur|last9=Chen|first9=Ziyuan|last10=Liu|first10=Xinfeng|last11=Kwan|first11=Patrick|last12=Campbell|first12=Bruce C.V.|title=The Association Between Atrial Fibrillation and Poststroke Seizures is Influenced by Ethnicity and Environmental Factors|journal=Journal of Stroke and Cerebrovascular Diseases|volume=27|issue=10|year=2018|pages=2755–2760|issn=10523057|doi=10.1016/j.jstrokecerebrovasdis.2018.05.044}}</ref>
 
==Differentiating [[epileptic heart]] from other Diseases==
 
*[[Epileptic heart]]  must be differentiated from other diseases that cause  [[loss of consciousness]] or [[sudden death]]  such as:
 
:*Sudden unexpected death in epilepsy( SUDEP)
:*[[Convulsion syncope]]
:*[[Epileptic seizure]]
 
{| style="border: 2px solid #4479BA; align=" left"
! style="width: 200px; background: #4479BA;" |{{fontcolor|#FFF|[[Epileptic heart]]}}
! style="width: 300px; background: #4479BA;" |{{fontcolor|#FFF|[[Sudden unexpected death in epilepsy]] [[SUDEP]]}}
! style="width: 300px; background: #4479BA;" |{{fontcolor|#FFF|[[Convulsion syncope]]}}
! style="width: 300px; background: #4479BA;" |{{fontcolor|#FFF|[[Epileptic seizure]]}}
|-
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*Structural and functional heart disease as a result of autonomous dysfunction due to the longstanding effect of [[seizure]] episodes on the [[heart]]
*Increased occurrence of [[sudden cardiac death]] related or unrelated to [[siezue]] episodes <ref name="ZackLuncheon2018">{{cite journal|last1=Zack|first1=Matthew|last2=Luncheon|first2=Cecily|title=Adults with an epilepsy history, notably those 45–64 years old or at the lowest income levels, more often report heart disease than adults without an epilepsy history|journal=Epilepsy & Behavior|volume=86|year=2018|pages=208–210|issn=15255050|doi=10.1016/j.yebeh.2018.05.021}}</ref>
*Increased occurrence of [[coronary artery disease]] in earlier age compared with patients without [[epilepsy]]
*[[Myocardial injury ]] due to  repeated [[sympathetic]] stimulation of [[seizure]] episodes
*[[Hypertrophy]] in the ventricular myocardium
*Increased occurrence of [[arrhythmia]] due to conduction, [[repolarization abnormality]], [[cardiac electerical instability]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*[[Sudden death]] related to [[pulmonary dysfunction]] and [[apnea]] in the [[postictal period]]<ref name="NashefSo2012">{{cite journal|last1=Nashef|first1=Lina|last2=So|first2=Elson L.|last3=Ryvlin|first3=Philippe|last4=Tomson|first4=Torbjörn|title=Unifying the definitions of sudden unexpected death in epilepsy|journal=Epilepsia|volume=53|issue=2|year=2012|pages=227–233|issn=00139580|doi=10.1111/j.1528-1167.2011.03358.x}}</ref>
*Not categorized as [[sudden cardiac death]]
*Common age:20-40 years old<ref name="TomsonWalczak2005">{{cite journal|last1=Tomson|first1=Torbjorn|last2=Walczak|first2=Ted|last3=Sillanpaa|first3=Matti|last4=Sander|first4=Josemir W. A. S.|title=Sudden Unexpected Death in Epilepsy: A Review of Incidence and Risk Factors|journal=Epilepsia|volume=46|issue=s11|year=2005|pages=54–61|issn=0013-9580|doi=10.1111/j.1528-1167.2005.00411.x}}</ref>
*[[Risk factors]]: [[youth]], early age at [[seizure]] onset, Presence of [[generalized tonic clonic seizure]], [[male]], being in bed at the time of [[death]]<ref name="SurgesThijs2009">{{cite journal|last1=Surges|first1=Rainer|last2=Thijs|first2=Roland D.|last3=Tan|first3=Hanno L.|last4=Sander|first4=Josemir W.|title=Sudden unexpected death in epilepsy: risk factors and potential pathomechanisms|journal=Nature Reviews Neurology|volume=5|issue=9|year=2009|pages=492–504|issn=1759-4758|doi=10.1038/nrneurol.2009.118}}</ref>
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*[[Cardiac]] [[syncope]] and [[seizure]] preceding each other
*[[Cardiac]] [[syncope]] definition: brief, reversible, [[transient loss of consciousness]] due to [[cerebral hypoperfusion]] following [[reflex mediated syncope]], [[structural heart disease]], [[arrhythmia]], [[orthostasis hypotension]]
*[[Seizure]] preceding  ictal [[sinus tachycardia]], [[ventricular fibrillation]], [[bradycardia]],[[asystole]]<ref name="ReevesNollet1996">{{cite journal|last1=Reeves|first1=Andrew L.|last2=Nollet|first2=Kenneth E.|last3=Klass|first3=Donald W.|last4=Sharbrough|first4=Frank W.|last5=So|first5=Elson L.|title=The Ictal Bradycardia Syndrome|journal=Epilepsia|volume=37|issue=10|year=1996|pages=983–987|issn=0013-9580|doi=10.1111/j.1528-1157.1996.tb00536.x}}</ref>
*[[Arrhythmia]] preceding [[seizure]]
*Identifying same genes mutation in [[brain]] and [[cardiac]] which are responsible of [[epilepsy]] and [[arrhythmia]]<ref name="NashefWalker1996">{{cite journal|last1=Nashef|first1=L|last2=Walker|first2=F|last3=Allen|first3=P|last4=Sander|first4=J W|last5=Shorvon|first5=S D|last6=Fish|first6=D R|title=Apnoea and bradycardia during epileptic seizures: relation to sudden death in epilepsy.|journal=Journal of Neurology, Neurosurgery & Psychiatry|volume=60|issue=3|year=1996|pages=297–300|issn=0022-3050|doi=10.1136/jnnp.60.3.297}}</ref>
 
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*[[Transient loss of consciousness]] due to abnormal neuronal discharge in the [[brain]]
*Repetitive
 
*High frequency of misdiagnosis with [[cardiac syncope]]
*[[Tongue biting]]
*[[Sense of deja vu]] or [[jamais vu]] before spells, preoccupation, [[hallucination]],[[ mood changes]], [[somatosensory auras]], [[trembling]]
*[[Unusual posturing]], [[Jerking limbs]]
*[[Blue face]], [[acrocyanosis]]
*Postictall blurred period
|-
|}
 
==Epidemiology and Demographics==
 
*The [[incidence]] of [[heart disease]] such as [[coronary artery disease]], [[heart attack]] in [[patients]] with [[epilepsy]] is approximately 25600 per 100,000 individuals between 45-64 years old. This amount in [[patients]] without [[epilepsy]] is 11500 per 100,000 individuals between 45-64 years old. <ref name="ZackLuncheon2018">{{cite journal|last1=Zack|first1=Matthew|last2=Luncheon|first2=Cecily|title=Adults with an epilepsy history, notably those 45–64 years old or at the lowest income levels, more often report heart disease than adults without an epilepsy history|journal=Epilepsy & Behavior|volume=86|year=2018|pages=208–210|issn=15255050|doi=10.1016/j.yebeh.2018.05.021}}</ref>
*In 2018, the incidence of [[sudden cardiac death ]] in epileptic patients was estimated to be 4400 cases per 100,000 individuals in the united states which was 4.5 fold of [[SUDEP]] cases. <ref name="BenjaminVirani2018">{{cite journal|last1=Benjamin|first1=Emelia J.|last2=Virani|first2=Salim S.|last3=Callaway|first3=Clifton W.|last4=Chamberlain|first4=Alanna M.|last5=Chang|first5=Alexander R.|last6=Cheng|first6=Susan|last7=Chiuve|first7=Stephanie E.|last8=Cushman|first8=Mary|last9=Delling|first9=Francesca N.|last10=Deo|first10=Rajat|last11=de Ferranti|first11=Sarah D.|last12=Ferguson|first12=Jane F.|last13=Fornage|first13=Myriam|last14=Gillespie|first14=Cathleen|last15=Isasi|first15=Carmen R.|last16=Jiménez|first16=Monik C.|last17=Jordan|first17=Lori Chaffin|last18=Judd|first18=Suzanne E.|last19=Lackland|first19=Daniel|last20=Lichtman|first20=Judith H.|last21=Lisabeth|first21=Lynda|last22=Liu|first22=Simin|last23=Longenecker|first23=Chris T.|last24=Lutsey|first24=Pamela L.|last25=Mackey|first25=Jason S.|last26=Matchar|first26=David B.|last27=Matsushita|first27=Kunihiro|last28=Mussolino|first28=Michael E.|last29=Nasir|first29=Khurram|last30=O’Flaherty|first30=Martin|last31=Palaniappan|first31=Latha P.|last32=Pandey|first32=Ambarish|last33=Pandey|first33=Dilip K.|last34=Reeves|first34=Mathew J.|last35=Ritchey|first35=Matthew D.|last36=Rodriguez|first36=Carlos J.|last37=Roth|first37=Gregory A.|last38=Rosamond|first38=Wayne D.|last39=Sampson|first39=Uchechukwu K.A.|last40=Satou|first40=Gary M.|last41=Shah|first41=Svati H.|last42=Spartano|first42=Nicole L.|last43=Tirschwell|first43=David L.|last44=Tsao|first44=Connie W.|last45=Voeks|first45=Jenifer H.|last46=Willey|first46=Joshua Z.|last47=Wilkins|first47=John T.|last48=Wu|first48=Jason HY.|last49=Alger|first49=Heather M.|last50=Wong|first50=Sally S.|last51=Muntner|first51=Paul|title=Heart Disease and Stroke Statistics—2018 Update: A Report From the American Heart Association|journal=Circulation|volume=137|issue=12|year=2018|issn=0009-7322|doi=10.1161/CIR.0000000000000558}}</ref>
*The [[incidence]] of [[heart disease]] in [[patients]] with [[epilepsy]] was 9% higher than [[patients]] without [[epilepsy]]. <ref name="ZackLuncheon2018">{{cite journal|last1=Zack|first1=Matthew|last2=Luncheon|first2=Cecily|title=Adults with an epilepsy history, notably those 45–64 years old or at the lowest income levels, more often report heart disease than adults without an epilepsy history|journal=Epilepsy & Behavior|volume=86|year=2018|pages=208–210|issn=15255050|doi=10.1016/j.yebeh.2018.05.021}}</ref>
 
===Age===
 
*[[Sudden cardiac death]] associated with chronic [[epilepsy]]  is more commonly observed among patients older than 40 years old. <ref name="SteckerReinier2013">{{cite journal|last1=Stecker|first1=Eric C.|last2=Reinier|first2=Kyndaron|last3=Uy-Evanado|first3=Audrey|last4=Teodorescu|first4=Carmen|last5=Chugh|first5=Harpriya|last6=Gunson|first6=Karen|last7=Jui|first7=Jonathan|last8=Chugh|first8=Sumeet S.|title=Relationship Between Seizure Episode and Sudden Cardiac Arrest in Patients With Epilepsy|journal=Circulation: Arrhythmia and Electrophysiology|volume=6|issue=5|year=2013|pages=912–916|issn=1941-3149|doi=10.1161/CIRCEP.113.000544}}</ref>
*[[Cardiac]] diseases associated to the [[chronic]] [[epilepsy]] is more commonly observed among patients between 45-64 years old. <ref name="ZackLuncheon2018">{{cite journal|last1=Zack|first1=Matthew|last2=Luncheon|first2=Cecily|title=Adults with an epilepsy history, notably those 45–64 years old or at the lowest income levels, more often report heart disease than adults without an epilepsy history|journal=Epilepsy & Behavior|volume=86|year=2018|pages=208–210|issn=15255050|doi=10.1016/j.yebeh.2018.05.021}}</ref>
 
===Gender===
 
*Males are more commonly affected with the epileptic heart than females.
 
===Race===
 
*There is no racial predilection for epileptic heart.
 
==Risk Factors==
 
*Common [[risk factors]] in the development of [[epileptic heart]] may include:
*Low [[socioeconomic status]] <ref name="ZackLuncheon2018">{{cite journal|last1=Zack|first1=Matthew|last2=Luncheon|first2=Cecily|title=Adults with an epilepsy history, notably those 45–64 years old or at the lowest income levels, more often report heart disease than adults without an epilepsy history|journal=Epilepsy & Behavior|volume=86|year=2018|pages=208–210|issn=15255050|doi=10.1016/j.yebeh.2018.05.021}}</ref>
*Long-standing [[antiepileptic]] therapy
*[[Hypertension]]
*[[Hyperlipidemia]]
*[[ Diabetes mellitus]]
*[[Male sex]]
*[[Smoking]]
*Aging
*Progression of underlying cardiac disease
 
==Screening==
Currently, there is no guideline statement that recommended routine [[cardiac]] evaluation of [[patients]] with [[epilepsy]]. However, a resting 12-lead [[EKG]] and/or ambulatory [[EKG]] patch recording may be useful in identifying the [[patients]] at risk of [[cardiac]] pathology and further follow the progression of their [[cardiac]] pathology. <ref name="VerrierPang2020">{{cite journal|last1=Verrier|first1=Richard L.|last2=Pang|first2=Trudy D.|last3=Nearing|first3=Bruce D.|last4=Schachter|first4=Steven C.|title=The Epileptic Heart: Concept and clinical evidence|journal=Epilepsy & Behavior|volume=105|year=2020|pages=106946|issn=15255050|doi=10.1016/j.yebeh.2020.106946}}</ref>
==Natural History, Complications and Prognosis==
 
*[[Patients]] with [[epileptic heart]] suffer from chronic [[epilepsy]] and [[antiepileptic drug]] resistance for many years.
*Early clinical features include manifestation related to [[cardiac involvement]] such as [[syncope]], [[chest discomfort]], [[exertional dyspnea]], and [[palpitation]].
*[[Patients]] with chronic [[epilepsy]] may progress to develop complications of [[arrhythmia]] and [[myocardial ischemia]].
*Common [[complications]] of the epileptic [[heart]] include [[coronary artery disease]], [[heart failure]], [[sudden cardiac arrest]], [[sudden cardiac death]].
*[[Prognosis]] is generally poor, and the 1-year mortality of [[patients]] with chronic [[epilepsy]] due to [[sudden cardiac death]] is approximately 4.4%. <ref name="BenjaminVirani2018">{{cite journal|last1=Benjamin|first1=Emelia J.|last2=Virani|first2=Salim S.|last3=Callaway|first3=Clifton W.|last4=Chamberlain|first4=Alanna M.|last5=Chang|first5=Alexander R.|last6=Cheng|first6=Susan|last7=Chiuve|first7=Stephanie E.|last8=Cushman|first8=Mary|last9=Delling|first9=Francesca N.|last10=Deo|first10=Rajat|last11=de Ferranti|first11=Sarah D.|last12=Ferguson|first12=Jane F.|last13=Fornage|first13=Myriam|last14=Gillespie|first14=Cathleen|last15=Isasi|first15=Carmen R.|last16=Jiménez|first16=Monik C.|last17=Jordan|first17=Lori Chaffin|last18=Judd|first18=Suzanne E.|last19=Lackland|first19=Daniel|last20=Lichtman|first20=Judith H.|last21=Lisabeth|first21=Lynda|last22=Liu|first22=Simin|last23=Longenecker|first23=Chris T.|last24=Lutsey|first24=Pamela L.|last25=Mackey|first25=Jason S.|last26=Matchar|first26=David B.|last27=Matsushita|first27=Kunihiro|last28=Mussolino|first28=Michael E.|last29=Nasir|first29=Khurram|last30=O’Flaherty|first30=Martin|last31=Palaniappan|first31=Latha P.|last32=Pandey|first32=Ambarish|last33=Pandey|first33=Dilip K.|last34=Reeves|first34=Mathew J.|last35=Ritchey|first35=Matthew D.|last36=Rodriguez|first36=Carlos J.|last37=Roth|first37=Gregory A.|last38=Rosamond|first38=Wayne D.|last39=Sampson|first39=Uchechukwu K.A.|last40=Satou|first40=Gary M.|last41=Shah|first41=Svati H.|last42=Spartano|first42=Nicole L.|last43=Tirschwell|first43=David L.|last44=Tsao|first44=Connie W.|last45=Voeks|first45=Jenifer H.|last46=Willey|first46=Joshua Z.|last47=Wilkins|first47=John T.|last48=Wu|first48=Jason HY.|last49=Alger|first49=Heather M.|last50=Wong|first50=Sally S.|last51=Muntner|first51=Paul|title=Heart Disease and Stroke Statistics—2018 Update: A Report From the American Heart Association|journal=Circulation|volume=137|issue=12|year=2018|issn=0009-7322|doi=10.1161/CIR.0000000000000558}}</ref>
 
==Diagnosis==
===Diagnostic Criteria===
 
*The diagnosis of the epileptic heart is made when the following  diagnostic criteria are met:
 
:*Resistant [[epilepsy]]
:*Longstanding use of [[antiepileptic]] drugs
:*Presence of  arrhythmia syncope and high level of [[T waves]] alternance  as a marker of [[repolarization abnormality]] and [[ventricular fibrillation]] on [[ECG]]
:*Presence of [[ischemic heart disease]] earlier than the common age
:*Evidence of [[myocardial injury]] such as  high level of [[troponin I]] <ref name="NassMotloch2019">{{cite journal|last1=Nass|first1=Robert D.|last2=Motloch|first2=Lukas J.|last3=Paar|first3=Vera|last4=Lichtenauer|first4=Michael|last5=Baumann|first5=Jan|last6=Zur|first6=Berndt|last7=Hoppe|first7=Uta C.|last8=Holdenrieder|first8=Stefan|last9=Elger|first9=Christian E.|last10=Surges|first10=Rainer|title=Blood markers of cardiac stress after generalized convulsive seizures|journal=Epilepsia|volume=60|issue=2|year=2019|pages=201–210|issn=0013-9580|doi=10.1111/epi.14637}}</ref>
 
===Hisory and Symptoms===
 
*[[Symptoms]] of the [[epileptic heart]] may include the following:
 
:*Abrupt [[palpitation]]
:*[[Shortness of breath]]
:*[[Angina pectori]]
:*[[lightheadness]]
:*[[Dizziness]]
:*[[Falling]]
:*[[Near falling]]
 
===Physical Examination===
 
*Physical examination associated with [[epilepsy]] include:
 
:*[[Automatic behaviors]]
:*[[Upward eye-rolling]]
:*[[Unconsciousness]]
:*[[Drolling]]
:*[[Cyanosis]]
:*[[Tachycardia]]
:*[[Hypertension]]
:*[[Postictal drowsiness]]
:*[[Fever]]
:*[[Mydriasis]]
:*[[Nystagmus]]
:*[[Urine]] and [[fecal incontinence]]
:*[[Disorientation]] to person, place, time
:*[[Altered mental status]]
 
*[[Physical examination]] associated with [[heart]] involvement in chronic [[epilepsy]] may include:
 
:*[[Syncope]]
:*[[Leg edema]]
:*Elevated [[JVP]]
:*[[S3]],[[S4]]
:*[[Tachypnea]]
:*[[ Hypotension]]
:*[[ Pulsus alternans]]
:*[[Systolic murmur]] in [[heart apex]]
:*[[Irregular pulses]]
 
===Laboratory Findings===
Common laboratory findings related to [[epileptic heart]] may include:
 
*An elevated concentration of serum [[troponin I]] as the  marker of [[ myocardial injury]] in patients with [[generalized tonic-clonic seizure]] <ref name="HajsadeghiAfsharian2009">{{cite journal|last1=Hajsadeghi|first1=Shekoufeh|last2=Afsharian|first2=Shila|last3=Fereshtehnejad|first3=Seyed-Mohammad|last4=Keramati|first4=Mohammad Reza|last5=Mollahoseini|first5=Reza|title=Serum Levels of Cardiac Troponin I in Patients with Uncomplicated Epileptic Seizure|journal=Archives of Medical Research|volume=40|issue=1|year=2009|pages=24–28|issn=01884409|doi=10.1016/j.arcmed.2008.10.002}}</ref>
*Increased [[CRP]], [[lipid]] profile due to induction of [[cytochrome P450]]  by [[antiepileptic]] drugs such as [[carbamazepine]], [[gabapentin]] <ref name="MintzerMiller2016">{{cite journal|last1=Mintzer|first1=Scott|last2=Miller|first2=Rachael|last3=Shah|first3=Krunal|last4=Chervoneva|first4=Inna|last5=Nei|first5=Maromi|last6=Skidmore|first6=Christopher|last7=Sperling|first7=Michael R.|title=Long-term effect of antiepileptic drug switch on serum lipids and C-reactive protein|journal=Epilepsy & Behavior|volume=58|year=2016|pages=127–132|issn=15255050|doi=10.1016/j.yebeh.2016.02.023}}</ref>
 
===Electrocardiogram===
An [[ECG]] may be helpful in the diagnosis of [[epileptic heart]]. Findings on an [[ECG]] suggestive of effects of [[seizure]] on the [[heart]] include: <ref name="M. RamadanEl-Shahat2013">{{cite journal|last1=M. Ramadan|first1=Mahmoud|last2=El-Shahat|first2=Nader|last3=A. Omar|first3=Ashraf|last4=Gomaa|first4=Mohamed|last5=Belal|first5=Tamer|last6=A. Sakr|first6=Sherif|last7=Abu-Hegazy|first7=Mohammad|last8=Hakim|first8=Hazem|last9=A. Selim|first9=Heba|last10=A. Omar|first10=Sabry|title=Interictal Electrocardiographic and Echocardiographic Changes in Patients With Generalized Tonic-Clonic Seizures|journal=International Heart Journal|volume=54|issue=3|year=2013|pages=171–175|issn=1349-2365|doi=10.1536/ihj.54.171}}</ref><ref name="LendeArends2019">{{cite journal|last1=Lende|first1=Marije|last2=Arends|first2=Johan B.|last3=Lamberts|first3=Robert J.|last4=Tan|first4=Hanno L.|last5=Lange|first5=Frederik J.|last6=Sander|first6=Josemir W.|last7=Aerts|first7=Arnaud J.|last8=Swart|first8=Henk P.|last9=Thijs|first9=Roland D.|title=The yield of long‐term electrocardiographic recordings in refractory focal epilepsy|journal=Epilepsia|volume=60|issue=11|year=2019|pages=2215–2223|issn=0013-9580|doi=10.1111/epi.16373}}</ref><ref name="OpeskinThomas2000">{{cite journal|last1=Opeskin|first1=Kenneth|last2=Thomas|first2=Anthony|last3=Berkovic|first3=Samuel F.|title=Does cardiac conduction pathology contribute to sudden unexpected death in epilepsy?|journal=Epilepsy Research|volume=40|issue=1|year=2000|pages=17–24|issn=09201211|doi=10.1016/S0920-1211(00)00098-X}}</ref>
 
*[[Bundle-branch block]]
*[[ST-segment changes]] indicating  [[myocardial ischemia]] in 40% of [[seizures]] <ref name="TigaranMolgaard2003">{{cite journal|last1=Tigaran|first1=S.|last2=Molgaard|first2=H.|last3=McClelland|first3=R.|last4=Dam|first4=M.|last5=Jaffe|first5=A.S.|title=Evidence of cardiac ischemia during seizures in drug refractory epilepsy patients|journal=Neurology|volume=60|issue=3|year=2003|pages=492–495|issn=0028-3878|doi=10.1212/01.WNL.0000042090.13247.48}}</ref>
*[[T-wave]] inversion
*[[Bradycardia]], [[asystole]] due to [[hypoxia]] or [[respiratory disturbance]] in [[postictal phase]]
*[[Sinus tachycardia]] in [[ictal phase]] due to [[sympathetic]] activity or reduction in [[vagal tone]] in 82% of cases
*[[QT interval ]] prolongation
*[[QT]] interval dispersion
*Increased [[T wave]] alternance in preictal and post ictal phases of [[generalized tonic-clonic seizure]] indicating [[repolarization]] abnormality
*Decreased [[heart rate variability]] indicating  decreased [[vagus nerve]] activity  during [[seizure]]
*[[Sinus tachycardia]], [[heart rate]] >150/min indicating sympathetic discharge
 
:*Common [[ECG]] markers associated [[sudden cardiac death]] include:
 
*[[Peri ictal]] [[QT]] prolongation
*Increased [[T waves alternance]]
*Decreased [[heart rate variability]] <ref name="LotufoValiengo2012">{{cite journal|last1=Lotufo|first1=Paulo A.|last2=Valiengo|first2=Leandro|last3=Benseñor|first3=Isabela M.|last4=Brunoni|first4=Andre R.|title=A systematic review and meta-analysis of heart rate variability in epilepsy and antiepileptic drugs|journal=Epilepsia|volume=53|issue=2|year=2012|pages=272–282|issn=00139580|doi=10.1111/j.1528-1167.2011.03361.x}}</ref>
 
::*Arrhythmia associated [[seizure]] include: <ref name="van der LendeSurges2015">{{cite journal|last1=van der Lende|first1=Marije|last2=Surges|first2=Rainer|last3=Sander|first3=Josemir W|last4=Thijs|first4=Roland D|title=Cardiac arrhythmias during or after epileptic seizures|journal=Journal of Neurology, Neurosurgery & Psychiatry|year=2015|pages=jnnp-2015-310559|issn=0022-3050|doi=10.1136/jnnp-2015-310559}}</ref>
 
*[[Ictal]] [[bradycardia]]
*[[Ictal]] [[AV conduction block]]
*[[Ictal]] [[asystole]]
*[[Post ictal]] [[asystole]]
*[[Post ictal]] [[AV conduction block]]
*[[Post ictal]] [[atrial flutter]]
*[[Post ictal]] [[ventricular fibrillation]] <ref name="EspinosaLee2009">{{cite journal|last1=Espinosa|first1=P. S.|last2=Lee|first2=J. W.|last3=Tedrow|first3=U. B.|last4=Bromfield|first4=E. B.|last5=Dworetzky|first5=B. A.|title=SUDDEN UNEXPECTED NEAR DEATH IN EPILEPSY: MALIGNANT ARRHYTHMIA FROM A PARTIAL SEIZURE|journal=Neurology|volume=72|issue=19|year=2009|pages=1702–1703|issn=0028-3878|doi=10.1212/WNL.0b013e3181a55f90}}</ref>
 
::*Ictal [[asystole]], [[bradycardia]], [[AV block]] were self limiting.
::*Post ictal arrhythmia such as [[asystole]], [[AV block]], [[atrial fibrillation]], [[ventricular fibrillation]] were associated with near [[SUDEP]] or [[convulsion syncope]].
 
===X-ray===
 
A [[Chest-x-ray]] may be helpful in the [[diagnosis]] of [[atherosclerosis]] associated with [[chronic epilepsy]]. Findings on an [[CXR]] suggestive of [[heart]] involvement in [[epilepsy]] include:
 
:*[[Aortic arch calcification]] <ref name="IijimaHashimoto2010">{{cite journal|last1=Iijima|first1=Katsuya|last2=Hashimoto|first2=Hiroko|last3=Hashimoto|first3=Masayoshi|last4=Son|first4=Bo-Kyung|last5=Ota|first5=Hidetaka|last6=Ogawa|first6=Sumito|last7=Eto|first7=Masato|last8=Akishita|first8=Masahiro|last9=Ouchi|first9=Yasuyoshi|title=Aortic arch calcification detectable on chest X-ray is a strong independent predictor of cardiovascular events beyond traditional risk factors|journal=Atherosclerosis|volume=210|issue=1|year=2010|pages=137–144|issn=00219150|doi=10.1016/j.atherosclerosis.2009.11.012}}</ref>
 
:*[[Cardiomegaly]]
:*[[Pulmonary congestion]]
:*[[Left atrial enlargement]]
:*[[Left ventricle enlargement]]
 
===Echocardiography or Ultrasound===
[[Echocardiography]]  may be helpful in the diagnosis of [[epilectic heart]]. Findings on an [[echocardiography]] diagnostic of [[epileptic heart]] include: <ref name="M. RamadanEl-Shahat2013">{{cite journal|last1=M. Ramadan|first1=Mahmoud|last2=El-Shahat|first2=Nader|last3=A. Omar|first3=Ashraf|last4=Gomaa|first4=Mohamed|last5=Belal|first5=Tamer|last6=A. Sakr|first6=Sherif|last7=Abu-Hegazy|first7=Mohammad|last8=Hakim|first8=Hazem|last9=A. Selim|first9=Heba|last10=A. Omar|first10=Sabry|title=Interictal Electrocardiographic and Echocardiographic Changes in Patients With Generalized Tonic-Clonic Seizures|journal=International Heart Journal|volume=54|issue=3|year=2013|pages=171–175|issn=1349-2365|doi=10.1536/ihj.54.171}}</ref>
 
*Increased [[left ventricular filling pressures]]
*Increased [[left atrial]] volume
*Increase [[left ventricular]] end systolic diameter
*Increased [[left ventricular]] [[end systolic volume]] 64,65,66
 
===CT scan===
 
[[Coronary CT angiography]] may be helpful in the diagnosis of [[ischemic heart disease]] in [[chronic epilepsy]]. Findings on [[coronary CTangiography]] suggestive of [[ischemic hear disease]] include:<ref name="KolossvárySzilveszter2017">{{cite journal|last1=Kolossváry|first1=Márton|last2=Szilveszter|first2=Bálint |last3=Merkely|first3=Béla |last4=Maurovich-Horvat|first4=Pál |title=Plaque imaging with CT—a comprehensive review on coronary CT angiography based risk assessment|journal=Cardiovascular Diagnosis and Therapy|volume=7|issue=5|year=2017|pages=489–506|issn=22233652|doi=10.21037/cdt.2016.11.06}}</ref>
 
*[[Coronary artery calcification]]
*Narrowing of the [[coronary arteries]]
*[[Plaque morphology]]
*[[Plaque burden]]
 
===MRI===
 
[[Cardiac magnetic resonance angiograpgy]] ([[MRA]]) may be helpful in the diagnosis of [[ischemic heart disease]] in chronic [[epilepsy]]. Findings on [[MRA]] suggestive of high-risk patients include: <ref name="YuanKerwin2004">{{cite journal|last1=Yuan|first1=Chun|last2=Kerwin|first2=William S.|title=MRI of atherosclerosis|journal=Journal of Magnetic Resonance Imaging|volume=19|issue=6|year=2004|pages=710–719|issn=1053-1807|doi=10.1002/jmri.20070}}</ref>
 
*Severe [[coronary artery]] stenosis(>70%)
*Plaque with thick lipid-rich core and a thin [[fibrous cap]] and [[intraplaque inflammation]]
 
===Other Imaging Findings===
There are no other imaging findings associated with [[epileptic heart]].
 
===Other Diagnostic Studies===
[[Holter ECG]] 24-48 hours may be helpful in the diagnosis of the arrhythmia-related [[epileptic heart]]. Findings suggestive the probability of the occurrence of [[ventricular fibrillation]]  include: <ref name="TakasugiGoto2016">{{cite journal|last1=Takasugi|first1=Nobuhiro|last2=Goto|first2=Hiroko|last3=Takasugi|first3=Mieko|last4=Verrier|first4=Richard L.|last5=Kuwahara|first5=Takashi|last6=Kubota|first6=Tomoki|last7=Toyoshi|first7=Hiroyuki|last8=Nakashima|first8=Takashi|last9=Kawasaki|first9=Masanori|last10=Nishigaki|first10=Kazuhiko|last11=Minatoguchi|first11=Shinya|title=Prevalence of Microvolt T-Wave Alternans in Patients With Long QT Syndrome and Its Association With Torsade de Pointes|journal=Circulation: Arrhythmia and Electrophysiology|volume=9|issue=2|year=2016|issn=1941-3149|doi=10.1161/CIRCEP.115.003206}}</ref>
 
:*Higher level of [[T waves]] alternance
:*Decrease [[heart rate variability ]]
:*[[QT prolongation]]
 
*Other [[diagnostic]] studies for epileptic include [[ECG]] patches which are worn for 14 days with a higher chance for detection of [[tachyarrhythmia]] compared with Holter [[ECG]].
 
==Treatment==
===Medical Therapy===
*The mainstay of therapy for [[epileptic heart]] is [[autonomic modulation]] by increased [[parasympathetic activity]], decreased [[sympathetic activity]] which is effective for reducing the [[seizure]] episodes and increased [[cardiac electrical]] stability by the following: <ref name="SchomerNearing2014">{{cite journal|last1=Schomer|first1=Andrew C.|last2=Nearing|first2=Bruce D.|last3=Schachter|first3=Steven C.|last4=Verrier|first4=Richard L.|title=Vagus nerve stimulation reduces cardiac electrical instability assessed by quantitative T-wave alternans analysis in patients with drug-resistant focal epilepsy|journal=Epilepsia|volume=55|issue=12|year=2014|pages=1996–2002|issn=00139580|doi=10.1111/epi.12855}}</ref>
 
:*Changing the [[arrhythmogenic]] [[antiepileptic drugs]] to other types
:*[[vagus nerve stimulation]] therapy for reducing [[sympathetic activity]] which is a major risk factor for [[ventricular fibrillation]] <ref name="SchomerNearing2014">{{cite journal|last1=Schomer|first1=Andrew C.|last2=Nearing|first2=Bruce D.|last3=Schachter|first3=Steven C.|last4=Verrier|first4=Richard L.|title=Vagus nerve stimulation reduces cardiac electrical instability assessed by quantitative T-wave alternans analysis in patients with drug-resistant focal epilepsy|journal=Epilepsia|volume=55|issue=12|year=2014|pages=1996–2002|issn=00139580|doi=10.1111/epi.12855}}</ref>
 
===Surgery===
 
*[[Vagus Nerve Stimulation]] ([[VNS]]) can be used in resistance [[epilepsy]] by inserting a [[pacemaker]] under the [[skin]] in the [[chest]] and sending regular, mild [[pulses]] to the [[brain]] via the [[vagus]] [[nerve]].<ref name="pmid29844694">{{cite journal |vauthors=Johnson RL, Wilson CG |title=A review of vagus nerve stimulation as a therapeutic intervention |journal=J Inflamm Res |volume=11 |issue= |pages=203–213 |date=2018 |pmid=29844694 |pmc=5961632 |doi=10.2147/JIR.S163248 |url=}}</ref>
 
===Prevention===
 
*[[Primary prevention]] measures in [[epileptic heart]] include:
 
:*Screening [[risk factors]] of [[coronary artery disease]] in every [[patients]] diagnosed with [[epilepsy]] consisting [[obesity]],[[hypertension]], [[hyperlipidemia]],[[diabetes mellitus]],[[smoking]]
:*The role of [[ICD]] implantation for [[primary prevention]] of [[ventricular tachyarrhythmia]] in patients with chronic [[epilepsy]] is unclear. <ref name="SteckerReinier2013">{{cite journal|last1=Stecker|first1=Eric C.|last2=Reinier|first2=Kyndaron|last3=Uy-Evanado|first3=Audrey|last4=Teodorescu|first4=Carmen|last5=Chugh|first5=Harpriya|last6=Gunson|first6=Karen|last7=Jui|first7=Jonathan|last8=Chugh|first8=Sumeet S.|title=Relationship Between Seizure Episode and Sudden Cardiac Arrest in Patients With Epilepsy|journal=Circulation: Arrhythmia and Electrophysiology|volume=6|issue=5|year=2013|pages=912–916|issn=1941-3149|doi=10.1161/CIRCEP.113.000544}}</ref>
 
*The strategy for [[secondary prevention]] in [[chronic epileptic]] patients who are at risk of arrhythmia include:
*Changing  [[arrhythmogenic]] drugs  that block [[sodium channel]] such as [[carbamazepine]], [[phenytoin]] to other types
*[[Vagus Nerve Stimulation]] therapy ([[VNS]]) for a reduction in [[T wave]] alternans <ref name="SchomerNearing2014">{{cite journal|last1=Schomer|first1=Andrew C.|last2=Nearing|first2=Bruce D.|last3=Schachter|first3=Steven C.|last4=Verrier|first4=Richard L.|title=Vagus nerve stimulation reduces cardiac electrical instability assessed by quantitative T-wave alternans analysis in patients with drug-resistant focal epilepsy|journal=Epilepsia|volume=55|issue=12|year=2014|pages=1996–2002|issn=00139580|doi=10.1111/epi.12855}}</ref>
 
::*[[Chronic epileptic]] patients should be followed up for detection of [[T waves]] alternans and finding the risk of [[ventricular fibrillation]] by: <ref name="VerrierPang2020">{{cite journal|last1=Verrier|first1=Richard L.|last2=Pang|first2=Trudy D.|last3=Nearing|first3=Bruce D.|last4=Schachter|first4=Steven C.|title=The Epileptic Heart: Concept and clinical evidence|journal=Epilepsy Behavior|volume=105|year=2020|pages=106946|issn=15255050|doi=10.1016/j.yebeh.2020.106946}}</ref><ref name="PangNearing2019">{{cite journal|last1=Pang|first1=Trudy D.|last2=Nearing|first2=Bruce D.|last3=Krishnamurthy|first3=Kaarkuzhali Babu|last4=Olin|first4=Bryan|last5=Schachter|first5=Steven C.|last6=Verrier|first6=Richard L.|title=Cardiac electrical instability in newly diagnosed/chronic epilepsy tracked by Holter and ECG patch|journal=Neurology|volume=93|issue=10|year=2019|pages=450–458|issn=0028-3878|doi=10.1212/WNL.0000000000008077}}</ref>
:* 12 lead [[ECG]]
:* Holter [[ECG]] 24-48 hours
:* Wireless [[ECG]] patches(patient-friendly tool, worn for 14 days, increased chance for detection of [[arrhythmia]] compared  with Holter [[ECG]])


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
[[Category:Cardiology]]
[[Category:Neurology]]
[[Category:Up-To-Date]]

Latest revision as of 04:02, 31 July 2021

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sara Zand, M.D.[2] Sahar Memar Montazerin, M.D.[3]

Overview

Chronic epileptic episodes and the subsequent catecholamine surges and hypoxic events may affect the heart and coronary vessels and result in the dysfunction of the heart. This condition is known as the "epileptic heart." This concept was first described by Dr. Richard L. Verrier and his colleagues in 2020.

Historical Perspective

  • Absence of cardiac activity during epileptic seizure was first described by Dr. A.E. Russell, an English physician, in 1906.[1]
  • The epileptic heart was first described by Drs. Verrier, Pang, Nearing, and Schachter, in 2020.[2]

Classification

  • There is no established system for the classification of the epileptic heart.

Pathophysiology

  • The exact mechanisms involved in the development of the epileptic heart are still being elucidated. However, the conceptual framework below provides helpful information on the development of heart disease in patients with epilepsy.[3]
 
 
 
 
 
 
 
 
 
Chronic epilepsy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Repeated hypoxia and subsequent myocardial ischemia
 
Accelerated atherosclerosis
 
Myocardial stunning
 
Vacuolization of myocytes and fibrosis
 
Catecholamine-induced cardiotoxicity
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Epileptic Heart
❑ Cardiac electrical instability
❑ T wave alternans
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Epilepsy and Cardiac Arrhythmia

Cardiac arrhythmias have long been observed in patients with epilepsy. Three different mechanisms explain this association:[4]

Epilepsy and Structural Heart Disease

Three mechanisms have been suggested to explain the association between epilepsy and structural heart disease:[4]

Causes

Epileptic heart may be caused by the following:

Differentiating epileptic heart from other Diseases

Epileptic heart Sudden unexpected death in epilepsy SUDEP Convulsion syncope Epileptic seizure

Epidemiology and Demographics

Age

Gender

  • Males are more commonly affected with the epileptic heart than females.

Race

  • There is no racial predilection for epileptic heart.

Risk Factors

Screening

Currently, there is no guideline statement that recommended routine cardiac evaluation of patients with epilepsy. However, a resting 12-lead EKG and/or ambulatory EKG patch recording may be useful in identifying the patients at risk of cardiac pathology and further follow the progression of their cardiac pathology. [2]

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Criteria

  • The diagnosis of the epileptic heart is made when the following diagnostic criteria are met:

Hisory and Symptoms

Physical Examination

  • Physical examination associated with epilepsy include:

Laboratory Findings

Common laboratory findings related to epileptic heart may include:

Electrocardiogram

An ECG may be helpful in the diagnosis of epileptic heart. Findings on an ECG suggestive of effects of seizure on the heart include: [32][33][34]

X-ray

A Chest-x-ray may be helpful in the diagnosis of atherosclerosis associated with chronic epilepsy. Findings on an CXR suggestive of heart involvement in epilepsy include:

Echocardiography or Ultrasound

Echocardiography may be helpful in the diagnosis of epilectic heart. Findings on an echocardiography diagnostic of epileptic heart include: [32]

CT scan

Coronary CT angiography may be helpful in the diagnosis of ischemic heart disease in chronic epilepsy. Findings on coronary CTangiography suggestive of ischemic hear disease include:[40]

MRI

Cardiac magnetic resonance angiograpgy (MRA) may be helpful in the diagnosis of ischemic heart disease in chronic epilepsy. Findings on MRA suggestive of high-risk patients include: [41]

Other Imaging Findings

There are no other imaging findings associated with epileptic heart.

Other Diagnostic Studies

Holter ECG 24-48 hours may be helpful in the diagnosis of the arrhythmia-related epileptic heart. Findings suggestive the probability of the occurrence of ventricular fibrillation include: [42]

  • Other diagnostic studies for epileptic include ECG patches which are worn for 14 days with a higher chance for detection of tachyarrhythmia compared with Holter ECG.

Treatment

Medical Therapy

Surgery

Prevention

  • 12 lead ECG
  • Holter ECG 24-48 hours
  • Wireless ECG patches(patient-friendly tool, worn for 14 days, increased chance for detection of arrhythmia compared with Holter ECG)

References

  1. ↑ Russell, A.E. (1906). "CESSATION OF THE PULSE DURING THE ONSET OF EPILEPTIC FITS,". The Lancet. 168 (4325): 152–154. doi:10.1016/S0140-6736(01)30477-4. ISSN 0140-6736.
  2. ↑ 2.0 2.1 2.2 Verrier, Richard L.; Pang, Trudy D.; Nearing, Bruce D.; Schachter, Steven C. (2020). "The Epileptic Heart: Concept and clinical evidence". Epilepsy & Behavior. 105: 106946. doi:10.1016/j.yebeh.2020.106946. ISSN 1525-5050.
  3. ↑ Verrier, Richard L.; Schachter, Steven C. (2018). "Is heart disease in chronic epilepsy a consequence of seizures or a fellow traveler?". Epilepsy & Behavior. 86: 211–213. doi:10.1016/j.yebeh.2018.06.027. ISSN 1525-5050.
  4. ↑ 4.0 4.1 Shmuely, S.; van der Lende, M.; Lamberts, R.J.; Sander, J.W.; Thijs, R.D. (2017). "The heart of epilepsy: Current views and future concepts". Seizure. 44: 176–183. doi:10.1016/j.seizure.2016.10.001. ISSN 1059-1311.
  5. ↑ Hamed, Sherifa A. (2014). "Atherosclerosis in epilepsy: Its causes and implications". Epilepsy & Behavior. 41: 290–296. doi:10.1016/j.yebeh.2014.07.003. ISSN 1525-5050.
  6. ↑ Mintzer, Scott; Trinka, Eugen; Kraemer, Günter; Chervoneva, Inna; Werhahn, Konrad J. (2018). "Impact of carbamazepine, lamotrigine, and levetiracetam on vascular risk markers and lipid-lowering agents in the elderly". Epilepsia. 59 (10): 1899–1907. doi:10.1111/epi.14554. ISSN 0013-9580.
  7. ↑ Leestma, Jan E.; Walczak, Thaddeus; Hughes, John R.; Kalelkar, Mitra B.; Teas, Shaku S. (1989). "A prospective study on sudden unexpected death in epilepsy". Annals of Neurology. 26 (2): 195–203. doi:10.1002/ana.410260203. ISSN 0364-5134.
  8. ↑ Falconer, Bertil; Rajs, Jovan (1976). "Post-mortem findings of cardiac lesions in epileptics: A preliminary report". Forensic Science. 8: 63–71. doi:10.1016/0300-9432(76)90048-0. ISSN 0300-9432.
  9. ↑ Bardai, Abdennasser; Blom, Marieke T; van Noord, Charlotte; Verhamme, Katia M; Sturkenboom, Miriam C J M; Tan, Hanno L (2015). "Sudden cardiac death is associated both with epilepsy and with use of antiepileptic medications". Heart. 101 (1): 17–22. doi:10.1136/heartjnl-2014-305664. ISSN 1355-6037.
  10. ↑ Hookana, Eeva; Ansakorpi, Hanna; Kortelainen, Marja-Leena; Junttila, M. Juhani; Kaikkonen, Kari S; Perkiömäki, Juha; Huikuri, Heikki V (2016). "Antiepileptic medications and the risk for sudden cardiac death caused by an acute coronary event: a prospective case-control study". Annals of Medicine. 48 (1–2): 111–117. doi:10.3109/07853890.2016.1140225. ISSN 0785-3890.
  11. ↑ Granbichler, Claudia A.; Oberaigner, Willi; Kuchukhidze, Giorgi; Bauer, Gerhard; Ndayisaba, Jean-Pierre; Seppi, Klaus; Trinka, Eugen (2014). "Cause-specific mortality in adult epilepsy patients from Tyrol, Austria: hospital-based study". Journal of Neurology. 262 (1): 126–133. doi:10.1007/s00415-014-7536-z. ISSN 0340-5354.
  12. ↑ Baysal-Kirac, Leyla; Serbest, Nail Güven; Şahin, Erdi; Dede, Hava Özlem; Gürses, Candan; Gökyiğit, Ayşen; Bebek, Nerses; Bilge, Ahmet Kaya; Baykan, Betül (2017). "Analysis of heart rate variability and risk factors for SUDEP in patients with drug-resistant epilepsy". Epilepsy & Behavior. 71: 60–64. doi:10.1016/j.yebeh.2017.04.018. ISSN 1525-5050.
  13. ↑ DeGiorgio, Christopher M.; Miller, Patrick; Meymandi, Sheba; Chin, Alex; Epps, Jordan; Gordon, Steven; Gornbein, Jeffrey; Harper, Ronald M. (2010). "RMSSD, a measure of vagus-mediated heart rate variability, is associated with risk factors for SUDEP: The SUDEP-7 Inventory". Epilepsy & Behavior. 19 (1): 78–81. doi:10.1016/j.yebeh.2010.06.011. ISSN 1525-5050.
  14. ↑ Zaccara, Gaetano; Lattanzi, Simona (2019). "Comorbidity between epilepsy and cardiac arrhythmias: Implication for treatment". Epilepsy & Behavior. 97: 304–312. doi:10.1016/j.yebeh.2019.05.038. ISSN 1525-5050.
  15. ↑ Renoux, Christel; Dell'Aniello, Sophie; Saarela, Olli; Filion, Kristian B; Boivin, Jean-François (2015). "Antiepileptic drugs and the risk of ischaemic stroke and myocardial infarction: a population-based cohort study". BMJ Open. 5 (8): e008365. doi:10.1136/bmjopen-2015-008365. ISSN 2044-6055.
  16. ↑ Kiechl, Stefan; Bardai, Abdennasser; Lamberts, Robert J.; Blom, Marieke T.; Spanjaart, Anne M.; Berdowski, Jocelyn; van der Staal, Sebastiaan R.; Brouwer, Henk J.; Koster, Rudolph W.; Sander, Josemir W.; Thijs, Roland D.; Tan, Hanno L. (2012). "Epilepsy Is a Risk Factor for Sudden Cardiac Arrest in the General Population". PLoS ONE. 7 (8): e42749. doi:10.1371/journal.pone.0042749. ISSN 1932-6203.
  17. ↑ Fineschi, V.; Silver, M.D.; Karch, S.B.; Parolini, M.; Turillazzi, E.; Pomara, C.; Baroldi, G. (2005). "Myocardial disarray: an architectural disorganization linked with adrenergic stress?". International Journal of Cardiology. 99 (2): 277–282. doi:10.1016/j.ijcard.2004.01.022. ISSN 0167-5273.
  18. ↑ Zhao, Haiting; Zhang, Honghai; Schoen, Frederick J.; Schachter, Steven C.; Feng, Hua-Jun (2019). "Repeated generalized seizures can produce calcified cardiac lesions in DBA/1 mice". Epilepsy & Behavior. 95: 169–174. doi:10.1016/j.yebeh.2019.04.010. ISSN 1525-5050.
  19. ↑ Chin, P. S.; Branch, K. R.; Becker, K. J. (2005). "Postictal neurogenic stunned myocardium". Neurology. 64 (11): 1977–1978. doi:10.1212/01.WNL.0000163858.77494.7A. ISSN 0028-3878.
  20. ↑ Naylor, Jillian; Churilov, Leonid; Johnstone, Benjamin; Guo, Ruibing; Xiong, Yunyun; Koome, Miriam; Chen, Ziyi; Thevathasan, Arthur; Chen, Ziyuan; Liu, Xinfeng; Kwan, Patrick; Campbell, Bruce C.V. (2018). "The Association Between Atrial Fibrillation and Poststroke Seizures is Influenced by Ethnicity and Environmental Factors". Journal of Stroke and Cerebrovascular Diseases. 27 (10): 2755–2760. doi:10.1016/j.jstrokecerebrovasdis.2018.05.044. ISSN 1052-3057.
  21. ↑ 21.0 21.1 21.2 21.3 21.4 Zack, Matthew; Luncheon, Cecily (2018). "Adults with an epilepsy history, notably those 45–64 years old or at the lowest income levels, more often report heart disease than adults without an epilepsy history". Epilepsy & Behavior. 86: 208–210. doi:10.1016/j.yebeh.2018.05.021. ISSN 1525-5050.
  22. ↑ Nashef, Lina; So, Elson L.; Ryvlin, Philippe; Tomson, Torbjörn (2012). "Unifying the definitions of sudden unexpected death in epilepsy". Epilepsia. 53 (2): 227–233. doi:10.1111/j.1528-1167.2011.03358.x. ISSN 0013-9580.
  23. ↑ Tomson, Torbjorn; Walczak, Ted; Sillanpaa, Matti; Sander, Josemir W. A. S. (2005). "Sudden Unexpected Death in Epilepsy: A Review of Incidence and Risk Factors". Epilepsia. 46 (s11): 54–61. doi:10.1111/j.1528-1167.2005.00411.x. ISSN 0013-9580.
  24. ↑ Surges, Rainer; Thijs, Roland D.; Tan, Hanno L.; Sander, Josemir W. (2009). "Sudden unexpected death in epilepsy: risk factors and potential pathomechanisms". Nature Reviews Neurology. 5 (9): 492–504. doi:10.1038/nrneurol.2009.118. ISSN 1759-4758.
  25. ↑ Reeves, Andrew L.; Nollet, Kenneth E.; Klass, Donald W.; Sharbrough, Frank W.; So, Elson L. (1996). "The Ictal Bradycardia Syndrome". Epilepsia. 37 (10): 983–987. doi:10.1111/j.1528-1157.1996.tb00536.x. ISSN 0013-9580.
  26. ↑ Nashef, L; Walker, F; Allen, P; Sander, J W; Shorvon, S D; Fish, D R (1996). "Apnoea and bradycardia during epileptic seizures: relation to sudden death in epilepsy". Journal of Neurology, Neurosurgery & Psychiatry. 60 (3): 297–300. doi:10.1136/jnnp.60.3.297. ISSN 0022-3050.
  27. ↑ 27.0 27.1 Benjamin, Emelia J.; Virani, Salim S.; Callaway, Clifton W.; Chamberlain, Alanna M.; Chang, Alexander R.; Cheng, Susan; Chiuve, Stephanie E.; Cushman, Mary; Delling, Francesca N.; Deo, Rajat; de Ferranti, Sarah D.; Ferguson, Jane F.; Fornage, Myriam; Gillespie, Cathleen; Isasi, Carmen R.; Jiménez, Monik C.; Jordan, Lori Chaffin; Judd, Suzanne E.; Lackland, Daniel; Lichtman, Judith H.; Lisabeth, Lynda; Liu, Simin; Longenecker, Chris T.; Lutsey, Pamela L.; Mackey, Jason S.; Matchar, David B.; Matsushita, Kunihiro; Mussolino, Michael E.; Nasir, Khurram; O’Flaherty, Martin; Palaniappan, Latha P.; Pandey, Ambarish; Pandey, Dilip K.; Reeves, Mathew J.; Ritchey, Matthew D.; Rodriguez, Carlos J.; Roth, Gregory A.; Rosamond, Wayne D.; Sampson, Uchechukwu K.A.; Satou, Gary M.; Shah, Svati H.; Spartano, Nicole L.; Tirschwell, David L.; Tsao, Connie W.; Voeks, Jenifer H.; Willey, Joshua Z.; Wilkins, John T.; Wu, Jason HY.; Alger, Heather M.; Wong, Sally S.; Muntner, Paul (2018). "Heart Disease and Stroke Statistics—2018 Update: A Report From the American Heart Association". Circulation. 137 (12). doi:10.1161/CIR.0000000000000558. ISSN 0009-7322.
  28. ↑ 28.0 28.1 Stecker, Eric C.; Reinier, Kyndaron; Uy-Evanado, Audrey; Teodorescu, Carmen; Chugh, Harpriya; Gunson, Karen; Jui, Jonathan; Chugh, Sumeet S. (2013). "Relationship Between Seizure Episode and Sudden Cardiac Arrest in Patients With Epilepsy". Circulation: Arrhythmia and Electrophysiology. 6 (5): 912–916. doi:10.1161/CIRCEP.113.000544. ISSN 1941-3149.
  29. ↑ Nass, Robert D.; Motloch, Lukas J.; Paar, Vera; Lichtenauer, Michael; Baumann, Jan; Zur, Berndt; Hoppe, Uta C.; Holdenrieder, Stefan; Elger, Christian E.; Surges, Rainer (2019). "Blood markers of cardiac stress after generalized convulsive seizures". Epilepsia. 60 (2): 201–210. doi:10.1111/epi.14637. ISSN 0013-9580.
  30. ↑ Hajsadeghi, Shekoufeh; Afsharian, Shila; Fereshtehnejad, Seyed-Mohammad; Keramati, Mohammad Reza; Mollahoseini, Reza (2009). "Serum Levels of Cardiac Troponin I in Patients with Uncomplicated Epileptic Seizure". Archives of Medical Research. 40 (1): 24–28. doi:10.1016/j.arcmed.2008.10.002. ISSN 0188-4409.
  31. ↑ Mintzer, Scott; Miller, Rachael; Shah, Krunal; Chervoneva, Inna; Nei, Maromi; Skidmore, Christopher; Sperling, Michael R. (2016). "Long-term effect of antiepileptic drug switch on serum lipids and C-reactive protein". Epilepsy & Behavior. 58: 127–132. doi:10.1016/j.yebeh.2016.02.023. ISSN 1525-5050.
  32. ↑ 32.0 32.1 M. Ramadan, Mahmoud; El-Shahat, Nader; A. Omar, Ashraf; Gomaa, Mohamed; Belal, Tamer; A. Sakr, Sherif; Abu-Hegazy, Mohammad; Hakim, Hazem; A. Selim, Heba; A. Omar, Sabry (2013). "Interictal Electrocardiographic and Echocardiographic Changes in Patients With Generalized Tonic-Clonic Seizures". International Heart Journal. 54 (3): 171–175. doi:10.1536/ihj.54.171. ISSN 1349-2365.
  33. ↑ Lende, Marije; Arends, Johan B.; Lamberts, Robert J.; Tan, Hanno L.; Lange, Frederik J.; Sander, Josemir W.; Aerts, Arnaud J.; Swart, Henk P.; Thijs, Roland D. (2019). "The yield of long‐term electrocardiographic recordings in refractory focal epilepsy". Epilepsia. 60 (11): 2215–2223. doi:10.1111/epi.16373. ISSN 0013-9580.
  34. ↑ Opeskin, Kenneth; Thomas, Anthony; Berkovic, Samuel F. (2000). "Does cardiac conduction pathology contribute to sudden unexpected death in epilepsy?". Epilepsy Research. 40 (1): 17–24. doi:10.1016/S0920-1211(00)00098-X. ISSN 0920-1211.
  35. ↑ Tigaran, S.; Molgaard, H.; McClelland, R.; Dam, M.; Jaffe, A.S. (2003). "Evidence of cardiac ischemia during seizures in drug refractory epilepsy patients". Neurology. 60 (3): 492–495. doi:10.1212/01.WNL.0000042090.13247.48. ISSN 0028-3878.
  36. ↑ Lotufo, Paulo A.; Valiengo, Leandro; Benseñor, Isabela M.; Brunoni, Andre R. (2012). "A systematic review and meta-analysis of heart rate variability in epilepsy and antiepileptic drugs". Epilepsia. 53 (2): 272–282. doi:10.1111/j.1528-1167.2011.03361.x. ISSN 0013-9580.
  37. ↑ van der Lende, Marije; Surges, Rainer; Sander, Josemir W; Thijs, Roland D (2015). "Cardiac arrhythmias during or after epileptic seizures". Journal of Neurology, Neurosurgery & Psychiatry: jnnp-2015–310559. doi:10.1136/jnnp-2015-310559. ISSN 0022-3050.
  38. ↑ Espinosa, P. S.; Lee, J. W.; Tedrow, U. B.; Bromfield, E. B.; Dworetzky, B. A. (2009). "SUDDEN UNEXPECTED NEAR DEATH IN EPILEPSY: MALIGNANT ARRHYTHMIA FROM A PARTIAL SEIZURE". Neurology. 72 (19): 1702–1703. doi:10.1212/WNL.0b013e3181a55f90. ISSN 0028-3878.
  39. ↑ Iijima, Katsuya; Hashimoto, Hiroko; Hashimoto, Masayoshi; Son, Bo-Kyung; Ota, Hidetaka; Ogawa, Sumito; Eto, Masato; Akishita, Masahiro; Ouchi, Yasuyoshi (2010). "Aortic arch calcification detectable on chest X-ray is a strong independent predictor of cardiovascular events beyond traditional risk factors". Atherosclerosis. 210 (1): 137–144. doi:10.1016/j.atherosclerosis.2009.11.012. ISSN 0021-9150.
  40. ↑ Kolossváry, Márton; Szilveszter, Bálint; Merkely, Béla; Maurovich-Horvat, Pál (2017). "Plaque imaging with CT—a comprehensive review on coronary CT angiography based risk assessment". Cardiovascular Diagnosis and Therapy. 7 (5): 489–506. doi:10.21037/cdt.2016.11.06. ISSN 2223-3652.
  41. ↑ Yuan, Chun; Kerwin, William S. (2004). "MRI of atherosclerosis". Journal of Magnetic Resonance Imaging. 19 (6): 710–719. doi:10.1002/jmri.20070. ISSN 1053-1807.
  42. ↑ Takasugi, Nobuhiro; Goto, Hiroko; Takasugi, Mieko; Verrier, Richard L.; Kuwahara, Takashi; Kubota, Tomoki; Toyoshi, Hiroyuki; Nakashima, Takashi; Kawasaki, Masanori; Nishigaki, Kazuhiko; Minatoguchi, Shinya (2016). "Prevalence of Microvolt T-Wave Alternans in Patients With Long QT Syndrome and Its Association With Torsade de Pointes". Circulation: Arrhythmia and Electrophysiology. 9 (2). doi:10.1161/CIRCEP.115.003206. ISSN 1941-3149.
  43. ↑ 43.0 43.1 43.2 Schomer, Andrew C.; Nearing, Bruce D.; Schachter, Steven C.; Verrier, Richard L. (2014). "Vagus nerve stimulation reduces cardiac electrical instability assessed by quantitative T-wave alternans analysis in patients with drug-resistant focal epilepsy". Epilepsia. 55 (12): 1996–2002. doi:10.1111/epi.12855. ISSN 0013-9580.
  44. ↑ Johnson RL, Wilson CG (2018). "A review of vagus nerve stimulation as a therapeutic intervention". J Inflamm Res. 11: 203–213. doi:10.2147/JIR.S163248. PMC 5961632. PMID 29844694.
  45. ↑ Pang, Trudy D.; Nearing, Bruce D.; Krishnamurthy, Kaarkuzhali Babu; Olin, Bryan; Schachter, Steven C.; Verrier, Richard L. (2019). "Cardiac electrical instability in newly diagnosed/chronic epilepsy tracked by Holter and ECG patch". Neurology. 93 (10): 450–458. doi:10.1212/WNL.0000000000008077. ISSN 0028-3878.
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