Epileptic Heart
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2]
Synonyms and keywords:
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, 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 | |||||||||||||||||||||||||||||||||||
Epilepsy and Cardiac Arrhythmia
Cardiac arrhythmias have long been observed in patients with epilepsy. Three different mechanisms explain this association:[4]
- Direct (causal) pathway
- Co-existence of epilepsy and cardiac arrhythmia in the context of genetic disorders:
- Resultant association:
- Certain anti-epileptic medications with sodium channel blocking properties have been known to cause arrhythmia.
- Seizure may also cause arrhythmia.
- Ictal phase may be associated with tachycardia, asystole, bradycardia, and AV block.
- Postictal phase may be associated with asystole, AV block, atrial flutter or fibrillation, and ventricular fibrillation.
Epilepsy and Structural Heart Disease
Three mechanisms have been suggested to explain the association between epilepsy and structural heart disease:[4]
- 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.
- Resultant pathway:
- Epilepsy may stimulate myocardial ischemia and a Takotsubo-like syndrome.
- Certain anti-epileptic medications contribute to the development of arteriosclerosis, weight gain, non-alcoholic fatty liver disease and metabolic syndrome and result in a poorer cardiovascular risk profile.[5][6]
- 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.[7][8][9]
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
- Increased occurrence of arrhythmia due to hyperadrenergic state in seizure episodes
- Cardiac autonomic dysfunction due to repeated siezue episodes, a predisposing factor of arrhythmia
- Arrhythmogenic effect of antiepileptic drugs due to blockage of sodium channels on heart
- Susceptibility to ventricular fibrillation before or after seizure episods
- Structural myocardium damage due to repeated seizures, such as myocardial calcified lesions, myocardial stiffness, cardiomegaly, ventricular hypertrophy, left artial dilation
- Neurogenic stunned myocardium similar to tukotsubo, a reversible cardiomyopathy after a seizure episode
- Increased occurance of atrial fibrillation
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
| Epileptic heart | Sudden unexpected death in epilepsy SUDEP | Convulsion syncope | Epileptic seizure |
|---|---|---|---|
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Epidemiology and Demographics
- The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.
- In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].
Age
- Sudden cardiac death associated with epileptic heart is more commonly observed among patients older than 40 years old.
- Accelerated atherosclerosis associated to the epileptic heart is more commonly observed among younger age (mean age 55 years old) compared with the general population ( mean age 69-year-old)
Gender
- Males are more commonly affected with epileptic heart than females
Race
- There is no racial predilection for epileptic heart.
- [Disease name] usually affects individuals of the [race 1] race.
- [Race 2] individuals are less likely to develop [disease name].
Risk Factors
- Common risk factors in the development of epileptic heart may include:
- Low socioeconomic status
- Long standing antiepileptic therapy
- Hypertension
- Hyperlipidemia
- Diabetes mellitus
- Male sex
- Smoking
- Aging
- Progression of underlying cardiac disease
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, angina pectori.
- If left untreated, patients with chronic epilepsy may progress to develop complications of arrhythmia and myocardial ischemia.
- Common complications of epileptic heart include: coronary artery disease, heart failure disease, sudden cardiac arrest, sudden cardiac death.
- Prognosis is generally [excellent/good/poor], and the [1/5/10year mortality/survival rate] of patients with [disease name] is approximately [#%].
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
History and Symptoms
- Symptoms of the epileptic heart may include the following:
Physical Examination
- Physical examination associated with epilepsy include:
- Physical examination associated with heart involvement in chronic epilepsy may include:
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.41.63.67
- Increased CRP, lipid profile due to induction of cytochrome P450 by antiepileptic drugs such as carbamazepine, gabapentin
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:
- Bundle-branch block
- ST-segment changes indicating myocardial ischemia in 40% of seizures
- 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:
- QT prolongation
- Increased T waves alternance
- Decreased heart rate variability
X-ray
A Chest-x-ray may be helpful in the diagnosis of heart involvement 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
- 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:[13]
- 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:[14]
- 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 [disease name].
OR
[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
Other Diagnostic Studies
Holter ECG 24-48 hours may be helpful in the diagnosis of the arrhythmia-related epileptic heart. Findings suggestive of the occurance of ventricular fibrillation include:
- 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:
- Changing the arrhythmogenic antiepileptic drugs to other types
- vagus nerve stimulation therapy for reduction sympathetic activity which is a major risk factor for ventricular fibrillation
Surgery
- Left stellectomy can only be performed for patients with Long QT syndrome who are at risk of ventricular fibrillation.
Prevention
- There are no primary preventive measures available for the epileptic heart.
- The role of ICD implantation for primary prevention in patients with chronic epilepsy who are susceptible to arrhythmia is unclear.
- 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 alternance
- Chronic epileptic patients should be followed up for detection of T waves alternance and finding the risk of ventricular fibrillation by:.[2]
- 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
- ↑ 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.
- ↑ 2.0 2.1 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.
- ↑ 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.
- ↑ 4.0 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
Epidemiology and Demographics
Risk Factors
Screening
Currently, there is no guideline statement that recommends 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 to further follow the progression of their cardiac pathology.[1]
References
- ↑ 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.