Research progress on the epileptic heart: autonomic nervous system and cardiac structural and functional damage_Journal of Epilepsy

Authors：

LI Yang ^1,2 , LIANG Bianbian ^1,2 , CAO Wenli ^1,2 , WANG Jiangping ¹ ,  ZHANG Xiaodong ¹

1. Department of Neurology, Peking University First Hospital Taiyuan Hospital, Taiyuan 030009, China;
2. Changzhi Medical College, Changzhi 046099, China;

Corresponding?author：

ZHANG Xiaodong, Email: 1009934010@qq.com

Keywords：

Epileptic heart; Autonomic nervous system dysfunction; Cardiac structural injury; Cardiac dysfunction; Arrhythmia; Sudden cardiac death; Sudden unexpected death in epilepsy

DOI：

10.7507/2096-0247.202603024

Video：

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The pathological state of "epileptic heart" induced by epilepsy has shattered the perception that epilepsy is an isolated neurological disorder, reflecting the synergistic damage between chronic epilepsy and cardiac bioelectrical activity as well as mechanical function. Autonomic nervous system dysfunction is the core mediating link, which regulates the expression of myocardial ion channels and induces risks such as arrhythmias. In the long term, it also drives structural remodeling and functional impairment including left atrial enlargement and myocardial fibrosis. This kind of damage is influenced by factors such as classification of epilepsy, disease duration, and antiepileptic drugs—for instance, patients with drug resistant epilepsy or those on long-term polypharmacy suffer more significant damage. This article systematically reviews recent research progress, summarizes consensus and controversies, provides a basis for the precision management of cardiovascular risks in epilepsy patients, and contributes to reducing the incidence of SUDEP and improving long-term quality of life.

Citation： LI Yang, LIANG Bianbian, CAO Wenli, WANG Jiangping, ZHANG Xiaodong. Research progress on the epileptic heart: autonomic nervous system and cardiac structural and functional damage. Journal of Epilepsy, 2026, 12(4): 319-325. doi: 10.7507/2096-0247.202603024 Copy

1.	Beghi E. The epidemiology of epilepsy. Neuroepidemiology, 2020, 54(2): 185-191.
2.	李冰, 蘭措卓瑪, 梁福俐, 等. 心內科醫生對癲癇性猝死伴心律失常預防的認識: 問卷調查研究. 臨床心電學雜志, 2025, 34(4): 260-264.
3.	Ha FJ, Chong T, Cook MJ, et al. Epilepsy and cardiac arrhythmias: a state-of-the-art review. JACC Clin Electrophysiol, 2025, 11(1): 217-229.
4.	Surges R, Shmuely S, Dietze C, et al. Identifying patients with epilepsy at high risk of cardiac death: signs, risk factors and initial management of high risk of cardiac death. Epileptic Disord, 2021, 23(1): 17-39.
5.	Costagliola G, Orsini A, Coll M, et al. The brain-heart interaction in epilepsy: implications for diagnosis, therapy, and SUDEP prevention. Ann Clin Transl Neurol, 2021, 8(7): 1557-1568.
6.	Zaccara G, Lattanzi S. Comorbidity between epilepsy and cardiac arrhythmias: implication for treatment. Epilepsy Behav, 2019, 97: 304-312.
7.	Patros M, Sivathamboo S, Simpson HD, et al. The physiology, anatomy and stimulation of the vagus nerve in epilepsy. J Physiol, 2025, 603(8): 2201-2217.
8.	Sivathamboo S, Perucca P. Interictal autonomic dysfunction. Curr Opin Neurol, 2021, 34(2): 197-205.
9.	Dereli AS, Apaire A, Morrison EG, et al. Seizure-type-specific disruption of hypercapnic cardioventilatory responses in epilepsy models. Epilepsia, 2026, 2: epi. 70123.
10.	Wenker IC, Gehlbach BK, Isom LL, et al. Unraveling SUDEP: mechanisms of seizure-induced cardiac and respiratory impairment. Epilepsy Curr, 2026, 21: 10.1177.
11.	Kawai K. Epilepsy and autonomic nervous system. Brain Nerve, 2022, 74(3): 271-277.
12.	Szurhaj W, Leclancher A, Nica A, et al. Cardiac autonomic dysfunction and risk of sudden unexpected death in epilepsy. Neurology, 2021, 96(21): e2619-e2626.
13.	Thijs RD, Sander JW. Heart rate controversies in epilepsy: autonomic metrics and predictions. Neurology, 2021, 97(24): 1103-1104.
14.	Galli A, Lombardi F. Heart rate variability regression and risk of sudden unexpected death in epilepsy. Med Hypotheses, 2017, 99: 49-52.
15.	Sakamoto M, Jin K, Kitazawa Y, et al. Abnormal heart rate variability during non-REM sleep and postictal generalized EEG suppression in focal epilepsy. Clin Neurophysiol, 2022, 140: 40-44.
16.	Athira SB, Pal P, Nair PP, et al. Cardiovascular autonomic function and baroreflex sensitivity in drug-resistant temporal lobe epilepsy. Epilepsy Behav, 2023, 138: 109013.
17.	Yeh WC, Lin HC, Chuang YC, et al. Exploring factors associated with interictal heart rate variability in patients with medically controlled focal epilepsy. Seizure, 2021, 92: 24-28.
18.	Meghana A, Sriranjini SJ, Sathyaprabha T, et al. Autonomic function in reflex and non-reflex epilepsy--an exploratory study. Acta Neurol Scand, 2016, 133 (6): 459-465.
19.	Matthias C Borutta, Vayra Royle, Christina Rothballer, et al. If you care about autonomic modulation-do not let seizure. Diagnostics, 2026, 16(5): 11578.
20.	Nei M, Ho RT, Abou-Khalil BW, et al. EEG and ECG in sudden unexplained death in epilepsy. Epilepsia, 2004, 45(4): 338-345.
21.	Bermeo-Ovalle AC, Kennedy JD, Schuele SU. Cardiac and autonomic mechanisms contributing to SUDEP. J Clin Neurophysiol, 2015, 32(1): 21-29.
22.	Youngoh Bae, Chaeyoon Kang, et al. Time-dependent risk of dementia following epilepsy diagnosis: a nationwide Cohort study in South Korea. Epilepsia open, 2026, 11(1): 170-182.
23.	Yu YL, Li NN, Shi MT, et al. Analysis of heart rate variability-related indexes in the interictal period in patients with focal epilepsy. Life Sci, 2018, 209: 403-408.
24.	Litovchenko T, Grymailo V, Tondiy O, et al. The peculiarities of the heart rate variability and electroencephalogram changes in patients with epilepsy and cardiovascular pathology. Wiad Lek, 2019, 72(2): 165-168.
25.	Jehi L. Sudden death in epilepsy, surgery, and seizure outcomes: the interface between heart and brain. Cleve Clin J Med, 2010, 77 (Suppl 3): S51-S55.
26.	Wu ML, Hu DM, Wang JJ, et al. Pre- and postoperative heart rate variability and vagus nerve stimulation in patients with drug-resistant epilepsy - a meta-analysis. Epilepsy Behav, 2021, 123: 108247.
27.	韓文杰, 班俊杰, 黎振聲, 等. 離子通道基因在癲癇與心律失常共患病中的研究進展. 中華神經醫學雜志, 2025, 24(7): 728-733.
28.	Akyüz E, üner AK, K?klü B, et al. Cardiorespiratory findings in epilepsy: a recent review on outcomes and pathophysiology. J Neurosci Res, 2021, 99(9): 2059-2073.
29.	Akyüz E, Do?anyi?it Z, Paudel YN, et al. Increased ACh-associated immunoreactivity in autonomic centers in PTZ kindling model of epilepsy. Biomedicines, 2020, 8(5): 113.
30.	Shlobin NA, Li J, Sander JW, et al. Cardiac conduction delay for sodium channel antagonist antiseizure medications: an analysis of the Canadian longitudinal study on aging. Neurology, 2025, 104(4): e210302.
31.	Wang J, Huang PY, Yu QW, et al. Epilepsy and long-term risk of arrhythmias. Eur Heart J, 2023, 44(35): 3374-3382.
32.	Slater JD, Benbadis S, Verrier RL. The brain-heart connection: value of concurrent ECG and EEG recordings in epilepsy management. Epilepsy Behav Rep, 2024, 28: 100726.
33.	Shmuely S, Surges R, Helling RM, et al. Cardiac arrhythmias in Dravet syndrome: an observational multicenter study. Ann Clin Transl Neurol, 2020, 7(4): 462-473.
34.	Haridas B, Chuang DT, Nei M, et al. Sudden unexpected death in epilepsy: pathogenesis, risk factors, and prevention. Semin Neurol, 2022, 42(5): 658-664.
35.	Ufongene C, El Atrache R, Loddenkemper T, et al. Electrocardiographic changes associated with epilepsy beyond heart rate and their utilization in future seizure detection and forecasting methods. Clin Neurophysiol, 2020, 131(4): 866-879.
36.	Hassan NAI F, Toraih EA, Orz M, et al. Electrocardiographic abnormalities in epilepsy: analysis of cardiac conduction patterns and SUDEP risk. Neurol Sci, 2025, 46(10): 5287-5304.
37.	Fialho GL, Verrier RL, D'Avila A, et al. Dual assessment of abnormal cardiac electrical dispersion and diastolic dysfunction for early detection of the epileptic heart condition. J Electrocardiol, 2023, 78: 69-75.
38.	Dogan EA, Dogan U, Yildiz GU, et al. Evaluation of cardiac repolarization indices in well-controlled partial epilepsy: 12-lead ECG findings. Epilepsy Res, 2010, 90(1-2): 157-163.
39.	Demir TG, Gungoren F, Ethemoglu OU, et al. Epilepsy's effect on cardiac rhythm and the autonomic nervous system. Rev Assoc Med Bras, 2024, 70(2): e20230742.
40.	Gurses AA, Gen CE, Gurses KM, et al. QT interval alterations in epilepsy: a thorough investigation between epilepsy subtypes. J Clin Neurosci, 2022, 104: 113-117.
41.	Hamdy RM, Abd El Aziz OH, El Attar RS, et al. Evaluation of QT dispersion in epileptic patients and its association with SUDEP risk. Epilepsy Res, 2022, 180: 106860.
42.	Bartlett-Lee B, Dervan L, Miyake C, et al. Association of minor electrocardiographic (ECG) abnormalities with epilepsy duration in children: a manifestation of the epileptic heart? Seizure, 2024, 118: 1-7.
43.	Chan SW, Chun A, Nguyen L, et al. Associations between epilepsy, respiratory impairment, and minor ECG abnormalities in children. Seizure, 2024, 122: 39-44.
44.	Pernice R, Faes L, Feucht M, et al. Pairwise and higher-order measures of brain-heart interactions in children with temporal lobe epilepsy. J Neural Eng, 2022, 19(4): 046039.
45.	Pang TD, Nearing BD, Schachter SC, et al. Epileptic seizures and epilepsy monitoring unit admission disclose latent cardiac electrical instability. Epilepsy Behav, 2022, 135: 108881.
46.	Bianco M, Breviario S, Fraccalini T, et al. Epilepsy and syncope - a case report and narrative review of arrhythmias connected to temporal lobe epilepsy. J Electrocardiol, 2022, 73: 76-78.
47.	Daverio M, Ciccone O, Boniver C, et al. Supraventricular tachycardia during status epilepticus in Dravet syndrome: a link between brain and heart?. Pediatr Neurol, 2016, 56: 69-71.
48.	Frasier CR, Zhang H, Offord J, et al. Channelopathy as a SUDEP biomarker in Dravet syndrome patient-derived cardiac myocytes. Stem Cell Rep, 2018, 11(3): 626-634.
49.	Fialho GL, Pang TD, Kong WY, et al. Individuals with chronic epilepsy have elevated P-wave heterogeneity comparable to patients with atrial fibrillation. Epilepsia, 2023, 64(9): 2361-2372.
50.	Duran S, Boduroglu Y. Left atrial remodeling in epilepsy: a comparative echocardiographic study of left atrial emptying fraction and left atrial volumetric index in patients with epilepsy. Epilepsia, 2025, 66(10): 3964-3971.
51.	Miotto R, Cavagnollo MT, Lin K, et al. Strain analysis of cardiac chambers in individuals with temporal lobe epilepsy. Epilepsia, 2025, 66(6): 1589-1597.
52.	Akyuz E, Polat K, Ates S, et al. Investigating cardiac morphological alterations in a pentylenetetrazol-kindling model of epilepsy. Diagnostics (Basel), 2020, 10(6): 388.
53.	Powell KL, Liu Z, Curl CL, et al. Altered cardiac structure and function is related to seizure frequency in a rat model of chronic acquired temporal lobe epilepsy. Neurobiol Dis, 2021, 159: 105505.
54.	Sharma S, Sharma M, Rana AK, et al. Deciphering key regulators involved in epilepsy-induced cardiac damage through whole transcriptome and proteome analysis in a rat model. Epilepsia, 2021, 62(2): 504-516.
55.	Liu Z, Sivathamboo S, Thergajan P, et al. Cardiac structural and molecular alterations in rodent models of temporal lobe epilepsy. Epilepsia Open, 2025, 10(3): 809-821.
56.	Mahmoud M Noureldeen, Mohamed Mabrouk Tohamy, et al. Subclinical cardiac dysfunction detected by speckle-tracking echocardiography in children with drug-resistant epilepsy. Pediatric research, 2026, 2: s41390-026-04769-z.

1. Beghi E. The epidemiology of epilepsy. Neuroepidemiology, 2020, 54(2): 185-191.
2. 李冰, 蘭措卓瑪, 梁福俐, 等. 心內科醫生對癲癇性猝死伴心律失常預防的認識: 問卷調查研究. 臨床心電學雜志, 2025, 34(4): 260-264.
3. Ha FJ, Chong T, Cook MJ, et al. Epilepsy and cardiac arrhythmias: a state-of-the-art review. JACC Clin Electrophysiol, 2025, 11(1): 217-229.
4. Surges R, Shmuely S, Dietze C, et al. Identifying patients with epilepsy at high risk of cardiac death: signs, risk factors and initial management of high risk of cardiac death. Epileptic Disord, 2021, 23(1): 17-39.
5. Costagliola G, Orsini A, Coll M, et al. The brain-heart interaction in epilepsy: implications for diagnosis, therapy, and SUDEP prevention. Ann Clin Transl Neurol, 2021, 8(7): 1557-1568.
6. Zaccara G, Lattanzi S. Comorbidity between epilepsy and cardiac arrhythmias: implication for treatment. Epilepsy Behav, 2019, 97: 304-312.
7. Patros M, Sivathamboo S, Simpson HD, et al. The physiology, anatomy and stimulation of the vagus nerve in epilepsy. J Physiol, 2025, 603(8): 2201-2217.
8. Sivathamboo S, Perucca P. Interictal autonomic dysfunction. Curr Opin Neurol, 2021, 34(2): 197-205.
9. Dereli AS, Apaire A, Morrison EG, et al. Seizure-type-specific disruption of hypercapnic cardioventilatory responses in epilepsy models. Epilepsia, 2026, 2: epi. 70123.
10. Wenker IC, Gehlbach BK, Isom LL, et al. Unraveling SUDEP: mechanisms of seizure-induced cardiac and respiratory impairment. Epilepsy Curr, 2026, 21: 10.1177.
11. Kawai K. Epilepsy and autonomic nervous system. Brain Nerve, 2022, 74(3): 271-277.
12. Szurhaj W, Leclancher A, Nica A, et al. Cardiac autonomic dysfunction and risk of sudden unexpected death in epilepsy. Neurology, 2021, 96(21): e2619-e2626.
13. Thijs RD, Sander JW. Heart rate controversies in epilepsy: autonomic metrics and predictions. Neurology, 2021, 97(24): 1103-1104.
14. Galli A, Lombardi F. Heart rate variability regression and risk of sudden unexpected death in epilepsy. Med Hypotheses, 2017, 99: 49-52.
15. Sakamoto M, Jin K, Kitazawa Y, et al. Abnormal heart rate variability during non-REM sleep and postictal generalized EEG suppression in focal epilepsy. Clin Neurophysiol, 2022, 140: 40-44.
16. Athira SB, Pal P, Nair PP, et al. Cardiovascular autonomic function and baroreflex sensitivity in drug-resistant temporal lobe epilepsy. Epilepsy Behav, 2023, 138: 109013.
17. Yeh WC, Lin HC, Chuang YC, et al. Exploring factors associated with interictal heart rate variability in patients with medically controlled focal epilepsy. Seizure, 2021, 92: 24-28.
18. Meghana A, Sriranjini SJ, Sathyaprabha T, et al. Autonomic function in reflex and non-reflex epilepsy--an exploratory study. Acta Neurol Scand, 2016, 133 (6): 459-465.
19. Matthias C Borutta, Vayra Royle, Christina Rothballer, et al. If you care about autonomic modulation-do not let seizure. Diagnostics, 2026, 16(5): 11578.
20. Nei M, Ho RT, Abou-Khalil BW, et al. EEG and ECG in sudden unexplained death in epilepsy. Epilepsia, 2004, 45(4): 338-345.
21. Bermeo-Ovalle AC, Kennedy JD, Schuele SU. Cardiac and autonomic mechanisms contributing to SUDEP. J Clin Neurophysiol, 2015, 32(1): 21-29.
22. Youngoh Bae, Chaeyoon Kang, et al. Time-dependent risk of dementia following epilepsy diagnosis: a nationwide Cohort study in South Korea. Epilepsia open, 2026, 11(1): 170-182.
23. Yu YL, Li NN, Shi MT, et al. Analysis of heart rate variability-related indexes in the interictal period in patients with focal epilepsy. Life Sci, 2018, 209: 403-408.
24. Litovchenko T, Grymailo V, Tondiy O, et al. The peculiarities of the heart rate variability and electroencephalogram changes in patients with epilepsy and cardiovascular pathology. Wiad Lek, 2019, 72(2): 165-168.
25. Jehi L. Sudden death in epilepsy, surgery, and seizure outcomes: the interface between heart and brain. Cleve Clin J Med, 2010, 77 (Suppl 3): S51-S55.
26. Wu ML, Hu DM, Wang JJ, et al. Pre- and postoperative heart rate variability and vagus nerve stimulation in patients with drug-resistant epilepsy - a meta-analysis. Epilepsy Behav, 2021, 123: 108247.
27. 韓文杰, 班俊杰, 黎振聲, 等. 離子通道基因在癲癇與心律失常共患病中的研究進展. 中華神經醫學雜志, 2025, 24(7): 728-733.
28. Akyüz E, üner AK, K?klü B, et al. Cardiorespiratory findings in epilepsy: a recent review on outcomes and pathophysiology. J Neurosci Res, 2021, 99(9): 2059-2073.
29. Akyüz E, Do?anyi?it Z, Paudel YN, et al. Increased ACh-associated immunoreactivity in autonomic centers in PTZ kindling model of epilepsy. Biomedicines, 2020, 8(5): 113.
30. Shlobin NA, Li J, Sander JW, et al. Cardiac conduction delay for sodium channel antagonist antiseizure medications: an analysis of the Canadian longitudinal study on aging. Neurology, 2025, 104(4): e210302.
31. Wang J, Huang PY, Yu QW, et al. Epilepsy and long-term risk of arrhythmias. Eur Heart J, 2023, 44(35): 3374-3382.
32. Slater JD, Benbadis S, Verrier RL. The brain-heart connection: value of concurrent ECG and EEG recordings in epilepsy management. Epilepsy Behav Rep, 2024, 28: 100726.
33. Shmuely S, Surges R, Helling RM, et al. Cardiac arrhythmias in Dravet syndrome: an observational multicenter study. Ann Clin Transl Neurol, 2020, 7(4): 462-473.
34. Haridas B, Chuang DT, Nei M, et al. Sudden unexpected death in epilepsy: pathogenesis, risk factors, and prevention. Semin Neurol, 2022, 42(5): 658-664.
35. Ufongene C, El Atrache R, Loddenkemper T, et al. Electrocardiographic changes associated with epilepsy beyond heart rate and their utilization in future seizure detection and forecasting methods. Clin Neurophysiol, 2020, 131(4): 866-879.
36. Hassan NAI F, Toraih EA, Orz M, et al. Electrocardiographic abnormalities in epilepsy: analysis of cardiac conduction patterns and SUDEP risk. Neurol Sci, 2025, 46(10): 5287-5304.
37. Fialho GL, Verrier RL, D'Avila A, et al. Dual assessment of abnormal cardiac electrical dispersion and diastolic dysfunction for early detection of the epileptic heart condition. J Electrocardiol, 2023, 78: 69-75.
38. Dogan EA, Dogan U, Yildiz GU, et al. Evaluation of cardiac repolarization indices in well-controlled partial epilepsy: 12-lead ECG findings. Epilepsy Res, 2010, 90(1-2): 157-163.
39. Demir TG, Gungoren F, Ethemoglu OU, et al. Epilepsy's effect on cardiac rhythm and the autonomic nervous system. Rev Assoc Med Bras, 2024, 70(2): e20230742.
40. Gurses AA, Gen CE, Gurses KM, et al. QT interval alterations in epilepsy: a thorough investigation between epilepsy subtypes. J Clin Neurosci, 2022, 104: 113-117.
41. Hamdy RM, Abd El Aziz OH, El Attar RS, et al. Evaluation of QT dispersion in epileptic patients and its association with SUDEP risk. Epilepsy Res, 2022, 180: 106860.
42. Bartlett-Lee B, Dervan L, Miyake C, et al. Association of minor electrocardiographic (ECG) abnormalities with epilepsy duration in children: a manifestation of the epileptic heart? Seizure, 2024, 118: 1-7.
43. Chan SW, Chun A, Nguyen L, et al. Associations between epilepsy, respiratory impairment, and minor ECG abnormalities in children. Seizure, 2024, 122: 39-44.
44. Pernice R, Faes L, Feucht M, et al. Pairwise and higher-order measures of brain-heart interactions in children with temporal lobe epilepsy. J Neural Eng, 2022, 19(4): 046039.
45. Pang TD, Nearing BD, Schachter SC, et al. Epileptic seizures and epilepsy monitoring unit admission disclose latent cardiac electrical instability. Epilepsy Behav, 2022, 135: 108881.
46. Bianco M, Breviario S, Fraccalini T, et al. Epilepsy and syncope - a case report and narrative review of arrhythmias connected to temporal lobe epilepsy. J Electrocardiol, 2022, 73: 76-78.
47. Daverio M, Ciccone O, Boniver C, et al. Supraventricular tachycardia during status epilepticus in Dravet syndrome: a link between brain and heart?. Pediatr Neurol, 2016, 56: 69-71.
48. Frasier CR, Zhang H, Offord J, et al. Channelopathy as a SUDEP biomarker in Dravet syndrome patient-derived cardiac myocytes. Stem Cell Rep, 2018, 11(3): 626-634.
49. Fialho GL, Pang TD, Kong WY, et al. Individuals with chronic epilepsy have elevated P-wave heterogeneity comparable to patients with atrial fibrillation. Epilepsia, 2023, 64(9): 2361-2372.
50. Duran S, Boduroglu Y. Left atrial remodeling in epilepsy: a comparative echocardiographic study of left atrial emptying fraction and left atrial volumetric index in patients with epilepsy. Epilepsia, 2025, 66(10): 3964-3971.
51. Miotto R, Cavagnollo MT, Lin K, et al. Strain analysis of cardiac chambers in individuals with temporal lobe epilepsy. Epilepsia, 2025, 66(6): 1589-1597.
52. Akyuz E, Polat K, Ates S, et al. Investigating cardiac morphological alterations in a pentylenetetrazol-kindling model of epilepsy. Diagnostics (Basel), 2020, 10(6): 388.
53. Powell KL, Liu Z, Curl CL, et al. Altered cardiac structure and function is related to seizure frequency in a rat model of chronic acquired temporal lobe epilepsy. Neurobiol Dis, 2021, 159: 105505.
54. Sharma S, Sharma M, Rana AK, et al. Deciphering key regulators involved in epilepsy-induced cardiac damage through whole transcriptome and proteome analysis in a rat model. Epilepsia, 2021, 62(2): 504-516.
55. Liu Z, Sivathamboo S, Thergajan P, et al. Cardiac structural and molecular alterations in rodent models of temporal lobe epilepsy. Epilepsia Open, 2025, 10(3): 809-821.
56. Mahmoud M Noureldeen, Mohamed Mabrouk Tohamy, et al. Subclinical cardiac dysfunction detected by speckle-tracking echocardiography in children with drug-resistant epilepsy. Pediatric research, 2026, 2: s41390-026-04769-z.

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