An Algorithm to Predict Life-Threatening Complications using Heart Rate Variability and the Circadian Heart Rate Difference with a Special Interest on Covid-19, Sudep Children with Congenital Heart Disease and Obesity


  • Reiner Buchhorn Caritas-Krankenhaus Bad Mergentheim, Department of Pediatrics, Uhlandstraße 7, Bad Mergentheim, Germany



COVID-19 virus disease; sudden unexplained death in autonomic nervous system; heart rate variability; congenital heart disease


Corona virus disease (COVID-19) has been declared as a pandemic by the WHO with a global mortality rate of about 3.4%. More recently the neuroinvasive potential of SARS-CoV2 was emphasized as a potential cause for respiratory failure. Such pathophysiology has been investigated in sudden unexplained death in epilepsy (SUDEP) including functional neuroimaging that demonstrates alterations to networks involved in central autonomic and respiratory control located in the brainstem. For risk stratification in these patients, one method may be heart rate and heart rate variability (HRV) monitoring. Method: For a better understanding, we compare HRV monitoring in two cases; 1.) Twenty Holter ECGs of a boy with generalized tonic-clonic seizures up to his dead at the age of 10.5 years with special interest on an acute respiratory failure at the age of 5.4 years. 2.) Thirty one Holter ECGs of a 58-year old pediatric cardiologist who survived an infection with COVID-19. During his disease 24-hour Holter electrocardiography (ECG) was performed continuously over 10 days. Moreover, 24-hour Holter ECGs from the last 10 years were available. The derived algorithm that depends on the global heart rate variability and circadian heart rate difference was proofed in 151 healthy children, 26 children with a fatal outcome or transplantation, 151 patients with operated congenital heart disease, 130 obese children and healthy adult data from literature. Results: In both cases we observe a decline of the global heart rate variability SDNN together with a loss of the circadian heart rate difference. The derived algorithm differentiate healthy children from children with a fatal outcome. The algorithm identify 7.3% of 151 patients with operated congenital heart disease and 5.4% of children with obesity as candidates for COVID-19 complications. Conclusions: A sudden decline of HRV together with a loss of the circadian heart rate difference may indicate a life-threatening complication in critical illness.


(1) Vincent JL, Taccone FS. Understanding pathways to death in patients with COVID-19. The Lancet Respiratory medicine. 2020;8(5):430-2.

(2) Kuck KH. Arrhythmias and sudden cardiac death in the COVID-19 pandemic. Herz. 2020.

(3) Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. Journal of medical virology. 2020.

(4) Gandhi S, Srivastava AK, Ray U, Tripathi PP. Is the Collapse of the Respiratory Center in the Brain Responsible for Respiratory Breakdown in COVID-19 Patients? ACS chemical neuroscience. 2020.

(5) Mueller SG, Nei M, Bateman LM, Knowlton R, Laxer KD, Friedman D, et al. Brainstem network disruption: A pathway to sudden unexplained death in epilepsy? Human brain mapping. 2018;39(12):4820-30.

(6) Allen LA, Harper RM, Lhatoo S, Lemieux L, Diehl B. Neuroimaging of Sudden Unexpected Death in Epilepsy (SUDEP): Insights From Structural and Resting-State Functional MRI Studies. Frontiers in neurology. 2019;10:185.

(7) Myers KA, Bello-Espinosa LE, Symonds JD, Zuberi SM, Clegg R, Sadleir LG, et al. Heart rate variability in epilepsy: A potential biomarker of sudden unexpected death in epilepsy risk. Epilepsia. 2018;59(7):1372-80.

(8) Singh N, Moneghetti KJ, Christle JW, Hadley D, Froelicher V, Plews D. Heart Rate Variability: An Old Metric with New Meaning in the Era of Using mHealth technologies for Health and Exercise Training Guidance. Part Two: Prognosis and Training. Arrhythmia & electrophysiology review. 2018;7(4):247-55.

(9) De Bock F, Jarczok MN, Hoffmann K, Buchhorn R. Do our children lose vagus activity? Potential time trends of children's autonomic nervous system activity. Int J Cardiol. 2013;170(2):e30-e2.

(10) Bonnemeier H, Richardt G, Potratz J, Wiegand UK, Brandes A, Kluge N, et al. Circadian profile of cardiac autonomic nervous modulation in healthy subjects: differing effects of aging and gender on heart rate variability. Journal of cardiovascular electrophysiology. 2003;14(8):791-9.

(11) Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation. 1996;93(5):1043-65.

(12) Hood S, Amir S. The aging clock: circadian rhythms and later life. The Journal of clinical investigation. 2017;127(2):437-46.

(13) Luo Y, Zhang J, Li R, Gao Y, Hou Y, Li J, et al. [Effects of circadian heart rate variation on short-term and long-term mortality in intensive care unit patients: a retrospective cohort study based on MIMIC-II database]. Zhonghua wei zhong bing ji jiu yi xue. 2019;31(9):1128-32.

(14) Cuspidi C, Facchetti R, Bombelli M, Sala C, Tadic M, Grassi G, et al. Night-time heart rate nondipping: clinical and prognostic significance in the general population. Journal of hypertension. 2018;36(6):1311-7.

(15) Sun H, Ning R, Tao Y, Yu C, Deng X, Zhao C, et al. Risk factors for mortality in 244 older adults with COVID-19 in Wuhan, China: a retrospective study. Journal of the American Geriatrics Society. 2020.

(16) Kass DA, Duggal P, Cingolani O. Obesity could shift severe COVID-19 disease to younger ages. Lancet. 2020.

(17) Silva CA, Queiroz LB, Fonseca CB, Silva L, Lourenco B, Marques HHS. Spotlight for healthy adolescents and adolescents with preexisting chronic diseases during the COVID-19 pandemic. Clinics (Sao Paulo, Brazil). 2020;75:e1931.




How to Cite

Buchhorn, R. . (2020). An Algorithm to Predict Life-Threatening Complications using Heart Rate Variability and the Circadian Heart Rate Difference with a Special Interest on Covid-19, Sudep Children with Congenital Heart Disease and Obesity. Journal of Biomedical Engineering and Medical Imaging, 7(4), 01–10.