Cardiac Autonomic Neuropathy: Comparative performance of Phase-Rectified Signal Averaging methods with Cardiac Autonomic Reflex Tests and Time Domain Heart rate variability
Main Article Content
Keywords
Cardiac Autonomic Function, Phase-Rectified Signal Averaging, Deceleration capacity, Acceleration capacity, Heart Rate Variability, Cardiac Autonomic Reflex Tests
Abstract
Background:Phase-Rectified Signal Averaging (PRSA) methods, Deceleration (DC), and Acceleration Capacity (AC), provide a comprehensive assessment of cardiac autonomic function (CAN). There are no published studies comparing PRSA methods with conventional methods such as Time Domain Heart Rate Variability (TD-HRV) or Cardiac Autonomic Reflex Tests (CARTs), nor have they described a cut-off value for AC and DC to distinguish patients with CAN (+ve) from those without CAN (-ve). Our study compares PRSA methods with conventional methods and defines cut-off values for AC and DC to diagnose CAN.
Methodology:We studied two cohorts: 126 individuals with normal ventricular function (derivation cohort) and 143 individuals with Left Ventricular Dysfunction (validation cohort). These patients underwent CARTs and supine, resting ECG recordings for 2 to 3 minutes. The patients were categorized as CAN +Ve and CAN -Ve based on TD-HRV parameters and the CARTs. Two different CART criteria were studied: the All-India Institute of Medical Sciences (AIIMS-AFT) criteria and the 2011 Toronto Consensus recommendations. Patients with and without CAN were segregated by AC and DC values, and the methods were compared. The cutoff values for DC and AC were calculated using the ROC curve method from the derivation cohort and verified in the validation cohort.
Results:A reduction in DC values and an increase in AC values indicate a higher chance of CAN. The cut-off values of -7 for AC and 7 for DC provide the highest accuracy in detecting CAN prevalence. Both values have an AUC of nearly 0.9. Reclassifying both cohorts as CAN +Ve based on the derived cut-offs and comparing with the prevalence determined by conventional methods results in kappa values ranging from 0.5 to 0.7.
Conclusions:A decrease in DC value and an increase in AC value are associated with a higher probability of CAN. An AC value ≥ -7 and a DC value ≤ 7 indicate good accuracy in identifying CAN.
References
Xing-De Wang, Li Zhou, Chao-Yu Zhu, Bin Chen, Zhong Chen, Li Wei. Autonomic function, as indicated by heart rate deceleration capacity and deceleration runs, in type 2 diabetes patients with or without essential hypertension. Clin Interv Aging. 2018;13:1169–1176. doi:10.2147/CIA.S149920.
Wei Hu, Xian Jin, Peng Zhang, Qiang Yu, Guizhi Yin, Yi Lu, Hongbing Xiao, Yueguang Chen, Dadong Zhang. Deceleration and acceleration capacities of heart rate associated with heart failure with high discriminating performance. Sci Rep. 2016;6:23617. doi:10.1038/srep23617.
Cao Zou, Hongkai Dong, Fengyan Wang, Meiwen Gao, Xingmei Huang, Jianling Jin, Bingyuan Zhou, Xiangjun Yang. Heart acceleration and deceleration capacities associated with dilated cardiomyopathy. Eur J Clin Invest. 2016;46(4):312–320. doi:10.1111/eci.12594.
Martin Duckheim, Martin Gaebler, Lars Mizera, Juergen Schreieck, Sven Poli, Ulf Ziemann, Meinrad Gawaz, Christine S. Meyer-Zuern, Christian Eick. Deceleration capacity for rapid risk stratification in patients suffering from acute ischemic stroke: a prospective exploratory pilot study. Medicine (Baltimore). 2021;100(13):e25333. doi:10.1097/MD.0000000000025333.
Liyuan Yan, Jianling Jin, Xin Zhao, Xingmei Huang, Wei Zhu, Shili Jiang, Meiwen Gao, Jiamin Yuan. Heart rate acceleration and deceleration capacities associated with circadian blood pressure variation. Ann Noninvasive Electrocardiol. 2020;25(4):e12748. doi:10.1111/anec.12748.
Yaping Wang, Mingyan Liu, Yaping Liu, Xiaowei Tang, Xiangming Tang. Assessment of heart rate deceleration capacity, heart rate deceleration runs, heart rate acceleration capacity, and lipoprotein-related phospholipase A2 as predictors in individuals with dementia. Front Neurol. 2025;15:1438736. doi:10.3389/fneur.2024.1438736.
Hongyun Liu, Ping Zhan, Jinlong Shi, Guojing Wang, Buqing Wang, Weidong Wang. A refined method of quantifying deceleration capacity index for heart rate variability analysis. Biomed Eng Online. 2018;17:184. doi:10.1186/s12938-018-0618-x.
Alexander Steger, Petra Barthel, Alexander Müller, Ina-Maria Rückert-Eheberg, Birgit Linkohr, Julia Allescher, Melanie Maier, Alexander Hapfelmeier, Eimo Martens, Helene Hildegard Heidegger, Arne Michael Müller, Konstantinos D. Rizas, Stefan Kääb, Moritz F. Sinner, Daniel Sinnecker, Karl-Ludwig Laugwitz, Annette Peters, Georg Schmidt. Deceleration capacity derived from a five-minute electrocardiogram predicts mortality in the general population. Sci Rep. 2024;14:30566. doi:10.1038/s41598-024-83712-w.
Johnson TW, Dar IA, Donohue KL, Xu YY, Santiago E, Selioutski O, Marinescu MA, Maddox RK, Wu TT, Schifitto G, Gosev I, Choe R, Khan IR. Cerebral blood flow hemispheric asymmetry in comatose adults receiving extracorporeal membrane oxygenation. Front Neurosci. 2022;16:858404. doi:10.3389/fnins.2022.858404.
Lippman N, Stein KM, Lerman BB. Comparison of methods for removal of ectopy in measurement of heart rate variability. Am J Physiol. 1994;267(1 Pt 2):H411–H418. doi:10.1152/ajpheart.1994.267.1.H411.
Salo MA, Huikuri HV, Seppänen T. Ectopic beats in heart rate variability analysis: effects of editing on time and frequency domain measures. Ann Noninvasive Electrocardiol. 2001;6(1):5–17. doi:10.1111/j.1542-474x.2001.tb00080.x.
Peltola MA. Role of editing of R–R intervals in the analysis of heart rate variability. Front Physiol. 2012;3:148. doi:10.3389/fphys.2012.00148.
Ewing DJ, Martyn CN, Young RJ, Clarke BF. The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care. 1985;8(5):491–498. doi:10.2337/diacare.8.5.491.
Spallone V, Ziegler D, Freeman R, Bernardi L, Frontoni S, Pop-Busui R, Stevens M, Kempler P, Hilsted J, Tesfaye S, Low P, Valensi P. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev. 2011;27(7):639–653. doi:10.1002/dmrr.1239.
Pattnaik S, Gupta S, Saxena U, Matlani M, Kapoor R. Comparison of autonomic function tests and high-sensitivity C-reactivity protein in overweight patients of polycystic ovarian syndrome and overweight controls. Indian J Physiol Pharmacol. 2020;64(4). doi:10.25259/IJPP_72_2020.
Spallone V, Bellavere F, Scionti L, Maule S, Quadri R, Bax G, Melga P, Viviani GL, Esposito K, Morganti R, Cortelli P. Recommendations for the use of cardiovascular tests in diagnosing diabetic autonomic neuropathy. Nutr Metab Cardiovasc Dis. 2011;21(1):69–78. doi:10.1016/j.numecd.2010.07.005.
Voss A, Schroeder R, Heitmann A, Peters A, Perz S. Short-term heart rate variability— influence of gender and age in healthy subjects. PLoS One. 2015;10(3):e0118308. doi:10.1371/journal.pone.0118308.
Campana LM, Owens RL, Clifford GD, Pittman SD, Malhotra A. Phase-rectified signal averaging as a sensitive index of autonomic changes with aging. J Appl Physiol. 2010;108(6):1668–1673. doi:10.1152/japplphysiol.00013.2010.
Duca ST, Tudorancea I, Haba MS, Costache AD, Șerban IL, Pavăl DR, Loghin C, Costache-Enache II. Enhancing comprehensive assessments in chronic heart failure caused by ischemic heart disease: the diagnostic utility of Holter ECG parameters. Medicina (Kaunas). 2024;60(8):1315. doi:10.3390/medicina60081315.
Wang JJ, Xu JY, Qiu YY, Yang RK, Wang WT, Gao CY. Cardiac deceleration capacity and acceleration capacity have diagnostic value in patients with vasovagal syncope regardless of age. Front Cardiovasc Med. 2024;11:1495129. doi:10.3389/fcvm.2024.1495129.
Zheng LH, Sun W, Liu SY, Liang EP, Du ZP, Guo JR, Wu LM, Asirvatham SJ, Yao Y. The diagnostic value of cardiac deceleration capacity in vasovagal syncope. Circ Arrhythm Electrophysiol. 2020;13(12):e008659. doi:10.1161/CIRCEP.120.008659.
Yang Y, Wang F, Zou C, Dong H, Huang X, Zhou B, Li X, Yang X. Male patients with dilated cardiomyopathy exhibiting a higher heart rate acceleration capacity or a lower deceleration capacity are at higher risk of cardiac death. Front Physiol. 2018;9:1774. doi:10.3389/fphys.2018.01774.
Arsenos P, Manis G, Gatzoulis KA, Dilaveris P, Gialernios T, Angelis A, Papadopoulos A, Venieri E, Trikas A, Tousoulis D. Deceleration capacity of heart rate predicts arrhythmic and total mortality in heart failure patients. Ann Noninvasive Electrocardiol. 2016;21(5):508–518. doi:10.1111/anec.12343.
Liu X, Xiang L, Tong G. Predictive values of heart rate variability, deceleration and acceleration capacity of heart rate in post-infarction patients with LVEF ≥35%. Ann Noninvasive Electrocardiol. 2020;25(6):e12771. doi:10.1111/anec.12771.
Xu YH, Wang XD, Yang JJ, Zhou L, Pan YC. Changes of deceleration and acceleration capacity of heart rate in patients with acute hemispheric ischemic stroke. Clin Interv Aging. 2016;11:293–298. doi:10.2147/CIA.S99542.
Arsenos P, Manis G, Gatzoulis KA, Dilaveris P, Gialernios T, Angelis A, Papadopoulos A, Venieri E, Trikas A, Tousoulis D. Deceleration capacity of heart rate predicts arrhythmic and total mortality in heart failure patients. Ann Noninvasive Electrocardiol. 2016;21(5):508–518. doi:10.1111/anec.12343.
Chessa M, Butera G, Lanza GA, et al. Role of heart rate variability in the early diagnosis of diabetic autonomic neuropathy in children. Herz. 2002;27(8):785–790. doi:10.1007/s00059-002-2340-4.
