Cardiac autonomic modulation in drug-resistant epilepsy patients after vagus nerve stimulation therapy
Abstract
The positive effect of vagus nerve stimulation (VNS) in patients with drug-resistant epilepsy is considered to be mediated by the afferent pathways of the vagus nerve, but the efferent pathways may influence the cardiac autonomic activity.
Aim of the study. To assess the effects of VNS on cardiac autonomic modulation in epilepsy patients, over three months of neurostimulation.
Clinical rationale for the study. Linear and non-linear heart rate variability (HRV) analysis can provide information on the sympathovagal balance and reveal particularities of the central control of the autonomic cardiovascular function.
Materials and Methods. Using Biopac Acquisition System, we analysed HRV parameters in resting condition and during sympathetic and parasympathetic activation tests in five patients with drug-resistant epilepsy, who underwent VNS procedure.
Results. During the sympathetic and vagal activation tests, all five patients presented normal responses of cardiac autonomic activity, reflected in RMSSD, HFnu and LF/HF dynamics in both HRV evaluations. No bradycardia, cardiac arrhythmia or orthostatic hypotension was registered during the two evaluations.
Conclusions. Our results indicate that VNS appears not to alter the cardiac autonomic function after three months of neurostimulation. HRV analysis is a useful tool for evaluating cardiac autonomic modulation in epilepsy patients during VNS therapy.
Clinical Implications. Patients with decreased HRV should be periodically monitored. Cardiac changes in patients with epilepsy are important because of the additional risk of arrhythmias mediated through the autonomic dysfunction.
Keywords: drug-resistant epilepsyvagus nerve stimulationcardiac autonomic modulationheart rate variabilitylinear and non-linear analysis
References
- Lee SW, Kulkarni K, Annoni EM, et al. Stochastic vagus nerve stimulation affects acute heart rate dynamics in rats. PLoS One. 2018; 13(3): e0194910.
- Premchand RK, Sharma K, Mittal S, et al. Extended Follow-Up of Patients With Heart Failure Receiving Autonomic Regulation Therapy in the ANTHEM-HF Study. J Card Fail. 2016; 22(8): 639–642.
- Garamendi I, Acera M, Agundez M, et al. Cardiovascular autonomic and hemodynamic responses to vagus nerve stimulation in drug-resistant epilepsy. Seizure. 2017; 45: 56–60.
- Henry TR. Therapeutic mechanisms of vagus nerve stimulation. Neurology. 2002; 59: S3–14.
- Schachter SC, Saper CB. Vagus nerve stimulation. Epilepsia. 1998; 39(7): 677–686.
- Amark P, Stödberg T, Wallstedt L. Late onset bradyarrhythmia during vagus nerve stimulation. Epilepsia. 2007; 48(5): 1023–1024.
- Schomer AC, Nearing BD, Schachter SC, et al. Vagus nerve stimulation reduces cardiac electrical instability assessed by quantitative T-wave alternans analysis in patients with drug-resistant focal epilepsy. Epilepsia. 2014; 55(12): 1996–2002.
- Bernardi L, Bianchini B, Spadacini G, et al. Demonstrable cardiac reinnervation after human heart transplantation by carotid baroreflex modulation of RR interval. Circulation. 1995; 92(10): 2895–2903.
- 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): 1043–1065.
- Hilz MJ. Quantitative autonomic functional testing in clinical trials. In: Brown WF, Bolton CF, Aminoff MJ. ed. Neuromuscular function and disease. Basic, clinical and electrodiagnostic aspects. WB Saunders, Philadelphia 2002: 1899–1929.
- Saul JP, Berger RD, Albrecht P, et al. Transfer function analysis of the circulation: unique insights into cardiovascular regulation. Am J Physiol. 1991; 261(4 Pt 2): H1231–H1245.
- Huikuri HV, Mäkikallio TH, Perkiömäki J. Measurement of heart rate variability by methods based on nonlinear dynamics. J Electrocardiol. 2003; 36 Suppl: 95–99.
- Voss A, Kurths J, Kleiner HJ, et al. The application of methods of non-linear dynamics for the improved and predictive recognition of patients threatened by sudden cardiac death. Cardiovasc Res. 1996; 31(3): 419–433.
- Golińska AK. Detrended fluctuation analysis (DFA) in biomedical signal processing: Selected examples. Studies in Logic, Grammar and Rhetoric. 2012; 29: 107–115.
- Chen C, Jin Yu, Lo IL, et al. Complexity Change in Cardiovascular Disease. Int J Biol Sci. 2017; 13(10): 1320–1328.
- Mäkikallio TH, Koistinen J, Jordaens L, et al. Heart rate dynamics before spontaneous onset of ventricular fibrillation in patients with healed myocardial infarcts. Am J Cardiol. 1999; 83(6): 880–884.
- Mäkikallio TH, Seppänen T, Niemelä M, et al. Abnormalities in beat to beat complexity of heart rate dynamics in patients with a previous myocardial infarction. J Am Coll Cardiol. 1996; 28(4): 1005–1011.
- Varadhan R, Chaves PHM, Lipsitz LA, et al. Frailty and impaired cardiac autonomic control: new insights from principal components aggregation of traditional heart rate variability indices. J Gerontol A Biol Sci Med Sci. 2009; 64(6): 682–687.
- Tsuji H, Venditti FJ, Manders ES, et al. Reduced heart rate variability and mortality risk in an elderly cohort. The Framingham Heart Study. Circulation. 1994; 90(2): 878–883.
- Myers KA, Bello-Espinosa LE, Symonds JD, et al. Heart rate variability in epilepsy: A potential biomarker of sudden unexpected death in epilepsy risk. Epilepsia. 2018; 59(7): 1372–1380.
- Constantinescu V, Matei D, Constantinescu I, et al. Heart Rate Variability and Vagus Nerve Stimulation in Epilepsy Patients. Transl Neurosci. 2019; 10: 223–232.
- Budrejko S, Kempa M, Chmielecka M, et al. Analysis of Heart Rate Variability During Head-Up Tilt-Test in Patients with Vasovagal Syncope. Eur J Transl Clin Med. 2018; 1(1): 24–36.
- Shaffer F, Ginsberg JP. An Overview of Heart Rate Variability Metrics and Norms. Front Public Health. 2017; 5: 258.
- Mourot L, Bouhaddi M, Perrey S, et al. Decrease in heart rate variability with overtraining: assessment by the Poincaré plot analysis. Clin Physiol Funct Imaging. 2004; 24(1): 10–18.
- Mourot L, Bouhaddi M, Perrey S, et al. Quantitative Poincaré plot analysis of heart rate variability: effect of endurance training. Eur J Appl Physiol. 2004; 91(1): 79–87.
- Peng CK, Havlin S, Stanley HE, et al. Quantification of scaling exponents and crossover phenomena in nonstationary heartbeat time series. Chaos. 1995; 5(1): 82–87.
- Corino VDA, Ziglio F, Lombardi F, et al. Detrended Fluctuation Analysis of Atrial Signal during Adrenergic Activation in Atrial Fibrillation. Computers in Cardiology. 2006; 33: 141–144.
- Yeh RG, Shieh JS, Chen GY, et al. Detrended fluctuation analysis of short-term heart rate variability in late pregnant women. Auton Neurosci. 2009; 150(1-2): 122–126.
- Rodriguez E, Echeverria J, Alvarez-Ramirez J. Detrended fluctuation analysis of heart intrabeat dynamics. Physica A. 2007; 384(2): 429–438.
- Acharya RU, Lim CM, Joseph P. Heart rate variability analysis using correlation dimension and detrended fluctuation analysis. ITBM-RBM. 2002; 23(6): 333–339.
- Absil PA, Sepulchre R, Bilge A, et al. Nonlinear analysis of cardiac rhythm fluctuations using DFA method. Physica A: Statistical Mechanics and its Applications. 1999; 272(1-2): 235–244.
- Germán-Salló Z, Germán-Salló M. Non-linear Methods in HRV Analysis. Procedia Technology. 2016; 22: 645–651.
- Pikkujämsä SM, Mäkikallio TH, Sourander LB, et al. Cardiac interbeat interval dynamics from childhood to senescence : comparison of conventional and new measures based on fractals and chaos theory. Circulation. 1999; 100(4): 393–399.
- Fornai F, Ruffoli R, Giorgi FS, et al. The role of locus coeruleus in the antiepileptic activity induced by vagus nerve stimulation. Eur J Neurosci. 2011; 33(12): 2169–2178.
- Ardell JL, Rajendran PS, Nier HA, et al. Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function. Am J Physiol Heart Circ Physiol. 2015; 309(10): H1740–H1752.
- Galbarriatu L, Pomposo I, Aurrecoechea J, et al. Vagus nerve stimulation therapy for treatment-resistant epilepsy: a 15-year experience at a single institution. Clin Neurol Neurosurg. 2015; 137: 89–93.
- Ryvlin P, Gilliam FG, Nguyen DK, et al. The long-term effect of vagus nerve stimulation on quality of life in patients with pharmacoresistant focal epilepsy: the PuLsE (Open Prospective Randomized Long-term Effectiveness) trial. Epilepsia. 2014; 55(6): 893–900.
- Stemper B, Devinsky O, Haendl T, et al. Effects of vagus nerve stimulation on cardiovascular regulation in patients with epilepsy. Acta Neurol Scand. 2008; 117(4): 231–236.
- Ben-Menachem E. Vagus nerve stimulation, side effects, and long-term safety. J Clin Neurophysiol. 2001; 18(5): 415–418.
- Vanderlei LC, Pastre CM, Hoshi RA, et al. Basic notions of heart rate variability and its clinical applicability. Rev Bras Cir Cardiovasc. 2009; 24(2): 205–217.
- Ronkainen E, Korpelainen JT, Heikkinen E, et al. Cardiac autonomic control in patients with refractory epilepsy before and during vagus nerve stimulation treatment: a one-year follow-up study. Epilepsia. 2006; 47(3): 556–562.
- Liu H, Yang Z, Meng F, et al. Deceleration and acceleration capacities of heart rate in patients with drug-resistant epilepsy. Clin Auton Res. 2019; 29(2): 195–204.
- Baysal-Kirac L, Serbest NG, Şahin E, et al. Analysis of heart rate variability and risk factors for SUDEP in patients with drug-resistant epilepsy. Epilepsy Behav. 2017; 71(Pt A): 60–64.
- Liu H, Yang Z, Huang L, et al. Heart-rate variability indices as predictors of the response to vagus nerve stimulation in patients with drug-resistant epilepsy. Epilepsia. 2017; 58(6): 1015–1022.
- Rousselet L, Le Rolle V, Ojeda D, et al. Influence of Vagus Nerve Stimulation parameters on chronotropism and inotropism in heart failure. Conf Proc IEEE Eng Med Biol Soc. 2014; 2014: 526–529.