High Skin Sympathetic Nerve Activity in Patients with Recurrent Syncope
Abstract
:1. Introduction
2. Materials and Methods
2.1. Participants
2.2. Head-Up Tilt Testing
2.3. neuECG
2.4. Heart Rate Variability
2.5. Statistics
3. Results
3.1. Patient Characteristics
3.2. The Comparisons of BP, HR and aSKNA in Different Phases
3.3. The Effect of aSKNA on BP and HR in Different Phases
3.4. Heart Rate Variability in Different Phases
3.5. Predictors of Syncope
4. Discussion
4.1. Autonomic Regulation and Syncope
4.2. Paradoxical Hemodynamic Response to Sympathetic Nerve Activity
4.3. Prediction of Syncope
4.4. Study Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Soteriades, E.S.; Evans, J.C.; Larson, M.G.; Chen, M.H.; Chen, L.; Benjamin, E.J.; Levy, D. Incidence and prognosis of syncope. N. Engl. J. Med. 2002, 347, 878–885. [Google Scholar] [CrossRef]
- Correction to: 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 2017, 136, e271–e272. [CrossRef] [Green Version]
- Kochiadakis, G.E.; Orfanakis, A.; Chryssostomakis, S.I.; Manios, E.G.; Kounali, D.K.; Vardas, P.E. Autonomic nervous system activity during tilt testing in syncopal patients, estimated by power spectral analysis of heart rate variability. Pacing Clin. Electrophysiol. 1997, 20, 1332–1341. [Google Scholar] [CrossRef]
- Theodorakis, G.N.; Kremastinos, D.T.; Avrambos, G.T.; Stefanakis, G.S.; Karavolias, G.K.; Toutouzas, P.K. Heart rate variability in patients with vasovagal syndrome. Pacing Clin. Electrophysiol. 1992, 15, 2221–2225. [Google Scholar] [CrossRef] [PubMed]
- Jardine, D.L.; Wieling, W.; Brignole, M.; Lenders, J.W.M.; Sutton, R.; Stewart, J. The pathophysiology of the vasovagal response. Heart Rhythm 2018, 15, 921–929. [Google Scholar] [CrossRef] [PubMed]
- Doytchinova, A.; Hassel, J.L.; Yuan, Y.; Lin, H.; Yin, D.; Adams, D.; Straka, S.; Wright, K.; Smith, K.; Wagner, D.; et al. Simultaneous noninvasive recording of skin sympathetic nerve activity and electrocardiogram. Heart Rhythm 2017, 14, 25–33. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jiang, Z.; Zhao, Y.; Doytchinova, A.; Kamp, N.J.; Tsai, W.C.; Yuan, Y.; Adams, D.; Wagner, D.; Shen, C.; Chen, L.S.; et al. Using skin sympathetic nerve activity to estimate stellate ganglion nerve activity in dogs. Heart Rhythm 2015, 12, 1324–1332. [Google Scholar] [CrossRef] [Green Version]
- Uradu, A.; Wan, J.; Doytchinova, A.; Wright, K.C.; Lin, A.Y.T.; Chen, L.S.; Shen, C.; Lin, S.F.; Everett, T.H.t.; Chen, P.S. Skin sympathetic nerve activity precedes the onset and termination of paroxysmal atrial tachycardia and fibrillation. Heart Rhythm 2017, 14, 964–971. [Google Scholar] [CrossRef] [PubMed]
- Kabir, R.A.; Doytchinova, A.; Liu, X.; Adams, D.; Straka, S.; Chen, L.S.; Shen, C.; Lin, S.F.; Everett, T.H.t.; Chen, P.S. Crescendo Skin Sympathetic Nerve Activity and Ventricular Arrhythmia. J. Am. Coll. Cardiol. 2017, 70, 3201–3202. [Google Scholar] [CrossRef]
- Virag, N.; Erickson, M.; Taraborrelli, P.; Vetter, R.; Lim, P.B.; Sutton, R. Predicting vasovagal syncope from heart rate and blood pressure: A prospective study in 140 subjects. Heart Rhythm 2018, 15, 1404–1410. [Google Scholar] [CrossRef]
- Pan, J.; Tompkins, W.J. A real-time QRS detection algorithm. IEEE Trans. Biomed. Eng. 1985, 32, 230–236. [Google Scholar] [CrossRef] [PubMed]
- van Dijk, J.G.; Ghariq, M.; Kerkhof, F.I.; Reijntjes, R.; van Houwelingen, M.J.; van Rossum, I.A.; Saal, D.P.; van Zwet, E.W.; van Lieshout, J.J.; Thijs, R.D.; et al. Novel Methods for Quantification of Vasodepression and Cardioinhibition During Tilt-Induced Vasovagal Syncope. Circ. Res. 2020, 127, e126–e138. [Google Scholar] [CrossRef] [PubMed]
- Yokoi, Y.; Aoki, K. Relationship between blood pressure and heart-rate variability during graded head-up tilt. Acta Physiol. Scand. 1999, 165, 155–161. [Google Scholar] [CrossRef] [PubMed]
- Lipsitz, L.A.; Mietus, J.; Moody, G.B.; Goldberger, A.L. Spectral characteristics of heart rate variability before and during postural tilt. Relations to aging and risk of syncope. Circulation 1990, 81, 1803–1810. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vissing, S.F.; Secher, N.H.; Victor, R.G. Mechanisms of cutaneous vasoconstriction during upright posture. Acta Physiol. Scand. 1997, 159, 131–138. [Google Scholar] [CrossRef]
- Shinohara, T.; Ebata, Y.; Ayabe, R.; Fukui, A.; Okada, N.; Yufu, K.; Nakagawa, M.; Takahashi, N. Cardiac autonomic dysfunction in patients with head-up tilt test-induced vasovagal syncope. Pacing Clin. Electrophysiol. 2014, 37, 1694–1701. [Google Scholar] [CrossRef]
- Folino, A.F.; Russo, G.; Porta, A.; Buja, G.; Cerutti, S.; Iliceto, S. Autonomic modulation and cardiac contractility in vasovagal syncope. Int. J. Cardiol. 2010, 139, 248–253. [Google Scholar] [CrossRef]
- Mehlsen, J.; Kaijer, M.N.; Mehlsen, A.B. Autonomic and electrocardiographic changes in cardioinhibitory syncope. Europace 2008, 10, 91–95. [Google Scholar] [CrossRef]
- Alboni, P.; Dinelli, M.; Gruppillo, P.; Bondanelli, M.; Bettiol, K.; Marchi, P.; Uberti, U.E. Haemodynamic changes early in prodromal symptoms of vasovagal syncope. Europace 2002, 4, 333–338. [Google Scholar] [CrossRef]
- Alehan, D.; Ayabakan, C.; Ozer, S. Heart rate variability and autonomic nervous system changes in children with vasovagal syncope. Pacing Clin. Electrophysiol. 2002, 25, 1331–1338. [Google Scholar] [CrossRef]
- Furlan, R.; Piazza, S.; Dell’Orto, S.; Barbic, F.; Bianchi, A.; Mainardi, L.; Cerutti, S.; Pagani, M.; Malliani, A. Cardiac autonomic patterns preceding occasional vasovagal reactions in healthy humans. Circulation 1998, 98, 1756–1761. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Morillo, C.A.; Eckberg, D.L.; Ellenbogen, K.A.; Beightol, L.A.; Hoag, J.B.; Tahvanainen, K.U.; Kuusela, T.A.; Diedrich, A.M. Vagal and sympathetic mechanisms in patients with orthostatic vasovagal syncope. Circulation 1997, 96, 2509–2513. [Google Scholar] [CrossRef]
- Kamiya, A.; Hayano, J.; Kawada, T.; Michikami, D.; Yamamoto, K.; Ariumi, H.; Shimizu, S.; Uemura, K.; Miyamoto, T.; Aiba, T.; et al. Low-frequency oscillation of sympathetic nerve activity decreases during development of tilt-induced syncope preceding sympathetic withdrawal and bradycardia. Am. J. Physiol. Heart Circ. Physiol. 2005, 289, H1758–H1769. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jacob, G.; Costa, F.; Shannon, J.; Robertson, D.; Biaggioni, I. Dissociation between neural and vascular responses to sympathetic stimulation: Contribution of local adrenergic receptor function. Hypertension 2000, 35, 76–81. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kumar, A.; Wright, K.; Uceda, D.E.; Vasallo, P.A., 3rd; Rabin, P.L.; Adams, D.; Wong, J.; Das, M.; Lin, S.F.; Chen, P.S.; et al. Skin sympathetic nerve activity as a biomarker for syncopal episodes during a tilt table test. Heart Rhythm 2020, 17, 804–812. [Google Scholar] [CrossRef] [PubMed]
- Mallat, Z.; Vicaut, E.; Sangaré, A.; Verschueren, J.; Fontaine, G.; Frank, R. Prediction of head-up tilt test result by analysis of early heart rate variations. Circulation 1997, 96, 581–584. [Google Scholar] [CrossRef] [PubMed]
- Ciliberti, M.A.P.; Santoro, F.; Di Martino, L.F.M.; Rinaldi, A.C.; Salvemini, G.; Cipriani, F.; Triggiani, A.I.; Moscatelli, F.; Valenzano, A.; Di Biase, M.; et al. Predictive value of very low frequency at spectral analysis among patients with unexplained syncope assessed by head-up tilt testing. Arch. Cardiovasc. Dis. 2018, 111, 95–100. [Google Scholar] [CrossRef]
- Ho, D.; Ghods, M.; Kumar, S.; Warrier, N.; Ilias Basha, H.; Budzikowski, A.S.; Kassotis, J. Early Hemodynamic Changes during Head-Up Tilt Table Testing Can Predict a Neurocardiogenic Response in an African-American Patient Population. Cardiology 2016, 133, 223–232. [Google Scholar] [CrossRef]
Tilt-Negative | Tilt-Positive | p Value | |||
---|---|---|---|---|---|
No. | (%) | No. | (%) | ||
Participants | 25 | (61.0) | 16 | (39.0) | |
Age (years) | 42.2 ± 14.0 | 46.6 ± 16.1 | 0.362 | ||
Sex (female) | 17 | (68.0) | 12 | (75.0) | 0.631 |
DM | 4 | (16.0) | 2 | (12.5) | 0.757 |
Hypertension | 4 | (16.0) | 4 | (25.0) | 0.478 |
CVA | 1 | (4.0) | 0 | (0) | 0.418 |
HBV | 3 | (12.0) | 3 | (18.8) | 0.551 |
VT | 1 | (4.0) | 0 | (0) | 0.418 |
AF | 1 | (4.0) | 0 | (0) | 0.418 |
COPD | 2 | (8.0) | 0 | (0) | 0.246 |
MVP | 3 | (12.0) | 2 | (12.5) | 0.962 |
LVEF (%) | 70.7 ± 5.7 | 68.2 ± 8.7 | 0.348 |
Phase | Tilt-Negative | Tilt-Positive | p Value | |||
---|---|---|---|---|---|---|
Mean | SD | Mean | SD | |||
Rest | SBP (mmHg) | 117.9 | 15.7 | 122.9 | 18.8 | 0.355 |
DBP (mmHg) | 75.4 | 15.7 | 75.6 | 9.5 | 0.970 | |
MBP (mmHg) | 89.6 | 11.7 | 91.4 | 12.0 | 0.636 | |
HR (beats/min) | 67.2 | 6.9 | 66.4 | 8.0 | 0.733 | |
aSKNA (μV) | 1.02 | 0.29 | 1.21 | 0.27 | 0.034 * | |
Tilt-up | SBP (mmHg) | 118.4 | 13.4 | 118.2 | 15.9 | 0.952 |
MBP (mmHg) | 76.1 | 9.9 | 77.5 | 9.9 | 0.678 | |
DBP (mmHg) | 90.2 | 10.6 | 91.0 | 11.3 | 0.823 | |
HR (beats/min) | 75.3 | 7.7 | 77.3 | 12.2 | 0.517 | |
aSKNA (μV) | 1.29 | 0.34 | 1.35 | 0.30 | 0.538 | |
Provocation | SBP (mmHg) | 109.9 | 12.5 | 101.2 | 13.1 | 0.040 * |
DBP (mmHg) | 69.8 | 9.6 | 66.5 | 9.8 | 0.300 | |
MBP (mmHg) | 83.2 | 10.2 | 78.1 | 10.6 | 0.136 | |
HR (beats/min) | 89.9 | 11.9 | 84.0 | 14.5 | 0.166 | |
aSKNA (μV) | 1.23 | 0.35 | 1.39 | 0.35 | 0.163 | |
Recovery | SBP (mmHg) | 111.2 | 15.7 | 108.8 | 14.3 | 0.613 |
DBP (mmHg) | 68.4 | 11.2 | 66.8 | 10.0 | 0.642 | |
MBP (mmHg) | 82.7 | 9.4 | 80.8 | 11.2 | 0.562 | |
HR (beats/min) | 69.8 | 10.7 | 60.2 | 6.3 | 0.003 * | |
aSKNA (μV) | 1.18 | 0.32 | 1.27 | 0.39 | 0.386 | |
Tilt-up/Rest | HR | 1.12 | 0.10 | 1.17 | 0.13 | 0.254 |
aSKNA | 1.30 | 0.29 | 1.13 | 0.18 | 0.038 * | |
Provocation/Rest | HR | 1.34 | 0.16 | 1.27 | 0.17 | 0.156 |
aSKNA | 1.24 | 0.31 | 1.16 | 0.22 | 0.351 | |
Provocation/Tilt-up | HR | 1.19 | 0.07 | 1.09 | 0.10 | <0.001 * |
aSKNA | 0.96 | 0.10 | 1.04 | 0.21 | 0.082 |
Tilt-Negative (n = 7) | Tilt-Positive (n = 8) | p for Difference in Adj. β d | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Phase | Outcomes | t a | Mean t b | Adj. β c | SE | p Value | t a | Mean t b | Adj. β c | SE | p Value | |
Rest | SBP (mmHg) | 28 | 4 | 5.48 | 5.42 | 0.311 | 32 | 4 | 11.39 | 3.84 | 0.003 * | 0.130 |
DBP (mmHg) | 3.18 | 3.28 | 0.334 | 2.76 | 3.52 | 0.433 | 0.639 | |||||
MBP (mmHg) | 3.96 | 3.49 | 0.256 | 1.00 | 2.86 | 0.726 | 0.921 | |||||
HR (bpm) | 3.55 | 4.47 | 0.427 | 6.73 | 2.18 | 0.002 * | 0.434 | |||||
Tilt-up | SBP (mmHg) | 70 | 10 | 2.03 | 3.24 | 0.530 | 80 | 10 | 1.27 | 3.15 | 0.686 | 0.834 |
DBP (mmHg) | 8.56 | 3.85 | 0.026 * | 1.50 | 2.45 | 0.541 | 0.340 | |||||
MBP (mmHg) | 7.28 | 3.08 | 0.018 * | 1.35 | 2.10 | 0.520 | 0.344 | |||||
HR (bpm) | 3.17 | 4.04 | 0.433 | −0.08 | 2.56 | 0.974 | 0.462 | |||||
Provocation | SBP (mmHg) | 98 | 14 | 19.32 | 3.50 | <0.001 * | 58 | 7.3 | −11.65 | 5.08 | 0.022 * | 0.038 * |
DBP (mmHg) | 7.31 | 3.95 | 0.064 | −13.75 | 3.82 | <0.001 * | 0.016 * | |||||
MBP (mmHg) | 11.00 | 3.62 | 0.002 * | −11.39 | 3.94 | 0.004 * | 0.026 * | |||||
HR (bpm) | 27.64 | 5.46 | <0.001 * | −3.57 | 4.36 | 0.413 | <0.001 * | |||||
Recovery | SBP (mmHg) | 21 | 3 | 11.80 | 5.61 | 0.035 * | 36 | 4.5 | 1.71 | 8.23 | 0.835 | 0.784 |
DBP (mmHg) | 8.58 | 4.99 | 0.086 | 11.79 | 3.75 | 0.002 * | 0.351 | |||||
MBP (mmHg) | 8.07 | 4.32 | 0.062 | 5.10 | 4.75 | 0.282 | 0.696 | |||||
HR (bpm) | 8.17 | 7.83 | 0.296 | 4.99 | 4.26 | 0.242 | 0.705 |
Phase | Tilt-Negative | Tilt-Positive | p Value | |||
---|---|---|---|---|---|---|
Median | Q1–Q3 | Median | Q1–Q3 | |||
Rest | SDNN (ms) | 35.6 | 26.3–65.5 | 31.8 | 26.6–36.9 | 0.415 |
RMSSD (ms) | 29.3 | 12.0–61.8 | 19.6 | 12.7–27.2 | 0.264 | |
LFnu (%) | 43.7 | 34.0–71.1 | 58.6 | 45.1–69.9 | 0.389 | |
LF/HF | 0.78 | 0.51–2.48 | 1.41 | 0.82–2.33 | 0.389 | |
Tilt up | SDNN (ms) | 37.2 | 24.3–50.6 | 40.2 | 35.8–52.4 | 0.775 |
RMSSD (ms) | 22.8 | 10.9–35.1 | 17.5 | 14.5–28.7 | 0.668 | |
LFnu (%) | 61.0 | 45.0–72.4 | 67.1 | 61.0–74.6 | 0.574 | |
LF/HF | 1.56 | 0.82–2.65 | 2.04 | 1.56–2.94 | 0.574 | |
Provocation | SDNN (ms) | 66.5 | 54.6–99.3 | 99.8 | 70.2–158.1 | 0.074 |
RMSSD (ms) | 22.4 | 9.5–37.2 | 31.3 | 21.4–52.1 | 0.496 | |
LFnu (%) | 79.7 | 48.6–88.8 | 65.3 | 47.5–69.9 | 0.070 | |
LF/HF | 3.93 | 0.95–7.92 | 1.88 | 0.91–2.32 | 0.070 | |
Recovery | SDNN (ms) | 53.4 | 27.6–89.6 | 61.5 | 52.7–62.4 | 0.238 |
RMSSD (ms) | 51.1 | 13.0–83.4 | 43.8 | 24.4–48.7 | 0.483 | |
LFnu (%) | 53.8 | 33.9–66.8 | 61.5 | 55.6–64.1 | 0.164 | |
LF/HF | 1.17 | 0.51–2.01 | 1.60 | 1.25–1.78 | 0.164 | |
Tilt-up/Rest | SDNN | 0.87 | 0.75–1.09 | 1.24 | 1.08–1.33 | 0.002 * |
RMSSD | 0.72 | 0.57–0.85 | 0.81 | 0.67–1.03 | 0.442 | |
LFnu | 1.28 | 0.98–1.55 | 1.10 | 0.92–1.58 | 0.364 | |
LF/HF | 1.85 | 0.97–2.72 | 1.28 | 0.83–2.64 | 0.745 | |
Provocation/Rest | SDNN | 1.91 | 1.06–2.43 | 3.08 | 2.33–5.77 | 0.020 * |
RMSSD | 0.59 | 0.37–0.88 | 1.70 | 0.60–2.82 | 0.042 * | |
LFnu | 1.41 | 1.15–1.95 | 0.94 | 0.78–1.38 | 0.042 * | |
LF/HF | 2.88 | 1.59–6.06 | 0.81 | 0.45–1.86 | 0.021 * | |
Provocation/Tilt-up | SDNN | 1.78 | 1.18–2.45 | 1.85 | 1.75–4.42 | 0.415 |
RMSSD | 0.80 | 0.61–1.46 | 1.26 | 0.69–4.38 | 0.234 | |
LFnu | 1.09 | 1.01–1.30 | 1.02 | 0.64–1.31 | 0.385 | |
LF/HF | 1.36 | 1.02–2.73 | 1.05 | 0.31–1.71 | 0.245 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Huang, T.-C.; Chi, N.-Y.; Lan, C.-S.; Chen, C.-J.; Jhuo, S.-J.; Lin, T.-H.; Liu, Y.-H.; Chou, L.-F.; Chang, C.-W.; Liao, W.-S.; et al. High Skin Sympathetic Nerve Activity in Patients with Recurrent Syncope. J. Pers. Med. 2021, 11, 1053. https://doi.org/10.3390/jpm11111053
Huang T-C, Chi N-Y, Lan C-S, Chen C-J, Jhuo S-J, Lin T-H, Liu Y-H, Chou L-F, Chang C-W, Liao W-S, et al. High Skin Sympathetic Nerve Activity in Patients with Recurrent Syncope. Journal of Personalized Medicine. 2021; 11(11):1053. https://doi.org/10.3390/jpm11111053
Chicago/Turabian StyleHuang, Tien-Chi, Nai-Yu Chi, Chih-Sung Lan, Chang-Jen Chen, Shih-Jie Jhuo, Tsung-Han Lin, Yi-Hsueh Liu, Li-Fang Chou, Chien-Wei Chang, Wei-Sheng Liao, and et al. 2021. "High Skin Sympathetic Nerve Activity in Patients with Recurrent Syncope" Journal of Personalized Medicine 11, no. 11: 1053. https://doi.org/10.3390/jpm11111053