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A narrative review on gender disparities in the pathogenesis and pathophysiology of Takotsubo syndrome: Implications for novel approaches to treatment?

Carola Y. Förster1* ,  Martin J. Herrmann2
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1 Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, Würzburg University, Würzburg, Germany
2 Center of Mental Health, Department of Psychiatry and Psychotherapy, University Hospital Würzburg, Würzburg, Germany
INNOSC Theranostics and Pharmacological Sciences, 3142 https://doi.org/10.36922/itps.3142
Submitted: 11 March 2024 | Accepted: 30 May 2024 | Published: 19 September 2024
© 2024 by the Author (s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Takotsubo syndrome is a type of cardiomyopathy characterized by transient and reversible left ventricular wall motion abnormalities within the ventricle. Depending on the severity of the injury, recovery can occur within a few hours or weeks. According to studies, older people are more likely to be affected by it, and the prevalence is particularly high among postmenopausal women. Stress factors, both physical and emotional, are widely discussed and generally recognized as triggers. The hypothalamic-pituitary-adrenal axis and its glucocorticoid-dependent negative feedback also play important roles in the resulting gender-specific immune response. Transcutaneous vagus nerve stimulation is proposed as a potential novel personalized therapeutic strategy in light of the gender disparities in autonomous nervous system activity and inflammatory response. Considering the modifiable risks involved in this pathology, such as stress which affects the heart and psychology, a strong emphasis should be placed on preventive medicine. In this paper, we propose the use of non-invasive (transcutaneous) vagus nerve stimulation, as a means of dampening sympathetic overdrive with negligible side effects.

Keywords
Takotsubo syndrome
Heart-brain
Inflammation
Gender
Central autonomic network
Stress
Funding
This work is supported by research grant DFG FO 315/5-1 awarded to C.Y.F.
Conflict of interest
The authors declare they have no competing interests.
References
  1. Nagai M, Shityakov S, Smetak M, et al. Blood biomarkers in Takotsubo syndrome point to an emerging role for inflammaging in endothelial pathophysiology. Biomolecules. 2023;13:995. doi: 10.3390/biom13060995

 

  1. Ittner C, Burek M, Stork S, Nagai M, Forster CY. Increased catecholamine levels and inflammatory mediators alter barrier properties of brain microvascular endothelial cells in vitro. Front Cardiovasc Med. 2020;7:73. doi: 10.3389/fcvm.2020.00073

 

  1. Herrmann MJ, Boehme S, Becker MP, et al. Phasic and sustained brain responses in the amygdala and the bed nucleus of the stria terminalis during threat anticipation. Hum Brain Mapp. 2016;37:1091-1102. doi: 10.1002/hbm.23088

 

  1. Brinkmann L, Buff C, Feldker K, et al. Distinct phasic and sustained brain responses and connectivity of amygdala and bed nucleus of the stria terminalis during threat anticipation in panic disorder. Psychol Med. 2017;47:2675-2688. doi: 10.1017/S0033291717001192

 

  1. Brinkmann L, Buff C, Neumeister P, et al. Dissociation between amygdala and bed nucleus of the stria terminalis during threat anticipation in female post-traumatic stress disorder patients. Hum Brain Mapp. 2017;38:2190-2205. doi: 10.1002/hbm.23513

 

  1. Ulrich-Lai YM, Herman JP. Neural regulation of endocrine and autonomic stress responses. Nat Rev Neurosci. 2009;10:397-409. doi: 10.1038/nrn2647

 

  1. Templin C, Hänggi J, Klein C, et al. Altered limbic and autonomic processing supports brain-heart axis in Takotsubo syndrome. Eur Heart J. 2019;40:1183-1187. doi: 10.1093/eurheartj/ehz068

 

  1. Béjean S, Sultan-Taïeb H. Modeling the economic burden of diseases imputable to stress at work. Eur J Health Econ. 2005;6:16-23. doi: 10.1007/s10198-004-0251-4

 

  1. De Kloet ER, Joëls M, Holsboer F. Stress and the brain: From adaptation to disease. Nat Rev Neurosci. 2005;6:463-475. doi: 10.1038/nrn1683

 

  1. Romier C, Bernassau JM, Cambillau C, Darbon H. Solution structure of human corticotropin releasing factor by 1H NMR and distance geometry with restrained molecular dynamics. Protein Eng. 1993;6:149-156. doi: 10.1093/protein/6.2.149

 

  1. Trainer PJ, Faria M, Newell-Price J, et al. A comparison of the effects of human and ovine corticotropin-releasing hormone on the pituitary-adrenal axis. J Clin Endocrinol Metab. 1995;80:412-417. doi: 10.1210/jcem.80.2.7852498

 

  1. Henckens MJA, Deussing JM, Chen A. Region-specific roles of the corticotropin-releasing factor-urocortin system in stress. Nat Rev Neurosci. 2016;17:636-651. doi: 10.1038/nrn.2016.94

 

  1. Carrasco GA, Van de Kar LD. Neuroendocrine pharmacology of stress. Eur J Pharmacol. 2003;463:235-272. doi: 10.1016/s0014-2999(03)01285-8

 

  1. McEwen BS, Sapolsky RM. Stress and cognitive function. Curr Opin Neurobiol. 1995;5:205-216. doi: 10.1016/0959-4388(95)80028-x

 

  1. McEwen BS. Protective and damaging effects of stress mediators. N Engl J Med. 1998;338:171-179. doi: 10.1056/nejm199801153380307

 

  1. De Kloet ER, Derijk R. Signaling pathways in brain involved in predisposition and pathogenesis of stress-related disease: Genetic and kinetic factors affecting the MR/GR balance. Ann N Y Acad Sci. 2004;1032:14-34. doi: 10.1196/annals.1314.003

 

  1. Joëls, M, Karst H, Alfarez D, et al. Effects of chronic stress on structure and cell function in rat hippocampus and hypothalamus. Stress. 2004;7:221-231. doi: 10.1080/10253890500070005

 

  1. Willner P. Chronic Mild Stress (CMS) revisited: Consistency and behavioural-neurobiological concordance in the effects of CMS. Neuropsychobiology. 2005;52:90-110. doi: 10.1159/000087097

 

  1. Malta MB, Martins J, Novaes LS, et al. Norepinephrine and glucocorticoids modulate chronic unpredictable stress-induced increase in the type 2 CRF and glucocorticoid receptors in brain structures related to the HPA axis activation. Mol Neurobiol. 2021;58:4871-4885. doi: 10.1007/s12035-021-02470-2

 

  1. Allen AP, Kennedy PJ, Cryan JF, Dinan TG, Clarke G. Biological and psychological markers of stress in humans: Focus on the trier social stress test. Neurosci Biobehav Rev. 2014;38:94-124. doi: 10.1016/j.neubiorev.2013.11.005

 

  1. Wallstrom S, Ulin K, Maatta S, Omerovic E, Ekman I. Impact of long-term stress in Takotsubo syndrome: Experience of patients. Eur J Cardiovasc Nurs. 2016;15:522-528. doi: 10.1177/1474515115618568

 

  1. Templin C, Ghadri JR, Diekmann J, et al. Clinical features and outcomes of takotsubo (Stress) cardiomyopathy. N Engl J Med. 2015;373:929-938. doi: 10.1056/NEJMoa1406761

 

  1. Chan C, Elliott J, Troughton R, et al. Acute myocardial infarction and stress cardiomyopathy following the Christchurch earthquakes. PLoS One. 2013;8:e68504. doi: 10.1371/journal.pone.0068504

 

  1. Sharkey SW, Windenburg DC, Lesser JR, et al. Natural history and expansive clinical profile of stress (tako-tsubo) cardiomyopathy. J Am Coll Cardiol. 2010;55:333-341. doi: 10.1016/j.jacc.2009.08.057

 

  1. Tagawa M, Nakamura Y, Ishiguro M, et al. Transient left ventricular apical ballooning developing after the Central Niigata prefecture earthquake: Two case reports. J Cardiol. 2006;48:153-158.

 

  1. Ghadri JR, Wittstein IS, Prasad A, et al. International expert consensus document on Takotsubo syndrome (Part I): Clinical characteristics, diagnostic criteria, and pathophysiology. Eur Heart J. 2018;39:2032-2046. doi: 10.1093/eurheartj/ehy076

 

  1. Nagai M, Kobayashi Y, Kobatake H, et al. Happy heart syndrome: A case of Takotsubo syndrome with left internal carotid artery occlusion. Clin Auton Res. 2020;30:347-350. doi: 10.1007/s10286-020-00696-z

 

  1. Ghadri JR, Sarcon A, Diekmann J, et al. Happy heart syndrome: Role of positive emotional stress in Takotsubo syndrome. Eur Heart J. 2016;37:2823-2829. doi: 10.1093/eurheartj/ehv757

 

  1. Scheitz JF, Mochmann HC, Witzenbichler B, Fiebach JB, Audebert HJ, Nolte CH. Takotsubo cardiomyopathy following ischemic stroke: A cause of troponin elevation. J Neurol. 2012;259:188-190. doi: 10.1007/s00415-011-6139-1

 

  1. Modi S, Baig W. Radiotherapy-induced Tako-tsubo cardiomyopathy. Clin Oncol (R Coll Radiol). 2009;21:361-362. doi: 10.1016/j.clon.2009.01.005

 

  1. Y-Hassan S, Settergren M, Henareh L. Sepsis-induced myocardial depression and takotsubo syndrome. Acute Card Care. 2014;16:102-109. doi: 10.3109/17482941.2014.920089

 

  1. Brezina P, Isler CM. Takotsubo cardiomyopathy in pregnancy. Obstet Gynecol. 2008;112:450-452. doi: 10.1097/AOG.0b013e3181662cfe

 

  1. Hjalmarsson C, Oras J, Redfors B. A case of intracerebral hemorrhage and apical ballooning: An important differential diagnosis in ST-segment elevation. Int J Cardiol. 2015;186:90-92. doi: 10.1016/j.ijcard.2015.03.187

 

  1. Stöllberger C, Wegner C, Finsterer J. Seizure-associated Takotsubo cardiomyopathy. Epilepsia. 2011;52:e160-e167. doi: 10.1111/j.1528-1167.2011.03185.x

 

  1. Riera M, Llompart-Pou JA, Carrillo A, Blanco C. Head injury and inverted Takotsubo cardiomyopathy. J Trauma. 2010;68:E13-E15. doi: 10.1097/TA.0b013e3181469d5b

 

  1. Samuels MA. The brain-heart connection. Circulation. 2007;116:77-84. doi: 10.1161/circulationaha.106.678995

 

  1. Napp LC, Ghadri JR, Cammann VL, Bauersachs J, Templin C. Takotsubo cardiomyopathy: Completely simple but not so easy. Int J Cardiol. 2015;197:257-259. doi: 10.1016/j.ijcard.2015.06.043

 

  1. Redfors B, Råmunddal T, Shao Y, Omerovic E. Takotsubo triggered by acute myocardial infarction: A common but overlooked syndrome? J Geriatr Cardiol. 2014;11:171-173. doi: 10.3969/j.issn.1671-5411.2014.02.001

 

  1. Y-Hassan S, Böhm F. The causal link between spontaneous coronary artery dissection and takotsubo syndrome: A case presented with both conditions. Int J Cardiol. 2016;203:828-831. doi: 10.1016/j.ijcard.2015.11.047

 

  1. Murakami T, Yoshikawa T, Maekawa Y, et al. Gender differences in patients with takotsubo cardiomyopathy: Multi-center registry from Tokyo CCU network. PLoS One. 2015;10:e0136655. doi: 10.1371/journal.pone.0136655

 

  1. Krishnamoorthy P, Garg J, Sharma A, et al. Gender differences and predictors of mortality in Takotsubo cardiomyopathy: Analysis from the national inpatient sample 2009-2010 database. Cardiology. 2015;132:131-136. doi: 10.1159/000430782

 

  1. Yoshizawa M, Itoh T, Morino Y, et al. Gender differences in the circadian and seasonal variations in patients with Takotsubo syndrome: A multicenter registry at eight university hospitals in East Japan. Intern Med. 2021;60:2749-2755. doi: 10.2169/internalmedicine.6910-20

 

  1. Lyon AR, Bossone E, Schneider B, et al. Current state of knowledge on Takotsubo syndrome: A position statement from the taskforce on Takotsubo syndrome of the heart failure Association of the European Society of Cardiology. Eur J Heart Fail. 2016;18:8-27. doi: 10.1002/ejhf.424

 

  1. Angelini P, Tobis JM. Is high-dose catecholamine administration in small animals an appropriate model for takotsubo syndrome? Circ J. 2015;79:897. doi: 10.1253/circj.CJ-15-0099

 

  1. Duma D, Collins JB, Chou JW, Cidlowski JA. Sexually dimorphic actions of glucocorticoids provide a link to inflammatory diseases with gender differences in prevalence. Sci Signal. 2010;3:ra74. doi: 10.1126/scisignal.2001077

 

  1. Lindheim SR, Legro RS, Bernstein L, et al. Behavioral stress responses in premenopausal and postmenopausal women and the effects of estrogen. Am J Obstetr Gynecol. 1992;167:1831-1836. doi: 10.1016/0002-9378(92)91783-7

 

  1. Kudielka BM, Schmidt-Reinwald AK, Hellhammer DH, Kirschbaum C. Psychological and endocrine responses to psychosocial stress and dexamethasone/corticotropin-releasing hormone in healthy postmenopausal women and young controls: The impact of age and a two-week estradiol treatment. Neuroendocrinology. 1999;70:422-430. doi: 10.1159/000054504

 

  1. Pelliccia F, Kaski JC, Crea F, Camici PG. Pathophysiology of Takotsubo syndrome. Circulation. 2017;135:2426-2441. doi: 10.1161/circulationaha.116.027121

 

  1. Lu J, Wu XY, Zhu QB, et al. Sex differences in the stress response in SD rats. Behav Brain Res. 2015;284:231-237. doi: 10.1016/j.bbr.2015.02.009

 

  1. Dumas JA, Albert KM, Naylor MR, Sites CK, Benkelfat C, Newhouse PA. The effects of age and estrogen on stress responsivity in older women. Am J Geriatr Psychiatry. 2012;20:734-743. doi: 10.1097/JGP.0b013e31825c0a14

 

  1. Gonzalez Ramirez C, Villavicencio Queijeiro A, Jiménez Morales S, et al. The NR3C1 gene expression is a potential surrogate biomarker for risk and diagnosis of posttraumatic stress disorder. Psychiatry Res. 2020;284:112797. doi: 10.1016/j.psychres.2020.112797

 

  1. Wirtz PH, von Känel R, Mohiyeddini C, et al. Low social support and poor emotional regulation are associated with increased stress hormone reactivity to mental stress in systemic hypertension. J Clin Endocrinol Metabol. 2006;91:3857-3865. doi: 10.1210/jc.2005-2586

 

  1. Li Y, Jiang W, Li ZZ, et al. Repetitive restraint stress changes spleen immune cell subsets through glucocorticoid receptor or β-adrenergic receptor in a stage dependent manner. Biochem Biophys Res Commun. 2018;495:1108-1114. doi: 10.1016/j.bbrc.2017.11.148

 

  1. Frank N, Herrmann MJ, Lauer M, Förster CY. Exploratory review of the Takotsubo syndrome and the possible role of the psychosocial stress response and inflammaging. Biomolecules. 2024;14:167. doi: 10.3390/biom14020167

 

  1. Quinn MA, Cidlowski JA. Endogenous hepatic glucocorticoid receptor signaling coordinates sex-biased inflammatory gene expression. FASEB J. 2016;30:971-982. doi: 10.1096/fj.15-278309

 

  1. Yaghouby F, Jang K, Hoang U, Asgari S, Vasudevan S. Sex differences in vagus nerve stimulation effects on rat cardiovascular and immune systems. Front Neurosci. 2020;14:560668. doi: 10.3389/fnins.2020.560668
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INNOSC Theranostics and Pharmacological Sciences, Electronic ISSN: 2705-0823 Print ISSN: 2705-0734, Published by AccScience Publishing
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