Sympathetic Nerve Activity and Response to Physiological Stress in Takotsubo Syndrome

Overview

Journal Clin Auton Res

Date 2024 Nov 15

PMID 39546154

Authors

Christina Ekenback

Jonas Persson

Per Tornvall

Lena Forsberg

Jonas Spaak

Affiliations

Soon will be listed here.

Abstract

Purpose: The prevailing hypothesis posits that Takotsubo syndrome (TTS) is caused by massive sympathetic activation, yet supporting evidence remains inconsistent. The objectives of the present study were to determine whether sympathetic activity and reactivity are enhanced in the recovery phase of TTS, and to evaluate the effect of selective β1-receptor blockade on sympathetic reactivity.

Methods: We conducted a case-control study that included 18 female patients with TTS and 13 age- and sex-matched controls. Muscle sympathetic nerve activity was measured through microneurography of the peroneal nerve at rest and during the cold pressor test. In the TTS group, recordings were repeated after randomisation to intravenous metoprolol or placebo. In 10 TTS patients, cardiac sympathetic activity was assessed using iodine 123-metaiodobenzylguanidine scintigraphy. Blood samples were collected during hospitalisation.

Results: Microneurography was performed a median of 27.5 days after patient admission. There were no significant differences in burst incidence, burst frequency, burst height or burst area between the TTS patients and the controls at rest, during stress or after administration of intravenous metoprolol. Iodine 123-metaiodobenzylguanidine scintigraphy was performed a median of 12.5 days after admission, revealing decreased early 1.54 ± 0.13 and late 1.40 ± 0.13 heart-to-mediastinum ratios, and an increased washout rate of 41.8 ± 12.1%. Catecholamine metabolites were comparable between the study groups.

Conclusion: General sympathetic hyperactivity or hyperreactivity unlikely contributes to TTS, as catecholamine levels and muscle sympathetic nerve activity at rest and during stress were similar between the TTS patients and the controls. As scintigraphy showed increased cardiac sympathetic activity, a pathological cardiac adrenergic response and vulnerability to sympathetic activation may be crucial for the development of the syndrome.

References

Ghadri J, Wittstein I, Prasad A, Sharkey S, Dote K, Akashi Y . International Expert Consensus Document on Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology. Eur Heart J. 2018; 39(22):2032-2046. PMC: 5991216. DOI: 10.1093/eurheartj/ehy076. View

Lyon A, Bossone E, Schneider B, Sechtem U, Citro R, Underwood S . 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. 2015; 18(1):8-27. DOI: 10.1002/ejhf.424. View

Templin C, Ghadri J, Diekmann J, Napp L, Bataiosu D, Jaguszewski M . Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy. N Engl J Med. 2015; 373(10):929-38. DOI: 10.1056/NEJMoa1406761. View

Redfors B, Vedad R, Angeras O, Ramunddal T, Petursson P, Haraldsson I . Mortality in takotsubo syndrome is similar to mortality in myocardial infarction - A report from the SWEDEHEART registry. Int J Cardiol. 2015; 185:282-9. DOI: 10.1016/j.ijcard.2015.03.162. View

Wittstein I, Thiemann D, Lima J, Baughman K, Schulman S, Gerstenblith G . Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med. 2005; 352(6):539-48. DOI: 10.1056/NEJMoa043046. View

Pelliccia F, Kaski J, Crea F, Camici P . Pathophysiology of Takotsubo Syndrome. Circulation. 2017; 135(24):2426-2441. DOI: 10.1161/CIRCULATIONAHA.116.027121. View

Lyon A, Citro R, Schneider B, Morel O, Ghadri J, Templin C . Pathophysiology of Takotsubo Syndrome: JACC State-of-the-Art Review. J Am Coll Cardiol. 2021; 77(7):902-921. DOI: 10.1016/j.jacc.2020.10.060. View

Omerovic E, Citro R, Bossone E, Redfors B, Backs J, Bruns B . Pathophysiology of Takotsubo syndrome - a joint scientific statement from the Heart Failure Association Takotsubo Syndrome Study Group and Myocardial Function Working Group of the European Society of Cardiology - Part 1: overview and the central.... Eur J Heart Fail. 2021; 24(2):257-273. DOI: 10.1002/ejhf.2400. View

Omerovic E, Citro R, Bossone E, Redfors B, Backs J, Bruns B . Pathophysiology of Takotsubo syndrome - a joint scientific statement from the Heart Failure Association Takotsubo Syndrome Study Group and Myocardial Function Working Group of the European Society of Cardiology - Part 2: vascular pathophysiology,.... Eur J Heart Fail. 2021; 24(2):274-286. DOI: 10.1002/ejhf.2368. View

10.

Akhtar M, Cammann V, Templin C, Ghadri J, Luscher T . Takotsubo syndrome: getting closer to its causes. Cardiovasc Res. 2023; 119(7):1480-1494. DOI: 10.1093/cvr/cvad053. View

11.

Christensen T, Bang L, Holmvang L, Skovgaard D, Oturai D, Soholm H . (123)I-MIBG Scintigraphy in the Subacute State of Takotsubo Cardiomyopathy. JACC Cardiovasc Imaging. 2016; 9(8):982-90. DOI: 10.1016/j.jcmg.2016.01.028. View

12.

Marfella R, Barbieri M, Sardu C, Rizzo M, Siniscalchi M, Paolisso P . Effects of α-lipoic acid therapy on sympathetic heart innervation in patients with previous experience of transient takotsubo cardiomyopathy. J Cardiol. 2015; 67(2):153-61. DOI: 10.1016/j.jjcc.2015.07.012. View

13.

Kume T, Kawamoto T, Okura H, Toyota E, Neishi Y, Watanabe N . Local release of catecholamines from the hearts of patients with tako-tsubo-like left ventricular dysfunction. Circ J. 2007; 72(1):106-8. DOI: 10.1253/circj.72.106. View

14.

Y-Hassan S, Henareh L . Plasma catecholamine levels in patients with takotsubo syndrome: Implications for the pathogenesis of the disease. Int J Cardiol. 2014; 181:35-8. DOI: 10.1016/j.ijcard.2014.11.149. View

15.

Y-Hassan S, Sorensson P, Ekenback C, Lundin M, Agewall S, Brolin E . Plasma catecholamine levels in the acute and subacute stages of takotsubo syndrome: Results from the Stockholm myocardial infarction with normal coronaries 2 study. Clin Cardiol. 2021; 44(11):1567-1574. PMC: 8571561. DOI: 10.1002/clc.23723. View

16.

Vaccaro A, Despas F, Delmas C, Lairez O, Lambert E, Lambert G . Direct evidences for sympathetic hyperactivity and baroreflex impairment in Tako Tsubo cardiopathy. PLoS One. 2014; 9(3):e93278. PMC: 3965544. DOI: 10.1371/journal.pone.0093278. View

17.

Naegele M, Flammer A, Enseleit F, Roas S, Frank M, Hirt A . Endothelial function and sympathetic nervous system activity in patients with Takotsubo syndrome. Int J Cardiol. 2016; 224:226-230. DOI: 10.1016/j.ijcard.2016.09.008. View

18.

Cimarelli S, Sauer F, Morel O, Ohlmann P, Constantinesco A, Imperiale A . Transient left ventricular dysfunction syndrome: patho-physiological bases through nuclear medicine imaging. Int J Cardiol. 2009; 144(2):212-8. DOI: 10.1016/j.ijcard.2009.04.025. View

19.

Sestini S, Pestelli F, Leoncini M, Bellandi F, Mazzeo C, Mansi L . The natural history of takotsubo syndrome: a two-year follow-up study with myocardial sympathetic and perfusion G-SPECT imaging. Eur J Nucl Med Mol Imaging. 2016; 44(2):267-283. DOI: 10.1007/s00259-016-3575-2. View

20.

Matsuura T, Ueno M, Iwanaga Y, Miyazaki S . Importance of sympathetic nervous system activity during left ventricular functional recovery and its association with in-hospital complications in Takotsubo syndrome. Heart Vessels. 2019; 34(8):1317-1324. DOI: 10.1007/s00380-019-01359-4. View