You're using an outdated browser. Please upgrade to a modern browser for the best experience.
Submitted Successfully!
Thank you for your contribution! You can also upload a video entry or images related to this topic. For video creation, please contact our Academic Video Service.
Version Summary Created by Modification Content Size Created at Operation
1 Pratik Agarwal -- 1014 2023-02-16 13:44:42 |
2 format correct Catherine Yang Meta information modification 1014 2023-02-17 01:29:44 |

Video Upload Options

We provide professional Academic Video Service to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Sethi, Y.; Murli, H.; Kaiwan, O.; Vora, V.; Agarwal, P.; Chopra, H.; Padda, I.; Kanithi, M.; Popoviciu, M.S.; Cavalu, S. Etiopathogenesis of Takotsubo Syndrome. Encyclopedia. Available online: https://encyclopedia.pub/entry/41306 (accessed on 13 December 2025).
Sethi Y, Murli H, Kaiwan O, Vora V, Agarwal P, Chopra H, et al. Etiopathogenesis of Takotsubo Syndrome. Encyclopedia. Available at: https://encyclopedia.pub/entry/41306. Accessed December 13, 2025.
Sethi, Yashendra, Hamsa Murli, Oroshay Kaiwan, Vidhi Vora, Pratik Agarwal, Hitesh Chopra, Inderbir Padda, Manasa Kanithi, Mihaela Simona Popoviciu, Simona Cavalu. "Etiopathogenesis of Takotsubo Syndrome" Encyclopedia, https://encyclopedia.pub/entry/41306 (accessed December 13, 2025).
Sethi, Y., Murli, H., Kaiwan, O., Vora, V., Agarwal, P., Chopra, H., Padda, I., Kanithi, M., Popoviciu, M.S., & Cavalu, S. (2023, February 16). Etiopathogenesis of Takotsubo Syndrome. In Encyclopedia. https://encyclopedia.pub/entry/41306
Sethi, Yashendra, et al. "Etiopathogenesis of Takotsubo Syndrome." Encyclopedia. Web. 16 February, 2023.
Etiopathogenesis of Takotsubo Syndrome
Edit
This entry is adapted from the peer-reviewed paper 10.3390/jcm12010125
Broken Heart Syndrome, also known as Takotsubo Syndrome (TS), is sudden and transient dysfunction of the left and/or right ventricle which often mimics Acute Coronary Syndrome (ACS).
Broken Heart Syndrome Takotsubo cardiomyopathy Happy Heart Syndrome

1. Introduction

The pathophysiology of Takotsubo Syndrome is elusive, the specificities of which are still being investigated, which makes the diagnosis and treatment more strenuous. Several mechanisms for TS development have been proposed. A plethora of research suggests that the primary cause of TS is a physically or emotionally stressful trigger [1]. The secondary cause includes medical, surgical, or psychiatric emergencies. Several diverse circumstances can predispose, trigger, and eventually result in TS [2]. These circumstances can be classified into three types, i.e., predisposing factors, triggers/stressors, and pathogenic mechanisms [3].

2. Predisposing Factors

Some of the modifiable risk factors for Takotsubo Syndrome were researched in a systematic review. In the absence of any coronary artery disease, the study found a high prevalence of cardiovascular risk factors in patients with TS. These risk factors included obesity (17%), smoking (22%), and pre-existing medical conditions such as hypertension (54%), dyslipidemia (32%), and diabetes (17%). Other comorbidities included psychological disorders (24%), pulmonary diseases (15%), malignancies (10%), neurologic diseases (7%), chronic kidney disease (7%), and thyroid diseases (6%) [4]. These factors were similar in frequency, as seen in patients with acute MI. These findings were consistent with Summer et al.’s prior observations, which demonstrated that the majority of patients with TS also had at least two of the aforementioned predisposing risk factors [5]. According to Martin et al., these cardiovascular risk factors can lead to endothelial dysfunction [6] which then can be another predisposing component [7].
The current evidence suggests gender be a non-modifiable risk factor for TS. Several reviews show a marked gender discrepancy with a higher prevalence of TS in females, especially postmenopausal women. This association can be explained by the effect of sex hormones on hypothalamo-sympathoadrenal outflow [8] and coronary vasoreactivity [9] and supports the hypothesis that estrogen deficiency plays a major role in the pathophysiology of TS.

3. Role of Stressors

Despite the ambiguity in the pathogenesis of TS, the current evidence agrees upon the impact of stressors in causing TS. Sudden somatic and/or emotional stress causes a rise in the levels of catecholamine, resulting in transient left ventricular dysfunction [1]. Stressors can be further classified into two groups: physical and emotional stresses; although the various triggering events recorded to date are diverse. A study showed that in patients with TS, about 39% experienced a triggering emotional stressor whereas 35% experienced a physical stressor [4]. Somatic or physical stressors researched to precede TS are vigorous exercise, hyperthyroidism, alcohol/opiate withdrawal, and postoperative pain, etc. [10]. Recent research has also discovered the intimate connection between TS and medical conditions such as ischemic stroke, subarachnoid hemorrhage (SAH), and epileptic seizures [11][12][13][14]. A study correlated cerebrovascular accidents with ten times increased likelihood of developing TS [1]. Thus, supporting a pathogenesis involving increased catecholamines as proposed by Greco et al. in the 1980s [15]. Emotional stressors can vary vastly and include grief (death or accident of a loved one), receiving unexpected or bad news (being diagnosed with a serious illness), fear (armed robbery, public speaking), change in residence, anger (fight with a partner), relationship discord (break-up or divorce), financial troubles (layoff, demotion), and being bullied. The importance of acute emotional stress in triggering TS led to the origination of name Stress-Induced Cardiomyopathy and Broken Heart Syndrome [4][10].

4. Pathogenic Mechanisms

The etiopathogenesis can be explained by cardiovascular and neuropsychiatric mechanisms.

4.1. Cardiovascular Mechanisms

The major cardiovascular hypotheses explaining the pathophysiology of TS have been categorized into vascular, myocardial, or both. In the vascular category, the cause of TS can be attributed to acute coronary spasm of multiple vasculatures, aborted myocardial infarction with spontaneous recanalization, or acute increased ventricular afterload. Multivessel coronary vasospasm was seen in 5–10% of individuals spontaneously and in 28% of individuals when provoked [16]. However, the argument against this hypothesis presents the role of dobutamine (vasodilator with minimal vasospastic effect) and epinephrine (coronary vasodilatory effect) in inducing TS. Another proposed vascular hypothesis is increased afterload causing TS. Increased afterload leading to TS can occur due to various reasons, but is mainly due to hypertension [16][17].
Under the myocardial category, the cardiac cause or manifestation is acute left ventricular outflow tract obstruction (LVOTO) and direct catecholamine-mediated myocardial stunning. Several studies support the LVOTO hypothesis which also leads to symptoms commonly associated with TS. For example, LVOTO compromises the forward stroke volume, and oxygen supply-demand mismatch and can lead to hypotension or cardiogenic shock in severe cases [1][18]. A research study found 25% of individuals with TS manifested LVOTO [1]. Risk factors predisposing patients to TS due to LVOTO were small left ventricle or localized sigmoid septum. Arguments against this hypothesis state that LVOTO cannot explain the apical-sparing and basal patterns seen in several patients with TS. Furthermore, the right ventricle is also involved in several cases which cannot be explained by an LVOTO hypothesis [1]. Therefore, LVOTO can be stated as a complication of TS and not a cause.

4.2. Neuropsychiatry and TS

Takotsubo Syndrome is believed to be a consequence of several psychiatric and neurological conditions as it is closely linked with various organs, especially the brain [10]. Depression and chronic stress have been linked to anatomical alterations in the cerebrum, including decreased hippocampal volume and gray matter loss which have been connected to changes in the HPA axis in response to stress [19]. Women diagnosed with TS were more likely to have a history of chronic anxiety disorder preceding the TS event compared to controls or patients with acute MI [5].
A study by El-Sayed et al. demonstrated that patients with anxiety and mood disorders show increased susceptibility to Takotsubo Syndrome presumably because they are linked to an increased likelihood of stressful occurrences [20]. If this is correct, it adds to the notion that Takotsubo encompasses both mental and somatic medicine, emphasizing the underlying relationship between the two. Two recent reviews also found that chronic stress and depression are associated with significant odds of developing Takotsubo Syndrome [20][21]. A study by Corrigan, Frank E 3rd et al., demonstrated that underlying psychiatric disorders or their exacerbation can increase an individual’s susceptibility to developing TS in response to a strong emotional and/or somatic stressor [22].

References

  1. Pilgrim, T.M.; Wyss, T.R. Takotsubo Cardiomyopathy or Transient Left Ventricular Apical Ballooning Syndrome: A Systematic Review. Int. J. Cardiol. 2008, 124, 283–292.
  2. Pelliccia, F.; Greco, C.; Vitale, C.; Rosano, G.; Gaudio, C.; Kaski, J.C. Takotsubo Syndrome (Stress Cardiomyopathy): An Intriguing Clinical Condition in Search of Its Identity. Am. J. Med. 2014, 127, 699–704.
  3. Lee, Y.P.; Poh, K.K.; Lee, C.H.; Tan, H.C.; Razak, A.; Chia, B.L.; Low, A.F. Diverse Clinical Spectrum of Stress-Induced Cardiomyopathy. Int. J. Cardiol. 2009, 133, 272–275.
  4. Pelliccia, F.; Parodi, G.; Greco, C.; Antoniucci, D.; Brenner, R.; Bossone, E.; Cacciotti, L.; Capucci, A.; Citro, R.; Delmas, C.; et al. Comorbidities Frequency in Takotsubo Syndrome: An International Collaborative Systematic Review Including 1109 Patients. Am. J. Med. 2015, 128, 654.e11–654.e19.
  5. Summers, M.R.; Lennon, R.J.; Prasad, A. Pre-Morbid Psychiatric and Cardiovascular Diseases in Apical Ballooning Syndrome (Tako-Tsubo/Stress-Induced Cardiomyopathy): Potential Pre-Disposing Factors? J. Am. Coll. Cardiol. 2010, 55, 700–701.
  6. Rosano, G.M.C.; Vitale, C.; Marazzi, G.; Volterrani, M. Menopause and Cardiovascular Disease: The Evidence. Climacteric 2007, 10 (Suppl. 1), 19–24.
  7. Martin, E.A.; Prasad, A.; Rihal, C.S.; Lerman, L.O.; Lerman, A. Endothelial Function and Vascular Response to Mental Stress Are Impaired in Patients with Apical Ballooning Syndrome. J. Am. Coll. Cardiol. 2010, 56, 1840.
  8. Hinojosa-Laborde, C.; Chapa, I.; Lange, D.; Haywood, J.R. Gender Differences in Sympathetic Nervous System Regulation. Clin. Exp. Pharm. Physiol. 1999, 26, 122–126.
  9. Sader, M.A.; Celermajer, D.S. Endothelial Function, Vascular Reactivity and Gender Differences in the Cardiovascular System. Cardiovasc. Res. 2002, 53, 597–604.
  10. Redfors, B.; Shao, Y.; Omerovic, E. Stress-Induced Cardiomyopathy (Takotsubo)—Broken Heart and Mind? Vasc. Health Risk. Manag. 2013, 9, 149.
  11. Singh, K.; Carson, K.; Usmani, Z.; Sawhney, G.; Shah, R.; Horowitz, J. Systematic Review and Meta-Analysis of Incidence and Correlates of Recurrence of Takotsubo Cardiomyopathy. Int. J. Cardiol. 2014, 174, 696–701.
  12. Yoshimura, S.; Toyoda, K.; Ohara, T.; Nagasawa, H.; Ohtani, N.; Kuwashiro, T.; Naritomi, H.; Minematsu, K. Takotsubo Cardiomyopathy in Acute Ischemic Stroke. Ann. Neurol. 2008, 64, 547–554.
  13. Ennezat, P.v.; Pesenti-Rossi, D.; Aubert, J.M.; Rachenne, V.; Bauchart, J.J.; Auffray, J.L.; Logeart, D.; Cohen-Solal, A.; Asseman, P. Transient Left Ventricular Basal Dysfunction without Coronary Stenosis in Acute Cerebral Disorders: A Novel Heart Syndrome (Inverted Takotsubo). Echocardiography 2005, 22, 599–602.
  14. Das, M.; Gonsalves, S.; Saha, A.; Ross, S.; Williams, G. Acute Subarachnoid Haemorrhage as a Precipitant for Takotsubo Cardiomyopathy: A Case Report and Discussion. Int. J. Cardiol. 2009, 132, 283–285.
  15. Greco, C.; Cavalletti, C.; di Piero, V.; Argentino, C.; Scopinaro, F. Scintigraphic Demonstration of Myocardial Ischaemia. Lancet 1988, 2, 281.
  16. Y-Hassan, S.; Tornvall, P. Epidemiology, Pathogenesis, and Management of Takotsubo Syndrome. Clin. Auton. Res. 2018, 28, 53–65.
  17. Couch, L.S.; Channon, K.; Thum, T. Molecular Mechanisms of Takotsubo Syndrome. Int. J. Mol. Sci. 2022, 23, 12262.
  18. Lyon, A.R.; Bossone, E.; Schneider, B.; Sechtem, U.; Citro, R.; Underwood, S.R.; Sheppard, M.N.; Figtree, G.A.; Parodi, G.; Akashi, Y.J.; 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.
  19. Gianaros, P.J.; Jennings, J.R.; Sheu, L.K.; Greer, P.J.; Kuller, L.H.; Matthews, K.A. Prospective Reports of Chronic Life Stress Predict Decreased Grey Matter Volume in the Hippocampus. Neuroimage 2007, 35, 795–803.
  20. El-Sayed, A.M.; Brinjikji, W.; Salka, S. Demographic and Co-Morbid Predictors of Stress (Takotsubo) Cardiomyopathy. Am. J. Cardiol. 2012, 110, 1368–1372.
  21. Deshmukh, A.; Kumar, G.; Pant, S.; Rihal, C.; Murugiah, K.; Mehta, J.L. Prevalence of Takotsubo Cardiomyopathy in the United States. Am. Heart J. 2012, 164, 66–71.
  22. Corrigan, F.E.; Kimmel, M.C.; Jayaram, G. Four Cases of Takotsubo Cardiomyopathy Linked with Exacerbations of Psychiatric Illness. Innov. Clin. Neurosci. 2011, 8, 50.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Cardiac & Cardiovascular Systems
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : Yashendra Sethi , Hamsa Murli , Oroshay Kaiwan , Vidhi Vora , Pratik Agarwal , Hitesh Chopra , Inderbir Padda , Manasa Kanithi , Mihaela Simona Popoviciu , Simona Cavalu
View Times: 666
Revisions: 2 times (View History)
Update Date: 17 Feb 2023
Table of Contents
    Notice
    You are not a member of the advisory board for this topic. If you want to update advisory board member profile, please contact office@encyclopedia.pub.
    OK
    Confirm
    Only members of the Encyclopedia advisory board for this topic are allowed to note entries. Would you like to become an advisory board member of the Encyclopedia?
    Yes
    No
    ${ textCharacter }/${ maxCharacter }
    Submit
    Cancel
    There is no comment~
    ${ textCharacter }/${ maxCharacter }
    Submit
    Cancel
    ${ selectedItem.replyTextCharacter }/${ selectedItem.replyMaxCharacter }
    Submit
    Cancel
    Confirm
    Are you sure to Delete?
    Yes No
    Academic Video Service
    Feedback