Stress & The Broken Heart Syndrome

Takotsubo syndrome (TTS) - also known as the ‘broken heart syndrome’, stress cardiomyopathy, or apical ballooning syndrome, was first described in Japan in 1990.¹ 

Initially considered a rare event, the syndrome has gained worldwide attention within medical circles^1,2 as a typical representation of the brain-heart axis, thereby prompting the emergence of a new medical field described as ‘neurocardiology’.³

TTS is an acute and often reversible heart failure syndrome that is characterized by transient left ventricular systolic and diastolic dysfunction, electrocardiographic (ECG) changes and elevations in cardiac enzymes similar to those seen in acute myocardial infarction (MI).⁴ Chest pain and dyspnoea are common symptoms, with others including palpitations, syncope, nausea and vomiting.² Typically, at end-systole, the apical ballooning of the left ventricle resembles the ‘Takotsubo’ (Japanese octopus trap) with its narrow neck and globular lower portion.^2,4

The disease may lead to severe complications, including death, and occurs almost entirely in postmenopausal women (∼90% of reported cases) following sudden and intense triggers such as severe physical or emotional stress (i.e. natural disasters, domestic abuse, unexpected deaths in the family, physical trauma or surgery, as well as extreme happy events).^2,5

TTS is estimated to occur in 1% to 3% of patients with suspected acute coronary syndrome (ACS).^1,5 However, its true prevalence is likely underestimated as diagnostic criteria are often incomplete.^4,5  Early recognition of at-risk patients in clinical settings is therefore essential and can be lifesaving.

Aetiology & Pathophysiology

The exact aetiology of TTS is unknown, however, enhanced sympathetic nervous system (SNS) stimulation caused by acute emotional stress is considered the most likely cause.^2,6-8 On a physiological level, SNS stimulation induces intense brain activation and a two to three-fold release of catecholamines (norepinephrine, epinephrine) and neuropeptide Y (NPY),^2,9 as well as increases in cortisol.¹⁰ This intense catecholamine surge then results in contractile dysfunction of the left ventricle,² epicardial spasm, microvascular dysfunction, and direct myocyte injury due to adrenergic-receptor–mediated calcium overload (see Figure 1).^1,6

Figure 1 | Pathophysiology of Stress Cardiomyopathy.¹

Apart from excessive SNS stimulation, traumatic stress results in inadequate parasympathetic activation and has damaging effects on mental health and almost every organ system in the body.¹¹ It is also noteworthy that the precipitation of TTS is dependent on age, as well as the amount, frequency and intensity of risk factors (as demonstrated in Figure 2). However, approximately 30% of patients with TTS have no identifiable trigger at all.⁶

Figure 2 | Precipitation of TTS by Triggers of Variable Intensity.⁶

Several risk factors are involved in the pathogenesis of TTS, of which the most important include:^6,8,12-14

• Increased sympathetic tone due to:
  • Oestrogen deficiency
  • Mood disorders (anxiety, depression)
  • Mourning and grief
  • Sympathomimetic medications (antidepressants, β2 receptor agonists, decongestants, with i.e. antidepressants blocking the reuptake of catecholamines, thereby promoting resulting in an accumulation)
  • Chronic autonomic dysfunction (sympathetic/parasympathetic imbalance)
• Increased sensitivity to catecholamines from:
  • Oestrogen deficiency
  • Endothelial dysfunction
  • Genetic factors

Moreover, users of antidepressant medication are at increased risk as many of these drugs block the reuptake of catecholamines, thereby significantly increasing catecholamine levels.¹⁵ Other less important risk factors include diabetes, asthma, substance and alcohol abuse.^1,13

Diagnosis

Diagnostic criteria for TTS include amongst others:⁴

• ECG changes such as a raised ST-segment, ST depression, left bundle branch block (LBBB), T-wave inversion, and/or QTc prolongation during the acute phase / first 3 months.
• Changes in cardiac biomarkers such as natriuretic peptide (BNP or NT-proBNP) during the acute phase, small elevation in troponin levels, and mild elevations in C-reactive protein (CRP).
• Echocardiography changes to assess apical ballooning amongst others.

Symptoms of chest pain occur in over 75% of cases, while dyspnoea occurs in 50% of patients.¹

Identification & Complementary Medicine Care for TTS Patients

Identifying a potential TTS patient is very challenging as sudden events of severe physical or emotional stress cannot be predicted. However, considering the most common risk factors will enable practitioners to determine vulnerable patients and hence provide suitable treatment. In addition, at-risk patients may be screened for symptoms of chest pain and dyspnoea, with menopausal women deserving special attention.

Patients considered at-risk should also be referred to their medical practitioners where they can be assessed for possible heart failure and receive primary care for any life-threatening complications. Unfortunately, there is currently no clinical evidence to support medical treatment recommendations for TTS other than to provide supportive care in order to sustain life and to minimise complications.^1,4

For the complementary medicine practitioner, supportive and preventive care is focused on limiting major risk factors, which are increased sympathetic tone and catecholamine sensitivity. This can be achieved by:

• Strengthening the patient’s ability to resist physical and mental stress by supporting the HPA axis,
• Alleviating overall adverse effects of stress on various body systems,
• Supporting overall cardiovascular function, such as contractile and endothelial function, and
• Addressing oestrogen deficiency and regulating hormone levels, if present.

For further information on suggested treatment options for these please also refer to additional resources suggested below.

Clinical Take-Away Message

Identifying and managing at-risk TTS patients in clinical practice can potentially prevent serious disease and even death, especially where suspected cases are also referred to medical services at an early stage. Moreover, supportive and preventive complementary medicine treatments can increase survival rates and quality of life.

For additional information on treatment suggestions for various body systems, please refer to these resources:

• MediHerb® Liquid Blends for Stress
• MediHerb® Liquid Blends for Cardiovascular System
• MediHerb® Women’s Health Clinical Management Practitioner Guide
• Endothelial Health: A Powerful Trio of Ginkgo, Grape Seed & Gotu Kola

References

1. Medina de Chazel H et al. Stress Cardiomyopathy Diagnosis and Treatment: JACC State-of-the-Art Review. J Am Coll Cardiol. 018 Oct, 72(16)1955–1971.
2. Khalid N, Ahmad SA, Shlofmitz E, et al. Pathophysiology of Takotsubo Syndrome. [Updated 2020 Nov 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538160/
3. Prasad Hrishi A, Ruby Lionel K, Prathapadas U. Head Rules Over the Heart: Cardiac Manifestations of Cerebral Disorders. Indian J Crit Care Med. 2019 Jul;23(7):329-335.
4. Lyon AR, Bossone E, Schneider B, Sechtem U, Citro R, Underwood SR, 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 Jan;18(1):8-27.
5. Kato K, Lyon AR, Ghadri JR, Templin C. Takotsubo syndrome: aetiology, presentation and treatment. Heart. 2017 Sep;103(18):1461-1469.
6. Wittstein IS. The Sympathetic Nervous System in the Pathogenesis of Takotsubo Syndrome. Heart Fail Clin. 2016 Oct;12(4):485-98.
7. Potu KC, Raizada A, Gedela M, Stys A. Takotsubo Cardiomyopathy (Broken-Heart Syndrome): A Short Review. S D Med. 2016 Apr;69(4):169-71.
8. Oliveri F, Goud HK, Mohammed L, Mehkari Z, Javed M, Althwanay A, et al. Role of Depression and Anxiety Disorders in Takotsubo Syndrome: The Psychiatric Side of Broken Heart. Cureus. 2020 Sep 11;12(9):e10400.
9. Goldfinger JZ, Nair A, Sealove BA. Brain-heart interaction in takotsubo cardiomyopathy. Heart Fail Clin. 2013 Apr;9(2):217-23, ix.
10. Pelliccia F, Pasceri V, Patti G, Tanzilli G, Speciale G, Gaudio C, et al. Long-Term Prognosis and Outcome Predictors in Takotsubo Syndrome: A Systematic Review and Meta-Regression Study. JACC Heart Fail. 2019 Feb;7(2):143-154.
11. Kastaun S, Gerriets T, Tschernatsch M, Yeniguen M, Juenemann M. Psychosocial and psychoneuroendocrinal aspects of Takotsubo syndrome. Nat Rev Cardiol. 2016 Nov;13(11):688-694.
12. Klein C, Leipold S, Ghadri JR, Jurisic S, Hiestand T, Hänggi J, et al. Takotsubo syndrome: How the broken heart deals with negative emotions. Neuroimage Clin. 2020;25:102124.
13. Carroll AJ, Goergen J, Wafford QE, Flaherty JD, Grady KL, Feingold KL. Psychiatric conditions in patients presenting with Takotsubo syndrome: A systematic review and synthesis of case studies. Gen Hosp Psychiatry. 2020 Jul-Aug;65:54-63.
14. Campos MTFS, Valente FMQ, Araújo RMA, Bressan J. Mourning and Takotsubo cardiomyopathy: neuroendocrine implications and nutritional management. Rev Assoc Med Bras (1992). 2018 Oct;64(10):952-959.
15. Zvonarev V. Takotsubo Cardiomyopathy: Medical and Psychiatric Aspects. Role of Psychotropic Medications in the Treatment of Adults with "Broken Heart" Syndrome. Cureus. 2019 Jul 19;11(7):e5177.