Review articleVariants of Takotsubo syndrome in the perioperative period: A review of potential mechanisms and anaesthetic implications
Introduction
Takotsubo syndrome (TS), also known as Takotsubo or stress cardiomyopathy, was first described in Japan in 1990 as transient cardiac dysfunction triggered by an acute psychological or physical stressor [1]. Patients classically presented with akinesis and ballooning of the apical segment of the left ventricle (LV) with preserved contractility of the base. Recently, the syndrome has been dichotomised into primary and secondary forms. The primary form is typically triggered by a psychological stressor in the outpatient setting and often presents with chest pain and dyspnoea. The secondary form is triggered by a physical stressor, often in the setting of critical illness or surgery, and presents with signs of heart failure including pulmonary oedema, arrhythmia, or cardiac arrest. Unsurprisingly, the secondary form carries a less favourable prognosis. Due to its relevance within anaesthesia and surgery, this narrative review specifically focuses on secondary TS.
As TS has gained recognition, further classification has developed on the basis of anatomical distribution of myocardial dysfunction. Reports of patients presenting with wall motion abnormalities in alternative anatomical, non-coronary distributions have been increasing in frequency. These reports include those with impaired motion of the midventricular, basal, and focal segments of the LV. Collectively, these subtypes comprised 20% of all reported cases between 2011 and 2014 [2], but closer to 30% of perioperative cases [3]. The historically low prevalence of the variant forms is likely due to under-recognition in the absence of the characteristic apical ballooning, as the proportion of reported atypical relative to typical cases has been increasing steadily over the past decade [2]. It is also possible that these subtypes may have a high associated fatality rate that precludes their diagnosis, imparting a survival bias. The latter emphasises the need for early recognition and tailored management strategies.
The reason for these variable ballooning patterns is poorly understood, and critical review of proposed mechanisms is a main topic of this paper. Regardless, there is enough clinical overlap between the classic and atypical variants to believe that these syndromes are far more alike than they are different, and patients presenting with either variant follow a similar clinical course. In the latter half of this paper we discuss the identification as well as the acute and long-term management strategies that are relevant to anaesthesia and critical care.
Section snippets
Diagnostic considerations
Multiple diagnostic criteria exist for TS, with perhaps the most widely recognised being those from the Mayo Clinic, which were first published in 2004 [4] and later revised in 2008 [5]. Widespread consensus on the specific diagnostic criteria is lacking, likely because TS has historically been poorly defined as a clinical entity. Up until recently, atypical and certain secondary forms of TS occurring in the presence of pheochromocytoma or neurologic injury were not consistently included in the
TS is caused by catecholamine toxicity
TS represents a state of transient myocardial dysfunction precipitated by acute adrenergic hyper stimulation. The role of excess adrenergic activity was first suspected based on markedly elevated levels of serum catecholamine levels in TS patients compared to baseline levels and compared to patients presenting with ACS [8]. A causal link between adrenergic stimulation and the development of TS has been demonstrated experimentally in rats [9], and observed clinically in patients where
Adrenergic signalling in TS pathogenesis
The majority (80%) of beta-receptors in the heart are of the beta-1 subtype and are activated by norepinephrine and epinephrine to induce chronotropic and inotropic effects by coupling with the G stimulatory protein (Gs). Norepinephrine is released locally from cardiac postganglionic sympathetic neurons as well as from the adrenal medulla into the bloodstream, while epinephrine is released from the adrenal medulla. Beta-2 receptors are activated primarily by epinephrine and exhibit a phenomenon
Current hypotheses on the anatomical variation in TS
Despite recent advances in our understanding of TS as a syndrome of catecholamine overload, explanation for the variable anatomic distributions and their relation to the underlying pathophysiology remain unknown. The aggregation of case reports into patient registries has allowed for observational comparison between those diagnosed with typical and atypical forms of TS to determine distinguishing characteristics, some of which are summarised in Fig. 2. Note that the basal, midventricular, and
Early identification in the perioperative period
Preoperative investigation can help identify at-risk patients. While there is a predilection for postmenopausal women, this should not preclude the diagnosis in younger and/or male populations. One of the most important indicators is a history of prior episode(s), as TS has an estimated 4-year recurrence rate of 11.4% [32]. Other populations with elevated risk include those with pheochromocytomas, neurologic injury or illness, and underlying endocrine disorders such as thyroid disease.
Even in
Acute management of perioperative TS
Transthoracic echocardiography (TTE) is readily accessible in most perioperative settings and should be employed early to aid in the diagnosis of TS. Because it is non-invasive and can be performed rapidly, a focused TTE should be performed once TS is suspected to assess gross LV function, determine the presence and location of wall motion abnormalities, and to assess for LV outflow track obstruction. For patients in whom TTE is difficult, such as due to body habitus or suboptimal positioning,
Management strategies
Evidence-based guidelines for the management of TS are lacking. Treatment relies on supportive care and avoidance of further adrenergic stimulation. Given that these patients exhibit myocardial dysfunction despite elevated circulating levels of catecholamines, it is unlikely that additional adrenergic agents would provide much improvement in the acute setting. At least one retrospective study has shown an associated increase in mortality with catecholamine administration in these patients [36],
Complications
Although TS was previously believed to be a rather benign entity, recent meta-analyses have demonstrated an overall in-hospital mortality of about 5% and an associated annual mortality rate of 3.5% over a two-year follow-up [47]. This is comparable to in-hospital mortality rates for NSTEMI and only slightly less than that for STEMI [48]. While it is true that most patients achieve complete recovery within 2–4 weeks, there is substantial morbidity and mortality in the acute phase of TS.
Anaesthetic approach for at-risk patients
TS can present in otherwise low-risk settings such as routine outpatient procedures and in healthy patients in whom such events are unexpected and may easily be misdiagnosed or overlooked. One prior review [3] identified a total of 131 perioperative cases of TS reported in the literature between 2000 and 2016. Of these, 66% occurred under general anaesthesia, 10% with spinal, 2% with epidural, 4% with combined general and regional, and 3% with only local anaesthesia. The most common time of
Conclusion
While our understanding of TS has increased substantially over the past decade, many fundamental questions remain unanswered. Pathophysiologic explanation for the phenotypic variation observed in TS through adrenergic signalling is an area that demands further research into the influence of structural, molecular, temporal, neurologic, and mechanical factors. TS variants are not as rare as previously believed, and awareness amongst anaesthesiologists and other perioperative care providers will
Disclaimer
The views expressed in the following article are those of the authors and not their affiliated institutions.
Source of support
No financial or other forms of support were provided for this article.
Disclosure of interest
The authors do not have any relevant conflicts of interest to disclose.
Acknowledgements
Assistance with the study: None.
Prior presentations: None.
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