Diagnostic criteria
1. Transient regional wall motion abnormalities of the left and/or right ventricular (RV) myocardium, which are frequently, but not always, preceded by a stressful trigger (emotional or physical).
2. Regional wall motion abnormalities usually extending beyond a single epicardial vascular distribution, often resulting in circumferential dysfunction of the ventricular segments involved (apical and/or mid- LV or basal segments).
3. Absence of culprit atherosclerotic coronary artery disease including acute plaque rupture, thrombus formation and coronary dissection or other pathological conditions to explain the pattern of temporary LV dysfunction observed (e.g. hypertrophic cardiomyopathy, viral myocarditis).
4. New and reversible electrocardiogaphy (ECG) abnormalities (ST-segment elevation, ST depression, left bundle branch block, T-wave inversion and/or QTc prolongation) during the acute phase.
5. Significantly elevated serum natriuretic peptide (B-type natriuretic peptide [BNP] or N-terminal pro b-type natriuretic peptide [NTproBNP]) level during the acute phase.
6. Positive but relatively small elevation in cardiac troponin measured using a conventional assay (i.e. disparity between the troponin level and the amount of the dysfunctional myocardium present).
7. Recovery of ventricular systolic function on cardiac imaging at follow up.
Clinical Subtypes – Primary and Secondary Takotsubo Syndrome
The medical community has reported a variety of clinical scenarios and contexts in which patients with Takotsubo syndrome present to medical attention. These can be classified into two groups:
Primary Takotsubo Syndrome
Primary Takotsubo syndrome occurs in individuals when the specific symptoms described are the primary reason for their acute presentation. These include patients with or without clearly identifiable stress triggers (these are often emotional) and any potential co-existing medical conditions that may serve as predisposing risk factors, but are not the primary cause for the catecholamine rise. These cases can be considered primary Takotsubo syndrome, with clinical management directed to the specific complications.
Secondary Takotsubo Syndrome
A significant proportion of cases occur in individuals already hospitalised for other medical, surgical, anaesthetic, obstetric or psychiatric conditions. These individuals have a sudden activation of their sympathetic nervous system and/or a rise in catecholamines and develop an acute Takotsubo syndrome as a complication of their primary condition or its treatment. These should be diagnosed as secondary Takotsubo syndrome, thereby focusing on the management pathway not only for Takotsubo syndrome and its cardiac complications, but also for the primary underlying disease and its treatment that served as the trigger for the secondary Takotsubo syndrome.
Anatomical Variants
Primary and secondary Takotsubo syndromes can present with an array of possible anatomical variants.17–19 The initial definition of Takotsubo syndrome described what is now considered the classic pattern of LV regional wall motion abnormalities, with apical and circumferential mid-ventricular hypokinesia and basal hypercontractility. At end-systole the left ventricle has the typical appearance of the Takotsubo with a narrow neck and globular lower portion, giving the appearance of virtual ‘apical ballooning’. This typical Takotsubo syndrome variant with apical dysfunction is present in ~50–80 % cases depending on the various series reported, but a number of other anatomical variants may also occur. The two most common atypical variants are the inverted Takotsubo or basal variant, with circumferential basal hypokinesia and apical hypercontractility – also referred to as the ‘nutmeg’ or ‘artichoke’ heart – and the mid-ventricular variant with circumferential mid- ventricular hypokinesia and both basal and apical hypercontractility.20–22 This has a unique end-systolic appearance which has been likened to either a Greek vase or the ‘ace of spades’, although the basal variant also can have the ace of spades appearance. In both inverted and mid-LV Takotsubo variants, the similar principle exists of reversible LV dysfunction affecting more than one coronary territory, usually circumferential pattern, in the absence of culprit coronary artery disease.
Other rarer variants have been described, including biventricular apical dysfunction, dysfunction sparing the apical tip (possibly a form of the mid-ventricular Takotsubo variant) and isolated RV Takotsubo syndrome.19,23–25 These different morphological variants may depend upon the timing of early segment recovery and clinical evaluation. Recurrent cases have been described with different anatomical variants in the same individual, suggesting that an individual can be susceptible to more than one subtype.26,27
Epidemiology
Several series in Asian and Western, predominantly Caucasian, populations suggest around 1–2 % of patients with suspected acute coronary syndrome (ACS) are eventually diagnosed with Takotsubo syndrome.17,28 With increasing awareness and more widespread access to early coronary angiography, the syndrome is now being recognised and appreciated more frequently.
In the first study, Takotsubo syndrome was diagnosed in 0.02 % of all acute hospitalisations (6,837/33,506,402 patients).29 The majority were elderly post-menopausal women (90 %, aged from 66–80 years), a demographic repeated across many published cohorts, with risk factors including smoking, alcohol abuse, anxiety states and hyperlipidaemia. A higher Takotsubo syndrome rate was observed in whites compared with African Americans and Hispanics (67.4 % versus 4.4 % and 4.3 %, respectively).29 The second study and largest cohort to date reported details of 24,701 patients with a discharge code for Takotsubo syndrome. The study found similar demographics with 89 % women, with a mean age of 66.9 ± 30.7 years, and most patients (59.6 %) were ≥65 years old.30