Clinical Radiology 71 (2016) e110ee119

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Cardiac magnetic resonance assessment of takotsubo cardiomyopathy A. Abbas*, E. Sonnex, R.S. Pereira, R.A. Coulden Department of Radiology and Diagnostic Imaging, University of Alberta Hospital, 8440 112 Street NW, Edmonton, Alberta, T6G 2B7, Canada

article in formation Article history: Received 29 April 2015 Received in revised form 4 September 2015 Accepted 20 October 2015

Takotsubo cardiomyopathy is an important condition that can be difficult to differentiate from acute coronary syndrome on the basis of clinical, electrocardiogram, and cardiac enzyme assessment alone. Although coronary angiography remains important in the acute assessment of patients with suspected takotsubo cardiomyopathy, cardiac magnetic resonance (CMR) has emerged over the last decade as an important non-invasive imaging tool in the diagnosis and follow-up of this condition. We present a review highlighting the CMR features of takotsubo cardiomyopathy and its complications with particular focus on differentiating this condition from acute myocardial infarction and myocarditis. Crown Copyright Ó 2015 Published by Elsevier Ltd on behalf of The Royal College of Radiologists. All rights reserved.

Introduction Since its initial description in 1991, takotsubo cardiomyopathy has emerged as an important consideration in the differential diagnosis of acute chest pain.1e4 It accounts for at least 2% of patients presenting with acute coronary syndrome (ACS) and is identified in 0.02% of all patients hospitalised in the United States each year.4,5 Over 90% of reported cases are among women, with an incidence in post-menopausal women almost five-times that of women under the age of 55 years.3,5 Due to under recognition of this condition, it is likely that the true prevalence is greater than that reported.2,3 The term “takotsubo cardiomyopathy” was first coined because the apical “ballooning” morphology of the left

* Guarantor and correspondent: A. Abbas, Department of Radiology and Diagnostic Imaging, University of Alberta Hospital, 8440 112 Street NW, Edmonton, Alberta, T6G 2B7, Canada. Tel.: þ1 01189617945. E-mail address: [email protected] (A. Abbas).

ventricle (LV) during systole resembles that of a traditional Japanese octopus fishing trap (“tako-tsubo”), which has a narrow neck and wide bottom.2,3 It has since been referred to in the literature by a variety of names including “broken heart syndrome”, “stress-induced cardiomyopathy”, and “transient LV apical ballooning syndrome”.2,3 Although controversy and debate persists regarding the nomenclature and pathophysiology of this condition, the American Heart Association has classified it as an acquired cardiomyopathy.3 Takotsubo cardiomyopathy is characterised by transient regional wall motion abnormalities that extend beyond recognised epicardial coronary distributions and can be difficult to distinguish from ACS on the basis of history, physical examination, electrocardiogram (ECG), and cardiac enzymes.2,3 Formal coronary catheter angiography remains integral to the assessment of ACS and raises the possibility of takotsubo cardiomyopathy or acute myocarditis when there is a typical appearance on LV angiography without obstructive epicardial coronary artery disease2,3 (Fig 1). Cardiac magnetic resonance (CMR) has emerged over the last decade as an important imaging technique in the acute assessment and 0009-9260/Crown Copyright Ó 2015 Published by Elsevier Ltd on behalf of The Royal College of Radiologists. All rights reserved.

A. Abbas et al. / Clinical Radiology 71 (2016) e110ee119


Figure 1 A 56-year-old female patient with a history of recent bereavement who presented to the emergency department with chest pain. Images during systole (a) and diastole (b) from LV angiogram performed as part of catheter angiography. This shows classical LV apical ballooning morphology (black arrow) and basal hyper-contraction (white arrows).

follow-up of these patients.6e8 In particular, CMR provides accurate assessment of global ventricular function, defines regional wall motion abnormalities, shows the presence or absence of myocardial oedema, and detects common complications associated with takotsubo cardiomyopathy.6e10 In addition, CMR allows differentiation of these patients from those with occult myocardial infarction without obstructive coronary disease and acute myocarditis.6e10

dysfunction also potentially accounts for the slow distal coronary perfusion, sometimes seen in these patients during coronary angiography.15 Whether microvascular dysfunction contributes to the pathogenesis of takotsubo cardiomyopathy, or merely represents a secondary effect, has yet to be established.


Patients with takotsubo cardiomyopathy most commonly present with acute, sustained chest pain, which may be indistinguishable from ACS.3,16 Less common presentations include dyspnoea, syncope, arrhythmias, and even cardiac arrest.16 Patients without typical clinical features are sometimes identified during inpatient hospital stays during the work-up of incidental ECG or cardiac enzyme abnormalities.3 Characteristically takotsubo cardiomyopathy is provoked by pronounced negative emotional, psychological, or physical stress.2,3,16 Common emotional triggers include anger and sadness, which may relate to recent arguments, bereavements, or financial difficulties.3,16 Physical stressors include surgery, neurological disorders, severe pain, recreational cocaine use, and opiate withdrawal.16 A number of iatrogenic triggers have been reported in association with takotsubo cardiomyopathy, including dobutamine stress imaging, exogenous catecholamine administration, and pain or anxiety related to a variety of medical procedures.2,3 Although a preceding trigger is not always identified, a careful history must be elicited from these patients, as critical information is not always disclosed during the initial clinical assessment.3 ECG findings in patients with takotsubo cardiomyopathy are varied but may resemble those of ST-elevation or nonST-elevation myocardial infarction.2,3,17 Marked STelevation is seen in up to 34% of patients, most typically in the anterior leads.17 Cardiac biomarkers are frequently elevated, usually peaking within 24-hours of presentation.2,3,16 Levels, however, are lower than would be expected for the severity of associated wall motion

Detailed understanding of the pathophysiology of takotsubo cardiomyopathy remains lacking.2,3 Catecholamine excess, microvascular dysfunction, and epicardial coronary spasm have all been postulated as potential mechanisms underlying this condition.3 It is likely that catecholamine excess plays an important role as circulating plasma catecholamine levels have been shown to be significantly elevated in many patients with takotsubo cardiomyopathy.2,3,11 Exogenous administration of catecholamine or excess catecholamine secretion by phaeochromocytomas, can provoke takotsubo cardiomyopathy.2,3,12 It has been postulated that high levels of plasma epinephrine switches b-2 adrenoreceptor coupling from the positively inotropic Gs-cyclic adenosine monophosphate (cAMP) mediated pathway to the negatively inotropic Gi signaling pathway.13 Interestingly, the density of sympathetic nerve endings is much higher at the apex, corresponding to the site of greatest LV dysfunction in the classical form of takotsubo cardiomyopathy.14 Although promising, this proposed mechanism requires further validation and does not explain why postmenopausal women are affected disproportionately or why some patients present with non-classical patterns of takotsubo cardiomyopathy.2,3 Epicardial coronary spasm is no longer believed to be important in the pathogenesis of takotsubo cardiomyopathy, although microvascular dysfunction, as indicated by reduced coronary flow reserve on cardiac positronemission tomography (PET) perfusion imaging, may be seen acutely in this group of patients.2,3 Microvascular

Clinical presentation


A. Abbas et al. / Clinical Radiology 71 (2016) e110ee119

Figure 2 Standard CMR protocol used for evaluating patients with suspected takotsubo cardiomyopathy at our institution. Localiser imaging sequences shaded in grey. Sequence names provided in parenthesis.

abnormalities and the extent of ECG findings.2 Even allowing for this, it may be impossible to distinguish takotsubo cardiomyopathy from acute myocardial infarct or myocarditis, and further investigations are often required. The absence of obstructive coronary artery disease on catheter angiography plays an important part in

differentiating takotsubo cardiomyopathy from acute myocardial infarct2,3; however, a study of 97 patients with confirmed takotsubo cardiomyopathy reported a 10% incidence of bystander coronary disease (defined as >75% diameter stenosis of a major epicardial coronary artery).18 Although severe multi-vessel epicardial coronary disease

Figure 3 CMR images from same patient as Fig 1. Two-chamber long-axis cine CMR sequence during systole (a) and diastole (b). The LV shows typical morphology of takotsubo cardiomyopathy with circumferential akinesia of the mid and apical LV myocardium and hyper-dynamic contraction of the base (white arrows) in systole. This mirrors the appearance on LV angiography.

A. Abbas et al. / Clinical Radiology 71 (2016) e110ee119


is uncommon in this patient group, the presence of bystander coronary disease should not, in itself, preclude the diagnosis of takotsubo cardiomyopathy.2,3,18

CMR imaging protocol and appearances

Figure 4 Three-chamber short-tau inversion recovery (STIR) image (oedema CMR) showing concentric increased signal in apical and mid-myocardium with normal myocardial signal at the base (arrowheads). High signal myocardial oedema matched the site of wall motion abnormality on cine CMR imaging. Note the abrupt transition in signal between oedematous mid- and non-oedematous basal myocardium (white arrow), which is typical of takotsubo cardiomyopathy.

Our CMR protocol for the investigation of suspected takotsubo cardiomyopathy is shown in Fig 2. In patients with classical takotsubo cardiomyopathy, cine CMR sequences demonstrate a circumferential LV regional wall motion abnormality (hypokinesia or, more typically, akinesia) involving the mid- and apical myocardial segments with normal or hyper-dynamic contraction of the base.6,7 Unlike patients with acute myocardial infarction, the pattern of LV apical ballooning during systole does not correlate with expected coronary artery anatomy (Fig 3).2,6,7 Not surprisingly, given the extent of regional wall motion abnormalities, patients with takotsubo cardiomyopathy often show resting systolic LV impairment with a reduced ejection fraction and abnormally elevated indexed endsystolic volume.6,8 CMR is the reference standard for assessing resting LV systolic function and can reliably quantify functional improvement seen in patients with takotsubo cardiomyopathy on subsequent follow-up.8,19

Figure 5 Single-shot SSFP images performed in two-chamber (a), basal short axis (b) and apical short axis planes (d), STIR images (oedema CMR) performed in basal short axis (c) and apical short axis (e) planes in a patient presenting with acute takotsubo cardiomyopathy. Circumferential myocardial oedema is indicated by high signal in the mid- and apical LV (white arrows) with sparing of the basal myocardial segments. Note how the single-shot SSFP sequences provide excellent contrast between normal and oedematous myocardium that mirrors the high signal on T2weighted STIR images and provides a useful adjunct to routine oedema CMR images.


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Figure 6 A 53-year-old woman presenting with chest pain, ST elevation, and unobstructed coronaries on angiography. LGE images performed in three-chamber (a) and four-chamber (b) planes. Transmural low-intensity enhancement circumferentially involves the mid- and apical myocardial segments (white arrows) and spares the base. This pattern is typical in patients with takotsubo cardiomyopathy and is seen in approximately 10e40% of patients.

Figure 7 LGE images performed in two-chamber (a) and mid-short axis (b) planes showing multiple foci of subepicardial and mid-myocardial bright late enhancement (white arrows) in a patient with acute myocarditis. Note how the distribution of late enhancement differs markedly from the concentric transmural low-intensity enhancement seen in takotsubo cardiomyopathy.

The role of oedema CMR imaging is well established for the assessment of myocardial oedema in acute cardiac diseases.10 Patients with takotsubo cardiomyopathy often demonstrate a circumferential transmural increase in T2 signal intensity in the mid- and apical LV corresponding to the wall motion abnormality seen on cine CMR (Fig 4).6,10 This pattern of oedema is frequently mirrored on the single-shot, relatively T2-weighted steady-state free-procession (SSFP) short axis localizers acquired at the beginning of the study and can be a useful alternative for assessing myocardial oedema when T2-weighted images are poor (Fig 5).20 Although non-specific, elevated LV muscle mass and a subtle increase in myocardial wall thickness are surrogate markers of myocardial oedema and may also be seen on CMR.10 It is important to remember that the pattern of oedema differs from that seen in acute myocardial infarction or myocarditis. In acute infarction, the distribution of oedema corresponds to a recognised

epicardial coronary artery territory and, in myocarditis, oedema tends to be basal, lateral, and subepicardial.6,10 Late gadolinium enhancement (LGE) sequences are important in differentiating takotsubo cardiomyopathy from acute myocardial infarction and acute myocarditis.9,21,22 Although it was initially thought that LGE was not a feature of takotsubo cardiomyopathy, more recent data have emerged showing that LGE may be identified acutely in 10e40% of patients.21,22 The distribution of LGE typically matches the sites of wall motion abnormality and myocardial oedema (Fig 6). This is in contrast to acute myocarditis, which shows non-circumferential oedema and LGE in a mid-wall or epicardial distribution at the LV base (Fig 7).21,22 Although oedema and LGE may be focal in acute myocarditis, wall motion abnormalities are typically global. Regional wall motion abnormalities only occur when regional involvement is particularly severe. When LGE is present in takotsubo cardiomyopathy it is frequently less bright (“low-intensity LGE”) than the LGE

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Figure 8 Pre-contrast single-shot SSFP (a) and STIR images (oedema CMR) (b) both performed in mid-short axis planes along with LGE images performed in mid-short axis (c) and two-chamber (d) planes in a patient with an acute myocardial infarct. Myocardial oedema (white arrows [aeb]), low-intensity LGE (interrupted white arrows [ced]) and intense late enhancement (black arrow) are all confined to the right coronary artery territory. This patient presented with an acute inferior ST elevation MI. Note how the endocardial bright LGE differs from the transmural low-intensity enhancement seen in patients with takotsubo cardiomyopathy (Fig 6) and is confined to a recognised coronary vascular territory. Low-intensity late enhancement in the setting of acute infarction may represent oedema without infarction.

Table 1 Differences in CMR features of takotsubo cardiomyopathy, acute myocardial infarction, and acute myocarditis. Takotsubo cardiomyopathya Site of wall motion abnormality Concentric mid- and apical LV wall Myocardial oedema LV impairment

Typically transmural in a concentric mid and apical LV wall distribution Yes: typically impaired ejection fraction with elevated indexed end systolic volume

RV impairment

>33% of patients

LGE Site of LGE

Maybe (10e40%) Concentric transmural mid and apical LV wall

Type of LGE Microvascular obstruction Resolution at 3 months

Low-intensity LGE No Yes

Myocardial infarction


Follows expected epicardial coronary artery distribution Subendocardial or transmural at sites of wall motion abnormalities Yes: typically impaired ejection fraction with elevated indexed end systolic volume May be seen, particularly if right coronary artery territory involved Yes Typically subendocardial or transmural in recognised epicardial coronary artery distribution Bright LGEb Maybe No

Usually global unless regional oedema/LGE is severe Subepicardial, mid-myocardial or transmural Yes, but may show only mild/ borderline low normal ejection fraction Rarely impacts on RV function

CMR, cardiac magnetic resonance imaging; LV, left ventricle; RV, right ventricle; LGE, late gadolinium enhancement. a CMR features listed are those of classical subtype of takotsubo cardiomyopathy. b Myocardium at risk may show low-intensity LGE in acute myocardial infarction.

Often Mid-myocardial or subepicardial in a focal non-coronary artery distribution Low-intensity or Bright LGE No Potentially but may show residual myocardial fibrosis and impairment


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Figure 9 A 54-year-old female patient presenting to the emergency department following an argument with her partner. Images from twochamber long-axis cine CMR sequence during systole (a) and diastole (b). LV demonstrates striking circumferential mid-akinesia with normal basal and apical contraction. This pattern of wall motion abnormality represents mid-variant sub-type takotsubo cardiomyopathy.

usually associated with myocardial infarction (Fig 8).21,22 A threshold signal intensity of more than 5 standard deviations (SD) above the mean of a region of interest in remote normal myocardium has been used to define intense LGE. Regions with a signal intensity greater than 2 or 3 SD and less than 5 SD are considered to be low-intensity LGE.9,21,22 The key CMR features that help differentiate takotsubo cardiomyopathy from acute myocardial infarction and acute myocarditis are summarised in Table 1. Although the majority of takotsubo cardiomyopathy patients demonstrate classical LV apical ballooning, different morphological sub-types of takotsubo cardiomyopathy can occur.2,3,23 These include mid-variant takotsubo cardiomyopathy, characterized by circumferential mid-LV akinesia with hyper-dynamic basal and apical contraction (Fig 9), and the less commonly reported reverse variant, which demonstrates circumferential basal and mid-LV akinesia with hyper-dynamic apical LV contraction.2,3 On CMR the distribution of myocardial oedema and LGE (if present) matches the sites of wall motion abnormality shown by these takotsubo variant subtypes. Interestingly, patients with recurrent episodes of takotsubo cardiomyopathy may demonstrate a different pattern of wall motion abnormality with each presentation.23,24 Takotsubo cardiomyopathy was initially thought to be restricted to the LV with only occasional reports of right ventricular (RV) involvement in the early literature.2,3 It is

now realized that RV impairment was underappreciated in these reports as the diagnosis was based on the left ventriculogram performed at the time of coronary angiography.3 Recent CMR studies have shown that RV systolic dysfunction is relatively common, occurring in up to 40% of patients.8,22 Although isolated RV involvement has been described, it is exceptionally rare.25,26

Complications and follow-up Although takotsubo cardiomyopathy is generally associated with a favourable long-term prognosis, lifethreatening complications may occur during the acute phase with reported mortality rates of up to 8% (Table 2).2,8,15 Evidence of heart failure, including pleural effusions, pericardial effusion, and pulmonary oedema are often seen on localiser and black-blood CMR sequences (Fig 10). Apical LV thrombus develops in approximately 5%

Table 2 Complications associated with acute takotsubo cardiomyopathy. -

Heart failure Left ventricular thrombus Left ventricular outflow tract obstruction Mitral regurgitation Life threatening arrhythmia Cardiogenic shock Left ventricular rupture Death

Figure 10 Axial black-blood CMR image showing pulmonary oedema (white arrows) and bilateral pleural effusions (black arrows) in a patient with acute left-sided heart failure caused by takotsubo cardiomyopathy.

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Figure 11 Images from four-chamber cine CMR during systole (a) and apical short-axis cine CMR (b) demonstrate thrombus within LV apex (white arrows) in a patient with takotsubo cardiomyopathy.

Figure 12 Three-chamber cine CMR images during systole (a) and diastole (b) demonstrating dynamic LV outflow tract narrowing in a patient with takotsubo cardiomyopathy. Systolic anterior motion (SAM) of the anterior mitral valve leaflet (black arrow) and accelerated flow jet through LV outflow tract (white arrow) is shown along with classical systolic apical LV ballooning morphology (interrupted arrow).

of cases and anticoagulant therapy is needed to avoid systemic emboli (Fig 11).6,8,27 In a small proportion of patients with takotsubo cardiomyopathy, hyper-dynamic basal myocardial contraction can lead to LV outflow tract obstruction and venturi-related systolic anterior motion of the anterior mitral valve leaflet (Fig 12).6,22 This is reversible and will resolve as the cardiomyopathy resolves. Detailed evaluation for the presence of these life-threatening complications is a vital part of CMR assessment in the acute setting. All patients with takotsubo cardiomyopathy should have follow-up imaging 3e4 months after their acute presentation, as complete recovery of LV systolic dysfunction helps to confirm the initial diagnosis.3 Although some patients may recover within a few days of presentation, recovery usually takes longer with the vast majority showing complete resolution at 3 months (Fig 13).2,3 In a small number of cases (

Cardiac magnetic resonance assessment of takotsubo cardiomyopathy.

Takotsubo cardiomyopathy is an important condition that can be difficult to differentiate from acute coronary syndrome on the basis of clinical, elect...
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