Download Dobutamine stress echo-induced apical ballooning (Takotsubo

European Journal of Echocardiography (2009) 10, 395–399
doi:10.1093/ejechocard/jen292
Dobutamine stress echo-induced apical ballooning
(Takotsubo) syndrome
Ronan Margey*, Pauline Diamond, Hugh McCann, and Declan Sugrue
Department of Cardiology, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland
Received 10 July 2008; accepted after revision 28 September 2008; online publish-ahead-of-print 22 October 2008
KEYWORDS
Dobutamine stress echo;
Apical ballooning;
Takotsubo cardiomyopathy;
Broken heart syndrome;
Catecholamine-induced
transient cardiomyopathy
Introduction
Takotsubo cardiomyopathy, also known as transient LV apical
ballooning syndrome, was originally described in Japan in
1991, due to the resemblance of the LV ventriculogram to
the appearance of a particular octopus pot.1,2 It has since
been described in a number of ethnic groups.3,4
In a systematic review of this condition, it is estimated
to account for 2% of all acute myocardial infarction presentations.4 It is most commonly triggered by significant
emotional, physical, or mental stress, accounting for 30–
50% of all cases, although it has been described to occur
with underlying medical disorders such as phaeochromocytoma, subarachnoid haemorrhage, exacerbation of bronchial
asthma, Guillain-Barré syndrome, non-cardiac surgery,
sepsis, and critical illness experienced by patients in intensive care units.5,6
Dobutamine stress echocardiography (DSE) is a commonly
performed diagnostic non-invasive test to assess the
stress-induced regional wall abnormalities indicative of
ischaemia, and also to assess viability and contractile
* Corresponding author. Tel: þ353 1 8034367; fax: þ353 1 8034775.
E-mail address: [email protected]
reserve in specific situations. Three case reports exist
demonstrating the potential of DSE to induce apical ballooning syndrome, although the exact mechanism remains poorly
understood.
Herein, we describe a case of Takotsubo cardiomyopathy
caused by DSE, and postulate that it occurred as a result
of apical hyper-responsiveness to adrenergic stimulation.
Case
A 61-year-old lady was referred for assessment of exertional
shortness of breath. She had a prior history of hypertension
and a 40-pack year smoking habit. There was a family
history of premature vascular disease. Her baseline electrocardiogram (ECG) showed hypertensive change, with
inferolateral repolarization abnormalities, and on that
basis, a dobutamine stress echocardiogram was performed
(Figures 1–4).
A standard dobutamine/atropine protocol was used with
10 mcg/kg/min dose increments at 3 min intervals. Her
resting echocardiogram and blood pressure were normal.
At 70% of her age-predicted heart rate, on 40 mg/min infusion of dobutamine, she developed typical cardiac chest
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Aims We report a case of dobutamine stress echocardiography (DSE) resulting in transient apical ballooning syndrome to highlight this rare condition as a potential complication of DSE.
Background Takotsubo cardiomyopathy, or transient apical ballooning syndrome, is a recently described
form of left ventricular (LV) dysfunction induced by stress. Clinically it can mimic acute coronary
syndrome in its presentation. It is characterized by an atypical distribution of LV dysynergy with
apical ballooning and compensatory basal hyperkinesis. Coronary angiography is normal. It has preponderance in females.
Although the aetiology of Takotsubo syndrome remains obscure catecholamine release appears to be
the principal trigger.
Results We report a case of dobutamine-induced transient LV apical ballooning in a woman without
coronary disease, during a dobutamine stress echocardiogram. There was evidence of ventricular
recovery by 72 h.
To our knowledge, only three other case reports describe dobutamine-induced Takotsubo
cardiomyopathy.
Conclusion Dobutamine stress echocardiography is a widely performed diagnostic test, however, it can
rarely result in presumed catecholamine-induced transient apical ballooning syndrome.
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R. Margey et al.
Figure 3
Baseline apical four-chamber view at end-systole.
Figure 2 Baseline short-axis view at end-systole.
Figure 4
Baseline apical two-chamber view at end-systole.
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Figure 1 Baseline parasternal long-axis view at end-systole.
pain, with associated inferolateral ST elevation, hyperacute
anterolateral T-waves, and ventricular bigeminy. On review
of the DSE images, it was apparent that there was severe
akinesis of the apical, anteroseptal, and apicolateral
segments at peak dobutamine infusion (Figures 5 and 6).
No evidence of a mid-cavity obstruction gradient was
demonstrated. She was immediately transferred to the
cardiac catheterization laboratory and underwent coronary
angiography. Her epicardial vessels were normal and a
mid-left anterior descending coronary artery segment of bridging was noted. Left ventriculography revealed hyperdynamic
basal myocardial segments with near-cavity obliteration,
distal anterior, inferior, lateral, and apical akinesis, and the
LV end diastolic pressure was 22 mmHg (Figures 7–9).
She was transferred to the coronary care unit, where she
was commenced on beta-blockade, and anti-coagulated.
Troponin I peaked at 4.8 ng/dL (0.01–0.04) and creatinine
kinase peaked at 243 mg/dL (21–232). Her in-hospital
course was complicated by atrial fibrillation with rapid ventricular response rates, requiring chemical cardioversion
with amiodarone, and by mild left ventricular (LV) failure,
requiring intravenous diuresis. Repeat echocardiography at
72 h showed near-normal LV function with mild residual
apical and anteroseptal hypokinesia.
Figure 5 Apical four-chamber view at peak dobutamine infusion,
end-systole [note the large apical balloon (arrow)].
Repeat cardiac catheterization before discharge on day
five, revealed markedly improved LV function, with an estimated ejection fraction of 50–55%, and mild residual anteroapical hypokinesia.
Apical ballooning syndrome
397
Figure 6 Apical two-chamber view at peak dobutamine infusion at
end-systole [note the apical ballooning (arrow)].
Figure 8 Left coronary angiogram anteroposterior projection
cranial view.
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Figure 7 Left ventriculogram at end-systole right anterior oblique
projection view (note the apical ballooning).
She has been symptom free since discharge and repeat
echocardiogram at 8 weeks, revealed complete recovery
of LV function.
Figure 9 Right coronary angiography left anterior oblique projection cranial view.
Discussion
Takotsubo cardiomyopathy is a recently described clinical
condition, originally described in 1991.1
Typically, it presents with symptoms and signs resembling
an acute coronary syndrome, which can lead to inappropriate therapy, e.g. thrombolytic administration.7,8
It has preponderance in females (9:1). In most reported
series, it commonly affects post-menopausal women, with
an average age range of 62–75 years, although it has been
reported in individuals aged 10–91 years.8
It commonly presents with chest pain (68%), although it
may present with shortness of breath (20%), cardiogenic
shock (4%), or ventricular arrhythmia (2%).5–7
Electrocardiogram typically shows ST elevation typical of
acute myocardial infarction, deep global T-wave inversion,
or prolongation of the QT interval; and the ECG changes
can affect multiple territories. The ECG changes typically
resolve over within months.7,8
It is associated with mild elevation in cardiac enzymes,
disproportionately low given the extent of wall motion
abnormality.7,8
Echocardiography shows a typical appearance of significant LV dysfunction, with preserved basal segment function,
and moderate to severe dysfunction of the mid- and apical
segments. The echocardiographic appearance improves
rapidly over 3–5 days.
398
this, it is well described that females appear more
vulnerable to sympathetically mediated stunning, and postmenopausal alteration of endothelial function in response to
decreased oestrogen levels has been associated advocated
as a possible explanation.11
A recent paper postulated that the condition arises due to
the hyperdynamic basal segments creating an intracavity
gradient causing excess release or dehydration of catecholamine, resulting in an isolated apical chamber that produces
myocardial stunning without infarction.12–14 It is known that
up to 20% of patients undergoing DSE develop a dynamic LV
mid-cavity obstruction, and perhaps this reflects the potential mechanism of apical ballooning induced by DSE.13,14
In our case, no clear emotional or stress trigger could be
identified. The only apparent initiation factor would
appear to be dobutamine infusion. We postulate that
increased apical responsiveness to adrenergic stimulation
previously described, offers a potential mechanism as to
how DSE could culminate in transient apical ballooning. In
addition to overstimulation of the apical adrenergic receptors, dobutamine may also has worsened the hyperdynamic
basal systolic function, creating an artificial LVOT gradient,
and further stressing the myocardium, which was not
demonstrated in our case. This mechanism, however, was
demonstrated in a previous series where patients with
Takotsubo cardiomyopathy underwent low-dose DSE following recovery, which provoked an LV mid-cavity gradient at
peak dose.14
Conclusion
Dobutamine stress echocardiography is a widely performed
test, and is largely safe, although induction of myocardial
infarction is well recognized. Our report highlights the
potential of DSE to induce transient apical ballooning,
through a combination of adrenergic overstimulation and
LV mid-cavity obstruction. All centres performing DSE
should be aware of the potential complication of apical ballooning syndrome.
Conflict of interest: none declared.
Funding
R.M. research position is kindly funded by an educational
grant from the Irish Heart Foundation, the Health Services
Executive of Ireland, and by an unrestricted educational
bursary from Medtronic Corporation, Ireland.
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Cardiac magnetic resonance (CMR) does not show any evidence of myocardial necrosis, and endomyocardial biopsy
tends to show a mononuclear infiltrate without any evidence
of myocarditis or myocardial necrosis. Occasionally, contraction band necrosis can be observed, which is well described
in catecholamine-induced myocyte injury.5,7,8
Angiography in the vast majority of described cases shows
normal coronaries. Spontaneous or provoked multivessel
epicardial vessel spasm has been described.5
The combination of apical and mid-ventricular wall
motion abnormalities can cause intracavity LV gradient,
which can cause haemodynamic instability, and result in systolic anterior motion of the anterior mitral leaflet, producing posteriorly directed mitral regurgitation.8
Recovery is usually rapid, although heart failure, cardiogenic shock, ventricular arrhythmia, mitral incompetence,
LV outflow tract (LVOT) obstruction, and free wall rupture
have all been described as a complication of this condition.
In the published literature, it is associated with a 3.5% risk of
recurrence. Right ventricular dysfunction has been
described in up to one-third of cases. These patients are
particularly prone to LV thrombus formation.7,8
In-hospital mortality has been estimated at 1.1%, with
up to 20% experiencing heart failure. The commonest
reported causes of mortality are cardiogenic shock and
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Management is largely supportive, with fluid resuscitation
(if no pulmonary congestion), beta-blockade, and occasionally afterload augmentation with phenylephrine in those
with an LVOT gradient. Consideration should be given to
therapeutic anti-coagulation to prevent thromboembolism.
For those with haemodynamic instability, inotropes and
intra-aortic balloon counterpulsation may be required.7,8
The exact mechanism of occurrence remains poorly
understood, but several hypotheses exist.
Epicardial coronary spasm has been demonstrated in up to
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remains unclear. Microvascular spasm and microvascular
obstruction have been hypothesized, but the lack of subendocardial infarction on CMR undermines this theory.5,8
Catecholamine levels are significantly elevated in individuals with this condition, reflecting increased synthesis,
reuptake, and removal metabolism of the adrenergic
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myocyte, resulting in direct myocyte injury.5 Catecholamines may also stimulate oxygen-free radical generation,
which can cause local myocyte injury.5
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and may be vulnerable to surges in circulating catecholamine levels.9 Local release of catecholamines from adrenergic neurones in the myocardium seems unlikely as there
is a higher norepinephrine content and concentration of
sympathetic nerves at the base of the heart compared
with the apex.9 A base-to-apex perfusion gradient may
exist as occurs in individuals with coronary risk factors.10
Finally, sex differences may account for the condition
occurring predominately in females, although it is worthwhile noting that higher circulating basal levels of catecholamines occur in men, and males produce a more marked
elevation in catecholamines in response to stress.6 Despite
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