Neurol Med Chir (Tokyo) 50, 393¿395, 2010

Takotsubo Cardiomyopathy Induced by Dobutamine
Infusion During Hypertensive Therapy for Symptomatic
Vasospasm After Subarachnoid Hemorrhage
—Case Report—
Ryuta SAITO, Toshie TAKAHASHI, Nobuo NOSHITA,
Ayumi NARISAWA, Ken NEGI*, Kazuyasu TAKEI*, and Uichi KANEKO
Departments of Neurosurgery and *Cardiology, Saitama Red Cross Hospital, Saitama

Abstract
A 65-year-old female with subarachnoid hemorrhage (SAH) developed takotsubo cardiomyopathy induced by dobutamine infusion for vasospasm 9 days after onset of SAH. She underwent neck clipping of
the ruptured cerebral aneurysm on day 1. Course after surgery was uneventful, but she developed motor
aphasia on day 9. Hypertensive therapy was carried out under the diagnosis of symptomatic vasospasm.
Half an hour after initiation of dobutamine infusion at 6 mg/kg/min, sudden symptoms of takotsubo
cardiomyopathy developed. Fortunately, her symptoms recovered in a few days with supportive therapy
without any consequences. Takotsubo cardiomyopathy is one pattern of cardiac dysfunction occasionally encountered after SAH. Possible mechanisms of this disorder include epicardial catecholamine cardiotoxicity. Therefore, generally, cardiac function is worst at the early stage of SAH, when
sympathetic activity is highest, and recovers thereafter. Dobutamine infusion seems to have triggered
the takotsubo cardiomyopathy in the present patient even 9 days after onset of SAH. Inotropic agents including dobutamine are often used during the course of SAH, and since takotsubo cardiomyopathy can
occur in patients with SAH, this complication must be considered.
Key words:

subarachnoid hemorrhage,

vasospasm,

Introduction

Case Report
A 65-year-old female with history of smoking and moderate obesity suffered sudden onset of severe headache. Her
consciousness was almost alert without limb paresis during ambulance transportation to our hospital and immediately after arrival she suffered another attack. Her conJune 29, 2009;

Accepted

takotsubo cardiomyopathy

sciousness level deteriorated to Glasgow Coma Scale
(GCS) 4 (E1V1M2). Brain computed tomography (CT) revealed SAH (Fig. 1A). After admission, her consciousness
gradually recovered. Three-dimensional CT angiography
demonstrated an anterior communicating artery
aneurysm (Fig. 1B), which was successfully clipped on the
next day with consciousness level at GCS 12 (E2V4M6)
(Fig. 1C). The postoperative course was uneventful until 9
days after onset.
She developed motor aphasia on day 9. Cerebral angiography performed a day before revealed vasospasm in
the left carotid and left middle cerebral arteries (Fig. 1D).
Hypertensive therapy was carried out with the diagnosis
of symptomatic vasospasm. Half an hour after initiation of
dobutamine infusion at 6 mg/kg/min, sudden symptoms of
heart failure developed. Electrocardiography showed
marked ST elevation in leads I, II, aVL, and V2-V6 (Fig. 2).
Emergency coronary angiography was performed suspecting acute myocardial infarction, but was negative (Fig.
3A, B). However, left ventriculography showed apical akinesis and basal hyperkinesis indicating takotsubo
cardiomyopathy (Fig. 3C, D). Hypertensive therapy was
stopped at this point. She was observed in the coronary
care unit for 3 days, her heart failure did not worsen and
gradually recovered. Her motor aphasia also recovered in

Cardiac dysfunction after subarachnoid hemorrhage
(SAH) is a well-recognized phenomenon. Electrocardiographical changes such as QT elongation and
ST-T changes are observed in as many as 90% of cases.3)
Left ventricular systolic dysfunction occurs in approx.
10% of patients with SAH.2,6,8) Although the pathophysiology of cardiac injury after SAH is still not clear, the most
likely cause of cardiac dysfunction after SAH is excessive
catecholamine release within the myocardium.4,5)
We report a case of SAH associated with takotsubo
cardiomyopathy which manifested after dobutamine infusion during hypertensive therapy for symptomatic
vasospasm 9 days after onset of SAH.

Received

dobutamine,

October 9, 2009

393

394

R. Saito et al.

Fig. 1 A: Brain computed tomography (CT) scan obtained on
admission. B: Three-dimensional CT angiogram (anteroposterior view) revealing an anterior communicating artery
aneurysm. C, D: Digital subtraction angiograms performed on
day 8 revealing complete clipping of the aneurysm (C: right
carotid angiography, anteroposterior view) and multiple
moderate to severe vasospasm (D: left carotid angiography, oblique view). E: Brain CT scan obtained just before the patient
was discharged to local hospital for further rehabilitation.

Fig. 3 A, B: Left (A) and right (B) coronary angiograms showing no obstruction or significant stenosis. C, D: Left ventriculograms (C: diastolic phase, D: systolic phase) showing apical akinesis (white arrow) and basal hyperkinesis (black arrow)
indicating takotsubo cardiomyopathy.

Discussion

Fig. 2 Electrocardiograms obtained on admission (A), just after manifestation of takotsubo cardiomyopathy (B), after emergency coronary angiography (C), and a day after onset of takotsubo cardiomyopathy (D).

a few days. After placement of a ventriculoperitoneal
shunt, she was discharged to another hospital for further
rehabilitation (Fig. 1E).

Takotsubo cardiomyopathy is one pattern of cardiac dysfunction occasionally found after SAH,11) characterized by
transient left ventricular apical wall motion abnormality
with electrocardiographic changes and minimal myocardial enzymatic release mimicking acute myocardial
infarction, but without significant coronary artery disease.7,16,17) Several possible mechanisms have been
proposed for takotsubo cardiomyopathy including
epicardial catecholamine cardiotoxicity. Most reported
cases of takotsubo cardiomyopathy have shown simple
clinical courses after onset. Usually cardiac function is
worst at the early stage of SAH, when sympathetic activity
is highest, and recovers thereafter. However, in our case,
dobutamine infusion 9 days after onset of SAH triggered
the manifestation of takotsubo cardiomyopathy. Although
the precise mechanism still remains unclear, sympathetic
overactivation may be important in takotsubo cardiomyopathy in patients with SAH.11,18) Excess sympathetic nervous activation occurs after SAH, with increased plasma
norepinephrine level within 48 hours that persists during
the 1st week after hemorrhage.10,12,14) Therefore, in many
cases, ejection fraction is worst during the early stage of
SAH and recovers afterward.11) A previous patient with
SAH had takotsubo cardiomyopathy which worsened in
the late phase of vasospasm.15) However, the takotsubo
cardiomyopathy was present at disease onset. In our
patient, electrocardiography on admission did not show
any evidence of takotsubo cardiomyopathy. Therefore, the
onset of takotsubo cardiomyopathy in our case was un-

Neurol Med Chir (Tokyo) 50, May, 2010

Dobutamine-Induced Takotsubo Cardiomyopathy
usual.
Dobutamine infusion seems to have triggered the
cardiac dysfunction in the present case. Direct release of
toxic levels of catecholamines into the myocardium by the
cardiac sympathetic nerve terminals is indicated as a
more likely cause of neurocardiogenic injury than adrenal
release of catecholamines into the systemic circulation in
animal models.13) No significant association was found between serum levels of either norepinephrine or
epinephrine and cardiac troponin I release that indicate
myocardial necrosis in patients with SAH.18) However, a
case of takotsubo cardiomyopathy resulting from dobutamine infusion was reproducible in the catheterization
laboratory, suggesting that catecholamine-induced microvascular dysfunction may be the predominant etiological
factor in takotsubo cardiomyopathy.1) A case of takotsubo
cardiomyopathy precipitated by dobutamine stress testing
was also reported in a morbidly obese woman who underwent a dobutamine nuclear stress test as preoperative
screening before bariatric surgery.16) In the present case,
known preceding psychological stressor was absent, so
dobutamine may have been the precipitant.
Treatment of takotsubo cardiomyopathy in a patient
with symptomatic cerebral vasospasm is complicated.
Hemodynamic augmentation, consisting of increasing intravascular volume and blood pressure parameters, is
difficult to attain.11) Cardiac output may need support with
dobutamine or milrinone, especially if the blood pressure
remains low. However, use of pressor could have resulted
in unfavorable outcome in our patient. We only could
maintain the systolic blood pressure at 100–120 mmHg,
which may not have been high enough during the phase of
cerebral vasospasm. Fortunately, motor aphasia observed
in our patient disappeared without any consequences.
One study demonstrated acute improvements in electrocardiographic and ventriculographic abnormalities
with intravenous propranolol infusion.9) Such new evidence may be a help for future management of similar
cases. Inotropic agents including dobutamine are often
used during the course of SAH, and since takotsubo
cardiomyopathy can occur in patients with SAH, the complication encountered in the present case must be considered.

5)
6)

7)

8)

9)

10)

11)

12)

13)

14)

15)

16)

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Address reprint requests to: Ryuta Saito, M.D., Department of
Neurosurgery, Saitama Red Cross Hospital, 8–3–33
Kami–ochiai, Chuo–ku, Saitama 338–8553, Japan.